Type of preoperative therapy and stage-specific survival after surgery for rectal cancer: a nationwide population-based cohort study

Preoperative chemoradiation therapy (CRT) may induce downstaging in rectal cancer (RC). Short-course radiation therapy (SC-RT) with immediate surgery does not cause substantial downstaging. However, the TNM classification adds the "y" prefix in both groups to indicate possible treatment effects. We aim to compare stage-specific survival in these patients. RC patients treated with surgery only, preoperative SC-RT followed by surgery within 10 days, or preoperative CRT, and diagnosed between 2008 and 2014 were included in this population-based study. Clinicopathological and outcome characteristics were analyzed. The study included 11,925 patients. Large discrepancies existed between clinical and pathological stages after surgery only. Surgery-only patients were older with more comorbidities compared with SC-RT and CRT and had worse 5-year survival (64%, 76%, and 74%, respectively; p < 0.001). Five-year survival for stage I was similar after CRT and SC-RT (85% vs. 85%; p = 0.167) and comparable between CRT-treated patients with stage I and those reaching a pathological complete response (pCR; 85% vs. 89%; p = 0.113). CRT was independently associated with worse overall survival compared with SC-RT for stage II (HR 1.57 [95%CI 1.27-1.95]; p < 0.001) and stage III (HR 1.43 [95%CI 1.23-1.70]; p < 0.001). Stage I disease after CRT has an excellent prognosis, comparable with pCR and with same-stage SC-RT-treated patients without regression. Stage II or III after CRT has worse prognosis than after SC-RT with immediate surgery. TNM should take the impact of preoperative therapy type on stage-specific survival into account. In addition, clinical stage was a poor predictor of pathological stage.