Endoscopic and imaging evaluations of neoadjuvant immunotherapy in patients with locally advanced colorectal cancer with dMMR/MSI-H or POLE/POLD1 mutation.

Abstract

In neoadjuvant immunotherapy, radiological assessment of pathological complete response (pCR) is frequently inaccurate, and atypical response patterns are occasionally observed. This study aims to investigate the diagnostic performance of new qualitative morphological changes for predicting pCR and to provide a comprehensive characterization of the imaging and endoscopic response patterns associated with neoadjuvant immunotherapy. A retrospective, single-center study was conducted to enroll consecutive patients with locally advanced colorectal cancer exhibiting dMMR/MSI-H or POLE/POLD1 mutation, who received first-line neoadjuvant immunotherapy. The diagnostic performance of the radiological complete response (rCR), morphological changes, endoscopy, and a combined model integrating morphological changes and endoscopy was assessed using the area under the receiver operating characteristic curve (AUC). Additionally, atypical response patterns and imaging features of immune-related adverse events (irAEs) were documented. Forty-three patients (mean age 53.84 ± 14.37; 23 males, 20 females) were included. Of these, 25 achieved pCR. Among pCR patients, 84% (21/25) had pseudoresidual disease. The combined model had a higher AUC than rCR and morphological changes alone, with numerical superiority over endoscopy alone (0.878 vs. 0.798, p = 0.07). Approximately 6.98% (3/43) of patients exhibited dissociated responses. Two cases of immunotherapy-induced Trousseau's syndrome were identified. Morphological changes exhibit predictive value for pCR, and the combined model further shows promising potential. Pseudoresidual disease and dissociated responses are atypical but common response patterns in neoadjuvant immunotherapy. Accurate recognition of imaging features associated with various irAEs is crucial to prevent misinterpretation as metastatic disease. Question Assessment of pathological complete response after neoadjuvant immunotherapy for locally advanced colorectal cancer is crucial, but it cannot be identified by the current radiological criteria. Findings Morphological changes exhibit predictive value for pathological complete response, and the combined model integrating morphological changes and endoscopy further shows promising potential. Clinical relevance Radiographic complete response alone is insufficient for accurately predicting pathological complete response (pCR). Pseudoresidual disease is common in pCR. Dissociated response may guide personalized treatment. Recognizing imaging features of immune-related adverse events is critical to avoid misdiagnosis as metastatic disease.