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CRS/HIPEC safety concerns may be outdated

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Risks and benefits of CRS/HIPEC remain unclear

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).



Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) appears safe, and concerns about high complication rates may be outdated, according to a retrospective study involving more than 34,000 cases.

Compared with four other surgical oncology procedures considered high risk, CRS/HIPEC had the lowest 30-day mortality rate, reported lead author Jason M. Foster, MD, of the University of Nebraska Medical Center in Omaha, and his colleagues.

“The perception of high morbidity, high mortality, and poor surgical outcomes remains a barrier to CRS/HIPEC patient referral as well as clinical trial development in the United States, despite the published noncomparative data establishing contemporary safety,” the investigators wrote in JAMA Network Open.

The study involved 34,114 patients from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database who underwent CRS/HIPEC (n = 1,822), trisegmental hepatectomy (n = 2,449), right lobe hepatectomy (n = 5,109), pancreaticoduodenectomy (Whipple; n = 16,793), or esophagectomy (n = 7,941) during 2005-2015. The investigators rates of overall 30-day postoperative mortality, superficial incisional infection, deep incisional infection, organ space infection, return to operating room, and length of hospital stay.

Analysis revealed that CRS/HIPEC had a 30-day mortality rate of 1.1%, which was lower than rates of 2.5%-3.9% for the comparative procedures. Similarly, organ space infection rate was lowest for CRS/HIPEC (7.2%). Superficial and deep incisional infection rates were 5.4% and 1.7%, respectively, for CRS/HIPEC, lower than all procedures except right lobe hepatectomy, with rates of 4.6% and 1.5%. Return to OR was necessary for 6.8% of CRS/HIPEC patients, a rate similar to the other procedures except esophagectomy, in which return to OR was necessary 14.4% of the time. Finally, CRS/HIPEC had a median length of stay of 8 days, which was slightly longer than right lobe or trisegmental hepatectomy (7 days), but shorter than Whipple procedure or esophagectomy (10 days.)

“This study found that CRS/HIPEC had the lowest mortality risk, almost 50%-75% lower than other advanced oncology surgical procedures,” the investigators noted. “These findings provide objective data to dispel the misperception of morbidity and mortality concerns surrounding CRS/HIPEC, and surgical risk should no longer remain a deterrent to patient referral or development of clinical trials for CRS/HIPEC.”

The study was funded by the Platon Foundation and the Hill Foundation. The authors reported no conflicts of interest.

SOURCE: Foster JM et al. JAMA Netw Open. 2019 Jan 11. doi: 10.1001/jamanetworkopen.2018.6847.

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