# Colorectal cancer

Source: https://nuclide.cc/indications/colorectal-cancer/  
Nuclide record `colorectal-cancer` (Indication). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

The third commonest cancer in the world and the second biggest cancer killer. Most of it is curable if caught before it spreads, which is why so much of the imaging effort goes into finding out whether it has.

## Summary

Colorectal cancer is an adenocarcinoma of the colon or rectum, usually arising from an adenomatous polyp over years. GLOBOCAN 2024 puts it third for incidence worldwide with 2,041,007 new cases and second for mortality with 917,895 deaths. In the United States, SEER projects 158,850 new cases and 55,230 deaths for 2026, with five-year relative survival of 65.4% overall but 91.3% for localised disease against 16.9% once it has spread to distant sites, and 23% of cases are already distant at diagnosis. That gradient is why every part of the pathway is organised around finding disease early and finding it completely.

Treatment splits by site and stage. Localised colon cancer is resected, with adjuvant oxaliplatin-based chemotherapy for stage III. Locally advanced rectal cancer has moved to total neoadjuvant therapy, giving all chemotherapy and chemoradiation before surgery, which the NCI's summary calls the preferred approach and which allows some patients with a complete clinical response to avoid surgery altogether under intensive surveillance. Metastatic disease is treated by biomarker: anti-EGFR antibodies only in RAS wild-type tumours, encorafenib with cetuximab for the roughly 10% with BRAF V600E, and pembrolizumab first line for the roughly 4% of stage IV disease that is mismatch-repair deficient, where KEYNOTE-177 gave median progression-free survival of 16.5 against 8.2 months.

Nuclear medicine's role here is narrow and specific, and that is the point for radiopharmaceutical development. FDG PET/CT is not indicated for routine staging or routine surveillance. Its accepted niches are equivocal conventional imaging, work-up before resection of potentially curable liver metastases, and the scenario that matters most for tracer development: a serially rising carcinoembryonic antigen with negative conventional imaging, where pooled FDG PET/CT sensitivity and specificity have been reported at 94.1% and 77.2%. The only agent ever approved specifically for occult colorectal recurrence, the anti-CEA antibody fragment arcitumomab, was withdrawn from the market in 2005 and nothing has replaced it.

## Fields

- Kind: Indication
- Last checked: 2026-09-23
- Also known as: bowel cancer; colon cancer; rectal cancer; CRC
- Tags: gastrointestinal; surveillance; recurrence
- Group: gastrointestinal
- Burden: GLOBOCAN 2024 reports 2,041,007 new cases a year worldwide, an age-standardised rate of 18.6 per 100,000, ranking third for incidence, and 917,895 deaths at 7.8 per 100,000, ranking second for cancer mortality. SEER projects 158,850 new US cases and 55,230 US deaths in 2026.
- Subtypes: Colon adenocarcinoma; Rectal adenocarcinoma; Mismatch-repair deficient / microsatellite instability-high disease (about 4% of stage IV); BRAF V600E-mutant disease (about 10% of metastatic cases); HER2-positive, RAS wild-type disease
- Biomarkers: RAS (KRAS/NRAS) mutation status, which decides whether anti-EGFR antibodies can be used; BRAF V600E, present in about 10% of metastatic cases and a marker of poor prognosis; Mismatch repair / microsatellite instability, by immunohistochemistry or molecular testing; HER2 amplification, for tucatinib with trastuzumab in RAS wild-type disease; Carcinoembryonic antigen (CEA) in serum, for surveillance rather than diagnosis; Tumour-informed circulating tumour DNA, validated for de-escalating adjuvant chemotherapy

## Standard of care

- Localised colon cancer: Surgical resection of the primary and regional nodes, with adjuvant oxaliplatin-based chemotherapy for stage III; adjuvant radiotherapy has no standard role.
- Locally advanced rectal cancer: Total neoadjuvant therapy is the preferred approach; patients with a complete clinical response may be managed non-operatively with intensive surveillance instead of resection.
- Metastatic disease, first line: Chemotherapy backbone with bevacizumab, plus anti-EGFR antibodies only in RAS wild-type tumours; pembrolizumab alone for mismatch-repair deficient disease.
- Surveillance after curative resection: CEA every three to six months for the first two years then six-monthly to five years, with contrast CT of chest, abdomen and pelvis; FDG PET/CT is not indicated routinely but is considered when CEA rises and conventional imaging is negative.

## State of the art

- Organ preservation is now a real option in rectal cancer: after total neoadjuvant therapy, a complete clinical response can be watched rather than operated on, though the optimal surveillance protocol has not been determined and about a quarter of these patients develop local regrowth, mostly within two years.
- Circulating tumour DNA has changed adjuvant decision-making in one direction only. The randomised DYNAMIC trial cut adjuvant chemotherapy use from 27.9% to 15.3% in stage II colon cancer while remaining non-inferior at five years, but ctDNA positivity has not yet reliably identified patients who benefit from escalating treatment.
- FDG PET/CT is used for the rising-CEA problem rather than for staging, with pooled sensitivity and specificity of 94.1% and 77.2% and sensitivity that rises with the CEA level, from 83.3% at a CEA of 3.4 ng/mL or below to 100% above 30 ng/mL.

## Open problems

- Nodal staging is unreliable: pooled CT sensitivity and specificity for nodal involvement are about 64 to 71% and 67%, and up to half of metastatic nodes are 5 mm or smaller, so CT-detected nodal involvement should not be relied on alone.
- Peritoneal metastases are systematically missed, with a CT detection rate of only 20 to 25% for nodules under 5 mm and underestimation of the surgical peritoneal cancer index by 12 to 33%.
- A positive ctDNA result with negative imaging is a management dilemma rather than an answer: nothing localises the disease it has detected, and no molecular imaging agent is approved for that scenario since arcitumomab was withdrawn in 2005.
- Watch-and-wait surveillance after rectal organ preservation has no agreed protocol, which makes it hard to know how often and with what modality to look.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Colorectal_cancer
- IARC GLOBOCAN 2024 colorectum factsheet: https://gco.iarc.who.int/media/globocan/factsheets/cancers/41-colorectum-fact-sheet.pdf
- SEER Cancer Stat Facts: colorectal cancer: https://seer.cancer.gov/statfacts/html/colorect.html
- NCI PDQ: colon cancer treatment, health professional version: https://www.cancer.gov/types/colorectal/hp/colon-treatment-pdq
- NCI PDQ: rectal cancer treatment, health professional version: https://www.cancer.gov/types/colorectal/hp/rectal-treatment-pdq
- Review of PET/CT in colorectal cancer, including the rising-CEA indication: https://www.mdpi.com/2072-6694/14/11/2668
- DYNAMIC five-year results, Nature Medicine 2025: https://www.nature.com/articles/s41591-025-03579-w

## Connected records

- targets: [5T4 (trophoblast glycoprotein)](https://nuclide.cc/targets/tpbg-5t4/), [CEACAM5](https://nuclide.cc/targets/ceacam5/)
- technologies: [FDG PET](https://nuclide.cc/technologies/fdg-pet/)
- opportunities: [CEACAM5 imaging for occult colorectal recurrence](https://nuclide.cc/opportunities/opp-ceacam5-imaging-colorectal/)

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