Preoperative Versus Postoperative Radiotherapy for Rectal Cancer - Decision Analysis and Outcome Prediction Using a Modified Markov Model
Andreas M. Kaiser*, Daniel Klaristenfeld, Robert W. Beart
USC Department of Colorectal Surgery, University of Southern California, Los Angeles, CA
Background Data: Treatment for resectable rectal cancer has evolved into a multi-modality approach. Reduction of local recurrences has been achieved by radiotherapy, but also by improved surgical technique (total mesorectal excision). Radiotherapy has been associated with significant adverse effects and cannot exceed local dose limits. We hypothesized that reserving radiotherapy as treatment tool for high risk tumors and local recurrences improves the overall outcome of the group.Objective: To simulate the benefit of preoperative versus selective postoperative radiotherapy in a theoretical Markov state-transition model with local recurrence and overall survival being the primary endpoints. Probabilities of life-time events were calculated based on a systematic literature review.Data Sources: Computerized literature search of MEDLINE for publications in English between 1996-2006, supplemented by manual review of the retrieved reference lists. Medical subject headings used were rectal cancer, radiotherapy, surgery, RCT, randomized, clinical trial, mortality, adverse effects.
Results: With baseline assumptions entered into the model, selective postoperative radiotherapy evolved as preferred strategy with cure rates of 65.6% vs. 63.7% for selective and neoadjuvant radiotherapy, respectively, and a decrease of radiation exposure to 42.9% of the cohort. The system was sensitive to (1) the fraction of stage I cancers included in the cohort, (2) the difference between local recurrence rates for neoadjuvant, adjuvant radiotherapy, or surgery-only approach, and (3) the compliance with the postoperative radiotherapy. After adjuvant radiotherapy, the local recurrrence threshold values to reverse the impact of compliance were 6.3%, 8.5%, and 18.3% if the surgery-only recurrence was set to 10%, 13%, and 27%, respectively.
Conclusion: In patients with resectable rectal cancer, routine preoperative radiotherapy does not improve cancer-specific survival of the cohort compared with modern surgery alone or with selective postoperative radiation of high-risk individuals and local recurrences.
