Colon Cancer: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Colon cancer (colorectal cancer, CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death in the US, with approximately 106,000 new colon cancer diagnoses and 52,000 colorectal cancer deaths estimated in 2023. The vast majority (95%) are adenocarcinomas, arising from the glandular cells lining the colon through the well-characterized adenoma-carcinoma sequence — where benign adenomatous polyps accumulate somatic mutations over 10-15 years before developing invasive malignant potential. Colon cancer encompasses cancers of the cecum, ascending, transverse, descending, and sigmoid colon (rectal cancer involving the rectum, though pathologically similar, is managed with distinct surgical and radiation approaches). The molecular landscape of colon cancer includes MSI-H/dMMR tumors (approximately 15%, highly immunogenic, excellent response to checkpoint inhibitors), RAS-mutated tumors (approximately 50%, resistant to anti-EGFR targeted therapy), and BRAF V600E-mutated tumors (approximately 10%, aggressive, treated with targeted BRAF/MEK inhibitor combinations).

The adenoma-carcinoma sequence is the dominant pathogenic pathway: chromosomal instability (CIN) involving sequential somatic mutations in APC, KRAS, SMAD4, and TP53 drives most sporadic CRC. Hereditary syndromes: Lynch syndrome (HNPCC) — germline mutations in mismatch repair genes MLH1, MSH2, MSH6, PMS2 — accounts for approximately 3-5% of all CRC and confers lifetime CRC risk of 50-80%; familial adenomatous polyposis (FAP) — APC germline mutation — accounts for approximately 1%, with near-100% lifetime CRC risk without prophylactic colectomy. Risk factors: age over 50 (though incidence is rising in under-50 adults), family history of CRC or advanced adenomas, prior adenomatous polyps, inflammatory bowel disease (ulcerative colitis, Crohn's colitis), obesity, physical inactivity, red and processed meat consumption, smoking, heavy alcohol consumption, and type 2 diabetes. Protective factors: aspirin use (reduces adenoma recurrence in Lynch syndrome), calcium, and high-fiber diet. Incidence under age 50 has risen by approximately 2% per year since the 1990s, prompting updated US Preventive Services Task Force (USPSTF) screening recommendations starting at age 45.

Colon cancer is frequently asymptomatic in early stages — the single strongest argument for population screening with colonoscopy or stool-based tests. When symptomatic: right-sided colon cancer (cecum, ascending colon) presents with occult or overt rectal bleeding causing iron deficiency anemia, fatigue, and palpable right lower quadrant mass — due to the larger caliber of the proximal colon, obstruction is less common; left-sided colon cancer (descending colon, sigmoid) presents with change in bowel habit (alternating diarrhea and constipation), bright red rectal bleeding, pencil-thin stools, and bowel obstruction from the narrower left colon lumen; transverse colon cancer may present with obstruction or perforation. Systemic symptoms in advanced disease: significant unintentional weight loss, anorexia, and fatigue. Metastatic colon cancer: right upper quadrant pain and jaundice from liver metastases; respiratory symptoms from pulmonary metastases; CEA (carcinoembryonic antigen) elevation is common.

Colonoscopy with biopsy is the definitive diagnostic test, enabling direct visualization and histological confirmation of adenocarcinoma. CT colonography (virtual colonoscopy) is an alternative imaging technique for polyp detection in patients unable to undergo optical colonoscopy. CT thorax, abdomen, and pelvis with contrast: primary staging to assess local tumor extent (T stage), regional lymph node involvement (N stage), and distant metastases (liver, lung — M stage). MRI pelvis: for locally advanced colon cancers extending to adjacent organs, and for all rectal cancers. PET-CT: for evaluating equivocal liver or lung lesions and staging. AJCC 8th edition TNM staging guides treatment decisions: Stage I (T1-2N0M0): 5-year OS approximately 90-95%; Stage II (T3-4N0M0): approximately 72-85%; Stage III (any T, N1-2, M0): approximately 40-83% by substage; Stage IV (any T, any N, M1): approximately 14-71% depending on resectability of metastases. Mandatory molecular testing for all newly diagnosed CRC: MSI/MMR status (IHC or PCR), KRAS/NRAS exon 2/3/4 mutation, BRAF V600E mutation, HER2 amplification, and NTRK1/2/3 fusion.

Surgical resection is the cornerstone of curative treatment. Laparoscopic or robotic right hemicolectomy, left hemicolectomy, or sigmoid colectomy with high ligation of the feeding vessel and en bloc lymph node dissection (minimum 12 lymph nodes required for adequate staging). Emergency colectomy with Hartmann's procedure for obstructing or perforated colon cancer. Stage II high-risk (T4, <12 nodes harvested, bowel perforation, poor differentiation): adjuvant FOLFOX or CAPOX chemotherapy for 3-6 months. Stage III (node-positive): 6 months adjuvant FOLFOX or CAPOX (oxaliplatin-based) chemotherapy significantly improves OS — capecitabine monotherapy for patients unable to tolerate oxaliplatin. Metastatic colon cancer (Stage IV): FOLFOX or FOLFIRI as first-line backbone; bevacizumab added to first-line FOLFOX/FOLFIRI extends PFS and OS in RAS-mutated disease; cetuximab or panitumumab added to FOLFIRI in RAS/BRAF wild-type disease. MSI-H/dMMR metastatic CRC: pembrolizumab monotherapy first-line (KEYNOTE-177, superior PFS 16.5 months vs 8.2 months, ORR 43% vs 33%); nivolumab plus ipilimumab for pembrolizumab-refractory MSI-H. BRAF V600E-mutated: encorafenib plus cetuximab (BEACON-CRC: ORR 20%, improved OS vs standard of care). Resectable liver and/or lung metastases: perioperative chemotherapy plus metastasectomy achieves 5-year OS 25-40%. Regorafenib and trifluridine-tipiracil (TAS-102) for refractory metastatic CRC.

Prognosis for colon cancer is strongly determined by TNM stage at diagnosis. Stage I (T1-2N0M0): 5-year overall survival approximately 90-95%. Stage IIA (T3N0M0): approximately 85-87%; Stage IIB (T4aN0M0): approximately 72-78%; Stage IIC (T4bN0M0): approximately 63-73%. Stage IIIA: approximately 80-83%; Stage IIIB: approximately 64-72%; Stage IIIC: approximately 44-58%. Stage IVA (limited metastatic sites): approximately 14-28%; Stage IVB (multiple metastatic sites): approximately 3-8% at 5 years. Molecularly selected patients with MSI-H/dMMR stage IV disease treated with pembrolizumab achieve substantially improved outcomes — 5-year OS approaching 30-40% in KEYNOTE-177. Resectable liver-only or lung-only metastases treated with perioperative chemotherapy plus metastasectomy achieve 5-year OS of approximately 25-40%. Early-onset colon cancer (under age 50) carries similar stage-adjusted prognosis to older adults, though this group has rising incidence. Without surgery, stage I-III colon cancer uniformly progresses to local invasion, metastasis, and death within 3-5 years. Key prognostic factors include TNM stage, MSI-H/dMMR status (adverse in stage II-III where it predicts reduced benefit from 5-FU-based adjuvant chemotherapy, but favorable in stage IV for immunotherapy response), KRAS/NRAS/BRAF V600E mutation status (determines anti-EGFR therapy eligibility), adequacy of lymph node sampling (minimum 12 nodes required), and completeness of surgical resection (R0). Post-treatment surveillance per NCCN guidelines: CEA every 3-6 months for 5 years, CT thorax and abdomen-pelvis every 6-12 months for 5 years, and colonoscopy 1 year post-resection then every 3-5 years if negative.

Colorectal cancer is largely preventable through screening — colonoscopy enables detection and removal of adenomatous polyps before malignant transformation, reducing CRC incidence and mortality by over 60%. USPSTF 2021 guidelines recommend average-risk adults begin CRC screening at age 45 (updated from 50) due to rising incidence in younger adults. Screening options: colonoscopy every 10 years; annual fecal immunochemical test (FIT) or fecal occult blood test (FOBT); stool DNA test (Cologuard) every 1-3 years; CT colonography every 5 years. High-risk individuals (Lynch syndrome, FAP, IBD, prior CRC/advanced polyps) require more frequent and earlier colonoscopy surveillance. Lifestyle prevention: maintaining healthy weight (obesity raises CRC risk by 30-40%), regular physical activity (150 min/week moderate activity reduces risk by approximately 20%), limiting red and processed meat consumption, reducing alcohol intake, and smoking cessation. Aspirin (81-325 mg daily) reduces adenoma recurrence in Lynch syndrome patients; calcium and vitamin D supplementation may reduce risk. NSAIDs and low-dose aspirin reduce colon polyp recurrence; COX-2 inhibitors (celecoxib) are FDA-approved for familial adenomatous polyposis polyp burden reduction.

Seek prompt medical evaluation for: rectal bleeding or blood in the stool, regardless of whether hemorrhoids are suspected (CRC must always be excluded in adults aged 45 and over); persistent change in bowel habit lasting more than 4-6 weeks, especially alternating constipation and diarrhea; iron deficiency anemia in adults aged 45 and over — this always requires investigation of the gastrointestinal tract for a source, as colon cancer in the right colon commonly presents with occult bleeding and anemia before any visible symptoms; unexplained weight loss over 4.5 kg (10 lb) in 6 months in combination with bowel symptoms; or a palpable abdominal mass. Adults aged 45 and over without symptoms should undergo routine colorectal cancer screening — a pre-cancerous polyp found and removed at colonoscopy prevents cancer from ever developing. Individuals with first-degree relatives diagnosed with CRC under age 60 should begin screening at age 40 or 10 years before the youngest affected relative's diagnosis, whichever is earlier. Anyone with suspected Lynch syndrome should be referred to clinical genetics for germline MMR gene mutation testing and cascade family screening.