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We applied an established prognostic model to high-risk prostate cancer (HRPC) patients treated with radiotherapy (RT) and evaluated the influence of clinical and treatment variables on treatment outcomes.In total, 1075 HRPC patients undergoing definitive radiotherapy (RT) between 1995 and 2010 were retrospectively reviewed. Median follow-up was 62.3 months. Patients received either dose-escalated external beam radiotherapy (n=628, EBRT) or combined-modality radiotherapy (n=447, pelvic RT and low-dose rate brachytherapy boost, CMRT). 82.9% received androgen-deprivation therapy (ADT). A prognostic model stratified patients into predefined groups (good, intermediate, and poor). Kaplan-Meier methods and Cox proportional hazards regressions assessed biochemical failure (BF), distant metastasis (DM), prostate cancer-specific mortality (PCSM) and overall mortality (OM). C-indices analyzed predictive value.The model was prognostic; C-indices for BF, DM, PCSM and OM were: 0.62, 0.64, 0.61, and 0.57. On multivariate analysis, CMRT and longer ADT (≥24 mo) were associated with improved BF, DM, and PCSM. Gleason score (GS) 9-10 was the strongest predictor of PCSM. C-indices for BF, DM, PCSM, and OM using a 4-compartment model incorporating GS 9-10 were: 0.62, 0.65, 0.68, and 0.56. In poor-prognosis patients (GS 8-10+additional risk factors), CMRT+LTADT (12 mo) had 10-year PCSM (3.7%±3.6%), comparing favorably to 25.8%±9.2% with EBRT+LTADT.The model applies to high-risk RT patients; GS 9-10 remains a powerful predictor of PCSM. Comparing similar prognosis patients, CMRT is associated with improved disease-specific outcomes relative to EBRT. In poor-prognosis patients, CMRT+LTADT yields superior 10-year PCSM, potentially improving RT treatment personalization for those with HRPC.

Objectives The aim of this study was to report treatment outcomes in patients with very high-risk prostate cancer (VHRPC) treated with dose-escalated radiotherapy. Methods We conducted a retrospective multi-institutional review on patients with VHRPC (those with at least 2 high-risk factors of prostate-specific antigen >20 ng/mL, Gleason score 8 to 10, or clinical T3 to T4 stage), treated with either dose-escalated external-beam radiotherapy (EBRT) or combined-modality radiotherapy (CMRT) consisting of pelvic irradiation and permanent interstitial brachytherapy. Results A total of 238 patients with VHRPC were identified. Of them, 69% of patients received EBRT and 31% received CMRT; 88% received androgen-deprivation therapy (ADT), 56% for ≥24 months (long-term ADT). The majority (69%) of patients were above 65 years old and were less likely to receive CMRT than younger patients (25% vs. 43%, P=0.006), although they did not differ from younger patients in tumor characteristics. Median follow-up was 61 months (interquartile range, 38 to 93 mo). Biochemical progression-free survival (BPFS), distant metastasis-free survival (DMFS), and cancer-specific survival (CSS) for all patients at 8 years were (±SE): 50.6%±4.7%, 68.5%±4.3%, 78.7%±3.8%, respectively, and were similar for patients 65 years and below versus above 65 years old (BPFS: HR=0.88, P=0.56; DMFS: HR=0.79, P=0.40; CSS HR=0.99, P=0.99). After adjustment for patient, tumor, and treatment-related covariates on multivariate analysis, CMRT was associated with improved BPFS (HR=0.44, P=0.012) with trends for DMFS (HR=0.52, P=0.10) and CSS (HR=0.55, P=0.21), whereas long-term ADT was independently associated with improved BPFS (HR=0.40, P=0.019), CSS (HR=0.20, P=0.002), and PCSM (HR=0.25, P=0.004). Conclusions Dose-escalated EBRT or CMRT with long-term ADT resulted in favorable clinical outcomes for patients with VHRPC.

OBJECTIVES To assess the performance of the Cancer of the Prostate Risk Assessment (CAPRA) prognostic tool for freedom-from-metastases (FFM) and cause-specific survival (CSS) in patients with localized prostate cancer treated with definitive external beam radiotherapy (EBRT), and to determine whether the performance of CAPRA is influenced by androgen deprivation therapy (ADT) use or the presence of Gleason pattern 5 (GP-5). MATERIALS AND METHODS A total of 612 patients from a prospective database of 718 patients treated with dose-escalated EBRT from 1998 to 2008 who met CAPRA scoring criteria were included in the study. Performance of CAPRA and association of CAPRA score, GP-5 and short-term or long-term ADT use (STAD or LTAD, respectively) with FFM and CSS were evaluated using Cox models. The impact of ADT use on accuracy of the CAPRA-based CaPSURE model for CSS was assessed. The discriminatory ability of the CAPRA model and modified models incorporating GP-5 and ADT use were compared using the C-index. RESULTS Increasing CAPRA score correlated with worse FFM and CSS, and was prognostic for FFM and CSS for the overall cohort. CAPRA showed poorer discrimination for FFM and CSS in patients treated with EBRT+LTAD than those who received EBRT alone or EBRT+STAD. The addition of GP-5 and ADT use to CAPRA score increased the predictive accuracy of the CAPRA model for both FFM (C-index 0.809 vs. 0.779, P

The objective of the study was to investigate prostate-specific antigen (PSA) nadir (nPSA) and time to nPSA (TnPSA) as prognostic variables for outcomes after definitive high-dose (75 Gy) external beam radiation therapy (RT) without androgen deprivation therapy while correcting for immortal-time bias.nPSA and TnPSA were available for 410 patients. nPSA and TnPSA's impact on freedom from biochemical failure, freedom from metastasis, and prostate cancer-specific survival was assessed on univariate and multivariate analysis using Kaplan-Meier and Cox proportional hazards regression. Outcomes were also evaluated relative to the time since achieving nPSA and not relative to the time of RT, given the intrinsic time bias in TnPSA.Median nPSA was 0.7 ng/mL (interquartile range: 0.4 to 1.1), with a median TnPSA of 25.0 months (IQR: 15.0 to 40.0). On univariate analysis both nPSA and TnPSA were predictive of all endpoints: freedom from biochemical failure, freedom from metastasis, and prostate cancer-specific survival, as categorical (all P0.0001) and continuous (all P0.01) variables. However, after adjusting for immortal-time bias the benefit of long TnPSA was mostly lost. On Cox proportional hazards, a TnPSA12 months did have worse prognosis for biochemical failure and distant metastasis as compared with longer TnPSA, but for those who achieved nadir12 months from the time of RT the TnPSA was no longer prognostic.For dose-escalated RT a lower nPSA is prognostic, but the benefit of a long TnPSA is largely an immortal-time bias and that a longer TnPSA is not in and of itself a significant favorable factor except as compared with those with the shortest TnPSA of12 months.

To describe 5- and 10-year rates of metastasis-free survival (MFS) stratified by Gleason score (GS) and prostate-specific antigen doubling time (PSADT) for patients receiving salvage radiation therapy (SRT) after biochemical recurrence (BR) postradical prostatectomy (RP).A total of 236 patients who underwent SRT without receiving concomitant androgen deprivation therapy at a single institution after BR post-RP were retrospectively reviewed. The Kaplan-Meier methods and log-rank analysis were used to determine the MFS rates.Median follow-up post-SRT was 7.1 years. As of last follow-up, 59 men (25%) had developed metastasis. On univariate analysis, both GS and PSADT predicted MFS (P0.001). Five- and 10-year rates of MFS were calculated for patients with GS 2 to 6, 7, and 8 to 10 and for patients with PSADT 3, 3 to 9, 9 to 15, and15 months, who received no additional salvage therapy until the development of metastases. The 5- and 10-year MFS for GS 8 to 10 were 62% and 50%, respectively, compared with 94% at both 5 and 10 years for GS 2 to 6. The 5- and 10-year MFS for PSADT 3 months were 70% and 61%, respectively, compared with 100% and 90% at 5 and 10 years, respectively, for PSADT15 months.After BR post-RP, SRT results in low 5- and 10-year rates of metastasis after initial BR. Importantly, a substantial proportion of patients with high-risk disease (GS 8 to 10 or PSADT 3 mo) are free from metastasis at these same time points. Therefore, SRT should not be withheld from patients based solely on the presence of adverse disease risk factors.