Dose-escalated External Beam Radiation Therapy Research Articles

Predictors of castration-resistant prostate cancer after dose-escalated external beam radiotherapy.

Castration-resistant prostate cancer (CRPC) is a near uniformly fatal form of prostate cancer; however, information on time to development and predictors for progression to CRPC is limited. We report a detailed longitudinal study for development of CRPC in men initially treated with external beam radiotherapy (EBRT). During 1991-2008, 2,478 patients with clinically localized prostate cancer were treated with dose-escalated EBRT at a single institution. The primary objective was to determine predictors of CRPC among men who failed definitive EBRT and progressed to salvage androgen-deprivation therapy (ADT). CRPC was defined as castrate levels of testosterone (<50 ng/dl) with progressive biochemical or radiographic disease. For the entire cohort (n = 2,478), the 10-year cumulative incidence rate for developing CRPC was 9.9%. For those that progressed to salvage ADT (n = 362), the 7-year cumulative incidence rates for developing CRPC from time of salvage ADT was 33.7%. Amongst this cohort, multivariable analysis demonstrated that PSA doubling-time (continuous; hazard ratio [HR], 0.98 [0.97-0.99], P < 0.001), higher Gleason score (HR, 1.96 [1.12-3.43]; P = 0.034), and duration of ADT at time of EBRT (continuous; HR, 1.02 [1.01-1.03]; P = 0.007) were associated with development of CRPC. This represents the first report of predictors of CRPC for patients treated with modern dose-escalated EBRT. We demonstrate that among the minority of patients not initially cured after EBRT, those treated with longer-course ADT have higher rates of resistance to the re-introduction of ADT. Future trials will need to test this subgroup with more aggressive or alternative forms of salvage therapies.

The Natural History and Predictors of Outcome Following Biochemical Relapse in the Dose Escalation Era for Prostate Cancer Patients Undergoing Definitive External Beam Radiotherapy

BackgroundThe management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting. ObjectiveWe sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT. Design, setting, and participantsThis retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients. Intervention(s)All patients received EBRT at doses of 75.6–86.4Gy. Outcome measurements and statistical analysisThe primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer–specific mortality (PCSM). Results and limitationsFrom the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions. ConclusionsClinical and pathologic factors can help identify patients at high risk of clinical progression following BF. Patient summaryIn this report, we look at predictors of outcome for patients with prostate cancer recurrence, as determined by prostate-specific antigen (PSA) levels, following radiation treatment. We found that the approximate median times to distant metastasis and death from prostate cancer for patients in this situation were 5 yr and 10 yr, respectively. Furthermore, we found that patients with a rapid increase in PSA levels following treatment, a short time to PSA recurrence, invasion of extraprostatic organs, or a high Gleason score had worse outcomes.

Prostate-Specific Antigen Bounce After Dose-Escalated Radiation Therapy for Prostate Cancer is an Independent Predictor for Distant Metastasis, Cancer-Specific Survival, and Overall Survival

Prostate-Specific Antigen Bounce After Dose-Escalated Radiation Therapy for Prostate Cancer is an Independent Predictor for Distant Metastasis, Cancer-Specific Survival, and Overall Survival

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Using multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.

Recent Developments in Androgen Deprivation Therapy for Locally Advanced Prostate Cancer

Locally advanced prostate cancer (LAPC) is often managed with a combination of external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). Clinical protocols combining ADT and EBRT for the treatment of LAPC were developed based on clinical trials that used conventional-dose EBRT (~70 Gy) and luteinizing hormone-releasing hormone (LHRH) analog monotherapy. However, dose-escalated EBRT (&gt;74 Gy) is in widespread clinical use and potent second-generation agents targeting the androgen axis have recently received US Food and Drug Administration (FDA) approval. These and other recent developments challenge the current standard of care for LAPC. Determining the optimal duration and potency of ADT in combination with dose-escalated EBRT in LAPC is an active area of clinical research seeking to balance the side-effect profile of ADT with its well-established therapeutic benefits. Prospective randomized clinical trials incorporating dose-escalated EBRT and second-generation androgen axis inhibitors are necessary to clarify the role of ADT in this new arena. Further, since biochemical response to neoadjuvant ADT predicts for efficacy of EBRT, new trials should seek to achieve maximal androgen suppression prior to EBRT to increase clinical benefit. Last, recent clinical and preclinical research efforts hold significant promise and seek to provide better predictive markers and expand the therapeutic target spectrum in prostate cancer.

Salvage low-dose-rate (125)I partial prostate brachytherapy after dose-escalated external beam radiotherapy.

PurposeTo report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine (125I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT).Material and methodsA retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR 125I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed.ResultsThe median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR 125I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL.ConclusionsIn carefully selected patients with local persistence of disease, partial LDR 125I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach.

Outcomes and Tolerance of Human Immunodeficiency Virus–Positive U.S. Veterans Undergoing Dose-Escalated External Beam Radiotherapy for Localized Prostate Cancer

IntroductionThere are little data on the outcomes and tolerance, as well as the impact on the CD4 counts, of human immunodeficiency virus (HIV)–positive patients with prostate cancer who undergo high-dose external beam radiotherapy. Materials and MethodsWe identified 15 HIV-positive patients with prostate cancer who were treated with external beam radiation to a dose ≥ 75.6 Gy at the New York Harbor Department of Veterans Affairs between 2003 and 2010. Kaplan-Meier analyses were used to measure biochemical control outcomes. Toxicity and CD4 counts before, after, and during treatments were analyzed. ResultsA total of 15 patients were identified, with a median follow-up period of 49 months. There were 2 biochemical failures, which occurred at 28 months and 63 months, respectively. In neither of these 2 patients was there evidence of metastatic disease. The overall 5-year biochemical control was 92.3%. There appeared to be a consistent decline in the CD4 counts both during and immediately after the radiation treatments. Most of these patients had a subsequent improvement in their CD4 counts. Toxicity was mild overall, though there was 1 patient who developed rectal bleeding 11 months post treatment, which required argon plasma coagulation. ConclusionDose-escalated external beam radiation is well tolerated in HIV-positive patients with durable biochemical control and mild toxicity. A substantial decline in CD4 counts is associated with the radiation; therefore, these counts need to be monitored closely, in conjunction with the infectious-disease specialist.

The Natural History and Patterns of Failure Following Biochemical Relapse in Prostate Cancer (PC) Patients Treated With Dose-Escalated External Beam Radiation Therapy (EBRT)

To date, a comprehensive analysis of patterns of failure and predictors of bone metastasis (BM) and prostate cancer specific mortality (PCSM) following biochemical failure (BF) has not been performed for patients with PC treated with EBRT in the dose escalation era.

Stratifying intermediate-risk patients for radiotherapy

Radiotherapy is not a well-established option for men with intermediate-risk prostate cancer and further substratification of these patients could help to guide treatment decisions. Researchers have developed a new risk-classification system for intermediate-risk patients undergoing dose-escalated external-beam radiation therapy, but how effective is this system?

Interval to Biochemical Failure Predicts Clinical Outcomes in Patients With High-Risk Prostate Cancer Treated by Combined-Modality Radiation Therapy

To validate the prognostic value of interval to biochemical failure (IBF) in patients with high-risk prostate cancer (HiRPCa) treated with combined-modality radiation therapy (CMRT) with or without androgen deprivation therapy (ADT). We conducted a retrospective review of HiRPCa (prostate-specific antigen >20 ng/mL, Gleason score [GS] 8-10, or clinical T stage T3-T4) treated with either dose-escalated external beam radiation therapy (EBRT) or CMRT. Interval to biochemical failure was classified as ≤18 or >18 months from the end of all therapy to the date of biochemical failure (BF). Kaplan-Meier methods and Cox proportional hazards regression were used to evaluate the prognostic value of IBF ≤18 months for distant metastasis (DM) and prostate cancer-specific mortality (PCSM). Of 958 patients with a median follow-up of 63.2 months, 175 patients experienced BF. In those with BF, there were no differences in pretreatment clinical characteristics between the EBRT and CMRT groups, except for a higher proportion of patients with GS 8-10 in the CMRT group (70% vs 52%, P=.02). Median IBF after all therapy was 24.0 months (interquartile range 9.6-46.0) in the EBRT group and 18.9 months (interquartile range 9.2-34.5) in the CMRT group (P=.055). On univariate analysis, IBF ≤18 months was associated with increased risk of DM and PCSM in the entire cohort and the individual EBRT and CMRT groups. On multivariate analysis, only GS 9-10 and IBF ≤18 months, but not the radiation therapy regimen or ADT use, predicted DM (hazard ratio [HR] 3.7, P<.01, 95% confidence interval [CI] 1.4-10.3 for GS 9-10; HR 3.9, P<.0001, 95% CI 2.4-6.5 for IBF ≤18 months) and PCSM (HR 14.8, P<.009, 95% CI 2.0-110 for GS 9-10; HR 4.4, P<.0001, 95% CI 2.4-8.1 for IBF ≤18 months). Short IBF was highly prognostic for higher DM and PCSM in patients with HiRPCa. The prognostic value of IBF for DM and PCSM was not affected by the radiation therapy regimen or ADT use.

Multi-institutional Prospective Evaluation of Bowel Quality of Life After Prostate External Beam Radiation Therapy Identifies Patient and Treatment Factors Associated With Patient-Reported Outcomes: The PROSTQA Experience

To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum ≥25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and predicted increased risks for moderate to big fecal incontinence (P=.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 ≥25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 ≥25% as having significant impact on patient-reported outcomes.

Timing Variability of Bladder Volumes in Men Receiving Radiotherapy to the Prostate

Background and PurposeDose-escalated external-beam radiotherapy improves outcomes for localized prostate cancer but risks increasing the toxicity. One strategy to decrease this toxicity may be larger and more consistent bladder volumes. The primary objective of this study was to determine the time required for 95% of patients on a dose-escalated external-beam radiotherapy protocol to comfortably achieve a 180-cc bladder volume. In addition, measurement of patients' subjective assessment of urgency related to bladder filling was obtained to determine the feasibility of bladder-filling instructions. MethodologyThirty consenting patients with localized prostate cancer treated with external-beam radiotherapy were assigned 1:1 to 250-cc vs. 500-cc water preload. After voiding, patients drank the specified fluid preload and had their bladder volume and urinary urgency assessed at regular intervals over 2 hours, repeated at weeks 1, 4, and 7. ResultsThe time required for 95% of patients to achieve a bladder volume of 180 cc was 75 and 57 minutes for groups 1 and 2, respectively (P = .03). Serum creatinine and use of bladder medications did not influence time to optimal bladder filling. Participants in group 2 reported moderate to severe urinary severity more frequently than participants in group 1. ConclusionsTime to optimal bladder volume was highly varied and was faster with a 500-cc fluid preload. Customizing the wait times based on calculated ultrasound-based filling rates appears feasible in a busy radiotherapy department.

A New Risk Classification System for Therapeutic Decision Making with Intermediate-risk Prostate Cancer Patients Undergoing Dose-escalated External-beam Radiation Therapy

BackgroundThe management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification. ObjectiveWe propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making. Design, setting, and participantsBetween 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥81Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥50%, or multiple intermediate-risk factors (IRFs; cT2b–c, prostate-specific antigen [PSA] 10–20, or Gleason score 7). InterventionAll patients received EBRT with ≥81Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT). Outcome measurements and statistical analysisUnivariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method. Results and limitationsMedian follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p<0.0001), PPBC ≥50% (HR: 2.72; p=0.0007), and multiple IRFs (HR: 2.20; p=0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p<0.0001) and PPBC ≥50% (HR: 4.08; p=0.002) but not multiple IRFs (HR: 1.74; p=0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p<0.0001), DM (HR: 4.34; p=0.0003), and PCSM (HR: 7.39; p=0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations. ConclusionsIntermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms.

Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to10.

Stability of white blood cell counts following standard radiation approaches for high-risk adenocarcinoma of the prostate: Implications for combination therapy.

201 Background: Traditional wisdom has suggested that under some circumstances radiation therapy may be immunosuppressive, thus obviating effective combination approaches with immunotherapy. Our purpose was to test whether standard radiation therapy for high-risk prostate cancer are immune modulating, thereby prohibiting potential combination with cellular based immunotherapies such as sipuleucel-T. Methods: Retrospective analysis of complete blood count with differential (CBC) data was performed on 26 patients with high-risk adenocarcinoma of the prostate undergoing external beam radiation therapy between January 2008 and November 2010. CBC data were collected prior to radiation therapy and at up to 4 time points thereafter, and compared to normal ranges from an outside reference lab (WBC 3,800-10,700/μL; ALC 910-4,280/μL). Results: The median age was 73 (range 62-86), and 16 patients were on concurrent androgen deprivation therapy. Patients received intensity modulated, dose-escalated external beam radiotherapy. Baseline and subsequent median white blood counts (WBC) and absolute lymphocyte counts (ALC) remained within the normal ranges. In the clinically relevant time frame of &lt;3 months following radiation therapy where sipuleucel-T could be considered, the WBC and ALC were 5,350 and 970, respectively. The median WBC and ALC then gradually increased to 5,800 and 1,250, respectively, at 6-12 months post radiation therapy. Conclusions: These data suggest that in the setting of external beam radiation approaches for high-risk adenocarcinoma of the prostate, no significant changes in either WBC or ALC were observed. The hematologic status in these patients remained stable, suggesting that combination radiation / cellular based immunotherapy approaches are feasible. Further analysis is warranted to test the potential of novel immunotherapeutic agents with radiation therapy. [Table: see text]

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy

Recent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT. Between April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. At 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p=0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p=0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p=0.14). Men with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern5.

The Influence of Age and Comorbidity on the Benefit of Adding Androgen Deprivation to Dose-escalated Radiation in Men With Intermediate-Risk Prostate Cancer

A recent analysis found androgen deprivation therapy (ADT) improves outcomes for men with intermediate-risk prostate cancer receiving dose-escalated external beam radiation therapy (EBRT). Older men and men with significant comorbidity may be more susceptible to the harms of ADT, therefore we aimed to determine if the ADT benefit extends to older men receiving dose-escalated EBRT and if this benefit is influenced by the severity of patient comorbid conditions.

The Addition of Low-dose-rate Brachytherapy and Androgen Deprivation Therapy Decreases Prostate Cancer Death Compared to Dose-escalated External Beam Radiation Therapy for High-risk Prostate Cancer

The ideal management of high-risk prostate cancer (PSA ≥20, T3-4, or Gleason sum (GS) 8-10; HiPCa) in the era of dose-escalated radiation therapy (RT) is unclear. The addition of low-dose rate brachytherapy or androgen-deprivation therapy (ADT) may improve outcomes.

PSA Bounce Predicts for a Favorable Prognosis Following Brachytherapy, but an Unfavorable Prognosis After External Beam Radiation Therapy: A Meta-analysis

benefit was more pronounced in healthy men who had no or mild comorbidity. Our study suggests that severity of comorbidity may be a more significant predictor of improved failure-free survival than age when considering the addition of ADT to dose-escalated EBRT in patients with intermediate-risk prostate cancer. Further studies are needed to confirm our findings. Author Disclosure: S. Bian: None. D.A. Kuban: None. L.B. Levy: None. J. Oh: None. S. Choi: None. S.E. McGuire: None. T.J. Pugh: None. P.L. Nguyen: None. A.K. Lee: None. K.E. Hoffman: None.

Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.