Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era

Abstract Purpose: To study the impact of biochemical failure on overall survival rates during the first 10 years after definitive radiotherapy for localized prostate cancer. Methods and Materials: The analysis was performed on 936 cases treated at a single institution between 1986 and 1998 with definitive radiotherapy. The median age of treatment was 69 years (range: 46–86 years). Pretreatment PSA levels (iPSA) and biopsy Gleason scores (bGS) were available for all cases. The clinical stage was T1/T2A in 63%, T2B/C in 27%, and T3 in 10%. The median iPSA level was 9.6 ng/mL (range: 0.4–692.9 ng/mL). The iPSA was ≤10 in 53% and >10 in 47%. The bGS was ≤6 in 59% and ≥7 in 41%. Androgen deprivation (AD) was administered in 181 cases (19%) for a median duration of 6 months (range: 1–6 months). All 181 cases received AD neoadjuvantly, i.e., before and/or during the radiotherapy. No AD was delivered after the completion of radiation. The median radiation dose was 70 Gy (range: 60–78 Gy). The radiotherapy technique was conformal in 376 (40%) cases. The American Society of Therapeutic Radiology and Oncology definition of biochemical failure (bF) was used; 316 cases (34%) had failed biochemically, and 620 (66%) had not. The end point was overall survival (OS). Time to death was determined from the time of definitive radiotherapy. The median PSA follow-up was 58 months. The median follow-up times for bF vs. no-bF cases were 77 and 49 months, respectively. A multivariate analysis of factors affecting OS using the proportional hazards model was performed for all cases using the following variables: age (>65 vs. ≤65 years), race (African-American vs. Caucasian), clinical T stage (T1–2A vs. T2B–C vs. T3), bGS (≤6 vs. 7 vs. ≥8), iPSA (continuous variable), use of AD (yes vs. no), year of therapy (continuous variable), radiation dose (continuous variable), radiation technique (conformal vs. standard), and biochemical failure (yes vs. no). Results: The 5-year OS rate for the entire group was 89% (95% CI [confidence interval]: 86–91%). The 5-year OS rates for bF vs. no-bF patients were 89% (95% CI: 86–93%) and 89% (95% CI: 86–92%), respectively. The 10-year OS rate for the entire group was 68% (95% CI: 61–75%). The 10-year OS rates for bF vs. no-bF patients were 65% (95% CI: 56–74%) and 77% (95% CI: 69–84%), respectively. The difference between bF and no bF was not significant in predicting overall survival in univariate analysis (log-rank test, p = 0.68). On multivariate analysis, bGS ( p p = 0.003), radiation dose ( p = 0.017), year of therapy ( p = 0.031), and age ( p = 0.020) were independent predictors of death. iPSA levels ( p = 0.33), race ( p = 0.80), radiation technique ( p = 0.16), and use of AD ( p = 0.09) were not predictive of OS. Biochemical failure ( p = 0.052) showed only a trend for independently predicting overall survival on multivariate analysis. Conclusion: Biochemical failure after definitive radiotherapy for localized prostate cancer is not associated with increased mortality within the first 10 years after initial therapy, although a trend toward worse outcome was observed at 10 years. Longer follow-up from initial therapy is needed to fully understand the impact of biochemical failure on overall survival. With longer follow-up, significant differences might be observed at 15 or 20 years after therapy.