Adding Androgen Deprivation Therapy Research Articles

Using the Cell-Cycle Risk Score to Predict the Benefit of Androgen-Deprivation Therapy Added to Radiation Therapy in Patients With Newly Diagnosed Prostate Cancer.

Guidelines recommend adding androgen-deprivation therapy (ADT) to radiation therapy (RT) in certain patients with localized prostate cancer. Individualized genomic testing may improve the prognostic accuracy of risk assessments. Herein, we describe a mathematical model of the benefit of adding ADT to RT as a function of the personalized clinical cell-cycle risk (CCR) score to inform 10-year metastasis risk. A model of absolute risk reduction (ARR) was built using a retrospective cohort of men tested with Prolaris who received RT alone (N = 467). The relative benefit of ADT added to RT to reduce distant metastasis was estimated at 41% on the basis of a meta-analysis of randomized trials. The ARR and number needed to treat (NNT) were computationally derived in patients clinically tested with Prolaris between January 1, 2020, and October 31, 2022 (N = 56,485). Risks were predicted using a cause-specific Cox proportional hazards model with CCR score predicting time to metastasis. A CCR score of 2.112 represents the validated multimodal treatment (MMT) threshold. The ARR from ADT increased from almost zero at low CCR scores to 17.1% at CCR = 3.690 with the corresponding NNT = 6, indicating that adding ADT to RT would prevent metastasis within 10 years for one of every six treated individuals. In the clinical cohort, the average ARR was 0.86% in individuals under the MMT threshold (NNT = 116). The average ARR was 8.19% in individuals above the MMT threshold (NNT = 12). Broad ranges of ADT benefit were observed within National Comprehensive Cancer Network risk categories. The precise and personalized risk estimate of metastasis provided by the CCR score can help inform patients and physicians when considering treatment intensification.

MP48-13 THE KEY ROLE OF CONCOMITANT ANDROGEN-DEPRIVATION THERAPY ON THE EFFICACY OF IMAGING GUIDED TREATMENTS IN MEN WITH BIOCHEMICAL RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY AND POSITIVE 68GA-PSMA PET/CT SCAN

MP48-13 THE KEY ROLE OF CONCOMITANT ANDROGEN-DEPRIVATION THERAPY ON THE EFFICACY OF IMAGING GUIDED TREATMENTS IN MEN WITH BIOCHEMICAL RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY AND POSITIVE 68GA-PSMA PET/CT SCAN

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

PurposeThe purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. Methods and MaterialsOverall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models. ResultsAfter propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality. ConclusionsA risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

Androgen deprivation therapy in men with node-positive prostate cancer treated with postoperative radiotherapy

BackgroundIn men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy. ObjectiveTo determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy. MethodsWe analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years. ResultsPatients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely. ConclusionsWe can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.

Does Androgen Deprivation Therapy Improve Ten-Year Clinical Outcomes of Intermediate Risk Prostate Cancer Patients Treated with Brachytherapy with or without External Beam Radiotherapy?

To determine whether adding androgen deprivation therapy (ADT) improves the biochemical control or survival of patients with intermediate risk prostate cancer undergoing brachytherapy with or without external beam radiotherapy (EBRT).

The Effect of Androgen Deprivation Therapy on Prostate Cancer-Specific Mortality in Patients With High-Risk Prostate Cancer Treated with I-125 Brachytherapy as the Sole Radiation Therapeutic Modality

Multiple trials have demonstrated the value of adding androgen deprivation therapy (ADT) to external beam radiotherapy for high-risk prostate cancer (HRCaP) patients. There have been few studies examining the use of ADT in HRCaP treated with I-125 (LDR) brachytherapy as monotherapy. With more clinical trials showing the importance of brachytherapy as a part of the treatment of HRCaP patients, we felt that a closer look at the effect of ADT on the efficacy of LDR for HRCaP would be helpful. An IRB-approved inception cohort study of LDR patients at a single institution was used to assess the effect of ADT on prostate cancer-specific mortality (PCSM) after LDR alone for HRCaP patients. The cumulative incidence method was used calculate the rates of PSCM, and competing risk regression was used to assess the impact of ADT on PCSM. Death from other causes was treated as a competing event. There were 615 patients total (374 had LDR + ADT; 241 had LDR alone). The median f/u was 48.9 months. For those patients who received ADT, the median duration was 6 months. There were 248 who qualified as HRCaP because of 2 intermediate-risk factors and 267 with at least one high-risk factor. Table 1 reports the 5- and 10-year rates of PCSM by ADT use. ADT use was not significant for PCSM (p = 0.42; HR 1.97, 95% CI = 0.38-10.2). The use of ADT does not affect PCSM in HRCaP patients treated with LDR.Abstract 2535TimeTreatmentLDR alone (n = 241)LDR + ADT (n = 374)5 YearsNumber at Risk48163Cumulative Incidence (%)1.24.295% CI (%)0.0-3.51.5-6.910 yearsNumber at Risk1426Cumulative Incidence (%)3.34.295% CI (%)0.0-7.91.5-6.9 Open table in a new tab

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy.

Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. After a median follow-up of 8.4years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

Comorbidity and androgen deprivation therapy use in men undergoing high-dose radiation for unfavorable intermediate- and high-risk prostate cancer.

41 Background: Despite evidence of prolonged survival when adding androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) in men with unfavorable intermediate- and high-risk prostate cancer (PC), some of these men are not receiving ADT. We explored whether comorbidity can explain this discrepancy given the observation that survival may be shortened in men with moderate to severe comorbidity who receive ADT. Methods: Between 10/1997 and 5/2013, 3,348 men with unfavorable intermediate- (2,380 patients; 70.7%) or high-risk (986 patients; 29.3%) PC were treated at the Prostate Cancer Foundation of Chicago using brachytherapy with or without neoadjuvant EBRT and/or ADT, and formed the study cohort. A multivariable logistic regression analysis was used to evaluate whether comorbidity (history of congestive heart failure [CHF] and/or myocardial infarction [MI]) was associated with decreased odds of ADT use in men with unfavorable intermediate- or high-risk PC, adjusting for age, PC prognostic factors, year of brachytherapy, and EBRT use. Results: Among patients with unfavorable-intermediate-risk PC, 31.2% received ADT, and in the high-risk cohort, 38.3%, 12.3%, and 4.8% received up to 6, &gt;6-18, or &gt;18 months of ADT respectively. In men with high-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use of any duration (all p values &gt;0.71), but the odds of ADT use decreased over time (adjusted odds ratio (AOR) 0.87, 95% confidence interval (CI) [0.83,0.91], p&lt;0.0001; AOR 0.93, 95% CI [0.87,0.99], p=0.023; AOR 0.92, 95% CI [0.83,1.01], p=0.089, for up to 6, &gt;6-18, and &gt;18 months respectively, with no ADT as the reference). Similarly, in men with unfavorable intermediate-risk PC, a history of CHF/MI was not significantly associated with decreased odds of ADT use (p=0.49), whereas the odds of ADT use decreased significantly over time (AOR 0.96, 95% CI [0.94,0.98], p=0.0009). Conclusions: While ADT use has decreased over time in men with unfavorable intermediate- and high-risk PC undergoing brachytherapy with or without supplemental EBRT, this decrease does not appear to be occurring in men with a history of CHF or MI.

Role of Androgen Deprivation Therapy in Early Salvage Radiation Among Patients With Prostate-Specific Antigen Level of 0.5 or Less

BackgroundThe Radiation Therapy Oncology Group 96-01 randomized trial demonstrated the benefit of adding androgen deprivation therapy (ADT) to salvage radiotherapy for an increasing prostate-specific antigen (PSA) after prostatectomy, but it is unknown whether modern patients followed with ultrasensitive PSA and salvaged at a low PSA (ie, ≤ 0.5) also benefit from ADT. Patients and MethodsThe cohort comprised 108 patients who received radical prostatectomy (RP), were followed by ultrasensitive PSA, and received salvage radiotherapy at a PSA of 0.5 or less. Sixty patients had negative margins, and 48 patients had positive margins at RP. Cox multivariable regression analysis was performed to identify factors associated with time to secondary PSA failure and included PSA at salvage, year of treatment, Gleason score, ADT use, margin status, T stage, and PSA doubling time. Occurrence of distant metastases was documented. ResultsMedian follow-up after radiation was 63.09 months. A total of 24 patients had a distant metastasis. In all patients, ADT use was associated with a decreased risk of recurrence (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.25-0.79; P = .006). On subgroup analysis, ADT was associated with a decreased risk of failure among patients with negative margins (HR, 0.27; 95% CI, 0.12-0.61; P = .002), but not among men with positive margins (HR, 0.78; 95% CI, 0.29-2.10; P = .63). ConclusionsEven patients followed with ultrasensitive PSA and salvaged early with a PSA ≤ 0.5 seem to benefit from the addition of ADT to salvage radiation. However, this benefit seemed to be limited to men with negative margins; thus, men with positive margins and PSA ≤ 0.5 may be good candidates for salvage radiation alone.

The impact of dose‐escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms

Randomized trials have demonstrated that escalated-dose external-beam radiotherapy (EDRT) is better than standard-dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen-deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT. From 1989 to 2007, 3215 men consecutively received definitive EDRT with or without ADT. In total, 2012 patients had complete records available for creating the nomogram. The duration of ADT varied for patients who received no RT (n = 1562), ≤6 months of RT (n = 145), from >6 months to <24 months of RT (n = 140), and ≥24 months of RT (n = 165) with a median follow-up of 65.7 months, 66.2 months, 60.1 months, and 63 months, respectively. The model included the following covariates: palpation T-category, biopsy Gleason score, the percentage of tumor cells with a Gleason pattern of 4 or 5, the percentage of tumor tissue, initial pretreatment prostate-specific antigen (PSA) level, ADT duration, and RT dose. Two nomograms, for outcomes with and without ADT, were created from a single competing-risks model. Biochemical failure was defined as a rise in serum PSA of 2 ng/mL over the post-treatment PSA nadir. According to the results from analyzing representative intermediate-risk to high-risk patient parameters, the gains from increasing the RT dose from 70 Gray (Gy) to 80 Gy were far less than the gains from adding ≥3 months of ADT. The nomograms provided unique patient-specific estimates of the effects of various doses and durations of RT and ADT. The results indicated that adding ADT to treatment for intermediate-risk and high-risk prostate cancer is far more beneficial than a modest RT dose escalation.

Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease. In patients with GS 4+3 or T2c disease, the addition of ADT to dose-escalated RT did improve FFF.

Is Androgen Deprivation Therapy Necessary in Intermediate Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

The benefit of adding androgen deprivation therapy (ADT) to dose- escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear, therefore, we assessed the impact of adding ADT to dose- escalated RT on PSA disease-free survival (bDFS). Three groups of men treated with IMRT or 3D conformal RT from 1993-2008 for prostate cancer with doses ranging from 75.6-78 Gy were identified: (1) 327 intermediate-risk patients (NCCN classification) treated with RT alone, (2) 218 intermediate-risk patients treated with RT and <6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis using Gleason Score (GS), T-Stage, and pretreatment PSA was applied to the intermediate-risk patients treated with RT alone to identify prognostic groups based on risk of PSA recurrence (Phoenix definition). All intermediate-risk patients were then stratified by these prognostic subgroups. Intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT and to low-risk patients treated with RT alone. Kaplan-Meier method was used to estimate the 5 year bDFS. Based on recursive partitioning analysis of 5 year bDFS, intermediate-risk patients treated with RT alone were classified into 3 prognostic groups: (1) 188 favorable patients with T1b-T2b GS 6 or T1b-c GS 3+4; (2) 71 marginal patients with T2a-b GS 3+4; and (3) 68 unfavorable patients with T2c or GS 4+3 disease. Associated hazard ratios (HR) for recurrence were 1.0, 2.1, and 4.5, respectively. PSA was not found to be a major contributing factor in this analysis. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (bDFS 74% vs. 94%; HR 0.234; p = .005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (bDFS 94% vs. 95%; p = 0.85), and bDFS for favorable intermediate-risk patients treated with RT alone approached the bDFS for low-risk patients treated with RT alone (98%). In the marginal prognosis subgroup, 5 year bDFS was 91% without ADT and 100% with ADT, p = .07. Patients with favorable intermediate- risk prostate cancer did not benefit from the addition of ADT to dose- escalated RT and their bDFS was nearly as good as patients with low-risk disease. However, in patients with GS 4+3 and higher volume disease, the addition of ADT to dose- escalated RT did improve bDFS. Since randomized trials addressing this issue in the high dose era are lacking, consideration should be given to a personalized approach, taking into account tumor characteristics and patient comorbidities.

Does Hormone Therapy Exacerbate the Adverse Effects of Radiotherapy in Men With Prostate Cancer? A Quality of Life Study

We examined whether short course androgen deprivation therapy as an adjunct to radiotherapy would impact health related quality of life outcomes in patients with localized prostate cancer treated definitively with external beam radiation therapy or permanent brachytherapy. From 1999 to 2003 patients were enrolled in a prospective study at our institution and completed validated health related quality of life surveys at defined pretreatment and posttreatment intervals. A total of 81 men received radiotherapy alone and 67 received radiotherapy plus androgen deprivation therapy. Median androgen deprivation therapy duration was 4 months. Univariate and multivariate analysis was done to compare time to return to baseline in 6 distinct health related quality of life domains. On univariate analysis the radiotherapy plus androgen deprivation therapy group achieved baseline urinary symptoms more rapidly than the radiotherapy group (5 months, p = 0.002). On multivariate analysis time to return to baseline in any of the 6 health related quality of life domains was not significantly affected by adding androgen deprivation therapy. Factors associated with longer time to return to baseline mental composite scores on multivariate analysis included nonwhite ethnicity, cerebrovascular disease history and alcohol abuse history. Men treated with permanent brachytherapy monotherapy experienced longer time to return to baseline for urinary function and symptoms. Baseline sexual function and lack of a partner were associated with longer time to sexual recovery. Adding androgen deprivation therapy to definitive radiotherapy does not significantly impact the time to return to baseline health related quality of life. These data may be valuable for patients and physicians when weighing the toxicity and benefits of androgen deprivation therapy when added to definitive radiotherapy.

Lack of benefit from a short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime

High-dose radiotherapy, delivered in an accelerated hypofractionated course, was utilized to treat prostate cancer. Therapy consisted of external beam radiotherapy (EBRT) and transrectal ultrasound (TRUS)-guided conformally modulated high-dose rate (HDR) brachytherapy. The purpose of this report is (1) to assess long-term comparative outcomes from three trials using similar accelerated hypofractionated regimes; and (2) to examine the long-term survival impact of a short course of < or =6 months adjuvant/concurrent androgen deprivation when a very high radiation dose was delivered. Between 1986 and 2000, 1,260 patients were treated at three institutions with pelvic EBRT (36-50 Gy) integrated with HDR prostate brachytherapy. The total dose including brachytherapy was given over 5 weeks. The biologic equivalent EBRT dose ranged between 90 and 123 Gy (median, 102 Gy) using an alpha /beta of 1.2. Patient eligibility criteria included a pretreatment prostate-specific antigen > or =10, Gleason score > or =7, or clinical stage > or =T2b. A total of 1,260 patients were treated, and 934 meet the criteria. Kiel University Hospital treated 198 patients; William Beaumont Hospital, 315; and California Endocurietherapy Cancer Center, 459 patients. Brachytherapy dose regimes were somewhat different between centers and the dose was escalated from 5.5 x 3 to 15 Gy x 2 Gy. Patients were divided for analysis between the 406 who received up to 6 months of androgen deprivation therapy and the 528 patients who did not. All patients had a minimum follow-up of 18 months (3 times the exposure to androgen deprivation therapy). The American Society for Therapeutic Radiology and Oncology biochemical failure definition was used. Mean age was 69 years. Median follow-up time was 4.4 years (range, 1.5-14.5); 4 years for androgen deprivation therapy patients and 4.9 for radiation alone. There was no difference at 5 and 8 years in overall survival, cause-specific survival, or biochemical control among the three institutions. The corresponding 8-year rates with and without androgen deprivation therapy were biochemical control 85% and 81%; overall survival 83% and 78%; cause-specific survival 89% and 94%; and metastatic rates of 16.6% and 7.3%. A multivariate analysis revealed androgen deprivation therapy did not predict for biochemical failure for either the entire group or the subset of 177 patients harboring all three poor prognostic factors. Moreover, adding androgen deprivation therapy strongly correlated with higher rates of both metastasis (p = 0.09; hazard ratio, 2.08) and cancer-related deaths (p = 0.02, hazard ratio 3.25). These negative results for the most unfavorable group led us to question if androgen deprivation therapy might have a deleterious impact through delay in delivery of the potentially curative radiation or whether there may be a biologic basis by fixing the cycling cells in G0. Accelerated hypofractionated pelvic EBRT integrated with TRUS-guided conformally modulated HDR administered to 1,260 patients in three institutions was an excellent method of delivering very high radiation dose to the prostate in 5 weeks. Similar high overall, cause-specific, and biochemical no evidence of disease survival rates achieved show that prostate HDR can be successfully delivered in academic and community settings. At 8 years, the addition of a course of < or =6 months of neoadjuvant/concurrent androgen deprivation therapy to a very high radiation dose did not confer a therapeutic advantage but added side effects and cost. Furthermore, for the most unfavorable group, there was a higher rate of distant metastasis and more prostate cancer-related deaths. We question the value of a short course of androgen deprivation therapy when used with high-dose radiation.