- What is adenocarcinoma
- Adenocarcinoma lung
- Esophageal adenocarcinoma
- Gastric adenocarcinoma
- Adenocarcinoma colon
- Adenocarcinoma colon causes
- Risk factors for adenocarcinoma colon
- Adenocarcinoma colon prevention
- Adenocarcinoma colon symptoms
- Adenocarcinoma colon diagnosis
- Adenocarcinoma colon treatment
- Adenocarcinoma colon survival rate
- Pancreatic adenocarcinoma
- Adenocarcinoma prostate
- Adenocarcinoma prostate causes
- Risk factors for prostate adenocarcinoma
- Adenocarcinoma prostate screening
- Adenocarcinoma prostate prevention
- Adenocarcinoma prostate symptoms
- Adenocarcinoma prostate diagnosis
- Adenocarcinoma prostate treatment
- Adenocarcinoma prostate survival rate
- Adenocarcinoma survival rate
What is adenocarcinoma
Adenocarcinoma is cancer that begins in glandular (secretory) cells. Glandular cells are found in tissue that lines certain internal organs and makes and releases substances in the body, such as mucus, digestive juices, or other fluids. Most cancers of the breast, pancreas, lung, prostate, and colon are adenocarcinomas.
Lung adenocarcinoma is the most common primary lung cancer seen in the United States 1). Lung adenocarcinoma falls under the umbrella of non-small cell lung cancer (NSCLC) and has a strong association with previous smoking. While incidence and mortality have declined, it remains the leading cause of cancer death in the United States. Adenocarcinoma of the lung usually evolves from the mucosal glands and represents about 40% of all lung cancers. Lung adenocarcinoma is the most common subtype to be diagnosed in people who have never smoked. Lung adenocarcinoma usually occurs in the lung periphery, and in many cases, may be found in scars or areas of chronic inflammation 2).
Although incidence and mortality of adenocarcinoma lung have declined since the 1980s, in 2015 there were 221,200 new cases of lung and bronchial cancers and more than 158,000 lung cancer deaths representing the most common cause of cancer death 3).
Lung cancer is also widespread globally. Over the past 4 decades, there has been a marked increased in lung adenocarcinoma in women, and this has been linked to smoking 4). The mean age of diagnosis of lung adenocarcinoma is 71 years, and this particular cancer is very rare before the age of 20. In the last 2 decades, adenocarcinoma has replaced squamous cell cancer of the lung as the most prevalent non-small cell cancer 5).
Lung adenocarcinoma is classified into 4 types:
- Adenocarcinoma in situ (AIS),
- Minimally invasive adenocarcinoma (MIA),
- Invasive adenocarcinoma, and
- Variants of adenocarcinoma.
Of these adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) have better outcomes when resected early. Local spread may involve spread directly to the pleura, diaphragm, pericardium, or bronchi with advanced disease spreading to the mediastinum, great vessels, trachea, esophagus, vertebral column, or adjacent lobe. Lymph node metastasis occurs in peribronchial lymph nodes before moving to mediastinal or subcarinal nodes and then the contralateral lung. Distant metastasis includes extension to a contralateral lobe, pleural nodules, malignant pleural or pericardial effusion, or any distant site such as the brain, bones, or liver. There is a subset of non-small cell lung cancer that have mutations in epidermal growth factor receptor, which sensitizes them to tyrosine kinase inhibitors, as well as anaplastic lymphoma kinase fusion oncogene rearrangements 6).
When the lung is biopsied, the histological analysis will reveal a tumor arising from the bronchial glands. Mucus production is also quite evident. The new World Health Organization (WHO) classification subclassifies adenocarcinomas as arising from the following:
- Acinar adenocarcinoma
- Papillary adenocarcinoma
- Bronchoalveolar adenocarcinoma
- Mucus-secreting adenocarcinoma
Except for Stage 1 lung cancer, adenocarcinoma carries a much worse prognosis than squamous cell cancer (SCC).
Adenocarcinoma lung cancer causes
By far, the main risk factor for any lung cancer, including lung adenocarcinoma, is smoking tobacco 7). Due to numerous carcinogens present in tobacco smoke, primary or secondary exposure increases risk proportional to the amount of exposure.
Other risk factors include a family history of lung cancer, or occupational exposure to other agents such as silica, asbestos, radon, heavy metals, and diesel fumes, though these are less prevalent. Resultant genetic mutations in the p53 gene are the most frequent cause of tumorigenesis in non-small cell lung cancer in 52% of cases 8).
Lung adenocarcinoma survival rate
Despite new treatments, the 5-year survival is less than 12% to 15% 9), 10).
- For Stage 1 disease, 5-year survival varies from 70% to 85%.
- For locally advanced disease, the survival drops to less than 30%.
- For distant metastases, less than 5% survive five years.
The majority of lung cancers are advanced at the time of diagnosis, and consequently, the prognosis is very poor. More than 80% of patients with advanced lung cancer are dead by 5 years. Despite all the advances, the longevity has not increased over the past 3 decades. Thus, today the emphasis is on screening for lung cancer and prevention 11).
Lung adenocarcinoma symptoms
Symptoms and physical signs are dependent on the stage of lung cancer. The earliest stages are often asymptomatic, with nodules found incidentally on radiographic images testing for other disease processes. Later stage disease may present with nonspecific symptoms such as a cough, hemoptysis, or unintentional weight loss. If the patient presents with a pleural effusion, he or she may have shortness of breath with decreased breath sounds. The vast majority of patients will have a smoking history and may have other associated diseases such as chronic obstructive pulmonary disease (COPD) or a family history of lung cancer.
Symptoms of lung cancer include:
- coughing up blood (hemoptysis)
- recurring bronchitis or pneumonia
- loss of appetite
- unexplained weight loss
- shortness of breath
- chest pain
A significant number of patients with lung adenocarcinoma will present with a locoregional spread that may include symptoms from:
- Superior vena cava obstruction
- Phrenic nerve palsy
- Horner syndrome
- Compression of brachial plexus
- Pericardial effusion
Paraneoplastic syndromes are rare with adenocarcinoma but may include:
- Cushing syndrome
- Eaton Lambert syndrome
- Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
- Hypertrophic osteoarthropathy
Lung adenocarcinoma diagnosis
High-risk patients like current and former heavy smokers are recommended to undergo screening with low-dose CT scan by the US Preventative Services Task Force 12).
If a lung nodule is found, the next step depends on the and imaging characteristics of the lung nodule. If a nodule is suspicious for lung cancer, PET/CT may be performed followed by biopsy or surgical excision. Based upon National Comprehensive Cancer Network Guidelines the next step is a full CT of the thorax and abdomen with contrast (including adrenals), bronchoscopy, mediastinal lymph node evaluation, complete blood count and blood chemistry profile.
Brain MRI is recommended for those with Stage 2, 3, or 4 disease to rule out metastasis. These results are then synthesized to generate a clinical stage to guide treatment.
If bone metastases are suspected, then a bone scan should be obtained.
PET scan is usually used to assess for recurrence of the disease.
Sputum cytology is rarely helpful as most adenocarcinomas are peripheral lesions.
Needle thoracentesis is done when an effusion is seen. It can be both diagnostic and therapeutic.
Additionally, any patients being considered for surgical resection should undergo pulmonary function testing to determine the feasibility of lung resection based on predicted postoperative lung function.
If the CT scan reveals mediastinal nodes, then a mediastinoscopy or thoracoscopy is recommended to stage the patient.
Staging of the patient is mandatory before recommending any treatment 13).
Lung adenocarcinoma treatment
- The treatment of lung adenocarcinoma depends on the stage. For early-stage disease, surgery is the treatment of choice.
- For advanced disease, a combination of surgery, chemotherapy, and radiation is used to manage pain and other complications.
- Overall, outcomes for localized disease are far superior to other forms of treatment.
- Airway obstruction can be managed with laser and stent placement.
- Chemotherapy with targeted therapy may prolong survival, but the cost of the medications is prohibitive.
- The majority of lung cancer patients require palliation.
- Radiation therapy is often used to manage bone and brain metastases.
Surgery is the treatment for patients with Stage 1 to Stage 3A adenocarcinoma of the lung. Lobectomy or a pneumonectomy are often performed.
Since these patients have a high risk of relapse, adjuvant chemotherapy is now standard.
Radiation therapy is only an option for patients who are not surgical candidates.
Because the majority of lung adenocarcinomas are incurable or advanced, chemotherapy is often used. Despite significant advances in chemotherapy, the survival of most patients with lung adenocarcinoma remains abysmal. Platinum-based regimens remain the mainstay of chemotherapy.
For patients with metastatic disease, molecular targeted therapy is being offered, but the results are not spectacular. At best the survival is increased by a few months, but the medications can cost over $20,000 a month 14).
These are limited invasive tumors or limited nodal disease. The tumor is assessed for resectability, and if operable, surgical resection is recommended with lymph node sampling. If the patient is not an operative candidate, then definitive radiotherapy with possible adjuvant chemotherapy may be performed if the patient has positive nodes or is high risk. Some specific invasive tumors may be treated with neoadjuvant chemoradiation before resection 15).
Stage 3B and Stage 4
These stages involve mediastinal, subcarinal, and/or contralateral nodes and metastatic disease. These stages are considered unresectable and are treated with chemoradiation. Some extrapulmonary sites may be treated as well for palliation.
The pathologic specimen is tested for epidermal growth factor receptor (EGFR) sensitizing mutations and anaplastic lymphoma kinase (ALK) mutation. Those that are positive for epidermal growth factor receptor (EGFR) may be treated with tyrosine kinase inhibitors, while those exhibiting the anaplastic lymphoma kinase (ALK) mutation may be treated with ALK inhibitors as first-line chemotherapy. If the tumor is epidermal growth factor receptor and anaplastic lymphoma kinase-negative, first-line chemotherapy is usually a platinum-based doublet, with bevacizumab as a possible third agent.
After treatment, patients need surveillance with CT Chest every six to 12 months for two years and annual low-dose CT. This should be done more frequently in those with residual disease. Locoregional occurrence may be treatable. Options include external beam radiation therapy, resection, chemotherapy, and photodynamic therapy depending on where the lesion has recurred and the associated symptoms 16).
Histologically, the majority of esophageal cancers are divided into squamous cell carcinoma (SCC) and adenocarcinoma 17). Over the past few decades, the rates of squamous cell cancers have declined, but the rates of adenocarcinoma have gradually increased, chiefly because of gastroesophageal reflux disease (GERD). Adenocarcinomas typically start in the lower esophagus and squamous cell carcinoma can develop throughout the esophagus 18). When stratified by anatomical location, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction (GEJ) continues to increase rapidly due to Barrett’s esophagus 19).
Adenocarcinomas, typically arising in Barrett esophagus, account for at least 50% of malignant lesions, and the incidence of this histology appears to be rising 20). Barrett esophagus contains glandular epithelium cephalad to the esophagogastric junction.
Three different types of glandular epithelium can be seen:
- Metaplastic columnar epithelium.
- Metaplastic parietal cell glandular epithelium within the esophageal wall.
- Metaplastic intestinal epithelium with typical goblet cells. Dysplasia is particularly likely to develop in the intestinal type mucosa.
In the United States, esophageal cancers represent the fifth most common gastrointestinal cancer with an estimated 16,940 cases per year and are the sixth most common cancer worldwide 21). The highest-risk area, called “esophageal cancer belt,” includes portions of northern Iran, southern Russia, central Asian countries, and northern China where squamous cell cancers dominate all cases by 90%. In this risk area, esophageal cancer is the fourth most common cause of cancer. In contrast, the United States is considered a low-risk area with an increase in the incidence of esophageal adenocarcinoma mostly due to an upsurge of obesity and GERD, and conversely a steady decrease in squamous cell carcinoma because of the long-term reduction in tobacco use and alcohol consumption. Adenocarcinoma is largely a disease of white, male individuals. Conversely, esophageal squamous cell carcinoma incidence rates are highest among blacks and Asians 22).
Estimated new cases and deaths from esophageal cancer in the United States in 2019 23):
- New cases: 17,650.
- Deaths: 16,080.
The incidence of esophageal cancer has risen in recent decades, coinciding with a shift in histologic type and primary tumor location. In the United States, squamous cell carcinoma has historically been more prevalent although the incidence of adenocarcinoma has risen dramatically in the last few decades in the United States and western Europe 24). Worldwide, squamous cell carcinoma remains the predominant histology, however, adenocarcinoma of the esophagus is now more prevalent than squamous cell carcinoma in the United States and western Europe 25). The incidence of adenocarcinoma has increased most notably among white males 26). In the United States, the median age of patients who present with esophageal cancer is 67 years 27). Most adenocarcinomas are located in the distal esophagus. The cause for the rising incidence and demographic alterations is unknown.
Tumors of the esophagus are conventionally described in terms of distance of the upper border of the tumor to the incisors. When measured from the incisors via endoscopy, the esophagus extends approximately 30 to 40 cm. The esophagus is divided into four main segments:
- Cervical esophagus (~15–20 cm from the incisors).
- Upper thoracic esophagus (~20–25 cm from the incisors).
- Middle thoracic esophagus (~25–30 cm from the incisors).
- Lower thoracic esophagus and gastroesophageal junction (~30–40 cm from the incisors).
Approximately 60% of adenocarcinoma of the distal esophagus and more typically, gastroesophageal junction cases, arise from Barrett’s esophagus metaplastic epithelium 28). The typical treatment for patients with Barrett’s esophagus is surveillance using upper endoscopy and biopsy to examine tissue for evidence of dysplasia. The incidence rate for adenocarcinoma among patients without dysplasia is 1.0 case per 1000 person-years; on the other hand, detection of low-grade dysplasia on the index endoscopy is associated with an adenocarcinoma incidence rate of 5.1 cases per 1000 person-years. The annual risk of esophageal adenocarcinoma is 0.12% 29). High-grade dysplasia should be managed aggressively, including the possibility for surgical resection. Early metastases occur in adjacent or regional lymph nodes. Predictors such as tumor markers, (TP53), may indicate potential progression to malignant disease.
Assessment of human epidermal growth factor receptor 2 (HER2) gene and protein expression has been implicated in tumor invasion and lymph node metastasis associated with poorer survival. HER2 is overexpressed more frequently in adenocarcinoma (30%) than squamous cell carcinoma (13%). HER2 is recommended for all metastatic adenocarcinomas, first using immunohistochemistry score (negative for 0 or 1+ and positive 3+, with reflex FISH for 2+) to confirm 30).
Esophageal adenocarcinoma causes
Most esophageal adenocarcinomas in the United States arise from Barrett’s metaplasia of which 80% of cases are attributed to a history of smoking, high body mass index, gastroesophageal reflux disease (GERD), and a low fruit and vegetable diet 31). Alcohol intake has not been associated with adenocarcinoma 32). Barrett’s esophagus metaplasia has been associated with epidermal growth factor polymorphisms, Helicobacter pylori infection, and other conditions which increase esophageal acid exposure including (e.g., Zollinger-Ellison syndrome, scleroderma, lower esophageal sphincter relaxing drugs, or procedures). Familial Barrett’s esophagus may be associated with rare autosomal inherited dominant susceptible alleles and should be suspected in a patient with esophageal or gastroesophageal junction adenocarcinoma, particularly in a white male, with GERD, and older than 40 years. High cereal diet, antioxidants, fruits and vegetables, folate, vitamin C, proton-pump inhibitors, and nonsteroidal anti-inflammatory drugs (NSAIDs) can protect against development and progression of Barrett’s esophagus, and hence, esophageal adenocarcinoma, but despite these associations, none has confirmed to be a preventive intervention 33).
In post-marketing surveillance, oral bisphosphonates have been linked to esophageal squamous cell carcinoma and adenocarcinoma.
Risk factors for esophageal adenocarcinoma
Risk factors associated with esophageal adenocarcinoma are less clear 34). Barrett esophagus is an exception and its presence is associated with an increased risk of developing adenocarcinoma of the esophagus. Chronic reflux is considered the predominant cause of Barrett metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma 35).
Risk factors for esophageal adenocarcinoma
Risk factors associated with esophageal adenocarcinoma are less clear 36). Barrett esophagus is an exception and its presence is associated with an increased risk of developing adenocarcinoma of the esophagus. Chronic reflux is considered the predominant cause of Barrett metaplasia. The results of a population-based, case-controlled study from Sweden strongly suggest that symptomatic gastroesophageal reflux is a risk factor for esophageal adenocarcinoma. The frequency, severity, and duration of reflux symptoms were positively correlated with increased risk of esophageal adenocarcinoma 37).
Esophageal adenocarcinoma symptoms
Esophageal cancers are often not detected until they are quite advanced, because there may not be any symptoms in the early stages of the disease. Symptoms of esophageal cancer include:
- difficulty or pain when swallowing
- pain in the top part of the abdomen when eating
- acid reflux or heartburn
- food coming back up
- weight loss
- feeling very tired
- a hoarse voice or a cough that doesn’t go away
- coughing or vomiting up blood
- black or bloody bowel motions
The most common clinical presentation of both esophageal adenocarcinoma and squamous cell carcinoma is progressive solid food dysphagia due to locally advanced cancer causing obstruction and dysphagia to liquid manifests in advanced stages. Cachexia and substantial weight loss are consequences of dysphagia, which may represent advanced disease causing many patients to be debilitated at the time of the diagnosis. Subtle non-specific symptoms may have preceded such as retrosternal discomfort or burning sensation. Hematemesis, melena, and anemia symptoms can be present at the initial diagnosis as part of overt or occult gastrointestinal bleeding. Regurgitation can also occur, but aspiration pneumonia is rare. Patients with tracheobronchial wall invasion causing fistulas can present clinically with laryngeal nerve paralysis, cough, and/or post-obstructive pneumonia.
All of these symptoms can be explained by something else. But if you are worried, tell your doctor.
Esophageal adenocarcinoma diagnosis
Clinical examination focused on lymph nodes in the supraclavicular and axillary regions is fundamental. If your doctor suspects you have esophageal adenocarcinoma, they may order tests such as an endoscopy (where a flexible tube is used to look down your throat and into your stomach), a biopsy (where a small sample of tissue is removed to be examined in the lab), and scans including CT or PET.
Multiple biopsies should provide sufficient histological material with a higher accuracy of obtaining a correct diagnosis (one biopsy 93% accuracy, four biopsies 95% accuracy, seven biopsies 98% accuracy). In vivo staining with Lugol’s iodine is not established 38).
Computed tomography (CT) of the thorax and abdomen should be performed to evaluate the extent of the primary tumor and search potential liver metastases and celiac lymphadenopathy. However, CT is inconsistent to differentiate tumor depth, has poor lymph node sensitivity, and occasionally fails to detect small metastases, particularly within the peritoneum.
Endoscopic ultrasound (EUS) has become the standard of therapy technique for locoregional staging, with up to 90% accuracy in assessing tumor depth and locoregional and mediastinal lymph nodes involvement. Additionally, endoscopic ultrasound allows a fine needle aspiration biopsy of suspicious lymph nodes (more than 1 cm) to confirm the presence of lymph node metastasis which is paramount for appropriate staging. A limitation of endoscopic ultrasound is that it cannot transverse tumor stenosis, clinically seen in a third of cases, which can result in an understated tumor. Endoscopic ultrasound (EUS) may be used after neoadjuvant therapy to restage local disease before surgery, but lacks sensitivity to assess complete response.
To evaluate distance metastases, positron emission tomography CT (PET/CT) has become part of the routine pretreatment diagnostic workup. Adenocarcinoma frequently metastasizes to intrabdominal sites, whereas squamous cell carcinoma is usually intrathoracic. PET allows to detect occult sites of distant metastatic spread, and spares the patient the morbidity of an aggressive local-regional treatment approach when unnecessary, in up to 20% of cases. PET/CT may be clinically useful in patients after induction therapy for the locally advanced disease to help exclude patients from sequential surgery if metastatic disease is found. This occurs in 8% of patients.
The use of diagnostic laparoscopy for resectable disease continues to be controversial, and not routinely recommended. Prior tumor, node, metastasis (TNM) staging provided separate esophageal squamous cell carcinoma and adenocarcinoma staging, but the eighth edition in 2017 grouped them back together. A major change is that esophagogastric junction (EGJ) tumors will be staged as esophageal if epicenter in origin and less than 2 cm into the proximal stomach (previously 5 cm). Esophagogastric junction (EGJ) are sub-classified by Siewert et al. depending on the distance to the anatomic junction into type 1 (less than 1 cm), 2 (1 to 2 cm), and 3 (more than 2 cm), the last occurring in more than 66% of cases. The number of lymph nodes is more important than location. Regardless of the histology, half of the patients will present with locally advanced or metastatic disease.
Esophageal adenocarcinoma treatment
An accurate preoperative staging will guide the most appropriate treatment selection 39). The general recommendations are as follows:
- Endoscopic resection for superficial, limited mucosa disease (less than T1a)
- Direct surgical resection with lymphadenectomy for lesions penetrating the submucosa with negative lymph nodes (more than T1b)
- Neoadjuvant chemoradiation of resectable lesions invading muscularis propria with positive lymph nodes (less than T2N1)
- Palliative systemic therapy for those locally advanced unresectable or metastatic disease
Table 1. Standard Treatment Options for Esophageal Cancer
|Stage (TNM Staging Criteria)||Treatment Options|
|Stage 0 Esophageal Cancer||Surgery|
|Stage 1 Esophageal Cancer||Chemoradiation therapy followed by surgery|
|Stage 2 Esophageal Cancer||Chemoradiation followed by surgery|
|Chemotherapy followed by surgery|
|Stage 3 Esophageal Cancer||Chemoradiation followed by surgery|
|Preoperative chemotherapy followed by surgery|
|Stage 4 Esophageal Cancer||Chemoradiation followed by surgery (for patients with stage IVA disease)|
|Chemotherapy, which has provided partial responses for patients with metastatic distal esophageal adenocarcinomas|
|Nd:YAG endoluminal tumor destruction or electrocoagulation|
|Endoscopic-placed stents to provide palliation of dysphagia|
|Radiation therapy with or without intraluminal intubation and dilation|
|Intraluminal brachytherapy to provide palliation of dysphagia|
|Recurrent Esophageal Cancer||Palliative use of any of the standard therapies, including supportive care|
Esophageal adenocarcinoma survival rate
For both adenocarcinoma and squamous cell cancer, the prognosis depends on the stage. In general, the survival rates per stage are similar for both cancers.
Once a patient has positive lymph nodes, the survival is decreased. Less than 20% of patients with esophageal cancer are alive at 5 years, with stage 4 having the worst prognosis 41).
Surgery has slightly increased survival rates but the postoperative complications are often serious, and the quality of life is poor 42).
Gastric cancer is the fifth most frequently diagnosed cancer and third leading cause of cancer deaths worldwide, albeit there has been a global decline since the last mid-century 43). Gastric adenocarcinoma accounts for 90% to 95% of all gastric cancers 44). In the United States, the incidence of gastric cancer has decreased during the past few decades although the incidence of gastroesophageal cancer has concomitantly increased.
There are two distinct types of gastric adenocarcinoma:
- Intestinal (well-differentiated) adenocarcinoma and
- Diffuse (undifferentiated) adenocarcinoma, which have distinct morphologic appearance, pathogenesis, and genetic profiles.
Estimated new cases and deaths from gastric cancer in the United States in 2019 45):
- New cases: 27,510.
- Deaths: 11,140.
The only potentially curative treatment approach for patients with gastric cancer is a surgical resection with adequate lymphadenectomy. Current evidence supports perioperative therapies to improve a patient’s survival. Regrettably, patients with an unresectable, locally advanced, or metastatic disease could solely be offered life-prolonging palliative therapy regimens.
Gastric adenocarcinoma causes
Factors linked with an increased risk of gastric cancer include nutritional factors such as high-salt (salt-preserved food), N-nitroso compounds consumption (dietary source), smoking, a low vitamin A and C diet, consuming large amounts of smoked or cured foods, a deficit of refrigerated foods, and contaminated drinking water 46). High body mass index (BMI), increased calorie consumption, gastroesophageal reflux and smoking are associated with an increased risk of adenocarcinomas of the distal esophagus, proximal stomach, and junction. Occupational exposure to rubber manufacturing, tin mining, metal processing, and coal also increases the risk. Helicobacter pylori infection has an attributable risk of 46% to 63%, while Epstein-Barr virus infection has an estimated of 5% to 10% worldwide. Radiation exposure and prior gastric surgery also have been implicated as risk factors.
Diverse meta-analysis has shown that high consumption of fiber, fruits and vegetables have a probable protective benefit against gastric cancer. Aspirin and other non-steroidal anti-inflammatory agent use have been associated with a lower risk of cancer of the gastroesophageal junction and other gastrointestinal tumors. Alcohol consumption has not been demonstrated as a risk factor, and in fact, some data suggest daily wine intake may be protective despite insufficient evidence. Chronic “iatrogenic” histamine-2-receptor antagonist or proton pump inhibitor has not been associated with gastric cancer.
Host factors include type A blood with an approximate 20% more gastric cancer cases than in blood groups O, B, or AB and particularly associated with the diffuse type. Pernicious anemia, an autoimmune chronic atrophic gastritis has up to six-fold increased risk of intestinal type gastric cancer. Benign gastric ulcer, hypertrophic gastropathy, and gastric polyps are risk factors and are associated with an increased risk of stomach cancer.
Most gastric cancers are sporadic, but 5% to 10% of cases have a family history of gastric cancer. Hereditary diffuse gastric cancer, gastric adenocarcinoma and proximal polyposis of the stomach, and familial intestinal gastric cancer are three major syndromes accounting up to 3% to 5% of hereditary familial gastric cancer. Other hereditary cancer syndromes are:
- Hereditary non-polyposis colon cancer (HNPCC 13% lifetime risk, predominantly intestinal type)
- Familial adenomatous syndrome (FAP, 10% risk)
- Peutz Jeghers syndrome (PJS, 29% risk)
- Juvenile polyposis syndrome (JPS, 21%)
- Li-Fraumeni syndrome
- Hereditary breast and ovarian cancer syndrome
- Phosphatase and tensin homolog (PTEN) or hamartoma tumor (Cowden’s) syndrome.
However, all these are rare causes of gastric cancer. It is recommended to follow screening guidelines on hereditary syndromes associated with gastric cancer accordingly to the risk they pose. Certain polymorphisms have been associated with gastric cancer, carriers of IL-1B-511*T/*T or IL-1B-511*T/*C that are up-regulated by H. pylori infection could cause a pro-inflammation and acid inhibition leading to malignancy. Intestinal-type gastric carcinogenesis may have overexpressed oncogenes (K-ras and c-met) or tumor suppressors (TP53, APC, TTF and CDKN1B,p27); although, not consistently present.
For cancer research, the World Health Organizations has classified Helicobacter pylori (H. pylori) as a definite gastric carcinogen and likewise concluded a positive association between consumption of processed meat and stomach cancer.
Risk factors for gastric adenocarcinoma
In the United States, gastric cancer ranks 14th in incidence among the major types of cancer. While the precise etiology is unknown, acknowledged risk factors for gastric cancer include the following 47):
- Helicobacter pylori gastric infection.
- Advanced age.
- Male gender.
- Diet low in fruits and vegetables.
- Diet high in salted, smoked, or preserved foods.
- Chronic atrophic gastritis.
- Intestinal metaplasia.
- Pernicious anemia.
- Gastric adenomatous polyps.
- Family history of gastric cancer.
- Cigarette smoking.
- Ménétrier disease (giant hypertrophic gastritis).
- Familial adenomatous polyposis.
Gastric adenocarcinoma symptoms
Some people have stomach cancer without having any symptoms at all. Some people get symptoms such as:
- losing weight
- swelling under their abdomen
Some find they are bleeding internally and have blood in their vomit or black stools.
In the United States, most patients have symptoms of an advanced stage at the time of presentation. Most common presenting symptoms for gastric cancers are non-specific weight loss, persistent abdominal pain, dysphagia, hematemesis, anorexia, nausea, early satiety, and dyspepsia. Patients presenting with a locally-advanced or metastatic disease usually present with significant abdominal pain, potential ascites, weight loss, fatigue, and have visceral metastasis on scans and can have a gastric-outlet obstruction.
The most common physical examination finding is a palpable abdominal mass indicating advanced disease. The patient may also present with signs of metastatic lymphatic spread distribution including Virchow’s node (left supraclavicular adenopathy), Sister Mary Joseph node (peri-umbilical nodule), and Irish node (left axillary node). Direct metastasis to peritoneum can present as Krukenberg’s tumor (ovary mass), Blumer’s shelf (cul-de-sac mass), ascites (peritoneal carcinomatosis), and hepatomegaly (often diffuse disease burden).
Paraneoplastic manifestations may include dermatological (diffuse seborrheic keratosis or acanthosis nigricans), hematological (microangiopathic hemolytic anemia and hypercoagulable state [Trousseau’s syndrome]), renal (membranous nephropathy), and autoimmune (polyarteritis nodosa) are rare clinical findings and none is specific to gastric cancer.
Gastric adenocarcinoma diagnosis
Your doctor will talk to you and examine you. You might be asked to have a number of tests to understand your symptoms and reach a diagnosis.
The tests include:
- endoscopy, where a thin tube with a camera on the end is passed down your throat and oesophagus to look at the digestive tract
- blood tests
- stool sample
- endoscopic ultrasound of the inside of your stomach and other parts
- X-ray, computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of your stomach and nearby organs
- taking a sample of tissue (biopsy) from your stomach wall
Patients presenting with any symptoms suspicious for gastric cancer should undergo an upper endoscopy over barium study (except for limited plastic presenting as leather-flask appearance). Although upper endoscopy is more invasive and costly, it offers tissue diagnosis by direct biopsy of esophageal, gastric or duodenal lesions. Any suspicious gastric ulcer should be biopsied multiple times for a higher diagnostic accuracy (one (70%) versus seven (98%) sensitivity). Gastric cancer screening by upper endoscopy has been successful in detecting early stages with higher curable rates after resection only in areas of high cancer incidence (Japan).
Staging pre-preoperative evaluations include chest and abdominal imaging to rule out metastasis and to determine surgical resectability. Abdominopelvic computerized tomography is performed early to rule out gross metastatic disease but does not accurately assess T, N, and small peritoneal metastases with an overall accuracy of 42% to 82%. Endoscopic ultrasound has a better diagnostic accuracy of tumor depth (57% to 88%) and lymph node status (30% to 90%), and hence, helps with accurate staging but is operator dependent. Suspicious solitary or oligometastatic sites should be confirmed by biopsies; similarly, paracentesis should be performed if malignant ascites is suspected. Chest computerized tomography (CT) is preferred over plain radiograph. If prior staging evaluation is negative for metastatic disease, positron emission tomography combined with computerized tomography imaging may be helpful to determine resectability of gastric cancers in select cases (T2N0). Serum markers (carcinoembryonic antigen, glycoprotein CA 125 antigen, carbohydrate antigen 19-9, and cancer antigen 72-4) have limited utility and may be elevated due to other causes. Staging laparoscopy with peritoneal cytology analysis is indicated prior surgery in the absence of visible spread particularly for clinical stages with higher than T1b, and it is recommended for patients receiving preoperative therapy. Positive peritoneal cytology in the absence of identifiable peritoneal spread is an independent predictor of high recurrence after curative resection, and hence, surgery is not recommended.
Gastric cancer has reported human epidermal growth factor receptor 2 (HER2) gene amplification in 12% to 27% of cases and protein overexpression in 9% to 23% of cases. The impact of HER2 positivity remains largely unclear, but it has been implicated in tumor invasion and lymph node metastasis and is associated with poorer survival. HER2 positivity is more frequently found in intestinal subtype (33%) than diffuse (8%) with lower rates in the United States (19% and 6%, respectively). HER2 testing is recommended for all mestatatic gastric cancer, first by using immunohistochemistry score; negative for 0 or 1+ and positive for 3+, with reflex, fluorescent, in situ hybridization for equivocal 2+ score to confirm. The United States Food and Drug Administration (FDA) has granted approval of immunotherapy for patients with microsatellite instability in solid tumors including gastric cancer and can evaluate the potential of immunotherapy in patients with metastatic disease who progressed on standard therapy. Gastric tumors positive for Epstein-Barr virus (EBV) have a better prognosis; however, staining for EBV is not yet recommended on routine clinical care.
Gastric adenocarcinoma treatment
Treatment for stomach cancer depends on the stage of your disease, the severity of symptoms and your overall health. The options include:
- surgery to remove all or part of your stomach
- chemotherapy to destroy cancer cells
- biological therapy (biotherapy), which helps your immune system fight the cancer
Radical surgery represents the standard form of therapy that has curative intent. However, the incidences of local failure in the tumor bed and regional lymph nodes, and distant failures via hematogenous or peritoneal routes, remain high 48). As such, adjuvant external-beam radiation therapy with combined chemotherapy has been evaluated in the United States.
In a phase 3 Intergroup trial (SWOG-9008), 556 patients with completely resected stage 1B to stage 4 (M0) adenocarcinoma of the stomach and gastroesophageal junction were randomly assigned to receive surgery alone or surgery plus postoperative chemotherapy (5-fluorouracil [5-FU] and leucovorin) and concurrent radiation therapy (45 Gy). With 5 years’ median follow-up, a significant survival benefit was reported for patients who received adjuvant combined modality therapy 49). Median survival was 36 months for the adjuvant chemoradiation therapy group and 27 months for the surgery-alone arm. Three-year overall survival rates were 50%, and relapse-free survival rates were 48% with adjuvant chemoradiation therapy versus 3-year overall survival rates of 41% and relapse-free survival rates of 31% for surgery alone. The rate of distant metastases was 18% for the surgery-alone arm and 33% for the chemoradiation-therapy arm. Because distant disease remains a significant concern, the aim of the Cancer and Leukemia Group B study (https://clinicaltrials.gov/ct2/show/NCT00052910) was to augment the postoperative chemoradiation therapy regimen used in INT-0116. Neoadjuvant chemoradiation therapy such as in the RTOG-9904 (https://clinicaltrials.gov/ct2/show/NCT00003862) trial, which is completed, and the SWOG-S0425 (https://clinicaltrials.gov/ct2/show/NCT00335959) trial, which is closed, was clinically evaluated 50).
Investigators in Europe evaluated the role of preoperative and postoperative chemotherapy without radiation therapy 51). In the randomized phase 3 trial (https://clinicaltrials.gov/ct2/show/NCT00002615), patients with stage 2 or higher adenocarcinoma of the stomach or of the lower third of the esophagus were assigned to receive three cycles of epirubicin, cisplatin, and continuous infusion 5-FU before and after surgery or to receive surgery alone. Compared with the surgery group, the perioperative chemotherapy group had a significantly higher likelihood of progression-free survival and of overall survival. Five-year overall survival was 36.3% for the perioperative chemotherapy group and 23% for the surgery group 52).
Gastric adenocarcinoma survival rate
The prognosis of patients with gastric cancer is related to tumor extent and includes both nodal involvement and direct tumor extension beyond the gastric wall 53). Tumor grade may also provide some prognostic information 54).
In localized distal gastric cancer, more than 50% of patients can be cured 55). However, early-stage disease accounts for only 10% to 20% of all cases diagnosed in the United States. The remaining patients present with metastatic disease in either regional or distant sites. The overall survival rate in these patients at 5 years ranges from almost no survival for patients with disseminated disease to almost 50% survival for patients with localized distal gastric cancers confined to resectable regional disease. Even with apparent localized disease, the 5-year survival rate of patients with proximal gastric cancer is only 10% to 15%. Although the treatment of patients with disseminated gastric cancer may result in palliation of symptoms and some prolongation of survival, long remissions are uncommon.
The American Joint Committee on Cancer/ Union for International Cancer Control (AJCC/UICC) Eight Edition 2017 has outlined an new staging scheme based on tumor, node, metastasis (TNM) with 5-year overall survival according to pathological stage and intervention (surgery only 1A-93.6%, 2A-81.8%, and 3A-54.2% or with neoadjuvant 1-76.5%, 2-46.3%, 3-18.3% and 4-5.7%) 56).
The majority of all colorectal cancer are carcinomas, and more than 90% of those are adenocarcinomas and others not frequently seen (adenosquamous, spindle, squamous and undifferentiated). Colorectal cancer adenocarcinoma can be further differentiated in cribriform comedo-type, medullary, micropapillary, serrated, mucinous and signet-ring cell. Adenocarcinomas are categorized by the percentage of gland formation into well (more than 95%), moderately (more than 50%) and poorly (less than 49%) differentiated, but further divided in two-tier low-grade (well-moderate)/high-grade (poor) with prognostic significance. Mucinous or signet ring cells classification describe that more than half of the stain cells posses that particular characteristic. Differential clinicopathological diagnosis is neuroendocrine, hamartomas, mesenchymal, and lymphomas. Cytokeratin 20 (CK20) and caudal-type homeobox 2 (CDX2) immunohistochemistry (IHC) can accurately identify colorectal cancer adenocarcinoma origin, except medullary carcinoma with MSI-H expressing other markers such calretinin, CK7, SABT2, and CDH17.
Colorectal cancer is the third most common diagnosis and second deadliest malignancy for both sexes combined 57).
Colorectal cancer has both strong environmental associations and genetic risk factors. The incidence of new cases and mortality has been steadily declining for the past years, except for younger adults (younger than 50 years), possibly related to an increase in cancer screening and better therapy modalities. Approximately 5% of all colorectal cancer are attributed to two inherited syndromes, Familial Adenomatous Polyposis, and Lynch syndrome. The change of the normal colonic epithelium to a precancerous lesion and ultimately an invasive carcinoma requires an accumulation of genetic mutations either somatic (acquired) and/or germline (inherited) in an approximately 10 to 15-year period. Chromosomal instability, mismatch repair, and CpG hypermethylation are the major pathways to colorectal cancer. The most important prognostic colon cancer indicator is the pathological stage at presentation. All new colorectal cancer cases should be universally screen for DNA mismatch repair/microsatellite status, and RAS/BRAF mutational testing when considering for prognostic and predictive of chemotherapy efficacy. In almost all patients, a diagnostic or screening colonoscopy is required for tissue biopsy pathological confirmation of colon carcinoma. Baseline computed tomography (CT) of the chest, abdomen, and pelvis with contrast and carcinoembryonic antigen (CEA) are the preferred cost-effective, colon-cancer staging studies done before surgical resection. Surgical resection is the main treatment modality for localized early-stage colon cancer. Adjuvant therapy could augment the chance of cure on high-risk colon cancer patients. Oligo-metastatic, liver and lung, and local-recurrence colon cancer patients are potential curable candidates with multimodality therapies. Palliative systemic therapy is reserved for non-surgical colon cancer candidates aiming to improve quality of life and prolong life expectancy.
Estimated new cases and deaths from colon and rectal cancer in the United States in 2019 58):
- New cases: 101,420 (colon cancer only).
- New cases of rectal cancer: 44,180.
- Deaths: 51,020 (colon and rectal cancers combined).
Because of the frequency of colon cancer, ability to identify high-risk groups, slow growth of primary lesions, better survival of patients with early-stage lesions, and relative simplicity and accuracy of screening tests, screening for colon cancer should be a part of routine care for all adults aged 50 years and older, especially for those with first-degree relatives with colorectal cancer.
Adenocarcinoma colon causes
Colon cancer could present as sporadic (70%), familial clustering (20%) and inherited syndromes (10%) 59). Sporadic colon cancer average age diagnosis is older than 50 years and mostly linked to environmental factors, different from a minority of patients with a true inherited pattern that carries a higher risk at a younger age (younger than 50 years), and the remaining 20% are familial clustering in the absence of identifiable inherited syndrome. The most common inherited colorectal cancer syndromes are familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]). Approximately 5% of all colorectal cancer cancers are attributed to these two inherited syndromes, but as many as 10% to 15% of unselected colorectal cancer patients will carry high-risk mutation not related to familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]).
Personal or family history of colorectal cancer, adenomatous polyps and polyps with villous or tubulovillous dysplasia indicate a high risk for synchronous and metachronous colorectal cancer primary cancer up to 3% to 5% at 5 years or even longer after resection requiring a closer screening interval. Inflammatory bowel disease (IBD), mainly ulcerative colitis, has a well-known association with Cca, with an estimated incidence 0.5% per year between 10 and 20 years after the time of IBD diagnosis and 1% per year after that reaching a 30% risk probability by the fourth decade of patients with pancolitis. Crohn’s disease may increase colon cancer risk, particularly if present in the ileocolic region.
Childhood cancer survivors who received abdominal radiation (greater than 30 Gy) are at risk of colorectal cancer, and screening is recommended 10 years later or at age 35. Other illnesses that increase the risk higher of colorectal cancer are diabetes mellitus/insulin resistance, uncontrolled acromegaly disease, and long-term immunosuppressed renal transplant.
Epidemiologic study results indicate strong environmental and lifestyle associations for colorectal cancer. Modest weak increased colorectal cancer risks are seen with obesity, red/processed meat, tobacco, alcohol, androgen deprivation therapy, and cholecystectomy among others. On the other hand, large population studies with variable strength evidence have found colorectal cancer protective factors such as physical activity, diet (fruits and vegetables, fiber, resistant starch, fish), vitamin supplements (folate, folic acid, pyridoxine B6, calcium, vitamin D, magnesium), garlic and coffee, and drugs [aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), hormonal replacement therapy in postmenopausal, statins, bisphosphonate and angiotensin inhibitors].
Interestingly, a randomized controlled clinical trial found that 600 mg of aspirin in Lynch syndrome had a protective effect against colorectal adenomas and cancer with substantially reduced cancer incidence after 55.7 months.
Risk factors for adenocarcinoma colon
Increasing age is the most important risk factor for most cancers. Other risk factors for colorectal cancer include the following:
- Family history of colorectal cancer in a first-degree relative 60)
- Personal history of colorectal adenomas, colorectal cancer, or ovarian cancer 61)
- Hereditary conditions, including familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) 62)
- Personal history of long-standing chronic ulcerative colitis or Crohn colitis 63)
- Excessive alcohol use 64)
- Cigarette smoking 65)
- Race/ethnicity: African American 66)
- Obesity 67)
Adenocarcinoma colon prevention
Get screened for colon cancer
Doctors recommend certain screening tests for healthy people with no signs or symptoms in order to look for early colon cancer. Finding colon cancer at its earliest stage provides the greatest chance for a cure. Screening has been shown to reduce your risk of dying of colon cancer.
People with an average risk of colon cancer can consider screening beginning at age 50. But people with an increased risk, such as those with a family history of colon cancer, should consider screening sooner. African-Americans and American Indians may consider beginning colon cancer screening at age 45.
Several screening options exist — each with its own benefits and drawbacks. Talk about your options with your doctor, and together you can decide which tests are appropriate for you. If a colonoscopy is used for screening, polyps can be removed during the procedure before they turn into cancer.
Make lifestyle changes to reduce your risk
You can take steps to reduce your risk of colon cancer by making changes in your everyday life. Take steps to:
- Eat a variety of fruits, vegetables and whole grains. Fruits, vegetables and whole grains contain vitamins, minerals, fiber and antioxidants, which may play a role in cancer prevention. Choose a variety of fruits and vegetables so that you get an array of vitamins and nutrients.
- Drink alcohol in moderation, if at all. If you choose to drink alcohol, limit the amount of alcohol you drink to no more than one drink a day for women and two for men.
- Stop smoking. Talk to your doctor about ways to quit that may work for you.
- Exercise most days of the week. Try to get at least 30 minutes of exercise on most days. If you’ve been inactive, start slowly and build up gradually to 30 minutes. Also, talk to your doctor before starting any exercise program.
- Maintain a healthy weight. If you are at a healthy weight, work to maintain your weight by combining a healthy diet with daily exercise. If you need to lose weight, ask your doctor about healthy ways to achieve your goal. Aim to lose weight slowly by increasing the amount of exercise you get and reducing the number of calories you eat.
Colon cancer prevention for people with a high risk
Some medications have been found to reduce the risk of precancerous polyps or colon cancer. However, not enough evidence exists to recommend these medications to people who have an average risk of colon cancer. These options are generally reserved for people with a high risk of colon cancer.
For instance, some evidence links a reduced risk of polyps and colon cancer to regular use of aspirin or aspirin-like drugs. But it’s not clear what dose and what length of time would be needed to reduce the risk of colon cancer. Taking aspirin daily has some risks, including gastrointestinal bleeding and ulcers, so doctors typically don’t recommend this as a prevention strategy unless you have an increased risk of colon cancer.
Adenocarcinoma colon symptoms
Signs and symptoms of colon cancer include:
- A change in your bowel habits, including diarrhea or constipation or a change in the consistency of your stool, that lasts longer than four weeks
- Rectal bleeding or blood in your stool
- Persistent abdominal discomfort, such as cramps, gas or pain
- A feeling that your bowel doesn’t empty completely
- Weakness or fatigue
- Unexplained weight loss
Many people with colon cancer experience no symptoms in the early stages of the disease. When symptoms appear, they’ll likely vary, depending on the cancer’s size and location in your large intestine.
Adenocarcinoma colon diagnosis
If your signs and symptoms indicate that you could have colon cancer, your doctor may recommend one or more tests and procedures, including:
Using a scope to examine the inside of your colon. Colonoscopy uses a long, flexible and slender tube attached to a video camera and monitor to view your entire colon and rectum. If any suspicious areas are found, your doctor can pass surgical tools through the tube to take tissue samples (biopsies) for analysis and remove polyps.
Blood tests. No blood test can tell you if you have colon cancer. But your doctor may test your blood for clues about your overall health, such as kidney and liver function tests.
Your doctor may also test your blood for a chemical sometimes produced by colon cancers (carcinoembryonic antigen or CEA). Tracked over time, the level of CEA in your blood may help your doctor understand your prognosis and whether your cancer is responding to treatment.
Staging colon cancer
Once you’ve been diagnosed with colon cancer, your doctor will order tests to determine the extent (stage) of your cancer. Staging helps determine what treatments are most appropriate for you.
Staging tests may include imaging procedures such as abdominal, pelvic and chest CT scans. In many cases, the stage of your cancer may not be determined until after colon cancer surgery.
The stages of colon cancer are:
- Stage 1. The cancer has grown through the superficial lining (mucosa) of the colon or rectum but hasn’t spread beyond the colon wall or rectum.
- Stage 2. The cancer has grown into or through the wall of the colon or rectum but hasn’t spread to nearby lymph nodes.
- Stage 3. The cancer has invaded nearby lymph nodes but isn’t affecting other parts of your body yet.
- Stage 4. The cancer has spread to distant sites, such as other organs — for instance, to your liver or lung.
Adenocarcinoma colon treatment
The type of treatment your doctor recommends will depend largely on the stage of your cancer. The three primary treatment options are surgery, chemotherapy and radiation.
Surgical resection is the main treatment modality for localized non-metastatic stage colon cancer at any age with acceptable performance status and optimized comorbidities. Endoscopic resection is reserved for selected favorable-risk and early-stage colon carcinomas found in a polyp (cT0-1). Neoadjuvant therapy is not standard of care for colon cancer and reserved for advanced disease surgical conversion intend. Adjuvant therapy is recommended for all colon cancer stage 3 (node-positive) and individualized by stage 2 with high-risk features. Surgery in conjunction with peri-chemotherapy may provide a curative option on oligo-metastatic lung and liver disease. Palliative systemic chemotherapy is offered to non-surgical candidates with unresectable locally advanced disease or high metastatic burden to improved quality of life and prolongs life expectancy. Individualized local-recurrent disease patients may achieve cure with further multimodality therapy.
Table 2. Standard Treatment Options for Stages 0–3 Colon Cancer
|Stage (TNM Staging Criteria)||Standard Treatment Options|
|Stage 0 Colon Cancer||Surgery|
|Stage 1 Colon Cancer||Surgery|
|Stage 2 Colon Cancer||Surgery|
|Stage 3 Colon Cancer||Surgery|
Table 3. Treatment Options for Stage 4 and Recurrent Colon Cancer
|Stage (TNM Staging Criteria)||Treatment Options|
|Treatment of Liver Metastasis||Surgery|
|Treatment of Stage IV and Recurrent Colon Cancer||Surgery|
|Chemotherapy and targeted therapy|
Adenocarcinoma colon survival rate
The Surveillance, Epidemiology, and End Results (SEER) observed overall survival at 5-years rates for colon in stage 1 includes 74%; stage 2A, 66%; stage 2B, 58%; stage 2C, 37%; stage 3A, 73%; stage 3B, 46%; stage 3C, 28%; and stage 4, 5% 70).
Pancreatic cancer refers to the carcinoma arising from the pancreatic duct cells, pancreatic ductal carcinoma. More than 90% of adenocarcinoma of the pancreas are duct cell adenocarcinomas with other types being cystadenocarcinoma and acinar cell carcinoma 71). Two-thirds arise in the pancreatic head; one-third arise in the rest (body and tail of pancreas). Several research articles have evaluated the genetic nature of various subtypes of pancreatic cancer, providing an overall genetic makeup of pancreatic cancer. These genetic patterns can later be used to create targeted therapy, potentially improving survival in pancreatic cancer patients. Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. Cancers of the pancreas are commonly identified by the site of involvement within the pancreas. Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas. Surgical resection is the only current option for a cure, but only 20% of pancreatic cancer is surgically resectable at the time of diagnosis.
Pancreatic cancer is difficult to detect and diagnose for the following reasons:
- There are no noticeable signs or symptoms in the early stages of pancreatic cancer.
- The signs of pancreatic cancer, when present, are like the signs of many other illnesses, such as pancreatitis or an ulcer.
- The pancreas is obscured by other organs in the abdomen and is difficult to visualize clearly on imaging tests.
To appropriately treat pancreatic cancer, it is crucial to evaluate whether the cancer can be resected.
Estimated new cases and deaths from pancreatic cancer in the United States in 2019 72):
- New cases: 56,770.
- Deaths: 45,750.
The incidence of carcinoma of the pancreas has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its cause is poorly understood 73).
Pancreatic adenocarcinoma causes
It’s not clear what causes pancreatic cancer in most cases. Doctors have identified factors, such as smoking, that increase your risk of developing the disease.
Pancreatic cancer occurs when cells in your pancreas develop mutations in their DNA. These mutations cause cells to grow uncontrollably and to continue living after normal cells would die. These accumulating cells can form a tumor. Untreated pancreatic cancer spreads to nearby organs and blood vessels.
Most pancreatic cancer begins in the cells that line the ducts of the pancreas. This type of cancer is called pancreatic adenocarcinoma or pancreatic exocrine cancer. Rarely, cancer can form in the hormone-producing cells or the neuroendocrine cells of the pancreas. These types of cancer are called islet cell tumors, pancreatic endocrine cancer and pancreatic neuroendocrine tumors.
Risk factors for pancreatic adenocarcinoma
Pancreatic cancer risk factors 74), 75), 76):
- Smoking (20% of pancreatic cancers are caused by smoking)
- Age older than 55 years old
- Chronic pancreatitis
- Cirrhosis of the liver
- Helicobacter pylori infection
- Work exposure to chemicals in the dry cleaning and metalworking industry
- Males more than females
- African Americans more than whites
- Family history of pancreatic cancer
- Family history of genetic syndromes that can increase cancer risk, including a BRCA2 gene mutation, Lynch syndrome and familial atypical mole-malignant melanoma (FAMMM) syndrome
Ten percent have a genetic cause such as genetic mutations or association with syndromes such as Lynch syndrome, Peutz-Jeghers syndrome, VonHipaul Lindau syndrome, MEN1 (multiple endocrine neoplasia type 1).
Possible risk factors include heavy alcohol consumption, coffee consumption, physical inactivity, high red meat consumption, and two or more soft drinks per day.
A large study demonstrated that the combination of smoking, long-standing diabetes and a poor diet increases the risk of pancreatic cancer beyond the risk of any one of these factors alone.
Pancreatic adenocarcinoma prevention
You may reduce your risk of pancreatic cancer if you:
- Stop smoking. If you smoke, try to stop. Talk to your doctor about strategies to help you stop, including support groups, medications and nicotine replacement therapy. If you don’t smoke, don’t start.
- Maintain a healthy weight. If you are at a healthy weight, work to maintain it. If you need to lose weight, aim for a slow, steady weight loss — 1 to 2 pounds (0.5 to 1 kilogram) a week. Combine daily exercise with a diet rich in vegetables, fruit and whole grains with smaller portions to help you lose weight.
- Choose a healthy diet. A diet full of colorful fruits and vegetables and whole grains may help reduce your risk of cancer.
Consider meeting with a genetic counselor if you have a family history of pancreatic cancer. He or she can review your family health history with you and determine whether you might benefit from a genetic test to understand your risk of pancreatic cancer or other cancers.
Pancreatic adenocarcinoma symptoms
Pancreatic cancer symptoms depend on the site of the tumor within the pancreas and the degree of tumor involvement.
In the early stages of pancreatic cancer there are not many noticeable symptoms. As the cancer grows, symptoms may include the following:
- Light-colored stools or dark urine.
- Pain in the upper or middle abdomen and back.
- Weight loss for no known reason.
- Loss of appetite.
Patients with adenocarcinoma of pancreas typically present with painless jaundice (70%) usually due to obstruction of the common bile duct from the pancreatic head tumor. Weight loss occurs in about 90% of patients. Abdominal pain occurs in about 75% of patients. Weakness, pruritus from bile salts in the skin, anorexia, palpable, non-tender, distended gallbladder, acholic stools, and dark urine. Sometimes, patients may present with recurrent deep vein thrombosis (DVT) due to hypercoagulability that prompts clinicians to suspect cancer and a full workup of cancer.
Patients can also present with recent-onset diabetes.
As pancreatic cancer progresses, it can cause complications such as:
A number of factors may cause weight loss in people with pancreatic cancer. The cancer itself may cause weight loss. Nausea and vomiting caused by cancer treatments or a tumor pressing on your stomach may make it difficult to eat. Or your body may have difficulty processing nutrients from food because your pancreas isn’t making enough digestive juices.
Your doctor may recommend pancreatic enzyme supplements to aid in digestion. Try to maintain your weight by adding extra calories where you can and making mealtime as pleasant and relaxed as possible.
Pancreatic cancer that blocks the liver’s bile duct can cause jaundice. Signs include yellow skin and eyes, dark-colored urine, and pale-colored stools. Jaundice usually occurs without abdominal pain.
Your doctor may recommend that a plastic or metal tube (stent) be placed inside the bile duct to hold it open. This is done with the help of a procedure called endoscopic retrograde cholangiopancreatography (ERCP). During ERCP an endoscope is passed down your throat, through your stomach and into the upper part of your small intestine. A dye is then injected into the pancreatic and bile ducts through a small hollow tube (catheter) that’s passed through the endoscope. Finally, images are taken of the ducts.
A growing tumor may press on nerves in your abdomen, causing pain that can become severe. Pain medications can help you feel more comfortable. Radiation therapy might help stop tumor growth temporarily to give you some relief.
In severe cases, your doctor might recommend a procedure to inject alcohol into the nerves that control pain in your abdomen (celiac plexus block). This procedure stops the nerves from sending pain signals to your brain.
Pancreatic cancer that grows into or presses on the first part of the small intestine (duodenum) can block the flow of digested food from your stomach into your intestines.
Your doctor may recommend a tube (stent) be placed in your small intestine to hold it open. Or surgery may be necessary to attach your stomach to a lower point in your intestines that isn’t blocked by cancer.
Pancreatic adenocarcinoma diagnosis
If your doctor suspects pancreatic cancer, he or she may have you undergo one or more of the following tests:
- Imaging tests that create pictures of your internal organs. These tests help your doctors visualize your internal organs, including the pancreas. Techniques used to diagnose pancreatic cancer include ultrasound, computerized tomography (CT) scans, magnetic resonance imaging (MRI) and, sometimes, positron emission tomography (PET) scans.
- Using a scope to create ultrasound pictures of your pancreas. An endoscopic ultrasound (EUS) uses an ultrasound device to make images of your pancreas from inside your abdomen. The device is passed through a thin, flexible tube (endoscope) down your esophagus and into your stomach in order to obtain the images.
- Removing a tissue sample for testing (biopsy). A biopsy is a procedure to remove a small sample of tissue for examination under a microscope. Your doctor may obtain a sample of tissue from the pancreas by inserting a needle through your skin and into your pancreas (fine-needle aspiration). Or he or she may remove a sample during EUS, guiding special tools into the pancreas.
- Blood test. Lab findings will include elevation in liver function tests, direct and total bilirubin levels, elevated amylase and lipase. Your doctor may test your blood for specific proteins (tumor markers) shed by pancreatic cancer cells (CA 19-9 and CEA). One tumor marker test used in pancreatic cancer is called CA19-9. But the test isn’t always reliable, and it isn’t clear how best to use the CA19-9 test results. Some doctors measure your levels before, during and after treatment.
No tumor-specific markers exist for pancreatic cancer; markers such as serum cancer antigen (CA) 19-9 have low specificity 77). Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during definitive therapy, the increase of CA 19-9 levels may identify patients with progressive tumor growth 78). The presence of a normal CA 19-9, however, does not preclude recurrence.
If your doctor confirms a diagnosis of pancreatic cancer, he or she tries to determine the extent (stage) of the cancer. Using information from staging tests, your doctor assigns your pancreatic cancer a stage, which helps determine what treatments are most likely to benefit to you.
The stages of pancreatic cancer are indicated by Roman numerals ranging from 0 to IV. The lowest stages indicate that the cancer is confined to the pancreas. By stage IV, the cancer has spread to other parts of the body.
The cancer staging system continues to evolve and is becoming more complex as doctors improve cancer diagnosis and treatment. Your doctor uses your cancer stage to select the treatments that are right for you.
Don’t hesitate to ask your doctor about his or her experience with diagnosing pancreatic cancer. If you have any doubts, get a second opinion.
Pancreatic adenocarcinoma treatment
Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection.
Pancreatic tumors are resistant to treatment with chemotherapy and radiation.
Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used.
If the adenocarcinoma of the pancreas is located in the head of the pancreas, then the Whipple procedure (pancreaticoduodenectomy) is the procedure of choice. If the tumor is in the body or tail of the pancreas, the distal resection is needed. Postoperatively, patients may receive chemotherapy with 5-FU, gemcitabine, and radiotherapy. If the hepatic artery is involved in the tumor, then the tumor is considered to be unresectable. However, if the superior mesenteric vein is involved in the tumor, then resection and vascular reconstruction. The same is true for portal vein involvement. It can be resected and reconstructed with graft.
Table 4. Treatment Options for Pancreatic Cancer
|Stage (TNM Staging Criteria)||Treatment Options|
|Stage 1 and stage 2 pancreatic cancer||Surgery|
|Postoperative chemoradiation therapy|
|Stage 3 pancreatic cancer||Palliative surgery|
|Stage 4 pancreatic cancer||Palliative therapy|
|Recurrent pancreatic cancer||Palliative therapy|
Pancreatic adenocarcinoma survival rate
The 5-year survival rate in the United States ranges from 5% to 15% 80). The overall survival rate is only 6% 81). The estimated global, 5-year survival rate for pancreatic cancer is about 5% 82).
Exocrine pancreatic cancer is rarely curable and has an overall survival rate of less than 6% 83).
The highest cure rate occurs when the tumor is truly localized to the pancreas; however, this stage of disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection is associated with an actuarial 5-year survival rate of 18% to 24% 84).
More than 95% of primary prostate cancers are adenocarcinomas 85). Prostate adenocarcinomas are frequently multifocal and heterogeneous in patterns of differentiation. Prostatic intraepithelial neoplasia ([PIN] noninvasive atypical epithelial cells within benign appearing acini) is often present in association with prostatic adenocarcinoma. Prostatic intraepithelial neoplasia is subdivided into low grade and high grade. The high-grade form may be a precursor for adenocarcinoma 86).
Prostate cancer is the most commonly diagnosed organ cancer in men and the second leading cause of male cancer death in the United States. (Lung cancer is first.) Worldwide, prostate cancer is the most commonly diagnosed malignancy and the sixth leading cause of cancer death in men 87). In 2012, this amounted to 1,100,000 newly diagnosed cases and 307,000 deaths around the world from prostate cancer.
Estimated new cases and deaths from prostate cancer in the United States in 2018 88):
- New cases: 164,690.
- Deaths: 29,430.
In 2015, there were an estimated 3 million prostate cancer survivors in the United States. This is expected to increase to 4 million by 2025.
According to the National Cancer Institute (NCI), every American man has a lifetime risk of 11.6% of developing clinically significant prostate cancer (Gleason 3 + 4 = 7 or higher).
For 2018, the National Cancer Institute is expecting 164,690 new cases of prostate cancer and 29,430 deaths in the United States which is an increase from 2017.
- The majority of new cases are diagnosed in men from 65 to 74 years of age (38.2%) with a median age at diagnosis of 66 years.
- There are currently 3,085,209 men living in the United States with prostate cancer, and the overall risk of an individual male dying from prostate cancer is 1 in 39 or about 2.6%.
- The median age of death for those men dying of prostate cancer is 80 years.
- Overall, the vast majority of men with prostate cancer will die from unrelated problems.
- Prostate cancer is uncommon in men younger than 45 years (0.5% of all newly diagnosed prostate cancer cases), but it can be very fast growing and lethal when it occurs in this age group.
The median age at diagnosis of carcinoma of the prostate is 66 years 89). More than 80% of men will develop prostate cancer by age 80 90). However, in this age group, it will probably be slow growing, lower grade, relatively harmless and have little impact on their survival. Prostate cancer may be cured when localized, and it frequently responds to treatment when widespread. The rate of tumor growth varies from very slow to moderately rapid, and some patients may have prolonged survival even after the cancer has metastasized to distant sites, such as bone. The 5-year relative survival rate for men diagnosed in the United States from 2001 to 2007 with local or regional prostate cancer was 100%, and the rate for distant prostate cancer was 28.7%; a 99% survival rate was observed for all stages combined 91). The approach to treatment is influenced by age and coexisting medical problems. Side effects of various forms of treatment should be considered in selecting appropriate management.
Many patients—especially those with localized tumors—may die of other illnesses without ever having suffered disability from the cancer, even if managed conservatively without an attempt at curative therapy 92). In part, these favorable outcomes are likely the result of widespread screening with the prostate-specific antigen (PSA) test, which can identify patients with asymptomatic tumors that have little or no lethal potential 93). There is a large number of these clinically indolent tumors, estimated from autopsy series of men dying of causes unrelated to prostate cancer to be in the range of 30% to 70% of men older than 60 years 94).
Because diagnostic methods have changed over time, any analysis of survival after treatment of prostate cancer and comparison of the various treatment strategies is complicated by the evidence of increasing diagnosis of nonlethal tumors. Nonrandomized comparisons of treatments may be confounded not only by patient selection factors but also by time trends.
For example, a population-based study in Sweden showed that, from 1960 to the late 1980s, before the use of PSA for screening purposes, long-term relative survival rates after the diagnosis of prostate cancer improved substantially as more sensitive methods of diagnosis were introduced. This occurred despite the use of watchful waiting or active surveillance or palliative hormonal treatment as the most common treatment strategies for localized prostate cancer during the entire era (<150 radical prostatectomies per year were performed in Sweden during the late 1980s). The investigators estimated that, if all prostate cancers diagnosed between 1960 and 1964 were of the lethal variety, then at least 33% of cancers diagnosed between 1980 and 1984 were of the nonlethal variety 95). With the advent of PSA screening as the most common method of detection in the United States, the ability to diagnose nonlethal prostate cancers has further increased.
Another issue complicating comparisons of outcomes among nonconcurrent series of patients is the possibility of changes in criteria for the histologic diagnosis of prostate cancer 96). This phenomenon creates a statistical artifact that can produce a false sense of therapeutic accomplishment and may also lead to more aggressive therapy.
Controversy exists regarding the value of screening, the most appropriate staging evaluation, and the optimal treatment of each stage of the disease 97).
Fortunately, the majority of prostate cancers tend to grow slowly and are low-grade with relatively low risk and limited aggressiveness.
There are no initial or early symptoms in most cases, but late symptoms may include fatigue due to anemia, bone pain and paralysis from spinal metastases, and renal failure from bilateral ureteral obstruction.
Diagnosis is primarily based on prostate-specific antigen (PSA) testing, and transrectal ultrasound-guided (TRUS) prostate tissue biopsies, although PSA testing for screening remains controversial.
When the cancer is limited to the prostate, it is considered localized and potentially curable.
If the disease has spread to the bones or elsewhere outside the prostate, pain medications, bisphosphonates, rank ligand inhibitors, hormonal treatment, chemotherapy, radiopharmaceuticals, immunotherapy, focused radiation, and other targeted therapies can be used. Outcomes depend on age, associated health problems, tumor histology and the extent of cancer.
Adenocarcinoma prostate causes
It’s not clear what causes prostate cancer.
Doctors know that prostate cancer begins when some cells in your prostate become abnormal. Mutations in the abnormal cells’ DNA cause the cells to grow and divide more rapidly than normal cells do. The abnormal cells continue living, when other cells would die. The accumulating abnormal cells form a tumor that can grow to invade nearby tissue. Some abnormal cells can also break off and spread (metastasize) to other parts of the body.
Risk factors for prostate adenocarcinoma
Factors that can increase your risk of prostate cancer include:
- Age. Your risk of prostate cancer increases as you age.
- Race. For reasons not yet determined, black men carry a greater risk of prostate cancer than do men of other races. In black men, prostate cancer is also more likely to be aggressive or advanced.
- Family history. If men in your family have had prostate cancer, your risk may be increased. Also, if you have a family history of genes that increase the risk of breast cancer (BRCA1 or BRCA2) or a very strong family history of breast cancer, your risk of prostate cancer may be higher.
- Obesity. Obese men diagnosed with prostate cancer may be more likely to have advanced disease that’s more difficult to treat.
The overall incidence increases as people get older; but fortunately, cancer aggressiveness decreases with age.
Prostate cancer risk factors include male gender, older age, positive family history, increased height, obesity, hypertension, lack of exercise, persistently elevated testosterone levels, Agent Orange exposure, and ethnicity.
These inhibitors such as finasteride and dutasteride may decrease low-grade cancer incidence but they do not appear to affect high-grade risk and thus, do not significantly improve survival. These medications will reduce PSA levels by about 50% which must be accounted for when comparing sequential PSA readings.
The cause of prostate cancer is unclear but genetics is certainly involved. Genetic background, ethnicity, and family history are all known to contribute to prostate cancer risk.
- Men with a first degree relative (father or brother) with prostate cancer have twice the risk of the general population.
- Risk increases with an affected brother more than an affected father.
- Men with two, first-degree relatives affected have a five-fold greater risk.
- Patients with a strong family history of prostate cancer tend to present with cancer at a younger age (2.9 years) and with more locally advanced disease.
- They also have a higher risk of biochemical recurrence after radical prostatectomy surgery.
- In the United States, black men are more commonly affected than white or Hispanic men, and it is more deadly in blacks.
- The incidence and mortality for Hispanic men is one third lower than for non-Hispanic whites.
- No single gene is responsible for prostate cancer, although many genes have now been implicated.
- Mutations in BRCA1 and BRCA2 have been associated with prostate cancer as well as breast cancer.
- P53 mutations in primary prostate cancer are relatively rare and are more frequently seen in metastatic disease. Therefore, p53 mutations are generally considered a late and ominous finding in prostate cancer.
- Over 100 Single Nucleotide Polymorphisms (SNPs) and other genes have been linked to an increased risk of prostate cancer. These include: hereditary prostate cancer gene 1, various androgen and Vitamin D receptors, HPC1, HPC2, HPCX, CAPB, mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), ataxia telangiectasia mutated (ATM), the TMPRSS2-ETS gene family; TMPRSS2-ERG and TMPRSS2-ETV1/4 which all tend to promote cancer cell growth. (Note: This is only a partial listing.)
- A Genetic Risk Score (GRS), including high risk genetic markers and SNPs, has been proposed to help with risk stratification of prostate cancer especially in families; but this type of testing is not yet ready for individual patient diagnostics.
Prostate cancer is generally linked to the consumption of the typical Western diet.
- There is little, if any, evidence that demonstrates an association between trans fat, saturated fat, or carbohydrate intake and prostate cancer.
- Vitamin supplements do not lower the risk, and in fact, some vitamins may increase it.
- High calcium intake is associated with advanced prostate cancer.
- Diets high in saturated fat and milk products seem to increase the risk.
- Whole milk consumption after a diagnosis of prostate cancer has been linked to an increased risk of recurrence, especially in overweight men.
- Lower Vitamin D blood levels may increase the risk of developing prostate cancer.
- Red meat and processed meats also appear to have little effect overall, but some studies suggest increased meat consumption is associated with a higher risk.
- Fish consumption may lower prostate cancer deaths, but does not affect occurrence rate.
- Some evidence supports the belief that a vegetarian diet lowers rates of prostate cancer, but this is not considered conclusive or a significant influence.
- Folic acid supplements have also not been shown to affect the risk of developing prostate cancer.
Prostate cancer is linked to some medications, medical procedures, and medical conditions.
- Use of statins and metformin may decrease prostate cancer risk as well as NSAIDs, especially those with anti-COX 2 activity.
- Regular aspirin, now used by an estimated 23.7 million men, also appears to reduce prostate cancer risk.
- This beneficial effect of NSAIDs appears to be more significant in aggressive prostate cancer and those with prostatitis.
- Agent Orange exposure may increase the risk of prostate cancer recurrence, particularly following surgery.
Multiple lifetime sexual partners or starting sexual activity early increases the risk of prostate cancer. Frequent ejaculation may decrease prostate cancer risk, but reduced ejaculatory frequency is not associated with any increased risk of advanced prostate cancer.
Infections may be associated with the incidence and development of prostate cancer.
- Infections with chlamydia, gonorrhea, or syphilis seem to increase the risk of developing prostate cancer.
- Human Papilloma Virus (HPV) has been proposed to have a role in prostate cancer incidence, but the evidence for this is inconclusive.
Vasectomy and Prostate Cancer
There was once thought to be an association between vasectomy and prostate cancer; but larger, follow-up studies have failed to confirm any such relationship.
Adenocarcinoma prostate screening
The issue of prostate cancer screening is controversial. In the United States, most prostate cancers are diagnosed as a result of screening, either with a PSA blood test or, less frequently, with a digital rectal examination. Randomized trials have yielded conflicting results 98). Systematic literature reviews and meta-analyses have reported no clear evidence that screening for prostate cancer decreases the risk of death from prostate cancer, or that the benefits outweigh the harms of screening 99).
Some medical organizations recommend men consider prostate cancer screening in their 50s, or sooner for men who have risk factors for prostate cancer.
Discuss your particular situation and the benefits and risks of screening with your doctor. Together, you can decide whether prostate cancer screening is right for you.
Prostate screening tests might include:
- Digital rectal exam (DRE). During a digital rectal examination, your doctor inserts a gloved, lubricated finger into your rectum to examine your prostate, which is adjacent to the rectum. If your doctor finds any abnormalities in the texture, shape or size of the gland, you may need further tests.
- Prostate-specific antigen (PSA) test. A blood sample is drawn from a vein in your arm and analyzed for PSA, a substance that’s naturally produced by your prostate gland. It’s normal for a small amount of PSA to be in your bloodstream. However, if a higher than normal level is found, it may indicate prostate infection, inflammation, enlargement or cancer.
PSA testing combined with digital rectal examination helps identify prostate cancers at their earliest stages. Hence, debate continues surrounding prostate cancer screening.
Adenocarcinoma prostate prevention
You can reduce your risk of prostate cancer if you:
- Choose a healthy diet full of fruits and vegetables. Avoid high-fat foods and instead focus on choosing a variety of fruits, vegetables and whole grains. Fruits and vegetables contain many vitamins and nutrients that can contribute to your health. Whether you can prevent prostate cancer through diet has yet to be conclusively proved. But eating a healthy diet with a variety of fruits and vegetables can improve your overall health.
- Choose healthy foods over supplements. No studies have shown that supplements play a role in reducing your risk of prostate cancer. Instead, choose foods that are rich in vitamins and minerals so that you can maintain healthy levels of vitamins in your body.
- Exercise most days of the week. Exercise improves your overall health, helps you maintain your weight and improves your mood. There is some evidence that men who don’t exercise have higher PSA levels, while men who exercise may have a lower risk of prostate cancer. Try to exercise most days of the week. If you’re new to exercise, start slow and work your way up to more exercise time each day.
- Maintain a healthy weight. If your current weight is healthy, work to maintain it by exercising most days of the week. If you need to lose weight, add more exercise and reduce the number of calories you eat each day. Ask your doctor for help creating a plan for healthy weight loss.
- Talk to your doctor about increased risk of prostate cancer. Men with a high risk of prostate cancer may consider medications or other treatments to reduce their risk. Some studies suggest that taking 5-alpha reductase inhibitors, including finasteride (Propecia, Proscar) and dutasteride (Avodart), may reduce the overall risk of developing prostate cancer. These drugs are used to control prostate gland enlargement and hair loss in men. However, some evidence indicates that men taking these medications may have an increased risk of getting a more serious form of prostate cancer (high-grade prostate cancer). If you’re concerned about your risk of developing prostate cancer, talk with your doctor.
Adenocarcinoma prostate symptoms
Prostate cancer may cause no signs or symptoms in its early stages. In the United States, most prostate cancers are diagnosed as a result of screening; therefore, symptoms of cancer are infrequent at the time of diagnosis 100).
Prostate cancer that’s more advanced may cause signs and symptoms such as:
- Trouble urinating
- Decreased force in the stream of urine
- Blood in semen
- Discomfort in the pelvic area
- Bone pain
- Erectile dysfunction
- Incomplete bladder emptying.
Although rare in the current era of widespread screening, prostate cancer may also present with symptoms of metastases, including bone pain, pathologic fractures, or symptoms caused by bone marrow involvement.
Adenocarcinoma prostate diagnosis
If a digital rectal examination or PSA test detects an abnormality, your doctor may recommend further tests to determine whether you have prostate cancer, such as:
- Ultrasound. If other tests raise concerns, your doctor may use transrectal ultrasound to further evaluate your prostate. A small probe, about the size and shape of a cigar, is inserted into your rectum. The probe uses sound waves to create a picture of your prostate gland.
- Collecting a sample of prostate tissue (prostate biopsy). If initial test results suggest prostate cancer, your doctor may recommend a procedure to collect a sample of cells from your prostate (prostate biopsy). Prostate biopsy is often done using a thin needle that’s inserted into the prostate to collect tissue. The tissue sample is analyzed in a lab to determine whether cancer cells are present.
- MRI fusion. While still being developed worldwide, MRI fusion to assist in prostate biopsy and diagnosis is being used more and more.
Needle biopsy is the most common method used to diagnose prostate cancer. Most urologists now perform a transrectal biopsy using a bioptic gun with ultrasound guidance. Less frequently, a transperineal ultrasound-guided approach can be used in patients who may be at increased risk of complications from a transrectal approach 101). Over the years, there has been a trend toward taking eight to ten or more biopsy samples from several areas of the prostate with a consequent increased yield of cancer detection after an elevated PSA blood test 102). However, a randomized trial has shown that, in experienced hands, a multiparametric magnetic resonance imaging (MRI)-directed biopsy is more accurate than a transrectal-guided biopsy to detect what are thought to be clinically significant cancers. In that multicenter study, MRI led to the detection of more Gleason score (≥7) lesions and fewer Gleason score (<7) lesions, with fewer biopsies overall 103).
Prophylactic antibiotics, especially fluoroquinolones, are often used before transrectal needle biopsies. There are reports of increasing rates of sepsis, particularly with fluoroquinolone-resistant E. coli, and hospitalization after the procedure 104). Therefore, men undergoing transrectal biopsy should be told to seek medical attention immediately if they experience fever after biopsy.
PSA and Other Pre-Biopsy Prostate Cancer Predictive Tests
Elevated Prostate Specific Antigen (PSA) levels (usually greater than 4 ng/ml) in the blood is how 80% of prostate cancers initially present even though elevated PSA levels alone correctly identify prostate cancer only about 25% to 30% of the time. We recommend at least 2 abnormal PSA levels or the presence of a palpable nodule on DRE to justify a biopsy and further investigation.
The value of PSA screenings remains controversial due to concerns about possible overtreatment of low-risk cancers, overdiagnosis, complications from “unnecessary biopsies,” the presumed “limited” actual survival benefit from early diagnosis and treatment, and the true value of definitive therapy intended to cure.
In an attempt to improve on PSA testing alone, many alternative pre-biopsy screening tests are now available:
Free and Total PSA
The percentage of free PSA in the blood can be a useful indicator of malignancy. If the total PSA is between 4 and 10 ng/ml, a free PSA percentage is considered valid. The free PSA percentage is calculated by multiplying the free PSA level by 100 and dividing by the total PSA value.
The actual risk estimates will vary by age group, but as a general guide:
- If the free PSA percentage is more than 25%, the cancer risk is less than 10%.
- If the free PSA percentage is less than 10%, the cancer risk is about 50%.
PSA Density is the total PSA divided by the prostatic volume as determined by MRI or ultrasound (US). The formula for the volume of the prostate is Prostate Volume = Width x Height x Length x Pi/6. For most purposes, Pi/6 can be estimated as 0.52 to make the calculations easier. The PSA density is intended to minimize the effect of benign prostatic enlargement. In general, if the PSA density is greater than 0.15, it is considered suggestive of malignancy.
PSA Velocity compares serial, annual PSA serum levels. An annual PSA increase of greater than 0.75 ng/ml or greater than 25% suggests a potential cancer of the prostate (total PSA 4 to 10 ng/ml). If the total PSA is 2.6 to 4 ng/ml, then an annual increase of 0.35 ng/ml would be considered suspicious.
Prostate Cancer Antigen 3 (PCA3)
Prostate Cancer Antigen 3 (PCA3) is an RNA based genetic test performed from a urine sample obtained immediately after a prostatic massage. PCA3 is a long, non-coding RNA molecule that is overexpressed exclusively in prostatic malignancies. It is upregulated 66 fold in prostate cancers. If PCA3 is elevated, it suggests the presence of prostate cancer. It is more reliable than PSA as it is independent of prostate volume. PCA3 is best used to determine the need for a repeat biopsy after an initial negative histology. Serial PCA3 testing may also be helpful in monitoring patients with low-grade prostate cancers on active surveillance.
The Prostate Health Index (PHI)
The Prostate Health Index (PHI) is a blood test that includes free PSA, total PSA, and the [-2] proPSA isoform of free PSA. A formula is used to combine these test results mathematically to give the PHI score. This PHI score appears to be superior to PSA, free and total PSA, and PCA3 in predicting the presence of prostate cancer.
The histologic grade of prostate adenocarcinomas is usually reported according to one of the variations of the Gleason scoring system, which provides a useful, albeit crude, adjunct to tumor staging in determining prognosis 105). The Gleason score is calculated based on the dominant histologic grades, from grade 1 (well differentiated) to grade 5 (very poorly differentiated). The classical score is derived by adding the two most prevalent pattern grades, yielding a score ranging from 2 to 10. Because there is some evidence that the least-differentiated component of the specimen may provide independent prognostic information, the score is often provided by its separate components (e.g., Gleason score 3 + 4 = 7; or 4 + 3 = 7) 106).
The “New” Gleason Scoring System
In 2016, the World Health Organization (WHO) proposed a new classification system based on clinical experience with the old Gleason scoring system that suggested very little difference in clinical outcomes in lower Gleason score patients, but somewhat different ones in the higher grades. The following is a summary of the “New” Gleason system:
- Grade Group 1 (Gleason score less than or equal to 6): Only individual discrete well-formed glands
- Grade Group 2 (Gleason score 3 + 4 = 7): Predominantly well-formed glands with a lesser component of poorly-formed, fused or cribriform glands
- Grade Group 3 (Gleason score 4 + 3 = 7): Predominantly poorly-formed, fused, or cribriform glands with a lesser component of well-formed glands
- Grade Group 4 (Gleason score 8): Only poorly-formed/fused/cribriform glands; or predominantly well-formed glands with a lesser component lacking glands; or predominantly lacking glands with a lesser component of well-formed glands
- Grade Group 5 (Gleason scores 9 or 10): Lacks gland formation (or with necrosis) with or without poorly-formed, fused or cribriform glands
In clinical practice, Group 1 is considered “Low Grade,” Group 2 is “Intermediate Grade,” and Group 3 or higher is “High Grade” disease.
There is evidence that, over time, pathologists have tended to award higher Gleason scores to the same histologic patterns, a phenomenon sometimes termed grade inflation 107). This phenomenon complicates comparisons of outcomes in current versus historical patient series. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004 108). The contemporary Gleason score readings were an average of 0.85 points higher than the same slides read a decade earlier. As a result, Gleason-score standardized prostate cancer mortality rates for these men were artifactually improved from 2.08 to 1.50 deaths per 100 person years—a 28% decrease even though overall outcomes were unchanged.
Determining how far the cancer has spread
Once a prostate cancer diagnosis has been made, your doctor works to determine the extent (stage) of the cancer. If your doctor suspects your cancer may have spread beyond your prostate, one or more of the following imaging tests may be recommended:
- Bone scan
- Computerized tomography (CT) scan
- Magnetic resonance imaging (MRI)
- Positron emission tomography (PET) scan
Doctors can also turn to prostate-specific membrane antigen (PSMA) studies to help detect the extent of newly diagnosed prostate cancer and whether the disease has spread to nearby lymph nodes.
Not every person should have every test. Your doctor will help determine which tests are best for your individual case.
Your doctor uses the information from these tests to assign your cancer a stage. Prostate cancer stages are indicated by Roman numerals ranging from I to IV. The lowest stages indicate the cancer is confined to the prostate. By stage IV, the cancer has grown beyond the prostate and may have spread to other areas of the body.
The cancer staging system continues to evolve and is becoming more complex as doctors improve cancer diagnosis and treatment. Your doctor uses your cancer stage to select the treatments that are right for you.
Adenocarcinoma prostate treatment
Your prostate cancer treatment options depend on several factors, such as how fast your cancer is growing, how much it has spread and your overall health, as well as the potential benefits or side effects of the treatment.
Immediate treatment may not be necessary
For men diagnosed with low-risk prostate cancer, treatment may not be necessary right away. Some men may never need treatment. Instead, doctors sometimes recommend active surveillance.
In active surveillance, regular follow-up blood tests, rectal exams and possibly biopsies may be performed to monitor progression of your cancer. If tests show your cancer is progressing, you may opt for a prostate cancer treatment such as surgery or radiation.
Active surveillance may be an option for cancer that isn’t causing symptoms, is expected to grow very slowly and is confined to a small area of the prostate. Active surveillance may also be considered for someone who has another serious health condition or who is of an advanced age that makes cancer treatment more difficult.
Active surveillance carries a risk that the cancer may grow and spread between checkups, making the cancer less likely to be cured.
Surgery to remove the prostate
Surgery for prostate cancer involves removing the prostate gland (radical prostatectomy), some surrounding tissue and a few lymph nodes. Radical prostatectomy can be performed in several ways:
- Using a robot to assist with surgery. During robot-assisted surgery, the instruments are attached to a mechanical device (robot) and inserted into your abdomen through several small incisions. The surgeon sits at a console and uses hand controls to guide the robot to move the instruments. Robotic prostatectomy may allow the surgeon to make more-precise movements with surgical tools than is possible with traditional minimally invasive surgery.
- Making an incision in your abdomen. During retropubic surgery, the prostate gland is taken out through an incision in your lower abdomen.
Discuss with your doctor which type of surgery is best for your specific situation.
Radical prostatectomy carries a risk of urinary incontinence and erectile dysfunction. Ask your doctor to explain the risks you may face based on your situation, the type of procedure you select, your age, your body type and your overall health.
Radiation therapy uses high-powered energy to kill cancer cells. Prostate cancer radiation therapy can be delivered in two ways:
- Radiation that comes from outside of your body (external beam radiation). During external beam radiation therapy, you lie on a table while a machine moves around your body, directing high-powered energy beams, such as X-rays or protons, to your prostate cancer. You typically undergo external beam radiation treatments five days a week for several weeks.
- Radiation placed inside your body (brachytherapy). Brachytherapy involves placing many rice-sized radioactive seeds in your prostate tissue. The radioactive seeds deliver a low dose of radiation over a long period of time. Your doctor implants the radioactive seeds in your prostate using a needle guided by ultrasound images. The implanted seeds eventually stop emitting radiation and don’t need to be removed.
Side effects of radiation therapy can include painful, frequent or urgent urination, as well as rectal symptoms such as loose stools or pain when passing stools. Erectile dysfunction can also occur.
Hormone therapy is treatment to stop your body from producing the male hormone testosterone. Prostate cancer cells rely on testosterone to help them grow. Cutting off the supply of testosterone may cause cancer cells to die or to grow more slowly.
Hormone therapy options include:
- Medications that stop your body from producing testosterone. Medications known as luteinizing hormone-releasing hormone (LH-RH) agonists prevent the testicles from receiving messages to make testosterone. Drugs typically used in this type of hormone therapy include leuprolide (Lupron, Eligard), goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas). Other drugs sometimes used include ketoconazole and abiraterone (Zytiga).
- Medications that block testosterone from reaching cancer cells. Medications known as anti-androgens prevent testosterone from reaching your cancer cells. Examples include bicalutamide (Casodex), nilutamide (Nilandron) and flutamide. The drug enzalutamide (Xtandi) may be an option when other hormone therapies are no longer effective.
- Surgery to remove the testicles (orchiectomy). Removing your testicles reduces testosterone levels in your body.
Hormone therapy is used in men with advanced prostate cancer to shrink the cancer and slow the growth of tumors. In men with early-stage prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy, which can increase the likelihood that radiation therapy will be successful.
Side effects of hormone therapy may include erectile dysfunction, hot flashes, loss of bone mass, reduced sex drive and weight gain.
Freezing prostate tissue
Cryosurgery or cryoablation involves freezing tissue to kill cancer cells.
During cryosurgery for prostate cancer, small needles are inserted in the prostate using ultrasound images as guidance. A very cold gas is placed in the needles, which causes the surrounding tissue to freeze. A second gas is then placed in the needles to reheat the tissue. The cycles of freezing and thawing kill the cancer cells and some surrounding healthy tissue.
Initial attempts to use cryosurgery for prostate cancer resulted in high complication rates and unacceptable side effects. However, newer technologies have lowered complication rates, improved cancer control and made the procedure easier to tolerate. Cryosurgery is more frequently used as a salvage therapy for men who haven’t been helped by radiation therapy.
Chemotherapy uses drugs to kill rapidly growing cells, including cancer cells. Chemotherapy can be administered through a vein in your arm, in pill form or both.
Chemotherapy may be a treatment option for men with prostate cancer that has spread to remote body locations. Chemotherapy may also be an option for cancers that don’t respond to hormone therapy.
Biological therapy (immunotherapy) uses your body’s immune system to fight cancer cells. One type of biological therapy called sipuleucel-T (Provenge) has been developed to treat advanced, recurrent prostate cancer.
This treatment takes some of your own immune cells, genetically engineers them in a laboratory to fight prostate cancer, then injects the cells back into your body through a vein. Some men do respond to this therapy with some improvement in their cancer, but the treatment is very expensive and requires multiple treatments.
Adenocarcinoma prostate survival rate
The 5-year relative survival rate for men diagnosed in the United States from 2001 to 2007 with local or regional prostate cancer was 100%, and the rate for distant prostate cancer was 28.7%; a 99% survival rate was observed for all stages combined 109).
Prognosis and Survival
In the United States, patients with localized or regional disease at the time of diagnosis have a 5-year survival rate of nearly 100% while patients presenting with distant metastases have a 5-year overall survival rate of only 29%.
In patients who undergo treatment, the most important prognostic indicators are patient age and general health at the time of diagnosis, as well as, the cancer stage, pre-therapy PSA level, and Gleason score.
A poorer prognosis is associated with higher grade disease, more advanced stage, younger age, increased PSA levels and a shorter “PSA doubling time.”
There is no clear evidence that either radical prostate surgery or radiation therapy have a significant survival advantage over the other, so treatment selection has relatively little effect on life expectancy.
- Patients with localized, low-grade disease (Gleason 2 + 2 = 4 or less) are unlikely to die of prostate cancer within 15 years.
- After 15 years, untreated patients are more likely to die from prostate cancer than any other identifiable disease or disorder.
- Older men with low-grade disease have approximately a 20% overall survival at 15 years, due primarily to death from other unrelated causes.
- Men with high-grade disease (Gleason 4 + 4 = 8 or higher) typically experience higher prostate cancer mortality rates within 15 years of diagnosis.
Adenocarcinoma survival rate
Survival rates tell you what portion of people with the same type and stage of cancer are still alive a certain amount of time (usually 5 years) after they were diagnosed. They can’t tell you how long you will live, but they may help give you a better understanding about how likely it is that your treatment will be successful.
5-year survival rate
Statistics on the outlook for a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer – often much longer – than 5 years. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer. For example, a 5-year survival rate of 90% means that an estimated 90 out of 100 people who have that cancer are still alive 5 years after being diagnosed.
Relative survival rates are a more accurate way to estimate the effect of cancer on survival. These rates compare women with breast cancer to women in the overall population. For example, if the 5-year relative survival rate for a specific type of cancer is 90%, it means that people who have that cancer are, on average, about 90% as likely as people who don’t have that cancer to live for at least 5 years after being diagnosed.
But remember, the 5-year relative survival rates are estimates – your outlook can vary based on a number of your specific factors.
Cancer survival rates don’t tell the whole story
Survival rates are often based on previous outcomes of large numbers of people who had the disease, but they can’t predict what will happen in any particular person’s case.
There are a number of limitations to remember:
- The numbers below are among the most current available. But to get 5-year survival rates, doctors have to look at people who were treated at least 5 years ago. As treatments are improving over time, people who are now being diagnosed with stage 4 metastatic cancer may have a better outlook than these statistics show.
- These statistics are based on the stage 4 cancer when it was first diagnosed. They do not apply to cancers that come back later, for example.
- Many other factors can affect a person’s outlook, such as age and health, the presence of hormone receptors on the cancer cells, the treatment received, and how well the cancer responds to treatment.
Your doctor can tell you how these numbers might apply to you, as he or she is familiar with your particular situation.
Table 5. Relative 5 Year Survival of Stage 4 Cancers (2008-2014)
|Oral Cavity and Pharynx||All races||Male and female||39.1%|
|White||Male and female||39.9%|
|Black||Male and female||29.1%|
|Esophagus||All races||Male and female||4.8%|
|White||Male and female||5.0%|
|Black||Male and female||3.5%|
|Stomach||All races||Male and female||5.2%|
|White||Male and female||5.0%|
|Black||Male and female||6.2%|
|Colon and Rectum||All races||Male and female||13.8%|
|White||Male and female||14.3%|
|Black||Male and female||10.4%|
|Liver and Intrahepatic Bile Duct||All races||Male and female||2.4%|
|White||Male and female||2.6%|
|Black||Male and female||0.9%|
|Gallbladder||All races||Male and female||1.7%|
|White||Male and female||1.9%|
|Black||Male and female||1.7%|
|Pancreas||All races||Male and female||2.7%|
|White||Male and female||2.7%|
|Black||Male and female||3.0%|
|Larynx||All races||Male and female||33.5%|
|White||Male and female||33.8%|
|Black||Male and female||31.2%|
|Lung and Bronchus||All races||Male and female||4.7%|
|White||Male and female||4.5%|
|Black||Male and female||4.6%|
|Bones and Joints||All races||Male and female||31.9%|
|White||Male and female||32.0%|
|Black||Male and female||28.3%|
|Soft Tissue including Heart||All races||Male and female||16.4%|
|White||Male and female||16.1%|
|Black||Male and female||17.3%|
|Melanoma of the Skin||All races||Male and female||22.5%|
|White||Male and female||22.2%|
|Black||Male and female||27.2%|
|Breast||All races||Male and female||26.9%|
|White||Male and female||28.1%|
|Black||Male and female||19.8%|
|Cervix Uteri||All races||Male and female|
|White||Male and female|
|Black||Male and female|
|Corpus and Uterus, not otherwise specified||All races||Male and female|
|White||Male and female|
|Black||Male and female|
|Ovary||All races||Male and female|
|White||Male and female|
|Black||Male and female|
|Prostate||All races||Male and female|
|White||Male and female|
|Black||Male and female|
|Testis||All races||Male and female|
|White||Male and female|
|Black||Male and female|
|Urinary Bladder||All races||Male and female||4.8%|
|White||Male and female||4.8%|
|Black||Male and female||3.4%|
|Kidney and Renal Pelvis||All races||Male and female||11.6%|
|White||Male and female||11.7%|
|Black||Male and female||9.4%|
|Eye and Orbit||All races||Male and female||30.1%|
|White||Male and female||27.7%|
|Black||Male and female||–|
|Brain and Other Nervous System||All races||Male and female||32.7%|
|White||Male and female||31.2%|
|Black||Male and female||38.6%|
|Thyroid||All races||Male and female||55.5%|
|White||Male and female||55.8%|
|Black||Male and female||47.0%|
|Hodgkin Lymphoma||All races||Male and female||78.2%|
|White||Male and female||78.4%|
|Black||Male and female||76.1%|
|Non-Hodgkin Lymphoma||All races||Male and female||64.1%|
|White||Male and female||65.0%|
|Black||Male and female||57.6%|
|Myeloma||All races||Male and female||49.6%|
|White||Male and female||48.7%|
|Black||Male and female||51.5%|
|Leukemia||All races||Male and female||61.4%|
|White||Male and female||61.8%|
|Black||Male and female||55.4%|
|Lymphocytic Leukemia||All races||Male and female||79.7%|
|White||Male and female||79.9%|
|Black||Male and female||70.2%|
|Acute Lymphocytic Leukemia||All races||Male and female||68.1%|
|White||Male and female||68.2%|
|Black||Male and female||63.6%|
|Chronic Lymphocytic Leukemia||All races||Male and female||84.2%|
|White||Male and female||84.2%|
|Black||Male and female||73.1%|
|Myeloid and Monocytic Leukemia||All races||Male and female||40.4%|
|White||Male and female||39.4%|
|Black||Male and female||43.7%|
|Acute Myeloid Leukemia||All races||Male and female||27.4%|
|White||Male and female||26.9%|
|Black||Male and female||28.8%|
|Acute Monocytic Leukemia||All races||Male and female||23.2%|
|White||Male and female||23.8%|
|Black||Male and female||25.2%|
|Chronic Myeloid Leukemia||All races||Male and female||67.6%|
|White||Male and female||66.4%|
|Black||Male and female||70.0%|
|Mesothelioma||All races||Male and female||7.2%|
|White||Male and female||7.2%|
|Black||Male and female||5.6%|
|Kaposi Sarcoma||All races||Male and female||45.0%|
|White||Male and female||50.3%|
|Black||Male and female||–|
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