Comment on: Efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy for locally advanced colorectal cancer (HIPECT4): final analysis of randomized clinical trial

Correspondence to: Serdar Gumus (email: seredargumus@hotmail.com)

Department of General Surgery

Faculty of Medicine

Çukurova University

Adana

Türkiye

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BJS Open, https://doi.org/10.1093/bjsopen/zrag002, published 27 March 2026

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We read with great interest the final analysis of the HIPECT4 trial by Arjona-Sánchez et al., which provides mature and valuable evidence on the role of mitomycin C-based HIPEC in reducing peritoneal recurrence in patients with locally advanced colon cancer1. The trial addresses a clinically important question, and the long-term follow-up data represent a meaningful contribution to the ongoing debate on prophylactic HIPEC, particularly given the discordant results of the COLOPEC trial2.

We would, however, like to raise a methodological point regarding the surgical procedure performed in both study arms. The original HIPECT4 protocol, published in 2018, specified that cytoreduction in both the experimental and control arms included standardized prophylactic resection of target organs — omentectomy, resection of the hepatic (falciform) round ligament, appendicectomy, and bilateral oophorectomy in post-menopausal women — in addition to colectomy3. This standardization was an important design choice intended to equalize the extent of surgical radicality between arms, so that any observed difference in locoregional control could be attributed specifically to the addition of HIPEC rather than to differences in the extent of resection.

In the final analysis manuscript, this detail is not restated. The Methods section refers the reader to the previously published protocol for inclusion and exclusion criteria1,3, but does not reiterate — even briefly — that the same extended cytoreductive procedure was applied uniformly to both the HIPEC and control groups. Given that this information directly bears on the internal validity of the comparison between arms, we believe a single confirmatory sentence in the final report would have been warranted, particularly since a decade separates the initial protocol publication from this final analysis and readers may reasonably approach the two articles independently.

We would therefore welcome clarification from the authors on whether the standardized target-organ resection described in the original protocol was indeed applied consistently to both study arms throughout the trial period (November 2015 to March 2021), and whether any deviations occurred across the 17 participating centres that might have influenced the locoregional control outcomes reported.

We congratulate the authors on completing this long-awaited final analysis and believe that addressing this point would further strengthen the interpretability of an already valuable dataset.