Factors predicting histopathologic response to neoadjuvant chemotherapy in patients with peritoneal metastases from colorectal cancer.

Abstract

Select patients with colorectal cancer with peritoneal metastases may undergo a curative-intent cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy after neoadjuvant systemic chemotherapy. Factors predicting pathologic complete response (CR) remain poorly defined, as do eligibility criteria for this aggressive therapy. We aimed to evaluate the pathologic CR rate following neoadjuvant chemotherapy and develop a predictive model for treatment response to optimize patient selection and benefit-risk assessment within the personalized medicine framework. This single-center retrospective cohort study included 178 patients treated with neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy between 2003 and 2019. After analyzing demographic, clinicopathologic, and perioperative variables, we performed a multivariate analysis. The median peritoneal carcinomatosis index was 9, complete cytoreduction was achieved in 88.7% of patients, and pathologic CR was observed in 19 (10.7%) patients. Tumor histological subtype, lymph node involvement, vascular invasion, and peritoneal carcinomatosis index were statistically significantly associated with histologic response (P = .016, P = .032, P = .035, and P < .001, respectively). In multivariate analysis, tumor histologic subtype was the only independent predictor of response (odds ratio, 0.271 [95% CI, 0.075-0.988], P = .048) and was used to generate a logistic regression model with moderate discriminative performance (area under the curve = 0.638 [95% CI, 0.519-0.757], P = .049). Mucinous histology is a negative prognostic factor, with approximately 3-fold lower probability of achieving pathologic CR compared with enteroid type. Although larger prospective studies are needed to validate these findings, our model supports the potential integration of histologic subtype into prognostic scoring systems to better define criteria for selecting patients more bound to respond to this aggressive therapy.