Survival outcomes in rectal cancer with ypTNM vs pTNM staging after neoadjuvant therapy.

e15694 Background: The TNM classification at pathological evaluation determines prognosis following cancer treatment. For rectal cancer patients who undergo neoadjuvant therapy, whether post-treatment (yp)TNM stage confers the same prognostic value as the corresponding pathologic (p)TNM stage is unknown. Current staging systems and management guidelines do not distinguish between pTNM and ypTNM stage. The objective of this study is to compare the prognostic value of ypTNM versus pTNM stage for rectal cancer using a large cancer registry database. Methods: We conducted a retrospective observational cohort study among patients with resected (y)p stage 0-III rectal cancer identified from the National Cancer Data Base (2010-2017). We compared the overall survival (OS) for patients who underwent upfront surgery (pTNM) and neoadjuvant therapy (ypTNM) for each pathological stage. To account for treatment selection bias, we conducted survival analysis stratified by receipt of guideline concordant care. Patients with pathological stage 0 or I disease who underwent upfront surgery for clinical stage II or III and patients with pathological stage II or III disease who underwent upfront surgery and did not receive any postoperative therapy (pT3-4N0) or adjuvant chemotherapy (pN+) were defined has not having received guideline-concordant care. Survival outcomes were analyzed using the Kaplan-Meier method and log-rank test. Hazard ratios (HR) were estimated by univariate and multivariable Cox proportional hazard models. Results: A total of 11,732 of 50,436 (23.3%) patients underwent upfront surgery (pTNM) and 38,704 (76.7%) received neoadjuvant therapy (ypTNM). Among patients who underwent upfront surgery, 78.8% (9,241 of 11,732) received guideline-concordant care (stage 0 -I, upfront surgery; stage II, upfront surgery with postoperative treatment; stage III, upfront surgery with adjuvant chemotherapy). After stratification by receipt of guideline concordant care, OS were similar between pTNM and ypTNM stage for patients with (y)p stage 0-I (HR, 1.05; 95% confidence interval [CI], 0.96-1.15; 5-year OS, 86.9% versus 87.7%), but were significantly worse for patients with ypTNM compared to pTNM in (y)p stage II (HR, 1.50; 95% CI, 1.27-1.77; 5-year OS, 75.6% versus 83.2%) and (y)p stage III (HR, 1.60; 95% CI, 1.46-1.75; 5-year OS, 67.0% versus 78.2%). The multivariable analysis showed that ypTNM stage was associated with worse OS compared to pTNM stage in each stage (HR, 1.18; 95% CI, 1.08-1.30, P < 0.001 in stage 0-I; HR, 1.51; 95% CI, 1.28-1.79, P < 0.001 in stage II; HR, 1.63, 95% CI, 1.49-1.78, P < 0.001 in stage III). Conclusions: Stage for stage, the ypTNM groups are associated with worse survival than the respective pTNM groups, with the survival disparity between pTNM and ypTNM increasing with increasing stage.