Hyperthermic intraperitoneal chemotherapy is associated with improved overall survival in advanced non-high-grade epithelial ovarian, fallopian tube, and primary peritoneal carcinoma.

OBJECTIVE: Non-high-grade epithelial cancers originating in the ovary, fallopian tube, or peritoneum are rare, and the role of hyperthermic intraperitoneal chemotherapy in patients with these cancers is undefined. We evaluated whether hyperthermic intraperitoneal chemotherapy is associated with improved overall survival and, secondarily, in which histologic subgroup the association was strongest. METHODS: Adults with stage III or IV non-high-grade epithelial ovarian, fallopian tube, or primary peritoneal carcinoma undergoing primary or interval cytoreductive surgery in the National Cancer Database (2004-2022) were classified by receipt of hyperthermic intraperitoneal chemotherapy. Overall survival was administratively censored at 10 years. The entire eligible cohort was analyzed with era-balanced 1:4 propensity-score matching, full-cohort inverse-probability and overlap weighting, multiple imputation, and E-values. RESULTS: Among 15,654 patients, 72 (0.5%) received hyperthermic intraperitoneal chemotherapy and were matched to 288 controls. In the matched cohort, 5- and 10-year overall survival were 64.5% and 48.4% with hyperthermic intraperitoneal chemotherapy versus 50.0% and 29.0% without. Hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival across estimators (overlap-weighted hazard ratio 0.66, 95% confidence interval 0.46 to 0.95, p = .024; inverse-probability-weighted hazard ratio 0.66, 95% confidence interval 0.47 to 0.95, p = .024; matched-set hazard ratio 0.52, 95% confidence interval 0.33 to 0.81, p = .004; multiply-imputed hazard ratio 0.66, 95% confidence interval 0.46 to 0.94, p = .023), with a directionally consistent multivariable estimate (hazard ratio 0.72, 95% confidence interval 0.49 to 1.04, p = .08). In exploratory analyses, the association was strongest in the 17 patients treated with hyperthermic intraperitoneal chemotherapy with mucinous carcinoma (multivariable hazard ratio 0.39, 95% confidence interval 0.17 to 0.88, p = .024) and was near-null in non-mucinous histologies (hazard ratio 0.93, 95% confidence interval 0.56 to 1.54); these estimates rest on small numbers. CONCLUSIONS: In this national cohort, hyperthermic intraperitoneal chemotherapy was associated with improved 10-year overall survival after adjustment for measured confounders, although unmeasured factors such as completeness of cytoreduction and tumor burden cannot be excluded. The association was strongest among patients with mucinous carcinoma. Pending prospective, histology-specific evaluation, these data may inform individualized discussion of hyperthermic intraperitoneal chemotherapy with selected patients at experienced centers, with counseling that high-level evidence is lacking.