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Cytoreductive surgery with chemotherapy often safer than other high-risk oncologic procedures

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February 26, 2019

Jason M. Foster MD
Jason M. Foster

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy proved to be as safe as or safer than other oncologic procedures with similar risks, according to results of a retrospective study published in JAMA Network Open.

However, although the surgery-chemotherapy combination has extended survival of patients with peritoneal metastasis worldwide, rates of referral remain low in the U.S. This is partly due to a misconception of high morbidity and mortality associated with the combination, according to researchers.

“The management of peritoneal metastasis continues to be one of the more challenging areas in oncology,” Jason M. Foster, MD, surgical oncologist at Fred & Pamela Buffett Cancer Center and associate professor of surgery in the division of surgical oncology at University of Nebraska Medical Center, and colleagues wrote. “The care of these patients requires balancing the adverse effects and tolerance of effective therapies that prolong survival and maximize quality of life, while also controlling symptoms arising from both the disease and its treatment.”

Foster and colleagues sought to evaluate the relative safety of cytoreductive surgery in combination with (CRS/HIPEC) in a study of 34,114 patients (median age, 63 years; interquartile range [IQR], 55-71; 42% women) listed in the American College of Surgeons National Surgical Quality Improvement Project database.

Researchers compared perioperative and 30-day postoperative morbidity and mortality rates among patients who received CRS/HIPEC (n = 1,822) with those who underwent other high-risk procedures, including right lobe hepatectomy (n = 5,109), trisegmental hepatectomy (n = 2,449), pancreaticoduodenectomy (n = 16,793) or esophagectomy (n = 7,941).

Patients who underwent CRS/HIPEC had a lower median age (57 years) than that of the entire cohort.

In comparison with CRS/HIPEC, several of the other procedures had higher rates of complications, including:

  • Superficial incisional infection — 5.4% (95% CI, 4.4-6.4) with CRS/HIPEC vs. 9.7% (95% CI, 9.3-10.1) with pancreaticoduodenectomy and 7.2% (95% CI, 6.6-7.8) with esophagectomy (P < .001);
  • Deep incisional infection — 1.7% (95% CI, 1.1-2.3) with CRS/HIPEC vs. 2.7% (95% CI, 2.5-2.9) with pancreaticoduodenectomy (P < .01);
  • Organ space infection — 7.2% (95% CI, 6-8.4) with CRS/HIPEC vs. 9% (95% CI, 8.2-9.8) with right lobe hepatectomy (P = .02); 12.4% (95% CI, 11.1-13.7) with trisegmental hepatectomy (P < .001) and 12.9% (95% CI, 12.4-13.4) with pancreaticoduodenectomy (P < .001); and
  • Return to the operating room — 6.8% (95% CI, 5.6-8) with CRS/HIPEC vs. 14.4% (95% CI, 13.6-15.2) with esophagectomy (P < .001).

Median length of hospital stay was 8 days (IQR, 5-11) for CRS/HIPEC, 10 days (IQR, 7-15) for pancreaticoduodenectomy, and 10 days (IQR, 8-16) for esophagectomy (P < .001).

Overall 30-day mortality was lower among those who underwent CRS/HIPEC (1.1%; 95% CI, 0.6-1.6) compared with pancreaticoduodenectomy (2.5%; 95% CI, 2.3-2.7), right lobe hepatectomy (2.9%; 95% CI, 2.4-3.4), esophagectomy (3%; 95% CI, 2.6-3.4) and trisegmental hepatectomy (3.9%; 95% CI, 3.1-4.7).

Limitations to this study included a lack of information about how each tumor type influenced surgical safety as well as unavailability of detailed operative data.

“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 U.S., despite the published noncomparative data establishing contemporary safety,” Foster and colleagues wrote. “The history of CRS/HIPEC in the U.S. in the 1980s and 1990s was fraught with poor surgical outcomes, and the echoes of this early data continue to fuel the contemporary misperceptions.”

The study creates a “straw man” by comparing CRS/HIPEC with other procedures for different indications, Margaret E. Smith, MD, MS, health services research fellow at University of Michigan’s Center for Healthcare Outcomes and Policy, and Hari Nathan, MD, PhD, assistant professor of surgery in the division of hepato-pancreato-biliary surgery at University of Michigan, wrote in an accompanying editorial.

“A patient with pancreatic cancer has no other curative option besides a [pancreaticoduodenectomy],” Smith and Nathan wrote. “A patient with peritoneal carcinomatosis, on the other hand, could be offered continued palliative systemic therapy for CRS without HIPEC.”

There must be more study of the actual benefit for patients who undergo CRS/HIPEC, Smith and Nathan wrote.

“Until the benefit for individual patients is more thoroughly understood, clinician referral and treatment practices will remain difficult to transform,” they wrote. – by John DeRosier

Disclosures: The Hill Foundation and the Platon Foundation funded this study. The researchers report no relevant financial disclosures. Smith reports funding from the NIH Obesity Surgery Scientist Training Grant. Nathan reports grants from the Agency for Healthcare Research and Quality and National Institute on Aging.


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Peritoneal and omental metastases are relatively common events in gastrointestinal and gynecologic malignancies, and studies have demonstrated benefits from locoregional therapy directed at these types of anatomical sites in ovarian, primary peritoneal and appendiceal malignancies, with some studies also suggesting possible benefit in gastric and colorectal cancer.

Recently, studies such as the PRODIGE-7 study, presented last year at ASCO Annual Meeting by Quenet and colleagues, have boosted interest in CRS, with or without HIPEC, as a key component of therapy for patients with peritoneal metastases from colorectal cancer. However, CRS and HIPEC are not widely available, reflecting and leading to some uncertainty about the procedures and their expected results and potential toxicities.

The report by Foster and colleagues provides useful information gleaned from the American College of Surgeons National Surgical Quality Improvement Project database to further understand and establish potential benchmark expectations for outcomes for CRS/HIPEC, in comparison to other oncologic surgical procedures that may be perceived as high risk.

However, there are some important considerations to bear in mind when assessing their findings. The authors appropriately note that the database on CRS/HIPEC included various tumor primary sites and histologies, which may limit the ability to use such data as a universal benchmark standard, because outcomes may be expected to vary for surgery for ovarian cancer, for example, compared with gastric or colorectal cancer.

Moreover, researchers compared CRS/HIPEC — which are performed at a relatively small number of institutions, with high case volumes at those locations — with the broader database on, for example, Whipple resection or esophagectomy, which may not be performed by similarly high-volume specialized centers, although the benefits of doing so have been demonstrated.

Even if these data are accepted as an appropriate benchmark going forward, the relative contributions of CRS, as opposed to HIPEC, to operative morbidity and length of stay are not possible to determine, which may be important. The PRODIGE-7 study suggested that the addition of HIPEC to CRS did not improve outcomes. Even in ovarian cancer, where the potential benefits of intraperitoneal chemotherapy are clear, the additional utility of HIPEC, compared with intraperitoneal chemotherapy, remains unclear.

This report is a good starting point that will be important in furthering the study of CRS, with or without HIPEC. CRS/HIPEC increasingly appear to be potentially important tools (or a tool) in optimizing and individualizing therapy for colorectal cancer.

However, much work remains to be done to better understand the role of these procedures in the management of colorectal cancer.


Quenet F, et al. Abstract LBA3503. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Jimmy J. Hwang, MD, FACP

HemOnc Today Editorial Board Member 
Levine Cancer Institute at Atrium Health

Disclosure: Hwang reports consultant roles with Bayer, Boehringer Ingelheim, Eisai, Eli Lilly and Genentech/Roche; research support from Boehringer Ingelheim; and speakers bureau roles with Amgen, Bristol-Myers Squibb, Celgene, Genentech/Roche, and Ipsen.