T‐stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics

BACKGROUND AND OBJECTIVES: Prior studies examining prognostic outcomes of locally advanced rectal adenocarcinomas achieving a complete pathological response following neoadjuvant chemoradiotherapy (nCRT) did not adjust for adverse prognostic factors in multivariate analyses and account for magnetic resonance imaging tumour staging inaccuracy pre‐nCRT. We aimed to clarify prognostic outcomes in mT3 rectal adenocarcinomas with ypT‐downstaging post‐nCRT in robust adjusted analyses. METHODS: Retrospective analysis of prospectively‐collected clinical data from 528 mT3 rectal adenocarcinomas ≤12 cm from the anal verge, any N‐stage, no metastases, post‐nCRT following total mesorectal excision (TME). Recurrence outcomes (local and distant combined) of tumours with complete ypT‐downstaging (ypT0) post‐nCRT before TME compared with no ypT‐downstaging (≥ypT3) were examined using multivariate Cox regression, adjusting for confounders and accounting for pre‐nCRT mT3‐staging inaccuracy using bootstrapping. RESULTS: Complete ypT‐downstaging was achieved in of 17.6% tumours and correlated strongly with complete pathological response. Complete ypT‐downstaging was not associated with reduced recurrence hazards compared with no ypT‐downstaging (hazard ratio = 0.60; 95% confidence interval [CI]: 0.23−1.56; p = 0.30). Lymphovascular invasion (LVI) and ypN+ve increased recurrence hazards by 1.8‐fold (95% CI: 1.10−2.79; p = 0.02) and 2.3‐fold (95% CI: 1.48−3.54; p = 0.0002), respectively. CONCLUSION: Complete ypT‐downstaging was not associated with reduced recurrence after adjusting for confounders and accounting for mT3‐staging inaccuracy, even in the absence of adverse prognostic factors (ypN+, LVI).