ypTNM versus pTNM staging after neoadjuvant therapy in rectal cancer

Abstract PURPOSE The TNM classification at pathological evaluation determines prognosis following cancer treatment. For rectal cancer patients undergoing neoadjuvant therapy, whether ypTNM likely confers different prognosis than pTNM. We compared survival outcomes of patients classified by ypTNM vs pTNM staging. PATIENTS AND METHODS Patients with resected locoregional rectal cancer from the National Cancer Database who underwent upfront surgery (pTNM) and had ≥5 years follow-up (2010 to 2017) were compared with those receiving neoadjuvant therapy followed by surgery (ypTNM). To address treatment selection bias, analyses were stratified by receipt of guideline-concordant care. Overall survival was compared using Kaplan-Meier and multivariable Cox regression analyses. RESULTS Of 50,436 patients (median age 60; 61.4% male), 11,732 (23.3%) underwent upfront surgery and 38,704 (76.7%) received neoadjuvant therapy; 78.8% of the upfront surgery group received guideline-concordant care. In analyses stratified by guideline-concordant care, overall survival was similar for stage 0-I (hazard ratio [HR] 1.05; 95% CI 0.96-1.15) but significantly worse for ypTNM vs pTNM in stage II (HR 1.50; 95% CI 1.27-1.77; 5-year OS 75.6% vs 83.2%) and stage III (HR 1.60; 95% CI 1.46-1.75; 5-year OS 67.0% vs 78.2%). Multivariable analysis confirmed ypTNM was associated with worse survival at each stage (stage 0-HR 1.14, P=.004; stage II: HR 1.49, P<.001; stage III: HR 1.60, P<.001). CONCLUSION Stage for stage, ypTNM classification is associated with worse survival than pTNM classification, with increasing difference at higher stages. Future staging systems and management guidelines should account for these differences to optimize prognostication and stratification for clinical trials and surveillance strategies.