Peritoneal metastases (PM) from colorectal cancer remain a challenging clinical entity. Approximately 10% of patients with metastatic colorectal cancer will develop PM and in approximately half of this population the peritoneal cavity is the only location of metastasis (1). Risk factors for development of PM include tumor perforation, T4 disease, and positive nodal status (2,3). Untreated, PM is associated with dismal mean overall survival (OS) of approximately 3-6 months (4). While treatment with modern systemic multi-chemotherapeutic regimens increases OS to 10-15 months, this survival remains 30-50% lower than in patients with stage IV colorectal cancer without PM (5).

Given poor response to medical therapy, aggressive surgical techniques were developed to eliminate visible peritoneal tumor, followed by peritoneal directed chemotherapy (6). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become an accepted treatment for select patients with colorectal cancer with peritoneal metastasis. Outcomes correlate with the extent of disease, which can be measured via PM-specific scoring systems. The peritoneal cancer index (PCI) calculates the extent of PM burden using a scale of 0-39 (Figure 1). It considers both the location of metastatic deposits across thirteen predefined regions and the size of metastatic lesions, which is a sub-score called the lesion size score (LS) (7). While there is no consensus on absolute thresholds, a PCI greater than 20 is considered a relative contraindication to CRS/HIPEC (8). Higher PCI is also associated with incomplete resection (9). An alternative scoring system, the Peritoneal Surface Disease Severity Score (PSDSS), incorporates the PCI along with histopathology and clinical symptoms (Table 1). The goal of surgery is complete cytoreduction with no residual visible tumor (CC0), although cytoreduction down to no deposit >2.5 mm (CC1) may offer benefit to patients as well (10). Incomplete cytoreduction (CC2/CC3) does not confer benefit and, if predicted, surgical intervention is not recommended.

In appropriately selected patients, CRS/HIPEC has demonstrated a survival benefit (11). If R1 resection can be achieved then 5-year survival approaches 50% with 48-month median survival (11). Our current approach is concordant with the Chicago consensus on peritoneal surface malignancies: management of colorectal metastases (9). In patients with predicted complete cytoreduction and an absence of high-risk features, CRS/HIPEC is performed using the closed technique with mitomycin C (Mutamycin, Accord Biopharma Inc., Durham, NC) with initial dose of 30 mg for 60 minutes, followed by re-dosing with 10 mg for an additional 40 minutes at a target temperature of 42 °C.

Complete cytoreduction is generally understood to improve outcomes, but the benefit of HIPEC has been questioned. HIPEC is associated with increased morbidity in some studies, but this finding is not universal. Randomized control trials have generated inconsistent conclusions regarding the long-term effect of HIPEC. This review will identify and analyze the key published and ongoing clinical trials regarding CRS/HIPEC for colorectal PM (Table 2).