Teaching pack: Colon cancer (adenocarcinoma of the colon)

The WHO classification of digestive tumours describes adenocarcinoma of the colon and rectum as one chapter, with the site recorded because staging and local treatment differ (Nagtegaal 2020). The colorectal page holds the molecular subtypes; this page is the anatomical entity that the corpus's rectal cancer page mirrors. Two identically designed adjuvant trials in 855 colon and 796 rectal cancer patients showed that adding folinic acid to fluorouracil improved seven-year overall survival in colon but not rectal cancer, with different patterns of recurrence (Clinical Colorectal Cancer 2013). Within the colon, right-sided (proximal) tumours are more often mismatch-repair deficient, BRAF-mutant, mucinous and worse-prognosis in the metastatic setting, and left-sided tumours respond better to EGFR antibodies; a pooled analysis of 2,879 metastatic patients found no outcome difference between left-sided colon and rectal primaries (European Journal of Cancer 2018).

How it differs from its parent: the colorectal page carries the shared biology and the metastatic drug pathways; colon cancer differs from rectal cancer in having no role for pelvic radiotherapy, in colectomy with regional lymphadenectomy as the operation, and in the stage III adjuvant standard of three or six months of FOLFOX or CAPOX set by the IDEA collaboration and recorded on the FOLFOX and CAPOX pages.

• PARADIGM (phase 3, n=823): Overall survival, left-sided: 37.9 months vs 34.3 months, HR 0.82
• MOSAIC (phase 3, n=2,246): Disease-free survival at 3 years: 78.2 percent vs 72.9 percent, HR 0.77
• ATOMIC (Alliance A021502) (phase 3, n=712): Disease-free survival at 3 years: 86.4 percent vs 76.6 percent, HR 0.5
• ALASCCA (phase 3, n=626): Time to recurrence at 3 years, group A (PIK3CA exon 9/20): 7.7% vs 14.1%, HR 0.49
• CRYSTAL & FIRE-3 (phase 3, n=1,198): FIRE-3: objective response (primary endpoint): 62 percent vs 58 percent
• SCOT (phase 3, n=6,088): Disease-free survival at 3 years: 76.7 percent vs 77.1 percent, HR 1.006

1. What did the dostarlimab rectal cancer study show?
   Answer

   In mismatch-repair-deficient locally advanced rectal cancer, dostarlimab alone produced a complete clinical response in 100% of patients, sustained in more than 40 patients by 2025, allowing surgery and radiation to be avoided.
2. Can a blood test decide who needs chemotherapy after colon cancer surgery?
   Answer

   Yes in stage II: the DYNAMIC trial used ctDNA to guide adjuvant chemotherapy, halving its use (15% vs 28%) with non-inferior recurrence-free survival (93.5% vs 92.4% at two years).
3. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
4. What were the first checkpoint inhibitor and the first ADC ever approved?
   Answer

   Ipilimumab (2011) was the first checkpoint inhibitor; gemtuzumab ozogamicin (Mylotarg, 2000) was the first ADC, withdrawn in 2010 and re-approved in 2017.
5. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.
6. What is exercise oncology and is there real evidence?
   Answer

   Structured exercise during and after treatment; the CHALLENGE trial (2025) randomised colon cancer survivors and showed improved disease-free and overall survival, the first level-1 evidence, plus less fatigue and neuropathy.

• NCI PDQ: colon cancer treatment: https://www.cancer.gov/types/colorectal/patient/colon-treatment-pdq
• Nagtegaal 2020, Histopathology: the 2019 WHO classification of tumours of the digestive system: https://doi.org/10.1111/his.13975
• Clinical Colorectal Cancer 2013: two adjuvant trials reveal differences between colon and rectal cancer: https://doi.org/10.1016/j.clcc.2012.07.005
• European Journal of Cancer 2018: left-sided colon and rectal cancer in 2,879 ARCAD trial patients: https://doi.org/10.1016/j.ejca.2018.08.020
• J Cancer Res Clin Oncol 2016: mucinous and signet ring cell colorectal cancer in 28,056 Munich registry patients: https://doi.org/10.1007/s00432-016-2224-2
• Wikipedia: https://en.wikipedia.org/wiki/Colorectal_cancer