# Delayed surgery for more than 9 weeks induces worse survival outcomes in locally advanced rectal cancer patients with poor response to neoadjuvant chemoradiotherapy: a propensity score matched cohort study

## TL;DR

Delays in surgery for rectal cancer patients who poorly respond to initial treatment are linked to worse survival outcomes, suggesting the need for timely surgery.

## Contribution

This study identifies 9 weeks as the optimal timing for surgery after neoadjuvant treatment and shows delayed surgery correlates with reduced survival and lower CD8+ T-cell density.

## Key findings

- Delayed surgery beyond 9 weeks after neoadjuvant treatment is associated with worse disease-free and cancer-specific survival.
- Longer delays correlate with decreased CD8+ T-cell density in tumor tissues.
- Propensity score matching confirms the negative impact of delayed surgery on survival outcomes.

## Abstract

The association between delayed surgery and survival outcomes in locally advanced rectal cancer patients with a poor response to neoadjuvant chemoradiotherapy (nCRT) remains unclear. This study aimed to determine the optimal timing of surgery following nCRT in these patients and to explore the association between delayed surgery and survival outcomes.

Restricted cubic spline curves were used to determine the optimal timing of surgery for patients with a poor response to nCRT (ypT2–4N0 or ypTxN+). The patients were divided into two groups: the early surgery group and the delayed surgery group. Propensity score matching (PSM) analysis was employed to reduce the selection bias and survival analysis was conducted to assess the survival differences. Immunostaining of post-operative specimens was performed to investigate whether the difference in survival was associated with the CD8+ T-cell density in the tumor.

A total of 583 patients were enrolled in this study. The optimal timing for surgery was determined to be 9 weeks after nCRT. In PSM analysis, delayed surgery was associated with worse disease-free survival (63.0% vs 76.3% at 5 years, 53.0% vs 76.3% at 10 years; P = 0.003) and cancer-specific survival (72.9% vs 85.5% at 5 years, 60.1% vs 81.8% at 10 years; P = 0.001). Immunostaining analysis showed that longer waiting times were associated with decreased CD8+ T-cell density in tumors (P = 0.017).

Patients who had a poor tumor response after nCRT, detected by using magnetic resonance imaging restaging or other assessments, need timely radical surgery without delay.