Predictors of Pathologic Non-response to Neoadjuvant Approaches in Locally Advanced Rectal Cancer

Approximately 10-20% of rectal cancer patients do not respond to neoadjuvant treatment. While the current literature has focused on pathological complete response, pinpointing those who will fail to benefit entirely from neoadjuvant approaches is crucial.

This study aimed to determine the risk factors associated with pathological non-response (pNR) to neoadjuvant treatment.

Patients with stage II-III rectal adenocarcinoma who underwent neoadjuvant treatment followed by curative surgical resection between 2018 and 2023 at a high-volume center were retrospectively reviewed. Patients were divided into two cohorts (pNR and pathologic responder [pR]) based on their response to neoadjuvant therapy. The pNR group included patients with a Tumor Regression Score of grade 3 or those upstaged on the final pathological report.

Of the 405 patients included in this study, 53 (13%) were pNR and 352 (87%) were pR. Among patients treated with standard neoadjuvant chemoradiation, 12% were pNR compared with 14% among those treated with total neoadjuvant therapy. Significantly more patients in the pNR cohort had perineural (31% vs. 8%; p < 0.001) and lymphovascular (22% vs. 6%, p = 0.001) invasions when compared with the pR cohort. After adjusting for age, sex, clinical T stages, and clinical nodal status on multivariable analysis, the presence of extramural vascular invasion (EMVI) on pretreatment magnetic resonance imaging (odds ratio 2.08, 95% confidence interval 1.03-4.20, p = 0.04) was identified as a significant predictor of pNR.

EMVI was an independent risk factor of pNR in patients with rectal cancer. Identifying pretreatment factors that predict pNR to neoadjuvant therapy is crucial as it allows for better risk stratification and personalized treatment strategies.