Dose-response for biochemical control among high-risk prostate cancer patients after external beam radiotherapy

The literature on dose-response characteristics of high-risk prostate cancer has been scarce in this era, when these patients are treated with hormone therapy along with radiotherapy. In this study, we estimated the dose-response of prostate-specific antigen (PSA) control probability in high-risk prostate cancer patients treated with radiotherapy alone.

The data set contains information on 363 high-risk prostate cancer patients who were treated with external beam radiotherapy without hormonal treatment between February 1987 and September 1998. These patients have one or more of the following adverse prognostic features: digital rectal examination stage > or =cT3, PSA >20 ng/mL, and biopsy Gleason score > or =8. These patients had biopsy-proven adenocarcinoma of prostate and were staged according to the 1992 AJCC staging system that was based on digital rectal examination. The logistic model was fitted to the data at various time points after treatment, and the dose-response parameters were estimated.

The dose required to have 50% tumor control, TCD50 (95% confidence interval), for high-risk patients is 75.5 (range: 70.7-80.2) Gy. The gamma 50 (95% confidence interval) is 1.7 (range: 0.7-2.7) around 75.5 Gy. Recursive partitioning analysis based on the null Martingale residuals identifies two subgroups within the high-risk group. The TCD50 estimates of the two subgroups (PSA < or = vs. >20 ng/mL) differ by 15 Gy at 5 years. There is a dose response in both subgroups.

We recognize that this study has the usual limitations of a retrospective study that includes treatment policy change that spanned a long time frame. However, our data strongly suggest a benefit of dose escalation for all the patients in the entire high-risk group. There is a steep dose response in PSA control probability around a modern dose of 78 Gy. A 5-Gy dose increase beyond 78 Gy may improve PSA control by about 10%.