Published online Dec 24, 2025. doi: 10.5306/wjco.v16.i12.112443
Revised: September 1, 2025
Accepted: November 7, 2025
Published online: December 24, 2025
Processing time: 149 Days and 0.7 Hours
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an established treatment for selected patients with peritoneal metastases (PM) from colorectal, ovarian, and gastric cancers, as well as for certain primary peritoneal tumors such as pseudomyxoma peritonei. However, evidence supporting its role in other uncommon indications remains limited, largely due to the rarity and heterogeneity of these malignancies and the absence of standardized treatment protocols. Understanding the potential survival benefit and safety profile of CRS + HIPEC in these contexts may help refine patient selection and guide clinical decision-making.
To evaluate surgical and oncologic outcomes, particularly overall survival (OS), in this heterogeneous patient population and assess perioperative morbidity and mortality to better define the safety profile of this aggressive multimodal strategy.
We retrospectively reviewed data from five tertiary cancer centers on patients who underwent CRS + HIPEC between January 2004 and December 2021 for PM from uncommon histologies, defined as any primary tumor other than colorectal, gastric, or ovarian carcinomas, pseudomyxoma peritonei, or malignant peritoneal mesothelioma. Baseline characteristics, operative details, complications (graded by the Clavien-Dindo classification), and survival outcomes were analyzed. OS was estimated using Kaplan-Meier analysis. Prognostic factors were evaluated using univariate and multivariate Cox proportional hazards models. The discriminatory ability and overall fit of the final model were assessed by the concordance index (C-index) and likelihood ratio test, respectively.
A total of 60 CRS + HIPEC procedures were performed in 60 patients (mean age = 58.5 years, 78.3% female). The most frequent primary tumors were uterine (35%) and breast cancer (20%). Median operative time was 405 minutes, and 75% of patients required perioperative transfusions. Major complications (Clavien-Dindo ≥ 3) occurred in 21.6% of patients, and 90-day mortality was 1.6%. Median OS for the entire cohort was 28 months. Kaplan-Meier analysis showed that breast cancer patients achieved the longest survival (median OS = 75 months) compared with uterine cancer (32 months) and other primaries (17 months). Multivariate analysis confirmed tumor origin as the strongest independent predictor of OS (C-index = 0.81; likelihood ratio test = 40.07; P < 0.001).
Our findings suggest that CRS + HIPEC can be performed safely in highly selected patients with PM from uncommon primary tumors, achieving meaningful long-term survival in subsets such as breast and uterine cancers. Tumor biology, rather than clinical factors, emerged as the key determinant of survival. Given the rarity and heterogeneity of these malignancies, collaborative multicenter efforts and prospective registries are essential to establish standardized selection criteria and optimize outcomes.
Core Tip: This multicenter retrospective study evaluates the safety and efficacy of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases (PM) from uncommon primary tumors. Among 60 patients treated across five high-volume centers, long-term survival was observed in selected cases, particularly those with breast or uterine cancer. Tumor origin emerged as the strongest independent predictor of overall survival, whereas timing of PM (synchronous vs metachronous) showed a variable prognostic impact. These findings support CRS + HIPEC as a potentially valuable option in rare indications when patients are carefully selected.