Oncologic outcomes of watch-and-wait compared to tumor regression grades after total mesorectal excision in rectal cancer.

BACKGROUND

Survival outcomes in patients managed nonoperatively ("watch-and-wait"; W&W) have been compared to those achieving pathological complete response after total mesorectal excision (TME). However, limited data exists on how these outcomes align across the spectrum of treatment responses in TME patients.

METHOD: Adult patients at Mayo Clinic (2017-2023) with clinical TNM stage II/III microsatellite-stable primary rectal adenocarcinoma treated with total neoadjuvant therapy were categorized into two cohorts: W&W and TME. The TME cohort was stratified by American Joint Committee on Cancer/College of American Pathologists tumor regression grade (TRG). Primary outcomes were 3-year distant-metastasis-free survival (3Y-DMFS) and disease-free survival (3Y-DFS).

RESULTS

Among 385 patients, 79 were in the W&W cohort; 306 underwent TME (81 TRG0, 75 TRG1, 114 TRG2, and 36 TRG3). W&W patients had significantly shorter tumor-anorectal junction distances, smaller tumors, less tumors with extramural vascular invasion on pretreatment MRI, less threatened/involved mesorectal fascia, and lower clinical T and N stages. At a median follow-up of 26.0 months, Kaplan-Meier and Cox-Regression analyses showed that the 3Y-DMFS of W&W cohort resembled TRG1 (near-complete response) and TRG2 (partial response), the 3Y-DFS was similar to TRG2 (partial response) and TRG3 (minimal to no response). In contrast, patients with TRG0 (pathological complete response) had a 100% 3Y-DMFS and 3Y-DFS.

CONCLUSION

Despite favorable baseline characteristics, W&W patients had prognoses similar to TME patients with suboptimal responses. Nonoperative management is a viable option for well-selected patients prioritizing organ preservation, but its cancer control outcomes appear not to match the well-established efficacy of definitive oncological resection.