Colorectal Cancer: Risk Factors, Screening and Treatment

Colorectal Cancer: Risk Factors, Screening and Treatment

Colorectal cancer (CRC) — cancer of the colon or rectum — is one of the three most common cancers in both men and women worldwide and the second leading cause of cancer death in Western countries. Despite this, it is also one of the most preventable cancers: the majority of colorectal cancers develop from benign polyps over a period of 10–15 years, providing a wide window during which screening can detect and remove them before they become malignant.

When detected at an early, localised stage, the five-year survival rate exceeds 90%. When diagnosed after distant spread, the five-year survival falls below 20%. This makes screening the single most impactful intervention in colorectal cancer prevention.

How Colorectal Cancer Develops

Almost all colorectal cancers (>95%) are adenocarcinomas — cancers arising from the glandular cells lining the inner wall of the colon and rectum. Most begin as small, benign mucosal growths called polyps — button-like protrusions from the bowel wall. Not all polyps become cancerous, but adenomatous polyps (adenomas) carry meaningful malignant potential.

The adenoma-to-carcinoma sequence — from normal mucosa → small adenoma → large adenoma → carcinoma — takes on average 10–15 years. This long pre-cancerous phase is why colonoscopy is so effective: it detects and removes polyps before they become invasive.

Once cancer develops, it invades progressively through the bowel wall layers, eventually reaching lymph nodes and then metastasising — most commonly to the liver (the first site for blood-borne spread from the colon) and lungs.

Risk Factors

Non-Modifiable Risk Factors

Age — incidence rises sharply after age 45; the majority of cases occur in people over 65.

Family history — having a first-degree relative (parent, sibling, child) with colorectal cancer roughly doubles the risk. With two or more affected relatives, risk rises three to four-fold.

Hereditary conditions:

• Lynch syndrome (HNPCC) — the most common hereditary CRC syndrome; caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2). Colorectal cancer risk in Lynch syndrome varies substantially by the affected gene, sex, age and surveillance; a single 70–80% estimate is not appropriate for all carriers. Genetic counselling can explain the individual risk and surveillance plan. Lynch syndrome also raises risk of endometrial, ovarian, gastric, urinary tract and brain cancers.
• Familial adenomatous polyposis (FAP) — caused by APC gene mutations; produces hundreds to thousands of colorectal polyps from adolescence; virtually all affected individuals develop CRC without prophylactic colectomy
• MUTYH-associated polyposis (MAP) — autosomal recessive; causes attenuated polyposis; lifetime CRC risk over 50%
• Peutz-Jeghers syndrome — hamartomatous polyps throughout the GI tract; elevated CRC risk
• Juvenile polyposis syndrome — multiple juvenile polyps; elevated GI cancer risk

Personal history of colorectal polyps or cancer — prior adenomas, especially large or villous, substantially raise risk of subsequent cancer. Prior colorectal cancer raises risk of a second primary.

Inflammatory bowel disease (IBD) — ulcerative colitis and colonic Crohn's disease both increase CRC risk, proportional to disease duration and extent. The risk varies with inflammatory activity and other factors, including primary sclerosing cholangitis, previous dysplasia and family history; a single cumulative percentage is not appropriate for every patient. A gastroenterology team should assess individual risk and plan colonoscopic surveillance.

Modifiable Risk Factors

Risk Factor	Effect
High red and processed meat intake	Consistently associated with increased risk (processed meat classified Group 1 carcinogen by IARC)
Low dietary fibre	Higher fibre intake associated with lower risk
Obesity and physical inactivity	Both independently increase CRC risk
Alcohol	Dose-dependent increased risk, especially with heavy use
Smoking	Increases risk of adenoma formation and CRC
Type 2 diabetes	Associated with 30–40% increased risk

Protective factors:

• Regular physical activity
• Aspirin or NSAIDs (demonstrated to reduce adenoma recurrence; not routinely recommended for prevention due to bleeding risk)
• Calcium and vitamin D supplementation (modest protective effect in observational studies)

Symptoms

Colorectal cancer often causes no symptoms until it is advanced. When symptoms occur, they depend on the tumour's location in the bowel.

Right colon (ascending colon):

• The right colon has a wider lumen and liquid stool; tumours here grow large before causing obstruction
• Occult blood loss — iron deficiency anaemia with fatigue and pallor, from slow chronic bleeding not visible to the naked eye
• Weight loss, loss of appetite

Left colon (descending and sigmoid colon):

• Narrower lumen; formed stool
• Change in bowel habits — new onset constipation, thinner stools, alternating constipation and diarrhoea
• Visible rectal bleeding — bright or dark blood in or on the stool
• Feeling of incomplete evacuation
• Cramping abdominal pain
• Large tumours may cause bowel obstruction: severe abdominal distension and pain

Rectum:

• Rectal bleeding — the most common first symptom; any rectal bleeding must be investigated for cancer even if haemorrhoids are known
• Tenesmus — persistent urge to defecate even when the rectum is empty
• Rectal pain — usually implies tumour extending beyond the rectum

Warning signs needing medical assessment:

• Unexplained rectal bleeding or a persistent change in bowel habit
• Iron deficiency anaemia without an obvious cause
• A palpable abdominal or rectal mass

These symptoms need assessment at any age; do not wait until age 40 or 50, or until six weeks have elapsed, before seeking advice. Heavy or continuous bleeding, large clots or collapse require emergency care. Symptoms can have other causes, but should not be dismissed on that basis.

Diagnosis

Colonoscopy

Colonoscopy is the gold-standard diagnostic and screening test. A flexible scope is passed through the entire colon under sedation, allowing direct visualisation of the mucosa. Suitable polyps may be removed during the procedure (polypectomy) for pathological analysis. Large, complex or potentially invasive lesions may require specialist assessment and a separate treatment session. Any suspicious lesions are biopsied.

Colonoscopy is both diagnostic (confirming cancer when present) and therapeutic (removing pre-cancerous polyps before cancer develops).

Alternative screening modalities:

Test	Interval	Advantage	Limitation
Faecal occult blood test (FOBT) or FIT	Annual	Non-invasive	Detects blood only; positive requires colonoscopy
Flexible sigmoidoscopy	Every 5 years	Examines rectum and left colon	Misses right-sided lesions
CT colonography (virtual colonoscopy)	Every 5 years	Non-invasive; full colon	Cannot remove polyps; colonoscopy required if lesion found

Screening start age: major guidelines now recommend starting average-risk screening at age 45 (US) or 50 (most of Europe), with earlier and more frequent screening for high-risk groups (family history, Lynch syndrome, IBD).

CEA (Carcinoembryonic Antigen)

A blood tumour marker. Elevated CEA before surgery, returning to normal after, then rising again — suggests recurrence. CEA is not sensitive or specific enough to diagnose CRC but is valuable for post-treatment surveillance.

Staging CT Scan

Once CRC is diagnosed on colonoscopy, contrast-enhanced CT of the chest, abdomen and pelvis determines whether the cancer has spread to lymph nodes, liver, lungs or other organs.

MRI of the pelvis is essential for rectal cancer — it precisely defines the relationship of the tumour to the mesorectal fascia (the surgical margin), predicts circumferential resection margin involvement, and guides decisions about pre-operative chemoradiotherapy.

PET-CT is used selectively — particularly to evaluate indeterminate lesions found on CT.

Molecular Testing

MMR/MSI testing is generally recommended in colorectal cancer. Additional molecular testing is selected according to stage and treatment decisions, particularly in metastatic disease:

• MMR/MSI testing — mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status predicts benefit from immunotherapy and has prognostic significance. Also identifies Lynch syndrome candidates.
• RAS (KRAS/NRAS) and BRAF mutation testing — helps select targeted treatment. RAS status, tumour location and the complete regimen matter; cetuximab can also be used with a BRAF inhibitor in BRAF V600E-mutant disease
• HER2 testing — can identify potential targeted options. The US FDA solid-tumour indication for trastuzumab deruxtecan requires HER2-positive IHC 3+ unresectable or metastatic disease in adults after prior systemic treatment with no satisfactory alternative options; amplification alone does not establish that indication. Local authorisation and the exact regimen must be checked
• NTRK fusion — rare but actionable in any solid tumour

Staging

TNM staging classifies colorectal cancer by depth of invasion (T), lymph node involvement (N), and distant metastasis (M):

Stage	Description	5-Year Survival
I	Confined to bowel wall layers; no nodal spread	~90%
II	Penetrates through bowel wall; no nodal spread	~73–75%
III	Spread to regional lymph nodes	~50–65%
IV	Distant metastases (liver, lung, peritoneum)	<20%

Treatment

Surgery

Surgery is the cornerstone of curative treatment.

Colon cancer:

• Laparoscopic (minimally invasive) colectomy — the standard approach at experienced centres; removal of the tumour-bearing colon segment with its draining lymph nodes (oncological resection). Laparoscopic approach offers faster recovery, less pain, shorter hospital stay, and equivalent oncological outcomes to open surgery.
• Open colectomy — used for large tumours, adhesions, emergency obstruction, or when laparoscopic approach is not feasible

Rectal cancer:

• Total mesorectal excision (TME) — the surgical standard; precise removal of the rectum and surrounding mesorectal envelope; significantly reduces local recurrence
• Low anterior resection (LAR) — for tumours in the upper or mid rectum; preserves the anus
• Abdominoperineal resection (APR) — for very low rectal tumours; requires permanent colostomy
• Transanal minimally invasive surgery (TAMIS) — a transanal platform for local excision, which may be appropriate for carefully selected cT1N0 rectal cancers without high-risk features. Local excision does not provide the mesorectal lymph-node removal and staging of radical TME.
• Transanal total mesorectal excision (TaTME) — a transanal approach to radical TME, distinct from TAMIS local excision; selection requires specialist multidisciplinary assessment and suitable surgical expertise. NICE recommends TaTME only in a research context.

Neoadjuvant Chemoradiotherapy for Rectal Cancer

For locally advanced rectal cancer (T3/T4 or node-positive on MRI), pre-operative chemoradiotherapy (long-course radiotherapy + 5-FU/capecitabine) or short-course radiotherapy reduces the tumour, lowers local recurrence risk, and may enable sphincter-preserving surgery. After a complete clinical response, a watch-and-wait approach (avoiding surgery) is feasible in selected patients.

Chemotherapy

Adjuvant chemotherapy (post-surgery) for stage III and selected high-risk stage II cancers:

• FOLFOX or CAPOX — 6 months of oxaliplatin-based chemotherapy reduces recurrence risk by ~25% in stage III disease

Metastatic CRC first-line:

• FOLFOX or CAPOX ± bevacizumab (anti-VEGF)
• FOLFIRI ± bevacizumab
• For RAS/BRAF wild-type left-sided tumours: FOLFOX + cetuximab or panitumumab (anti-EGFR)

Second-line and beyond: irinotecan-based regimens, regorafenib, TAS-102

Targeted Therapy

• Bevacizumab (anti-VEGF) — combined with chemotherapy in first and second-line metastatic CRC; extends progression-free survival
• Cetuximab and panitumumab (anti-EGFR) — selection with conventional chemotherapy depends on RAS status, tumour location and other factors; left-sided RAS wild-type disease is an important setting. BRAF V600E-mutant disease may instead be treated with an appropriate BRAF inhibitor–cetuximab combination
• BRAF-targeted treatment — encorafenib plus cetuximab has a role in previously treated BRAF V600E-mutant metastatic CRC. In February 2026 the US FDA also granted traditional approval to encorafenib with cetuximab and fluorouracil-based chemotherapy for adults with BRAF V600E-mutant metastatic CRC; the exact regimen and local authorisation require confirmation

Immunotherapy

• Pembrolizumab, or an appropriate nivolumab–ipilimumab combination, can be first-line options for eligible MSI-H/dMMR metastatic CRC. The US FDA approved nivolumab with ipilimumab for unresectable or metastatic MSI-H/dMMR CRC in April 2025; nivolumab monotherapy has a separate post-chemotherapy indication. Eligibility, contraindications and local approval must be checked; response is not guaranteed
• The majority of metastatic CRC is microsatellite stable (MSS) and does not respond to checkpoint immunotherapy

Liver Metastasis Treatment

When CRC has spread only to the liver (or lungs), aggressive treatment remains potentially curative:

• Surgical resection of liver metastases — 5-year survival 30–40% in selected patients; requires sufficient future liver remnant
• Hepatic artery infusion (HAI) chemotherapy — high-concentration chemotherapy delivered directly to liver metastases
• Ablation (RFA or MWA) — for small unresectable lesions
• SIRT (radioembolisation) — for diffuse liver-dominant metastases
• Conversion chemotherapy — intensive chemotherapy to downsize initially unresectable metastases to resectability

Colorectal Cancer Care in China

For planned colorectal cancer care in China, ask the receiving team to confirm the appropriate pathway and availability:

• Diagnostic pathway: diagnostic colonoscopy with biopsy, CT staging, MRI (for rectal cancer) and full molecular profiling (RAS, BRAF, MMR/MSI)
• Laparoscopic and robotic colorectal surgery: minimally invasive TME performed routinely by specialist colorectal surgeons; robotic platforms available at leading centres
• Multidisciplinary tumour board review integrating colorectal surgery, medical oncology, radiation oncology, interventional radiology and hepatobiliary surgery
• Liver metastasis surgery: hepatobiliary teams experienced in major hepatectomy, two-stage resection and portal vein embolisation to maximise resectability
• Systemic therapy selection and access — confirm the exact proposed regimen, biomarker requirements, local authorisation, supply and cost
• Language and coordination support — confirm the documents, visits, language pair and follow-up included in the agreed PriumCare service scope

Contact a PriumCare care navigator to arrange a colorectal cancer assessment, second opinion or treatment consultation.

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Background source: MSD Manual Professional: Colorectal Cancer, by Anthony Villano, MD, peer reviewed by Minhhuyen Nguyen, MD. Its full review is dated May 2025, with an update in July 2026. These names and dates credit the external source, not authorship or medical review of this PriumCare article.

Additional editorial source clarification

Editorial clarification: 25 October 2026. This targeted update addresses the specific diagnostic, treatment-selection or service claims identified in the sources below. It is not a clinical review of the whole article; the original publication date is retained.

• Source 1
• Source 2
• Source 3
• Source 4

Additional targeted source clarification

Editorial source check: 25 October 2026. These corrections address the specific assessment and treatment-selection statements above; this is not a whole-article medical review.

• Source 1

Targeted transanal-surgery source clarification

Editorial source check: 25 October 2026. This checks only the distinction between TAMIS local excision and TaTME clarified above; it is not a whole-article medical review and adds no named clinical reviewer. The original publication date is retained.

• ASCRS: rectal cancer local excision, mesorectal surgery and selection
• NICE HTG603: transanal total mesorectal excision

Targeted colitis-associated colorectal-cancer risk clarification

Editorial source check: 26 October 2026. This checks only the cumulative-risk statement clarified above; it is not a whole-article medical review and adds no named clinical reviewer. The original publication date is retained.

• BSG 2025: individual colorectal-cancer risk and surveillance in colonic IBD