BACKGROUND: Extended pelvic exenteration (EPE) is a key therapeutic strategy for locally advanced or recurrent rectal cancer. However, conventional postoperative assessments-including histopathology, serum tumor markers, and standard imaging-are limited by low sensitivity and a considerable temporal lag in detecting residual disease. Detection of molecular residual disease (MRD) via circulating tumor DNA (ctDNA) may provide a reliable biomarker to enable more precise postoperative management following EPE. This study evaluates the utility of ctDNA-based MRD assessment in determining molecular R0 resection status and in monitoring disease recurrence after pelvic exenteration for rectal cancer. METHODS: Between May 2022 and October 2023, a real-world study was conducted involving 100 patients with locally advanced or recurrent rectal cancer without evidence of distant metastasis who underwent radical resection at Shanghai Changzheng Hospital. Peripheral blood samples were collected preoperatively, postoperatively, following adjuvant therapy, and at 3-month intervals thereafter. MRD status was assessed using a personalized, tumor-informed panel based on whole-exome sequencing of the primary tumor. RESULTS: The cohort comprised 52 male patients (52%), with a mean (standard deviation) age of 50.8 (13.24) years. While all patients achieved pathologically negative margins, the postoperative MRD positivity rate (MRD1) remained at 35%, increasing to 41% following adjuvant therapy (MRD2). Over a median follow-up of 745 days (95% confidence interval, 697-793 days), the 1-year and 2-year disease-free survival (DFS) rates were 85.0% and 71.9%, respectively. Positivity at the MRD1 and MRD2 timepoints conferred an 8-fold and a 60-fold increased risk of recurrence, respectively, compared with MRD-negative status. Notably, MRD positivity detected tumor recurrence or metastasis significantly earlier than radiological confirmation, with a median lead time of 361 days (interquartile range, 158.5-468 days). CONCLUSIONS: ctDNA-based MRD detection demonstrates substantial clinical utility for recurrence surveillance and prognostic stratification. Postoperative MRD status provides a more accurate reflection of molecular R0 resection than conventional pathological margin assessment. Furthermore, MRD status upon completion of initial adjuvant therapy serves as an early indicator of therapeutic efficacy and a robust predictor of long-term prognosis.
Lu et al. (Mon,) studied this question.