Expanding the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A multicenter study on uncommon peritoneal malignancies

Our plain-English summary of Expanding the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A multicenter study on uncommon peritoneal malignancies, by M. Framarini, F. D'Acapito, P.V. Lippolis, et al (World Journal of Clinical Oncology, 2025).

The study

• Authors: M. Framarini, F. D'Acapito, P.V. Lippolis, A. Di Giorgio, D. Di Pietrantonio, A. Sommariva, P. Sammartino
• Journal: World Journal of Clinical Oncology
• Published: 2025;16(12):112443
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Aim: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.

In plain English

This retrospective study from five Italian centers covered 60 patients treated in 2004 to 2021 with surgery removing visible abdominal tumor plus heated chemotherapy in the abdomen (HIPEC). Most had cancer spread to the abdominal lining (peritoneum) from uncommon primary tumors, most often uterine (35%). Three patients had malignant peritoneal mesothelioma, which starts in the lining itself, although the abstract says it was excluded. Asbestos and other causes were not examined. Major complications occurred in 2 of 18 patients (11.1%) having only the lining removed and 11 of 42 (26.2%) also having organs removed, a difference not statistically significant. Among 51 patients followed at least six months, median overall survival was 28 months: 75 months for breast cancer (95% confidence interval 28 months to not reached), 32 for uterine cancer (21 to 51) and 17 for other tumors (15 to 26). Yet the article also reports no breast cancer deaths during follow-up. Mesothelioma survival did not differ significantly from breast cancer. The authors concluded that tumor type most strongly predicted survival, noting their small, mixed patient group limited the analyses.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective multicenter cohort study of patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC)
• Who was studied: 60 patients (mean age 58.5 years, 78.3% female) at five Italian centers, treated January 2004 to December 2021. Most had peritoneal metastases from uncommon primary tumors, with uterine tumors the most common (35%). The patient table also lists 3 patients with malignant peritoneal mesothelioma, a primary peritoneal cancer, although the abstract's eligibility definition excludes this disease.
• Exposure: No asbestos or other environmental exposure was studied. The study examined a treatment: complete cytoreductive surgery followed by HIPEC, given according to each center's own protocol.
• Main results:
  • Three patients (5%) in the patient table had malignant peritoneal mesothelioma.
  • Major complications (Clavien-Dindo grade 3 or higher) occurred in 2 of 18 patients (11.1%) who had peritonectomy alone and 11 of 42 patients (26.2%) who also had other procedures, with one postoperative death in the latter group. The risk ratio was 2.36 (95% CI 0.58 to 9.58), and the difference was not statistically significant (P = 0.31).
  • 90-day mortality for the whole cohort was 1.6%.
  • The overall survival analysis included 51 of the 60 patients. Patients with less than six months of follow-up at the data cut-off (December 31, 2021) were excluded.
  • Median overall survival for the cohort was 28 months.
  • Patients with breast cancer metastases had a median overall survival of 75 months (95% CI 28 to not reached), compared with 32 months (95% CI 21 to 51) for uterine cancer (P = 0.015).
  • Patients with other primary tumors had a median overall survival of 17 months (95% CI 15 to 26).
  • Elsewhere the article states that the breast cancer cases, all metachronous, had no observed deaths during follow-up. This does not fit the 75-month median survival reported for breast cancer.
  • In multivariate analysis, compared with breast cancer, the risk of death was higher for small bowel adenocarcinoma (HR 25.21, 95% CI 3.53 to 180.14), biliary tract cancer (HR 32.53), pancreatic cancer (HR 24.34) and uterine cancer (HR 6.71, 95% CI 1.72 to 26.11).
  • For malignant peritoneal mesothelioma compared with breast cancer, the hazard ratio was 1.33 (95% CI 0.30 to 5.83, P = 0.70). This was not statistically significant.
  • Age, sex, ASA score, PCI, and neoadjuvant or adjuvant chemotherapy were not independently associated with overall survival.
• The authors' conclusion: The authors concluded that primary tumor type was the most powerful independent predictor of survival. They wrote that breast and uterine cancer patients derived the greatest long-term benefit, and that the treatment can be performed safely in highly selected patients.
• Limitations the authors state:
  • The small number of patients and the mix of different primary tumors prevented statistically robust analyses by tumor origin.
  • Completeness of cytoreduction was recorded only as complete or incomplete, so CC-0 and CC-1 cases could not be compared.
  • The data did not allow useful PCI cut-off values to be defined for these indications.
  • The survival advantage seen for metachronous presentation was strongly influenced by the breast cancer cases, all of which were metachronous.

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Stomach Cancer, Overall Survival, Carcinoma, Peritoneal Mesothelioma, Concordance Index, Multivariate Analysis.

Related studies

• National Guidelines for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Malignancies: A Worldwide Systematic Review and Recommendations of Strength Analysis — M. Tonello, C. Cenzi, et al. (2025)
• Postoperative outcomes of laparoscopic vs open cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for treatment of peritoneal surface malignancies — G. Passot, N. Bakrin, et al. (2014)
• Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for disseminated intra-abdominal malignancies in children-a single-institution experience — O. Zmora, A. Hayes-Jordan, et al. (2018)
• A Canadian single-centre experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for abdominal malignancies — R. Nassabein, R. Younan, et al. (2022)
• Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for limited peritoneal metastasis. The PSOGI international collaborative registry — A. Arjona-Sanchez, O. Aziz, et al. (2021)
• Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies — P.M. Polanco, Y. Ding, et al. (2015)

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