Prostate specific antigen doubling time and disease relapse after radiotherapy for prostate cancer

BACKGROUND: Serum prostate specific antigen (PSA) correlates with prostate tumor volume. Therefore, PSA-doubling time (PSA-DT) in patients with a rising PSA profile after radiotherapy should be predictive of the time to clinical disease relapse. The purpose of this study was to characterize the relationship between PSA-DT and the time to disease relapse after the onset of a rising PSA (PSA-TTR) in 427 men treated in the PSA-era with high dose radiotherapy for Stages T1-4 adenocarcinoma of the prostate. METHOD: There were 119 patients with a rising PSA profile after radiotherapy, and of these, there was sufficient information to calculate PSA-DT using nonlinear least squares regression in 100. There were 44 patients in this cohort who had documented disease relapse. The median patient follow-up was 38 months. RESULTS: The average PSA-DT was 13.5 plus or minus 11.6 mo (+/- standard deviation). PSA-DT values correlated with tumor grade, pretreatment PSA, and stage. PSA-DT was also strongly related to the outcome measures of local relapse, distant metastases, and any disease relapse. The shorter the PSA-DT, the greater the risk of disease relapse. The average PSA-TTR was 10.1 plus or minus 8.2. The only prognostic factor that correlated with PSA-TTR was tumor grade. A linear regression analysis of normalized PSA-DT and PSA-TTR revealed a significant correlation in which a PSA-DT of 11 months predicted for disease relapse 24 months later. Because several factors including physician and patient preferences could alter this relationship, a comparison was made between the actuarial PSA rise time for patients treated in the PSA-era and actuarial clinical disease relapse using a cohort of similarly treated men from the pre-PSA-era (n = 798). The results showed the lead time to be over 40 months in the majority of patients and that this lead time was much shorter in those with high grade tumors. CONCLUSIONS: PSA-DT is a strong prognostic factor for patients with biochemical evidence of failure after radiotherapy. A short PSA-DT predicts for more rapid progression to symptoms. The timing of the progression from a rising PSA to clinical disease relapse is probably longer than expected and is estimated to be 40 months on average.