Observation or adjuvant therapy: The optimal regime for patients undergoing neoadjuvant chemoradiotherapy with postoperative yield pathological stage I.

e15590 Background: Neoadjuvant chemoradiotherapy (nCRT) has been leveraged in locally advanced rectal cancer (LARC) treatment before surgery, contributing to tumor shrinkage, an increased rate of R0 resection, and decrease of local recurrence. Nevertheless, the impact of nCRT on distant metastases (DM) is limited, which could be addressed with adjuvant chemotherapy. For patients with postoperative yield pathological stage (ypStage) I, the treatment decision usually swings between observation and adjuvant chemotherapy. Methods: In consideration of the risk stratification and adjuvant therapy regimens for stage II rectal cancer patients in the NCCN guidelines, we developed a risk stratification specifically for patients with pathological ypStage I after neoadjuvant treatment. We utilized poor histological differentiation, positive or undeterminable resection margin, nerve invasion and vascular lymphatic infiltration as high-risk factors for the stratification of patients undergoing nCRT and surgery with ypStage I, dividing 210 patients into high-risk and low-risk groups. The patients with pathological ypStage I with any of the above risk factors are classified as the high-risk group. Results: The low-risk group of the nCRT patients with ypStage I held noninferior survival compared with patients not receiving nCRT with pathological stage I, regardless of weather receiving adjutant therapy( P = 0.638, Recurrence Free Survival, RFS; P = 0.305, Disease Free Survival, DFS; P = 0.123, Cancer Specific Survival,CSS; P = 0.638, Overall Survival, OS) or not ( P = 0.812, RFS; P = 0.825, DFS; P = 0.576, CSS; P = 0.638, OS). These findings provided retrospective evidences for chemotherapy exemption for low-risk group, reducing the physical and economic treatment burden on patients. Whereas, the survival of high-risk group of the patients with ypStage I was significantly inferior to patients not receiving nCRT with pathological stage I ( P = 5.5e-07, RFS; P = 6.19e-07, DFS; P = 1.64e-07, DM; P = 0.0309, CSS; P = 0.00096, OS ) and similar to pathological stage II, which indicated the potential recommendation of adjuvant therapy for high-risk patients to decrease distant metastases. Conclusions: This study firstly proposed a risk stratification for LARC patients undergoing nCRT with ypStage I, indicating the possibility of chemotherapy exemption for the low-risk group.