BACKGROUND: Tumor markers are used routinely for surveillance in patients treated for colorectal cancer (CRC). However, the prognostic implications of elevated preoperative tumor markers in patients treated for CRC and peritoneal metastases (PM) has not been well defined. The utility of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and cancer antigen 125 (CA125) to predict outcome for these patients is reported. METHODS: Clinical and histologic features plus preoperative tumor markers were recorded within 1 week prior to CRS. Impact on overall survival of these factors was analyzed by univariate and multivariate analysis. RESULTS: Two hundred and four patients were in our database and 140 patients (75.3 %) had at least a single elevated preoperative tumor marker. In an analysis of clinical and histologic parameters preoperatively, a poorly differentiated tumor, signet ring morphology, a peritoneal cancer index (PCI) of ≥16 and an incomplete cytoreduction had a negative impact on median survival. In a multivariate analysis of clinical and histologic features together with tumor markers, an elevated CA19-9 and CA125 was independently associated with reduced overall survival (HR 2.7, p <
0.0002 and HR 2.2, p = 0.005), respectively. Quantitative assessment of CEA (HR 0.5, p = 0.0094) and CA19-9 (HR 4.9, p <
0.002) greater than x10 ULN showed reduced survival. CONCLUSION: Preoperative assessment of symptoms and histopathology, PCI and a complete CRS combined with tumor markers CEA, CA19-9 and CA125 are independent prognostic indicators for selection by the multidisciplinary team of CRC PM patients for CRS and HIPEC. All three tumor markers are needed for a meaningful assessment.