Gastrointestinal Cancers

Overview

Gastrointestinal (GI) cancers encompass a diverse group of malignancies that originate in the digestive system, from the mouth and esophagus to the anus, including organs like the stomach, intestines, liver, pancreas, and biliary tract. These cancers affect the tube-like structure that processes food, absorbs nutrients, and eliminates waste, making them critical to overall health. In simple terms, GI cancers occur when cells in these organs grow uncontrollably, often due to genetic mutations triggered by lifestyle, environmental, or inherited factors. The major types include esophageal cancer (affects the food pipe), gastric (stomach) cancer, colorectal cancer (involves the colon or rectum), liver cancer (hepatocellular carcinoma), pancreatic cancer, and gallbladder and biliary tract cancers. GI cancers as a group account for 20% (approx.) of all cancers.

Esophageal cancer ranks 5th in both new cases and deaths yearly (GLOBOCAN fact sheet 2022). Major risk factors are thought to include poor nutritional status, low intake of fruits and vegetables, and drinking beverages at high temperatures. Stomach cancer (GC) is the 7th leading cancer and the 6th leading cause of cancer in India. Approximately 50% of patients present as locoregional disease in India, and only one-half of those who appear to have locoregional tumor involvement can undergo potentially curative surgery. Almost a quarter of patients present with stage 4 disease with 5-year survival only 10%. Although several risk factors are described, Helicobacter pylori (H. pylori) infection and family history of gastric cancer are the two main risk factors for GC. High intake of salt and various traditional salt-preserved foods, such as salted fish, cured meat, and salted or pickled vegetables; exposure to nitroso compounds; excess body weight; smoking; and alcohol are other risk factors of GC. Colorectal cancer (CRC) ranks 6th in new cases and 7th in number of deaths annually. Environmental and genetic factors can increase the likelihood of developing CRC. Obesity, diabetes, tobacco use, excess consumption of alcohol, excess consumption of processed meat, and lack of physical activity are risk factors for CRC. Liver cancer (HCC) ranks 11th in new cases and 8th in number of deaths annually. Males, hepatitis B & C infections, chronic liver disease, alcohol, tobacco, and diabetes are risk factors for HCC. Pancreatic cancer is aggressive and rising, with 14,000 cases in 2022. Urban men aged 60+ are most affected, linked to smoking, diabetes, and obesity. Survival is dismal (<5% five-year), contributing to 5% of GI deaths. Gallbladder and biliary tract cancers (GBC) are uncommon but highly fatal malignancies. Chronic gallstones and infections drive 20,000 cases yearly.

Clinical Presentation

GI cancers often lurk silently, mimicking benign conditions, leading to 60-70% late-stage diagnoses in India. Symptoms vary by site but share themes like unexplained weight loss, fatigue, and digestive changes. Symptoms specific to the site are as follows:

Diagnosis

Diagnosing GI cancers involves a stepwise approach: history, exam, labs, imaging, and biopsy. Common lab investigations include CBC (anemia), liver function tests (jaundice), tumor markers—CEA (CRC), CA19-9 (pancreas), and AFP (liver)—and stool for occult blood. Site-specific diagnostics include:

Management

Management is multidisciplinary (surgeon and oncologist) and tailored by stage, type, and patient fitness. Curative intent to therapy is for early stages, palliative for advanced. Clinical management at South Gujarat Hematology Oncology Centre (SGHOC) is based on NCCN (American) and ESMO (European) guidelines, leading to the best outcomes for the presenting stage. Site-specific therapy options include:

• For very early stage I esophageal cancer, endoscopic submucosal dissection (ESD) is done. For localized cancer, preoperative chemoradiation followed by radical surgery (esophagectomy) is recommended. In stage IV or advanced cancers, chemotherapy with or without targeted therapy and immunotherapy is given. Stenting may be required to improve food intake. 5-year survival reaches 80% in stage I esophageal cancer but is <20% in stage IV.
• For very early stage I gastric cancer, endoscopic submucosal resection (ESD) is done. For localized cancer, preoperative chemotherapy followed by radical surgery (gastrectomy) is recommended. In stage IV or advanced cancers, chemotherapy with or without targeted therapy and immunotherapy is given. Molecular analysis for PDL1 and HER2 is done before initiating therapies in advanced-stage GC.
• For early-stage COLON cancer, radical surgery (colectomy) is done. For localized RECTAL cancer, preoperative chemoradiation followed by radical surgery (total mesorectal excision) is recommended. In stage IV or advanced cancers, chemotherapy with or without targeted therapy and immunotherapy is given. Molecular analysis for MSI, HER2, NRAS/KRAS, and BRAF is done before initiating therapies in advanced-stage CRC. Various biologics like cetuximab (anti-EGFR) and bevacizumab (anti-VEGF) are part of the therapeutic armamentarium.
• For early-stage liver cancer, resection, radiofrequency ablation (RFA), and transplant are therapeutic options. For intermediate-stage cancer, TACE (transarterial chemoembolization) is recommended. In stage IV or advanced cancers, immunotherapy with or without TKI (targeted oral medicines) is given. In India, the availability of cheaper, highly effective immunotherapy agents like toripalimab and tislelizumab has revolutionized the management of liver cancer. The median survival of advanced HCC is now reaching almost 2 years. HBV vaccination prevents 70% of cases in India.
• For early-stage pancreatic cancer, radical surgery (Whipple’s procedure) with chemotherapy is recommended. For localized borderline cancer, preoperative chemoradiation or perioperative chemotherapy followed by radical surgery is done. In stage IV or advanced cancers, chemotherapy with or without targeted therapy is given. Stenting may be required to improve jaundice.
• For early-stage gallbladder/biliary tract cancers, radical surgery (radical cholecystectomy or Whipple’s procedure) with chemotherapy is recommended. For localized borderline cancer, preoperative chemoradiation or perioperative chemoimmunotherapy followed by radical surgery is done. In stage IV or advanced cancers, chemotherapy with or without targeted therapy and immunotherapy is given. Biliary stenting may be required to improve jaundice.

Supportive care is essential in GI cancers, as most patients present in later stages. Pain management, nutritional support, and psychological therapy may be required. Clinical trials, if available, are offered to patients for novel therapies. With the availability of immunotherapies, targeted therapies, and antibody drug conjugates (ADCs), 5-year overall survival (average across all stages) now reaches almost 65% in CRC, 40% in GC, and 20% in HCC (liver) cancer. Overall, the 5-year survival rate in pancreatic cancer is dismal at just 10% despite recent therapeutic advances. Choosing the right therapy is crucial for improving the response rates and overall survival of the patient. However, there is no one therapy that fits for all cases. Combined modality approaches are required in GI cancers for long-term disease control. Which therapies to be chosen and in which combination is decided by the oncologist depending on the patient’s stage, anatomic site of cancer, comorbidities like diabetes, hypertension, heart problems, etc., and type of GI cancer.

Follow Up care

After completion of therapy, long-term follow-up is required to detect recurrences and second primary cancers and to look for late toxicities of chemotherapy and radiation. It is important to watch for symptoms that could signal the return of cancer—headaches, convulsions, shortness of breath, chronic cough, bony pains, abdominal pain or distension, jaundice, weight loss despite adequate food intake, etc. The general schedule for checkups is 3 monthly in the first 2 years, 6 monthly between years 3 and 5, and annually after 5 years. Check-ups specific to the site would be advised by the treating oncologist. Also, lifestyle modifications like quitting tobacco/alcohol, maintaining a healthy weight (BMI < 25), exercising 150 min/week, eating plenty of fruits and vegetables, and limiting red meat are advised.