Optimal Timing for Rectal Cancer Surgery After Total Neoadjuvant Therapy: When Does Surgery Get Really Challenging?

Background: Total neoadjuvant therapy is increasingly utilized for locally advanced rectal cancer. However, the optimal interval between total neoadjuvant therapy and surgery remains unclear. Existing trials report intervals ranging from 2-4 weeks to 11-18 weeks, and many surgeons believe surgery becomes more difficult after a certain point, but the exact timing and its impact on complications are unknown.

Objective: To identify the time point after total neoadjuvant therapy when surgery becomes more challenging and define an optimal window for minimizing postoperative complications in patients proceeding directly to resection.

Design: Retrospective cohort study.

Settings: Single tertiary care center.

Patients: Patients with locally advanced rectal cancer who completed total neoadjuvant therapy between 2015 and 2023 and underwent surgery due to primary disease or regrowth during a watch-and-wait strategy.

Intervention: Total neoadjuvant therapy followed by surgery.

Main outcome measures: The primary outcome was the association of time from total neoadjuvant therapy completion to surgery with postoperative complication rates. Secondary outcomes included perioperative and postoperative outcomes.

Results: Among 212 patients (median age 57 [IQR 50-66], 59% male), 42% experienced complications (15% Clavien-Dindo ≥3). Restricted cubic spline analysis suggested a dip in overall morbidity around 7-12 weeks, with increased risk beyond 24 weeks. Patients operated ≥24 weeks (n = 29) had higher rates of margin positivity (17% vs. 3%, p < 0.01), reoperations (21% vs. 8%, p = 0.04), and severe complications (28% vs. 13%, p = 0.03) compared to those operated earlier (n = 183).

Limitations: Single-center retrospective design, univariate spline analysis, and a relatively small subset beyond 24 weeks limit the generalizability.

Conclusion: Surgical timing after total neoadjuvant therapy is associated with perioperative outcomes. Delaying surgery beyond 24 weeks is linked to greater surgical difficulty and morbidity. Further multicenter studies are needed to confirm these findings and refine timing recommendations. See Video Abstract.