The impact of subdivisions of microscopically positive (R1) margins on patterns of relapse in stage III colorectal cancer – A retrospective cohort study

AIM: Microscopically positive (R1) margins are associated with poorer outcomes in patients with colorectal cancer. However, the impact of subdivisions of R1 margins, be they to the primary tumour (R1 tumour) or to lymph node metastases (R1LNM), on patterns of relapse is unknown. METHODS: Patients treated for stage III colorectal cancer from 01 January 2016 to 31 December 2019 in four specialist centres were identified from the Danish national cancer registry. Patients were stratified into three groups according to margin status (R0 vs. R1 tumour vs. R1LNM). The primary outcomes were local recurrence‐free survival (LRFS), distant metastases‐free survival (DMFS) and disease‐specific survival (DSS). RESULTS: A total of 1,164 patients were included, with R1 margins found in 237 (20.4%). Irrespective of tumour location, R1 tumour and R1LNM margins were independent prognostic factors for systemic relapse (R1 tumour HR 1.84, CI: 1.17–2.88, p = 0.008; R1LNM HR 1.59, CI: 1.12–2.27, p = 0.009) and disease‐related death (R1 tumour HR 2.08, CI: 1.12–3.85, p = 0.020; R1LNM HR 1.84, CI: 1.12–3.02, p = 0.016). Whereas R1 tumour margins were associated with poorer 3‐year LRFS in both colon and rectum cancer, R1LNM margins only reduced LRFS in patients with rectal cancer. Patterns of relapse differed between R1 subdivisions, with R1 tumour margins more likely to affect multiple anatomical sites, with a predilection for extra‐hepatic/pulmonary metastases. CONCLUSION: Subdivisions of R1 margins have a distinct impact on the oncological outcomes and patterns of disease relapse in patients with stage III colorectal cancer.