Highlights
- Colon cancer is the third most common cancer, with over 1.9 million new cases diagnosed in 2020.
- Early diagnosis through colonoscopy significantly improves survival rates and treatment outcomes.
- Advances in precision medicine and immunotherapy are transforming colorectal cancer treatment and enhancing patient care.
Summary and Overview
Colon cancer, or colorectal cancer (CRC), is the third most common cancer and fourth leading cause of cancer deaths worldwide, with over 1.9 million cases and nearly 900,000 deaths in 2020. Incidence is highest in developed regions like Australia, Europe, and the US, influenced by genetic, lifestyle, and environmental factors. While mostly affecting older adults, CRC rates are rising among younger populations in developed countries. Risk factors include hereditary syndromes (e.g., familial adenomatous polyposis and Lynch syndrome), diets high in processed meats, obesity, smoking, physical inactivity, and chronic inflammation from inflammatory bowel disease (IBD).
Early diagnosis via colonoscopy is vital for survival. Advances in molecular diagnostics, including mismatch repair deficiency and microsatellite instability, support personalized treatment. Standard treatment involves surgery and adjuvant chemotherapy, with immunotherapy showing promise for specific genetic subtypes. Prognosis varies by stage and socioeconomic factors, with ongoing research targeting precision medicine, immunotherapy, genetic risk, and health equity to improve outcomes.
Causes and Pathophysiology
CRC arises from genetic, environmental, and inflammatory factors. Chronic inflammation in IBD increases cancer risk by promoting carcinogenic changes. Hereditary syndromes like familial adenomatous polyposis (APC gene mutation) and Lynch syndrome (DNA mismatch repair gene mutations) significantly elevate CRC risk. Most CRCs develop from polyps with dysplastic changes and involve diverse molecular pathways affecting tumor behavior and treatment response. Modifiable risks include age, diet rich in red/processed meats, smoking, alcohol, and sedentary lifestyle.
Symptoms and Diagnosis
Early CRC may be asymptomatic; symptoms like rectal bleeding, blood in stool, anemia, abdominal discomfort, and changes in bowel habits often prompt evaluation. Overlapping symptoms with benign conditions can delay diagnosis. High-risk groups, including IBD patients, benefit from regular surveillance. Diagnosis relies primarily on colonoscopy, allowing visualization and biopsy, supplemented by imaging (CT colonography, barium enema) and molecular testing for hereditary syndromes. Biomarkers and staging (AJCC TNM system) guide prognosis and treatment. Emerging AI technologies enhance diagnostic accuracy.
Prevention
Primary prevention focuses on modifying risk factors such as unhealthy diet, obesity, smoking, and alcohol use, while promoting physical activity. Diets high in fruits, vegetables, and whole grains reduce CRC risk. Obesity notably increases colon and rectal cancer risk. Smoking contributes to 12% of CRC deaths by promoting polyp formation. Screening, mainly via colonoscopy starting at age 45 (earlier for high-risk individuals), enables early detection and removal of precancerous lesions, reducing incidence and mortality.
Treatment
Surgery is the main treatment for localized colon cancer, including polypectomy and colectomy with lymph node dissection. Adjuvant chemotherapy reduces recurrence risk, with regimens often combining oxaliplatin and 5-fluorouracil. Minimal residual disease (MRD) testing is emerging to personalize adjuvant therapy decisions. Immunotherapy with immune checkpoint inhibitors benefits metastatic CRC patients with mismatch repair deficiency or high microsatellite instability. Neoadjuvant immunotherapy shows promise in early-stage dMMR/MSI-H tumors, potentially reducing the need for extensive surgery or chemotherapy. Rectal cancer treatment often involves preoperative chemoradiotherapy and surgery, with limited adjuvant chemotherapy roles. Advanced cases require individualized treatments.
Prognosis
Survival depends largely on cancer stage at diagnosis; early-stage detection improves outcomes, while metastatic disease has poor prognosis. Socioeconomic disparities affect survival, with lower socioeconomic status linked to worse outcomes and reduced access to therapies. Early symptom recognition facilitates timely diagnosis. Biomarkers enhance early detection, prognosis, and treatment personalization, contributing to improved survival rates.
Research and Future Directions
Current research explores sex-based differences in CRC and integrates immunotherapy with chemotherapy and targeted agents, especially for Lynch syndrome and MSI-H tumors. Clinical trials investigate combinations of immune checkpoint inhibitors with standard treatments. Molecular screening for mismatch repair deficiency guides diagnosis and therapy. Experimental vaccines for Lynch syndrome prevention are under study. Biomarker development, including MRD testing, advances precision medicine. Addressing socioeconomic disparities remains a priority to improve global CRC outcomes.
The content is provided by Harper Eastwood, Scopewires
