Investigation of bladder dose and volume factors influencing late urinary toxicity after external beam radiotherapy for prostate cancer

Background: We sought to identify the bladder dose-volume factors associated with an increased risk of late urinary toxicity among prostate cancer patients treated with radiotherapy. Methods and Materials: This retrospective analysis included data from 128 prostate cancer patients treated on protocol with 2 Gy/fraction to 46 Gy followed by a boost to 78 Gy. The endpoint for this analysis was Grade 1 or greater late genitourinary (GU) toxicity occurring within two years of treatment. The Lyman-Kutcher-Burman, mean dose, threshold dose, and hottest volume models were fitted to the toxicity data using the maximum likelihood method. Results: Model fits based on dose-volume histograms tended to fit the toxicity data better than models based on dose-wall histograms. The hottest volume (hotspot) model was found to be the best-fitting model investigated. The best fit was for the hottest 2.9% of bladder (95% CI, 1.1-6.8%). This model has an area under the receiver operating characteristic curve of 0.74. The hotspot model separated the patients into clinically meaningful subgroups with similar to 25% of the patients who received < 78 Gy to the hottest 2.9% of bladder had GU toxicity at eight years compared with similar to 50% when the dose was >= 78 Gy (p = 0.002). Conclusion: This provides the first evidence supporting that bladder "hotspots" are related to GU toxicity within two years after external beam radiotherapy for prostate cancer. Confirming data are needed from other investigators. Particular attention should be given to hotspots higher than 78 Gy in bladder in radiation treatment planning. (c) 2007 Elsevier Inc.