Partial Responders to Neoadjuvant Therapy and the Risk of Distant Metastases: Longer Intervals to Definitive Resection Is Not a Risk Factor.

Abstract

Background: The timing of resection after neoadjuvant therapy for rectal cancer remains a debated topic. Longer intervals from radiation completion have been associated with increased rates of clinical and pathological complete response, but concerns remain regarding partial responders and the risk of distant metastasis.

Objective: To evaluate whether the interval between the end of neoadjuvant chemoradiation therapy and surgical resection affects the development of distant metastases in patients with an excellent partial response.

Design: Retrospective cohort study.

Settings: Multicenter analysis from three institutions: Angelita & Joaquim Gama Institute, Champalimaud Foundation, and University Hospital Bordeaux.

Patients: 165 patients with rectal cancer who achieved either a near-complete pathological response or a clinical complete response followed by local regrowth.

Interventions: Patients underwent total mesorectal excision or were managed by watch-and-wait with salvage surgery for local regrowth. The timing of surgery post- neoadjuvant chemoradiation therapy was analyzed.

Main outcome measures: The primary outcome was the development of distant metastases.

Results: 34 patients developed distant metastases. There was no significant difference in the time to resection between those who developed metastases and those who did not (9.2 months vs. 10.6 months, p = 0.55). A secondary analysis of patients with local regrowth also showed no significant difference in metastasis development based on resection timing (14.4 months vs. 17.9 months, p = 0.26).

Limitations: The study is limited by its retrospective nature and the subjective definition of excellent response in clinical settings.

Conclusions: In patients with an excellent partial response to neoadjuvant chemoradiation therapy, the interval between radiation completion and surgical resection does not appear to influence the risk of distant metastases. This suggests that factors other than time may play a role in the development of distant metastases in this population. See Video Abstract.