Objective: The aim of this study was to determine in what manner aggressive external beam radiotherapy (EBRT), chemotherapy, surgical resection, and intraoperative radiotherapy (IORT) impact relapse and survival in patients with locally unresectable primary colorectal cancer. Summary Background Data: Patients with colorectal cancer fixed to critical structures (eg, IVC and pelvic sidewall) are considered locally "unresectable" for cure and treated with palliative therapy. Methods: One hundred forty-six patients (65% males) with locally unresectable colon (40) and rectal (106) cancer were treated with EBRT, chemotherapy, surgical resection, and IORT. Final surgical margins were close, but negative in 100 patients (68%), microscopically positive in 28 (19%), and grossly positive in 18 (13%). Kaplan-Meier method was used to visualize survival and relapse curves; groups were compared using the log-rank test. Results: Median overall survival was 3.7 years. Median overall survival (years) favored patients with age <58 (7.6 vs. 3.6; P = 0.0012), those receiving adjuvant chemotherapy (9.4 versus 3.9; P = 0.0019), and those with negative or microscopic margins (6.3 vs. 1.9; P = 0.0006). There were no perioperative deaths. Fifteen complications occurred in 12 patients (8%) within 30 days of surgery/IORT. One hundred nineteen long-term complications occurred in 77 patients (53%), most commonly peripheral neuropathy (19%), bowel obstruction (14%), and ureteral obstruction (12%). Conclusions: Aggressive multimodality therapy for locally unresectable primary colorectal cancer results in excellent local disease control and a 5-year disease-free and overall survival rate of 43% and 52% respectively with no operative mortality and acceptable perioperative morbidities.
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