CRS/HIPEC safety concerns may be outdated

The recent study by Foster et al. provides insight into the national safety of reductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC); however, more detailed safety and efficacy data are needed to influence current practices, according to Margaret Smith, MD, and Hari Nathan, MD, PhD.

A closer look at the Foster et al. study reveals three key limitations: First, “cytoreductive surgery encompasses a wide range of procedures, from resection of one peritoneal nodule to multivisceral resection with peritoneal stripping, and, thus, reflects a wide range of possible morbidity,” the authors wrote in an editorial for JAMA Network Open. Therefore, the findings may not represent certain patient populations.

Second, “comparison with other procedures for different indications constructs a straw man.” In contrast with some candidates for CRS/HIPEC, “a patient with pancreatic cancer has no other curative option besides a Whipple procedure.” This imperfect comparison should be considered as such.

Third, the safety of CRS/HIPEC may not be the procedure’s primary limitation. “A more salient concern may be its oncologic effectiveness,” the authors wrote.

Although a clinical randomized trial from 2003 involving patients with colorectal peritoneal carcinomatosis showed a near doubling of overall survival with CRS/HIPEC, compared with systemic chemotherapy alone (22 vs. 12.5 months), a comprehensive understanding of safety and efficacy is lacking, particularly regarding the inclusion of HIPEC. For example, the recent phase 3 Prodige 7 trial showed that addition of HIPEC to CRS added morbidity without survival advantage in patients with colorectal peritoneal carcinomatosis; in contrast, a separate phase 3 trial in epithelial ovarian cancer showed that adding HIPEC to CRS did extend survival.

“…Others have cautioned against changing practice based on these results given concerns over small sample size, imbalances in effects seen across centers, and overall survival with CRS/HIPEC that was similar to other studies’ reported survival following interval debulking alone. Legitimate concerns regarding the efficacy of CRS/HIPEC exist, and appropriate patient selection for this aggressive treatment remains a challenge. Foster et al. demonstrates acceptable morbidity and mortality rates for CRS/HIPEC in this highly selected patient cohort. However, until the benefit for individual patients is more thoroughly understood, clinician referral and treatment practices will remain difficult to transform,” the authors wrote.

Dr. Smith and Dr. Nathan are affiliated with Michigan Medicine at the University of Michigan in Ann Arbor. These comments are adapted from the accompanying editorial (JAMA Netw Open 2019 Jan 11. doi:10.1001/jamanetworkopen.2018.6839).