Adjuvant chemotherapy after radical resection for rectal cancer was associated with lower mortality at five years in all three national cohorts of a new international analysis. In the Scottish cohort of 1,833 patients the adjusted hazard ratio for death at five years was 0.50 (95% CI 0.37 to 0.68), in the English cohort of 18,729 patients it was 0.66 (95% CI 0.61 to 0.71), and in the Dutch cohort of 12,649 patients it was 0.81 (95% CI 0.67 to 1.00). The study is published open access in Clinical Oncology (Hanna et al., 2026). Elizabeth Lemmon and Peter Hall of the Edinburgh Cancer Centre are among the authors.
Why could only a multi-country collaboration answer this question?
Randomised evidence on adjuvant chemotherapy in rectal cancer is thin because rectal patients were excluded from the trials that established fluoropyrimidine and oxaliplatin regimens, on grounds of toxicity and the confounding effect of radiotherapy (Carvalho and Glynne-Jones, 2017). Three of the six rectal-specific trials closed early for poor accrual, and a meta-analysis of individual patient data from 1,196 patients found a hazard ratio for overall survival of 0.97 (95% CI 0.81 to 1.17) (Breugom et al., 2015). NICE guideline NG151 makes no recommendation for rectal patients treated with long-course chemoradiotherapy, “because no evidence was identified in the available trials” (NICE, 2020).
What made this analysis possible was three northern European countries each holding population-scale, linkable records of cancer registration, surgery, radiotherapy and systemic therapy. The Scottish contribution combined the Scottish Cancer Registry, SMR01, National Records of Scotland deaths, Quality Performance Indicator returns and ChemoCare prescribing inside the Scottish National Safe Haven. Dutch records were transferred into the English trusted research environment for analysis. The value lies in the contrast between the systems rather than the total: adjuvant chemotherapy was given to 3.6 per cent of Dutch patients against 34.4 per cent in England and 33.1 per cent in Scotland, and the direction of association held across that tenfold difference in practice.
What does this mean for practice in Edinburgh?
The Edinburgh Cancer Centre has largely treated colon and rectal cancers the same way in the adjuvant setting, on the reasoning that the missing rectal evidence reflects trial design decisions rather than a demonstrated absence of benefit. This analysis supports that approach, as does SCOT, which confirmed non-inferiority of three months of treatment in its 1,087 rectal cancer patients (Iveson et al., 2026).
The estimates remain observational. Confounding by indication is the main concern, clinical stage was unknown for 50.9 per cent of the Scottish cohort, and extramural venous invasion, circumferential resection margin and mismatch repair status were not captured at all. The authors state that the survival benefit must be interpreted with caution. No trial is currently designed to test whether adjuvant chemotherapy adds anything after neoadjuvant chemotherapy.