Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence

Our plain-English summary of Repeated Cytoreduction Combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Selected Patients Affected by Peritoneal Metastases: Italian PSM Oncoteam Evidence, by E.M. Pasqual, A.P. Londero, M. Robella, et al (Cancers, 2023).

The study

• Authors: E.M. Pasqual, A.P. Londero, M. Robella, M. Tonello, A. Sommariva, M. De Simone, S. Bacchetti, G. Baiocchi, S. Asero, F. Coccolini, F. De Cian, M. Guaglio, A. Cinquegrana, C. Cenzi, S. Scaringi, A. Macrì
• Journal: Cancers
• Published: 2023;15(3)
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The reiteration of surgical cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients affected by recurrent peritoneal metastases is still questioned regarding safety and effectiveness. This study evaluates the safety, efficacy, and associated factors of iterative CRS combined with HIPEC. This multicentric retrospective study collected data from four surgical oncology centers, on iterative HIPEC. We gathered data on patient and cancer characteristics, the peritoneal cancer index (PCI), completeness of cytoreduction (CC), postoperative complications, and overall survival (OS). In the study period, 141 CRS-plus-HIPECs were performed on 65 patients. Nine patients underwent three iterative procedures, and one underwent five. No increased incidence of complications after the second or third procedure was observed. Furthermore, operative time and hospitalization stay were significantly shorter after the second than after the first procedure (p < 0.05). Optimal cytoreduction was achieved in more than 90% of cases in each procedure, whether first, second, or third. A five-year (5 y) OS represented 100% of the cases of diffuse malignant-peritoneal-mesotheliomas, 81.39% of pseudomyxoma peritonei, 34.67% of colorectal cancer (CRC), and 52.50% of ovarian cancer. During the second CRS combined with HIPEC, we observed a lower rate of complete cytoreduction and a non-significantly better survival in cases with complete cytoreduction (5 y-OS CC-0 56.51% vs. 37.82%, p = 0.061). Concomitant hepatic-CRC-metastasis did not compromise the CRS-plus-HIPEC safety and efficacy. This multicentric experience encourages repeated CRS-plus-HIPEC, showing promising results.

In plain English

This retrospective chart review covered 65 patients, who had 141 procedures at four Italian surgical oncology centers between January 1995 and May 2022. Each had cancer affecting the abdominal lining (peritoneal-surface malignancy) and had repeated surgery to remove it, combined with heated chemotherapy inside the abdomen (HIPEC). The study did not examine asbestos exposure. Four patients had diffuse malignant peritoneal mesothelioma and 33 had pseudomyxoma peritonei. Serious (grade III to IV) complications followed 20.00% of first and 10.77% of second procedures, not a statistically significant difference. Second operations and hospital stays were significantly shorter. Of nine pseudomyxoma peritonei patients given a third procedure, one (11.11%) had serious complications. Five-year survival from the first procedure was 100% for the four mesothelioma patients, 81.39% for pseudomyxoma peritonei (95% confidence interval 67.72 to 97.81%), 34.67% for colorectal cancer (14.46 to 83.13%) and 52.5% for epithelial ovarian cancer (27.22 to 100%). The authors concluded that their initial results encourage repeating the procedure in selected patients, and called for prospective studies. They noted the retrospective design, no control group, small numbers per cancer type and possible selection bias.

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: Multicentre retrospective chart review of patients who had repeated cytoreductive surgery plus HIPEC
• Who was studied: 65 patients who had at least two CRS-plus-HIPEC procedures (141 procedures in total) at four Italian centers (Candiolo, Padova, Udine, Messina), January 1995 to May 2022. Primary tumors: pseudomyxoma peritonei 33/65, colorectal cancer 15/65, epithelial ovarian cancer 10/65, diffuse malignant peritoneal mesothelioma 4/65, gastric cancer 2/65, sarcoma 1/65. Nine had three procedures and one had five.
• Exposure: Not an asbestos exposure study. The exposure studied was the treatment: repeated cytoreductive surgery with HIPEC. Drugs used alone or in combination included mitomycin C, cisplatin (CDDP), doxorubicin, oxaliplatin, 5-fluorouracil and irinotecan.
• Main results:
  • Grade III to IV surgical complications (Clavien–Dindo): 20.00% (13/65) after the first procedure vs 10.77% (7/65) after the second, not statistically significant (p = 0.145)
  • The second procedure was significantly shorter than the first (median 480 vs 570 minutes), and the hospital stay was also significantly shorter (median 12 vs 17 days) (p less than 0.05)
  • Complete cytoreduction (CC-0) was achieved in 73.85% of first and 66.15% of second procedures (p = 0.444)
  • Optimal cytoreduction (CC-0 or CC-1) was achieved in 98.46% of first and 90.77% of second procedures (p = 0.052)
  • Nine pseudomyxoma peritonei patients had a third procedure. Grade III to IV complications occurred in 11.11% (1/9), which the authors described as comparable to the first and second procedures. Optimal cytoreduction was achieved in 100% of cases and complete cytoreduction in 87.50%.
  • Five-year overall survival from the first HIPEC in diffuse malignant peritoneal mesothelioma was 100% (95% CI 100 to 100%): all four patients were alive after five years
  • Five-year overall survival from the first HIPEC in pseudomyxoma peritonei patients was 81.39% (95% CI 67.72 to 97.81%)
  • Five-year overall survival from the first HIPEC in colorectal cancer patients was 34.67% (95% CI 14.46 to 83.13%)
  • Five-year overall survival from the first HIPEC in epithelial ovarian cancer patients was 52.5% (95% CI 27.22 to 100%)
  • At the second procedure, survival was better with complete than with incomplete cytoreduction, but the difference was not statistically significant (p = 0.061)
  • By peritoneal cancer index (PCI) at the second procedure, five-year overall survival was 58.84% (95% CI 42.11 to 82.22%) with PCI of 14 or less vs 38.22% (95% CI 20.64 to 70.76%) with PCI above 14, not significant (p = 0.107)
  • The drug regimen was changed between the first and second procedure in 12 cases. Five-year overall survival was 45.12% in the drug-change group vs 51.39% in the no-drug-change group, not significant (p = 0.229).
• The authors' conclusion: The authors concluded that their initial results encourage repeating CRS and HIPEC, which they described as safe and effective. They said it should be a tailored strategy after adequate patient selection and that further prospective multicentre studies are required.
• Limitations the authors state:
  • Retrospective design and no proper control group
  • Small number of cases for each cancer type, which did not allow assessment of the factors influencing survival in each type
  • Possible selection bias
  • Immortality bias; the authors also measured survival from the date of each procedure to reduce it

Topics

Medical terms in this study, explained in our Lexicon: Cytoreductive Surgery, HIPEC, Peritoneal Cancer Index (PCI), Overall Survival, Mesothelioma, Colorectal Cancer, Ovarian Cancer, Metastasis.

Related studies

• Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis — N. Vassos, T. Förtsch, et al. (2016)
• The Role of Ki-67 and Pre-cytoreduction Parameters in Selecting Diffuse Malignant Peritoneal Mesothelioma (DMPM) Patients for Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — S. Kusamura, P.A. Torres Mesa, et al. (2016)
• 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)
• Multicystic peritoneal mesothelioma: outcomes and patho-biological features in a multi-institutional series treated by cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) — D. Baratti, M. Vaira, et al. (2010)
• Repeated cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy in patients with peritoneal carcinomatosis: A retrospective cohort study — C. Paasch, G. De Santo, et al. (2021)
• Preoperative Thrombocytosis Predicts Shortened Survival in Patients with Malignant Peritoneal Mesothelioma Undergoing Operative Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy — Y.C. Li, T. Khashab, et al. (2017)

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