Quick Answer
Colorectal cancer (CRC) features in 2 to 3 NEET PG questions per paper across Surgery, Medicine, Pathology and PSM. The high-yield anchors:
- Adenoma-carcinoma sequence — APC → KRAS → DCC/SMAD4 → TP53.
- Hereditary syndromes — FAP (APC, 100 percent risk by age 40), Lynch (MMR defect, MSI-high).
- Screening — colonoscopy every 10 years from age 45 to 50; iFOBT yearly.
- Staging — TNM/AJCC 8; CEA baseline and surveillance.
- Surgery — right hemicolectomy, left hemicolectomy, LAR, APR, total mesorectal excision (TME).
- Lymph node yield — minimum 12 nodes for adequate staging.
- Adjuvant — FOLFOX/CAPOX for stage III; neoadjuvant chemoradiation for rectal stage II to III.
Colorectal cancer is one of the fastest-growing surgical oncology topics in NEET PG because India is now seeing rising incidence in patients under 50 — a trend that mirrors global data and reshapes screening recommendations. The exam tests the full pipeline from molecular pathology through surgical decision-making to adjuvant therapy, and a single missed concept (lymph node yield, the APC-KRAS sequence, when to irradiate the rectum) often costs the question.
This NEETPGAI guide walks through molecular pathogenesis, hereditary syndromes, screening, staging, surgical options (right vs left hemicolectomy vs LAR vs APR, TME), neoadjuvant therapy for rectal cancer, adjuvant chemotherapy and the India-specific picture. Pair it with the intestinal obstruction guide and the gastrointestinal bleeding deep dive for a complete CRC pathway.
Molecular pathogenesis
Adenoma-carcinoma sequence (chromosomal instability, 85 percent)
Vogelstein model — step-wise accumulation over 10 to 15 years:
- Normal mucosa → small adenoma — APC loss (5q21). APC is the gatekeeper; loss releases beta-catenin into the nucleus, driving Wnt-pathway transcription.
- Small → large adenoma — KRAS activation (12p12). Sustained MAP-kinase signalling.
- Large adenoma → carcinoma — DCC/SMAD4 loss (18q) and TP53 loss (17p) — the guardian fails.
This sequence is why colonoscopy with polypectomy works — it interrupts a decade-long process.
Microsatellite instability (MSI, 15 percent)
DNA mismatch repair failure — MLH1, MSH2, MSH6, PMS2. Tumours accumulate insertion-deletion errors in microsatellite repeats. Two routes:
- Sporadic (12 percent) — somatic hypermethylation of the MLH1 promoter; right-sided tumours, older women, BRAF V600E mutation common.
- Hereditary (Lynch) (3 percent) — germline MMR mutation.
MSI-high tumours have better stage-for-stage prognosis but do not benefit from adjuvant 5-FU monotherapy — a critical NEET PG pearl. They respond strikingly to immune-checkpoint inhibitors (pembrolizumab) because they generate abundant neoantigens.
Hereditary syndromes
Familial adenomatous polyposis (FAP)
Autosomal dominant, APC mutation (5q21). Hundreds to thousands of colonic adenomas by adolescence; 100 percent CRC risk by age 40 if untreated. Variants:
- Classic FAP — over 100 polyps.
- Attenuated FAP — fewer (less than 100) polyps, later onset.
- Gardner syndrome — FAP + osteomas, desmoid tumours, epidermal cysts, supernumerary teeth.
- Turcot syndrome — FAP + CNS tumours (medulloblastoma) or Lynch + glioblastoma.
Management — annual sigmoidoscopy from age 10 to 12; prophylactic total proctocolectomy with ileal pouch-anal anastomosis (IPAA) by age 20 or earlier if dense polyposis. Surveillance for upper GI (duodenal adenomas around the ampulla) and desmoid tumours lifelong.
Lynch syndrome (HNPCC)
Autosomal dominant; MLH1, MSH2 (commonest two), MSH6, PMS2 or EPCAM mutation. Lifetime CRC risk 50 to 80 percent (predominantly right-sided), endometrial 25 to 60 percent, ovarian, gastric, urothelial, small bowel, hepatobiliary, brain.
Amsterdam II criteria — three relatives with HNPCC-spectrum cancer, one a first-degree relative of the other two, two successive generations, one diagnosed before age 50, FAP excluded.
Bethesda criteria prompt MSI/IHC testing of the tumour. Universal IHC for MMR proteins is now standard in most Indian tertiary centres.
Surveillance — colonoscopy every 1 to 2 years from age 20 to 25; endometrial sampling and transvaginal ultrasound annually from age 30 to 35; consider risk-reducing hysterectomy and BSO after childbearing.
Peutz-Jeghers, juvenile polyposis, MUTYH-associated polyposis
Less common but examinable. Peutz-Jeghers — STK11 (LKB1) mutation, mucocutaneous pigmentation, hamartomatous polyps, increased CRC and pancreatic risk. MUTYH-associated polyposis — biallelic MUTYH; mimics attenuated FAP.
Clinical presentation
Right-sided (caecum, ascending colon) — anaemia, melena, vague pain, palpable mass; bowel obstruction late because of liquid stool and wide lumen.
Left-sided (descending, sigmoid) — change in bowel habit, narrow-calibre stools, fresh bleeding, obstruction (apple-core lesion on barium enema).
Rectal — tenesmus, fresh bleeding, mucus discharge, urgency.
Red flags — iron-deficiency anaemia in a man or postmenopausal woman, change in bowel habit over age 40, weight loss, family history.
Screening
Average-risk adults — colonoscopy every 10 years from age 45 (US Preventive Services Task Force 2024) or 50 (older guidelines). Alternatives — annual iFOBT (faecal immunochemical test), flexible sigmoidoscopy every 5 years, CT colonography every 5 years, stool DNA every 3 years.
High-risk groups (Lynch, FAP, inflammatory bowel disease, first-degree relative with CRC under 60) need earlier and more frequent screening.
India has no national CRC screening programme as of 2026, though Ayushman Bharat HWCs are piloting opportunistic iFOBT in some states.
Investigations
- Colonoscopy + biopsy — diagnostic and therapeutic (polypectomy).
- CEA — baseline before surgery and during surveillance; not diagnostic.
- CT chest, abdomen, pelvis — staging; detects liver and lung metastases.
- MRI pelvis — local staging for rectal cancer (mesorectal fascia, circumferential resection margin, T and N stage).
- Endorectal ultrasound — early rectal cancer T staging.
- PET-CT — selected cases (equivocal CT, recurrence work-up).
- Tumour mutational profile — KRAS, NRAS, BRAF (for anti-EGFR therapy decisions); MMR/MSI status.
Staging (TNM/AJCC 8)
| Stage | T | N | M |
|---|
| 0 | Tis (in situ) | N0 | M0 |
| I | T1-T2 | N0 | M0 |
| II | T3-T4 | N0 | M0 |
| III | Any T | N1-N2 | M0 |
| IV | Any T | Any N | M1 |
Five-year survival roughly — I: 90 percent, II: 75 percent, III: 50 percent, IV: 14 percent (improving with modern systemic therapy).
Surgical management
Principles
- Oncologic resection — proximal and distal margins of at least 5 cm; circumferential margin clear; minimum 12 lymph nodes sampled (correlates with adequate staging).
- High vascular ligation at the origin of the feeding vessel (ileocolic, right colic, middle colic for right hemicolectomy; IMA for left).
- No-touch technique — ligate the vascular pedicle before manipulating the tumour.
Operation by tumour site
| Tumour location | Operation | Anastomosis | Vessel ligated |
|---|
| Caecum, ascending colon | Right hemicolectomy | Ileo-transverse | Ileocolic, right colic |
| Hepatic flexure, proximal transverse | Extended right hemicolectomy | Ileo-transverse | + middle colic |
| Distal transverse, splenic flexure | Extended left hemicolectomy or transverse colectomy | Colocolic | Left branch middle colic, left colic |
| Descending colon | Left hemicolectomy | Colocolic | Left colic |
| Sigmoid colon | Sigmoidectomy or anterior resection | Colorectal | IMA |
| Upper rectum (above 10 cm) | Anterior resection (AR) | Colorectal | IMA |
| Mid rectum (5 to 10 cm) | Low anterior resection (LAR) + TME | Colorectal or coloanal, diverting ileostomy | IMA |
| Low rectum (less than 5 cm), sphincter-invaded | Abdominoperineal resection (APR) + TME | None — permanent end colostomy | IMA |
Total mesorectal excision (TME)
En-bloc sharp dissection of the rectum within the mesorectal envelope along the holy plane (avascular areolar tissue between visceral and parietal pelvic fascia), preserving autonomic nerves. Heald's TME reduced local recurrence from over 25 percent to under 10 percent. Now standard for mid and low rectal cancer.
Emergency presentation
About 20 percent of CRC patients present with obstruction or perforation. Options — primary resection with anastomosis (right colon), Hartmann procedure (left colon obstruction, sigmoid perforation), self-expanding metal stent (SEMS) as bridge to elective resection (left-sided obstruction in stable patient), defunctioning loop colostomy.
Adjuvant and neoadjuvant therapy
Colon cancer
- Stage I — surgery alone.
- Stage II — surgery alone unless high-risk (T4, less than 12 nodes, lymphovascular or perineural invasion, perforation, poor differentiation, MSS) → 5-FU based adjuvant. MSI-high stage II tumours do NOT benefit from adjuvant 5-FU.
- Stage III — 6 months FOLFOX or CAPOX. IDEA trial — 3 months CAPOX non-inferior in low-risk T1 to T3 N1; reduces oxaliplatin neurotoxicity.
- Stage IV — palliative chemotherapy (FOLFOX, FOLFIRI), biologics (bevacizumab, cetuximab/panitumumab if RAS/BRAF wild-type), curative-intent resection of isolated liver or lung metastases.
Rectal cancer
- Stage I — surgery alone (TEM for T1 N0).
- Stage II to III (T3 to T4 or node-positive) — neoadjuvant long-course chemoradiation (50.4 Gy with concurrent 5-FU or capecitabine) or short-course radiation (25 Gy in 5 fractions) → surgery → adjuvant chemotherapy. Total neoadjuvant therapy (TNT) — all chemo + radiation before surgery — is increasingly preferred (PRODIGE 23, RAPIDO).
- Complete clinical response after TNT — watch-and-wait protocol in select centres.
Targeted therapy in metastatic disease
- RAS wild-type, left-sided — anti-EGFR (cetuximab, panitumumab) added to FOLFOX/FOLFIRI.
- VEGF — bevacizumab.
- BRAF V600E — encorafenib + cetuximab.
- MSI-high — pembrolizumab (first-line PD-1 blockade).
- HER2-amplified — trastuzumab combinations.
Surveillance after curative resection
- History, examination, CEA every 3 to 6 months for 2 years, then 6 months to year 5.
- CT chest, abdomen, pelvis annually for 3 to 5 years.
- Colonoscopy at 1 year, then every 3 to 5 years.
NEET PG MCQ traps
- APC mutation — initiates adenoma-carcinoma sequence; FAP germline defect.
- MSI-high tumours do NOT benefit from adjuvant 5-FU monotherapy but respond to pembrolizumab.
- Lynch syndrome IHC — loss of one MMR protein pair (e.g., MLH1+PMS2) on tumour tissue.
- Minimum 12 lymph nodes for adequate staging.
- TME reduces local recurrence in rectal cancer from over 25 percent to under 10 percent.
- APR — for low rectal tumour invading the sphincters; permanent end colostomy.
- Neoadjuvant chemoradiation is for rectal, not colon, cancer.
- Self-expanding metal stent (SEMS) — bridge to elective resection in left-sided obstruction.
- Right colon tumours — anaemia, vague pain (occult presentation).
- Left colon tumours — change in bowel habit, fresh bleeding, apple-core lesion.
- CEA — useful for surveillance, not diagnosis or screening.
- Familial adenomatous polyposis — 100 percent CRC risk by age 40; prophylactic proctocolectomy.
- Gardner syndrome — FAP + osteomas + desmoids + epidermal cysts.
- Turcot syndrome — colorectal polyposis + CNS tumours.
- Synchronous polyps — about 30 percent of CRC patients; full colonoscopy mandatory before surgery.
Recent updates and Indian context
- Rising incidence in young Indians under 50 — ICMR-NCRP data and the recent AIIMS, Tata Memorial, and PGI Chandigarh series show a younger median age (50 to 55) than Western cohorts. Suspected drivers — obesity, sedentary lifestyle, processed-food diet, undiagnosed Lynch.
- Ayushman Bharat PMJAY — covers CRC surgery (right hemicolectomy, LAR, APR) and adjuvant chemotherapy in empaneled hospitals; advanced biologics often require co-payment.
- National Cancer Grid has standardised CRC management guidelines across Tata Memorial-network hospitals; emphasises MMR/MSI testing, MRI pelvis for rectal staging and TME-quality surgery.
- TNT (total neoadjuvant therapy) is gaining adoption in Indian tertiary centres for locally advanced rectal cancer.
- Liquid biopsy (ctDNA) for minimal residual disease after surgery is in clinical trials.
Frequently asked questions
What is the adenoma-carcinoma sequence?
Most sporadic colorectal cancers arise from adenomatous polyps through a step-wise accumulation of mutations — APC loss (initiates adenoma), KRAS activation (drives small to large adenoma), DCC/SMAD4 loss and finally TP53 loss (carcinoma). The process takes 10 to 15 years, which is why colonoscopic polypectomy from age 45 to 50 is highly effective at preventing colorectal cancer. About 15 percent of tumours follow the alternative microsatellite-instability pathway.
How is Lynch syndrome (HNPCC) diagnosed?
Lynch syndrome is an autosomal dominant defect in DNA mismatch repair (MLH1, MSH2, MSH6, PMS2 or EPCAM). Suspect it using the Amsterdam II or revised Bethesda criteria — three relatives with HNPCC-spectrum cancer, two generations, one before age 50. Confirm by immunohistochemistry for the four MMR proteins on tumour tissue, microsatellite instability (MSI-high) testing and germline mutation analysis. Surveillance — colonoscopy every 1 to 2 years from age 20 to 25.
What is total mesorectal excision (TME) and why does it matter?
TME is en-bloc sharp dissection of the rectum within the embryologic mesorectal envelope (containing all draining lymph nodes and fat) along the avascular holy plane, preserving the autonomic pelvic nerves (hypogastric and pelvic splanchnics). It was popularised by Heald and reduces local recurrence in rectal cancer from over 25 percent to under 10 percent, while preserving urinary and sexual function. TME is the standard of care for mid and low rectal cancer.
When is neoadjuvant chemoradiation used in colorectal cancer?
Neoadjuvant chemoradiation (long-course 50.4 Gy with 5-FU or capecitabine, or short-course 25 Gy in 5 fractions) is used for locally advanced rectal cancer — stage II (T3 to T4) or any node-positive disease, mid and low rectum. It downstages tumours, improves R0 resection rates, preserves sphincters and reduces local recurrence. Total neoadjuvant therapy (TNT) — chemoradiation plus FOLFOX before surgery — is increasingly preferred. Colonic tumours are NOT routinely irradiated.
Which adjuvant chemotherapy is used for stage III colon cancer?
Stage III (node-positive) colon cancer receives 6 months of adjuvant chemotherapy after R0 resection — FOLFOX (5-FU, leucovorin, oxaliplatin) or CAPOX (capecitabine + oxaliplatin). The IDEA trial showed 3 months of CAPOX is non-inferior in low-risk stage III (T1 to T3 N1) and reduces oxaliplatin neurotoxicity. Stage II is observed unless high-risk features (T4, less than 12 nodes, lymphovascular invasion, perforation, MSI-low) prompt adjuvant 5-FU.
This content is for educational purposes for NEET PG exam preparation. It is not a substitute for professional medical advice, diagnosis, or treatment. Clinical information has been reviewed by qualified medical professionals.
Written by: NEETPGAI Editorial Team
Reviewed by: Pending SME Review
Last reviewed: May 2026
