Study Findings Show Highly Effective Colorectal Cancer Treatment is Underutilized

Patients receiving the same diagnosis, colorectal cancer (CRC) with synchronous peritoneal metastases (PM), were offered different treatments that led to dramatically different outcomes based upon the institution in which they were diagnosed. Findings presented at the 19th European Cancer Congress (ECCO 2017) revealed underutilization of a highly effective treatment, due to a lack of referral.

This study showed that only patients diagnosed at a hyperthermic intraperitoneal chemotherapy (HIPEC) center or an academic teaching hospital were likely to be offered cytoreductive surgery (CRS) and HIPEC treatment. During the 10 years that CRS/HIPEC treatment has been available, randomized controlled trials have demonstrated prolonged survival with the combination treatment as compared with the standard care of conventional surgery and systemic chemotherapy.¹

With CRS/HIPEC, surgeons remove all visible tumors from the abdominal cavity, which is then bathed with chemotherapy that has been heated to 42 degrees Celsius to kill any remaining cancer cells. Hyperthermia augments the cytotoxicity of chemotherapy, and intraperitoneal installation allows for delivery of much higher doses locally than are possible systemically, while minimizing toxicity, according to Koen P. Rovers, MD, Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands.

"HIPEC has demonstrated significant clinical benefit in 25% to 30% of patients with colorectal cancer and peritoneal metastasis, and is a vast improvement on systemic chemotherapy," said Rovers.

Rovers and colleagues used data contained in the Netherlands Cancer Registry, which is a nationwide registry that maintains records on every patient newly diagnosed with cancer in each of the 89 hospitals in the Netherlands. For this study, the investigators used all records for patients diagnosed with CRC and PM, but without concurrent systemic metastases, from 2005 to 2015.

Multivariate logistic regression analysis was done per hospital category (HIPEC center versus non-HIPEC, and academic/teaching hospital versus non-teaching) to devise the odds ratio (OR) for the use of CRS/HIPEC and the hazard ratio (HR) for the risk of death for the patients was calculated by multivariate Cox regression analysis. The analyses were adjusted by patient-related confounding variables, including age, gender, and socioeconomic status, and for tumor-related variables such as T-stage, N-stage, location, histology, and the degree of differentiation.

The study showed that only patients diagnosed with CRC plus PM in a HIPEC center stood a good chance of being offered CRS/HIPEC treatment. Out of the 154 (5%) patients newly diagnosed in a HIPEC center, 33% of patients were referred to this treatment, compared with 13% of the 2507 (94%) patients diagnosed with CRC plus PM in a non-HIPEC center.²

This disparity in the use of CRS/HIPEC treatment led to variations in patient outcome: Overall survival (OS) was 14.1 months for patients diagnosed in a HIPEC center compared with OS of 9.6 months for patients diagnosed in a non-HIPEC center (HR 0.82; 95% CI, 0.67-0.99).²

The investigators then reviewed the variability within non-HIPEC institutions by categorizing them as high (patients diagnosed = 778 [31%]) versus low frequency (patients diagnosed = 875 [35%]) hospitals per the number of cases, and found OS was 12.6 months in patients diagnosed in a high frequency institution versus 8.1 months in a low frequency hospital (HR = 0.73; 95% CI, 0.66-0.81).²

The comparison of OS between academic/teaching hospitals where 17% of patients were referred for CRS/HIPEC versus non-teaching hospitals where 11% of patient were referred for this treatment showed OS was 11.5 versus 8.7 months in patients diagnosed in the respective institutions (HR = 0.87; 95% CI, 0.80-0.95).²

“Diagnosis of colorectal cancer and synchronous peritoneal metastases in HIPEC centers and academic/teaching hospitals led to a higher likelihood of a patient being referred to and receiving CRS/HIPEC and a lower risk of death compared to patients diagnosed in non-HIPEC centers and non-teaching hospitals,” Rovers explained.

“Although available, CRS/HIPEC appears to be underutilized in the Netherlands, leading to suboptimal treatment of patients,” Rover commented.

No external funding was reported.

References:

1. Yang XJ, Huang CQ, Suo T, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.Ann Surg Oncol.2011;18(6):1575-1581. doi: 10.1245/s10434-011-1631-5.
2. Rovers K, Simkens G, Vissers P, et al. Survival of patients with colorectal peritoneal metastases is affected by treatment disparities among hospitals of diagnosis: a nationwide population-based study. Abstract presented at: 19th European Cancer Congress; January 27-30, 2017; Amsterdam, Netherlands.