Review
Cytoreduction and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) in colorectal cancer: Evidence-based review of patient selection and treatment algorithms

https://doi.org/10.1016/j.ejso.2016.09.012Get rights and content

Abstract

Cytoreduction and heated intraperitoneal chemotherapy (CS/HIPEC) is increasingly utilized as a treatment strategy for patients with peritoneal metastases from various primary tumor sites. For this heterogenous procedure, related to patient characteristics, patient selection, and the extent of surgical completeness of cytoreduction, high level evidence (ex: multiple randomized controlled trials) is not available to support efficacy. This review of the available literature supporting application of the procedure, focusing on colorectal cancer, provides a summary of current evidence for patient selection and treatment algorithms based on patient presentation.

Introduction

Peritoneal metastases (PM) occur commonly in colorectal cancer, with up to 10% of patients presenting synchronously with the primary tumor, and up to 25% presenting metachronously.1, 2 Treatment options have changed over the last two decades related to the paradigm shift of PM being viewed as a locoregional rather than a metastatic disease process. Accumulating evidence, stemming from large cohort studies and a randomized controlled trial have suggested that in select patients, cytoreductive surgery followed by heated intraperitoneal chemotherapy (CS/HIPEC) may provide improved overall and disease-free survival as compared to that conferred by systemic chemotherapy alone.3, 4, 5 Outcomes of this procedure are strongly correlated to scales specific to PM, including the Peritoneal Carcinomatosis Index (PCI, a number between 0 and 39) defining extent and location of PM and recommended to be less than 20 for best outcome, and the Completeness of Cytoreduction Score (CCR), recommended to be complete (CC-0) or minimal/microscopic disease remaining of <0.25 cm (CC-1).6

Supporting the trend towards increasing application of CS/HIPEC is the ability to safely perform this procedure with acceptable morbidity and mortality rates, in keeping with other major surgical oncology procedures.7

This review is written from the perspective that CS/HIPEC is beneficial for the treatment of patients with colorectal cancer and PM, and can be offered with acceptably low morbidity and mortality, in the absence of multiple randomized controlled trial data. The aims of this manuscript include an opportunity to comprehensively review evidence for patient selection for CS/HIPEC, including patient factors, tumor factors, and sequence of multimodal therapy. In addition, treatment algorithms based on the clinical presentation of patients are provided, guided by the evidence-based review.

Section snippets

Functional status

The Eastern Cooperative Oncology Group (ECOG) performance score quantifies the impact of disease on a patient's daily living activities. In a 2007 consensus statement from representatives of the major peritoneal surface malignancy centers from around the world, ECOG status ≤2 is one of the criteria for patient selection.8 Many centers have adopted this as a minimum and its importance has continued to be borne out in multiple analyses.9, 10, 11 The largest report to date is a retrospective

Work-up and imaging

Separate from patient characteristics, factors related to location and extent of PM, and other factors associated with tumor biology, are considered equally as important when deciding candidacy for CS/HIPEC.

Tumor perforation, direct extension (T4)

The liberation of tumor cells into the peritoneum as a result of either direct extension of a primary tumor through the serosa or via tumor perforation is problematic. By current TNM staging, T4a colon cancers penetrate to the surface of the visceral peritoneum and T4b tumors directly invade or are adherent to surrounding organs or structures. When evaluating T4 patients for the risk of peritoneal spread, a retrospective study of 200 patients found that synchronous and metachronous disease

Conflict of interest

The authors do not have any conflict of interest to disclose.

Acknowledgements

The authors would like to thank Theresa Zimmerman for her assistance in creating the figures for this manuscript.

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