Complete pathologic response surrogacy for survival and its predictors in locally advanced rectal cancer: a retrospective cohort study.

Background: Improved treatment techniques in locally advanced rectal cancer (LARC) with neoadjuvant chemoradiation and total mesorectal excision have resulted in higher rates of tumor downstaging and complete pathologic response (pCR). We aimed to explore the association of pCR with survival outcomes and its predictors.

Methods: We retrospectively enrolled 478 LARC patients referred to a tertiary cancer center from July 2008 to October 2023 who had received neoadjuvant long-course chemoradiation followed by definitive surgery. The patients were followed up, and the association of pCR with disease-free survival (DFS) and overall survival (OS), as well as its predictors, was analyzed.

Results: Ninety-one (22.5%) patients achieved a pCR and 167 (39.9%) patients were downstaged to ypT_0-2ypN₀. The 5-year OS and DFS rates were 64.1% and 56% in patients without a pCR and 90.3% and 91.8% in patients with a pCR, respectively (p-value < 0.001). Receipt of adjuvant chemotherapy in patients who did not achieve a pCR did not improve either DFS or OS (p-value 0.44 and 0.73, respectively). Clinical N2 and preoperative carcinoembryonic antigen (CEA) > 5ng/mL independently predicted for pCR.

Conclusions: Our study underscores the importance of pCR as an independent predictor of survival in LARC. Patients with higher nodal burden as well as an abnormal preoperative CEA are less likely to achieve a pCR.