# Clinical and treatment-related predictors of complete response after total neoadjuvant therapy for rectal cancer in a large multicenter analysis

## TL;DR

This study identifies factors that predict complete response to total neoadjuvant therapy in rectal cancer patients, including chemotherapy cycles and non-smoking status.

## Contribution

The study provides new insights into clinical and treatment-related predictors of complete response in rectal cancer patients undergoing total neoadjuvant therapy.

## Key findings

- Complete response rates increased with each additional chemotherapy cycle.
- Non-smoking status was associated with higher complete response rates.
- Short-course radiotherapy was linked to lower complete response rates compared to pyrimidine-based chemoradiotherapy.

## Abstract

•Multicenter analysis evaluating predictors of complete response (CR) after TNT.•CR improved with each chemotherapy cycle and non-smoking status.•Adding oxaliplatin to long-course chemoradiotherapy (LCRT) did not improve CR rates.•Short-course radiotherapy had lower CR rates than pyrimidine-based LCRT.•Short-term distant-metastasis-free survival was improved after CR.

Multicenter analysis evaluating predictors of complete response (CR) after TNT.

CR improved with each chemotherapy cycle and non-smoking status.

Adding oxaliplatin to long-course chemoradiotherapy (LCRT) did not improve CR rates.

Short-course radiotherapy had lower CR rates than pyrimidine-based LCRT.

Short-term distant-metastasis-free survival was improved after CR.

Complete response (CR) after total neoadjuvant therapy (TNT) in rectal cancer is linked to favorable local control and enables non-operative management (NOM). Achieving high CR rates is crucial. As no standard TNT protocol exists, we aimed to assess the impact of clinical factors and different protocols on CR rates.

Rectal cancer patients undergoing TNT with curative intent between 2015 and 2024 were included in this retrospective multicenter analysis (DRKS00033000). The primary endpoint was CR. Predefined clinical and therapeutic variables were treated as covariates and evaluated as potential predictors of CR in a multivariable logistic regression model.

Among 245 included patients (181 men) with a median age of 62 (Q1-Q3: 54–67) years, 113 (46.1%) reached a CR. Of those, 69 (28.2%) were active smokers. Short-course radiotherapy (SCRT) was applied in 107 (43.7%) patients. Chemoradiotherapy with pyrimidine-based monotherapy or concomitant oxaliplatin was used in 65 (26.5%) and 73 (29.8%) of patients, respectively. A median of 8 (Q1-Q3: 6–9) cycles of consolidation chemotherapy was administered. The CR likelihood increased with each additional chemotherapy cycle (OR 1.19, 95%-CI: 1.04–1.38). SCRT was associated with lower CR rates (OR 0.34, 95%-CI: 0.16–0.74) compared with concomitant pyrimidine-based chemoradiotherapy. Adding concomitant oxaliplatin to 5-FU did not further increase CR rates (OR 1.06, 95%-CI: 0.50–2.27). CR was more likely in non-smokers (OR 1.92, 95%-CI: 1.03–3.57). ESMO tumor classification and treatment duration were not associated with CR.

More intensive TNT protocols were associated with higher CR rates. Smoking cessation may be beneficial but requires external validation.