The relationship of increasing radiotherapy dose to reduced distant metastases and mortality in men with prostate cancer

BACKGROUND. The association of increasing radiotherapy (RT) dose with reduced biochemical failure (BF) is accepted widely. However, there is little direct evidence that dose escalation has an impact on distant metastasis (DM) or overall mortality (OM). These associations were examined in the current study. METHODS. The outcome of 835 patients who were treated at the Fox Chase Cancer Center (Philadelphia, PA) between 1989 and 1997 using 3-dimensional, conformal RT alone (median dose, 74 Gray [Gy]) was analyzed. Stepwise multivariate Cox proportional hazards regression analyses (MVAs) were performed with RT dose included as a covariate along with log-transformed initial pretreatment PSA level, Gleason score, palpation T status, age, and year of treatment (YOT), where indicated. To minimize the effect of YOT, an analysis was performed on a subgroup of 363 patients who were treated prior to 1994. RESULTS. With a median follow-up of 64 months, there were 220 PSA failures, 44 distant metastases, and 162 deaths. In MVA, FIT dose (as a continuous variable) was a significant predictor for BF, DM, and OM. When YOT was included as a covariate, it was related strongly to all endpoints, and the correlations of RT dose with DM and OM were lost. When the effect of YOT was minimized by limiting the MVA to patients who were treated prior to 1994, RT dose again emerged as a significant predictor of DM. CONCLUSIONS. Escalation of RT dose reduced the rates of BF, DM, and OM significantly in patients with prostate cancer. The inclusion of YOT had a pronounced effect on these correlations that may confound interpretation.