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Factors Associated with Survival Following Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Colorectal Cancer
Sean Dineen*1, Kristen Robinson2, Ching-Wei Tzeng1, Karen Beaty2, Paul Mansfield2, Richard Royal2, Keith Fournier2
1Surgical Oncology, University of Kentucky, Lexington, KY; 2MD Anderson Cancer Center, Houston, TX
Introduction: Patients with colorectal cancer and peritoneal carcinomatosis (CRC/PC) have a worse prognosis compared to patients with metastatic CRC to other organ sites, such as liver and lung. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) has been shown to improve survival for select patients with CRC/PC, but carries a high morbidity rate. This study sought to determine factors associated with survival following CRS/HIPEC.
Methods: Patients with CRC/PC evaluated in a peritoneal surface malignancy clinic between 2008 and 2014 were identified. Patients with appendiceal cancers and non-CRC were excluded. Clinicopathologic data were extracted from chart review, including peritoneal carcinomatosis index (PCI) and completeness of cytoreduction score. Factors associated with survival were assessed using univariate and multivariate analysis. 30-day complication rates were determined using the Clavien-Dindo classification.
Results: 52 patients underwent operation with intent for CRS/HIPEC. 43 patients (82.7%) underwent complete cytoreduction (CCR 0/1). There were no significant differences in demographics between the groups. Median disease specific survival (DSS) was 55.1 months in the patients undergoing complete cytoreduction, compared to 12.8 months in patients who underwent incomplete cytoreduction (p < 0.05). Disease burden was a significant predictor of survival, as patients with a PCI score ≤6 demonstrated a significantly longer DSS compared to those with higher scores (p < 0.01). In patients who received a complete cytoreduction, poorly differentiated tumors demonstrated worse DSS (55 months vs 13 months, p < 0.0001). In 37 patients in whom KRAS mutation status was known, there was no significant survival difference based on KRAS status. In patients with CCR 0/1 resection, postoperative complications occurred in 73.2% of patients; with 29.2% of patients experiencing grade 3-4 complications (no postoperative deaths). Experiencing a postoperative complication was associated with decreased survival (33 months vs. median DSS not reached, p<0.05). On multivariate analysis of patients who received CCR 0/1 resection, poorly differentiated histology was associated with decreased DSS (HR 9.5, CI 2.1 - 44.2, p < 0.01).
Conclusion: For patients with CRC/PC who qualify for CRS/HIPEC, intention for complete cytoreduction is essential for maximal oncologic benefit. Patients with lower volume of disease and less aggressive tumor grade also fare better in DSS. Given the high rate of complications and their negative survival impact, patient selection should be based on PCI, tumor grade, and performance status.
 A. Following CRS/HIPEC, patients without 30-day complications demonstrated superior DSS compared to those with any complication (p < 0.05).
B. In patients undergoing a complete cytoreduction, those with poorly differentiated tumors demonstrated significantly worse outcomes compared to those with less aggressive histology (p < 0.001).
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