Compared with other high-risk procedures in cancer, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal metastasis was associated with lower 30-day mortality rates and either similar or lower infection rates, a retrospective database study found.
The 30-day mortality rate was 1.1% for patients undergoing cytoreductive surgery/HIPEC, compared with rates ranging from 2.5% to 3.9% for pancreaticoduodenectomy (Whipple), esophagectomy, and right lobe or trisegmental hepatectomies, reported Jason M. Foster, MD, of the University of Nebraska Medical Center in Omaha, and colleagues.
“Cytoreductive surgery/HIPEC is not only safe when compared with procedures of similar risk, but is often associated with less morbidity,” the authors wrote in JAMA Network Open. “Cytoreductive surgery/HIPEC had the lowest mortality risk, almost 50% to 75% lower than other advanced oncology surgical procedures.”
Compared with Whipple, lower infection rates with cytoreductive surgery plus HIPEC were seen for both superficial (5.4% with HIPEC vs 9.7%, P<0.001) and deep incisional infections (1.7% with HIPEC vs 2.7%, P<0.01). Compared with esophagectomy, fewer HIPEC patients needed to return to surgery (6.8% with HIPEC vs 14.4%, P<0.001) and there were lower rates of superficial incisional infection (5.4% with HIPEC vs 7.2%, P<0.001).
Time in hospital was shorter in the HIPEC group, at 8 days compared with 10 days each for both esophagectomy and Whipple (P<0.001).
For organ space infections, rates with cytoreductive surgery plus HIPEC (7.2%) were significantly lower than those seen with Whipple (12.9%, P<0.001), and trisegmental (12.4%, P<0.001) or right lobe hepatectomies (9.0%, P=0.02).
“Cytoreductive surgery/HIPEC was performed with a high level of safety, providing evidence to dispel misperceptions rooted in the historic data,” Foster’s group wrote. “Safety concerns should no longer be a deterrent to routine referral to high-volume centers.”
The researchers noted that roughly 60,000 new cases of peritoneal metastasis are diagnosed each year (most commonly stemming from mesothelioma and cancers of the colon, ovaries, and appendix), yet in 2015, for example, cytoreductive surgery plus HIPEC was performed on fewer than 1,000 patients. They said that safety concerns, partly owing to a lack of available modern data, have played a part in the lack of referrals for this procedure, among other factors.
In an invited commentary that accompanied the study, Margaret E. Smith, MD, MS, and Hari Nathan, MD, PhD, both of the University of Michigan in Ann Arbor, wrote that comparing HIPEC with other high-risk surgeries for cancer constructs a “straw man.”
“A patient with pancreatic cancer has no other curative option besides a Whipple procedure,” they explained. “A patient with peritoneal carcinomatosis, on the other hand, could be offered continued palliative systemic therapy or cytoreductive surgery without HIPEC.”
They said that a more “salient concern” with HIPEC in patients with peritoneal carcinomatosis may be its effectiveness.
“The results of this study need to be interpreted in the context of emerging evidence questioning previously held assumptions regarding HIPEC and its survival benefit,” wrote Smith and Nathan, pointing to recent results from PRODIGE 7 in 265 patients with peritoneal carcinomatosis associated with colorectal cancer.
In that trial, results of which were presented at the 2018 American Society of Clinical Oncology meeting, the median overall survival was 41.7 months for cytoreductive surgery/HIPEC patients and 41.2 months for those treated with surgery alone, with 1-year survival rates of 86.9% and 88.3%, respectively. The rate of 30-day mortality was roughly 1.5% in each arm of the trial.
In the current study, Foster’s group examined 34,114 patients from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database who underwent cytoreductive surgery plus HIPEC (n=1,822), trisegmental hepatectomy (n=2,449), right lobe hepatectomy (n=5,109), esophagectomy (n=7,941), or pancreaticoduodenectomy (n=16,793) from 2005 to 2015.
The authors noted an extensive number of limitations to their findings, including younger age in the HIPEC group, higher American Society of Anesthesiologists classification in the esophagectomy group, and higher comorbidity rates in the esophagectomy and Whipple groups.
Smith and Nathan also pointed out that not all cytoreductive surgeries are created equally, as some may call for removal of a single peritoneal nodule while more complex operations might require multivisceral resection with peritoneal stripping, but this level of information is not captured by the NSQIP database.
Further, the authors noted that cytoreductive surgery plus HIPEC is only performed at high-volume centers, while the other procedures examined in the study included those performed at both high- and low-volume centers.
The study was funded in part by the Hill Foundation and Platon Foundation.
Foster and co-authors reported no conflicts of interest.
Smith disclosed a grant from the National Institute of Health. Nathan disclosed grants from the Agency for Healthcare Research and Quality and the National Institute on Aging.