Peritoneal metastasis in locally advanced colon cancer (T4 stage) is estimated around 25% at 3 years from surgical resection with a poor prognosis. There is controversy about the results using prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in this group of patients. We led a randomized controlled trial to determine the efficacy and safety of adjuvant HIPEC in patients with locally advanced colon cancer.
We did an open-label, randomized phase III study in 17 hospitals in Spain. Eligible patients were aged 18-75 years and had locally advanced primary colorectal cancer diagnosed preoperatively (cT4NxM0). Patients were randomly assigned (1:1) to surgery or surgery plus HIPEC (mitomycin C 30 mg/m2 during 60 minutes), both followed by systemic adjuvant chemotherapy. Randomisation was done via a web-based system, with stratification by treatment centre and gender. The primary outcome was 3 years loco-regional control rate, defined as the time from treatment to peritoneal disease recurrence or death form any cause, analysed by intention to treat (ITT). DFS and OS were secondary endpoints.
Between November 2015 and January 2021 184 patients were recruited and randomized (89 experimental vs. 95 control). The median of follow-up was 36 (IQR 27-36) months. Demographic, tumour features, surgical management and final pathology reports were similar between both groups. The loco-regional control (LC) was improved in the experimental arm (35,3 ± 0.4 vs. 33.2 ± 0.8 months) with a 3 years LC rate of 97% vs. 87% (p = 0.025). No differences were observed in DFS and OS. The pT4 subgroup showed a clear benefit of LC in the HIPEC arm. No differences in morbidity were observed between groups.
The addition of hyperthermic intraperitoneal chemotherapy with mitomycin C to a complete surgical resection for locally advanced colon cancer improves the loco-regional control rate. This benefit becomes more evident in the subgroup of patients with pT4 colon cancer.
Clinical trial identification
Legal entity responsible for the study
IMIBIC Maimonides Biomedical research Institute cordoba, Spain. Universitary Hospital Reina Sofia, Cordoba, Spain.
FIBICO (Biomedical Research Foundation, Cordoba) and Spanish Surgeon's Association (AEC).
All authors have declared no conflicts of interest.
The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.
Keywords: colorectal peritoneal carcinomatosis; cytoreductive surgery; hyperthermic intraperitoneal chemotherapy (HIPEC).
Conflict of interest statement
The authors declare no conflict of interest.
Management of colorectal cancer patients at high risk of peritoneal metastases.J BUON. 2015 May;20 Suppl 1:S71-9.PMID: 26051336
Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastases from colorectal cancer in the Czech Republic in 2018.Klin Onkol. 2021 Summer;34(4):278-282. doi: 10.48095/ccko2021278.PMID: 34905928 English.
The absence of benefit of perioperative chemotherapy in initially resectable peritoneal metastases of colorectal cancer origin treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective analysis.Eur J Surg Oncol. 2021 Jul;47(7):1661-1667. doi: 10.1016/j.ejso.2021.01.018. Epub 2021 Feb 3.PMID: 33602530
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases - The Hong Kong experience and literature review.Asian J Surg. 2021 Jan;44(1):221-228. doi: 10.1016/j.asjsur.2020.05.010. Epub 2020 Jun 27.PMID: 32605790 Review.
Status of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer.J Gastrointest Oncol. 2019 Dec;10(6):1251-1265. doi: 10.21037/jgo.2019.01.36.PMID: 31949946 Free PMC article. Review.
Pharmacologic Targeting of MMP2/9 Decreases Peritoneal Metastasis Formation of Colorectal Cancer in a Human Ex Vivo Peritoneum Culture Model.Cancers (Basel). 2022 Aug 2;14(15):3760. doi: 10.3390/cancers14153760.PMID: 35954423 Free PMC article.