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Background: Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks., Objective: To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT., Design, Setting, and Participants: An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted., Intervention: Short-term ADT., Outcome Measurements and Statistical Analysis: We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score., Results and Limitations: T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards., Conclusions: Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT., Patient Summary: We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Importance: As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians., Objective: To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up., Design, Setting, and Participants: A pooled secondary analysis of patients treated with external-beam radiotherapy alone and enrolled in the prospective randomized clinical trials RTOG 0126 and RTOG 0415 was performed. Patients included for analysis were enrolled between March 2002 and December 2009 with a median follow-up of 6.9 years. Overall survival was calculated using the Kaplan-Meier method at various survivorship time points. Cumulative incidence was used to calculate BF rates using the Phoenix definition, as well as PCSD. Risk factors such as Gleason score, tumor (T) stage, prostate-specific antigen level, and the equivalent dose in 2 Gy fractions of prescribed dose were analyzed at different time points using multivariable Cox proportional hazards modeling. Data were analyzed from November 2021 to February 2023., Main Outcomes and Measures: Conditional risks of BF and PCSD after completion of external-beam radiotherapy., Results: A total of 2591 patients (median [IQR] age, 69 [63-73] years) were included in the study with a mean (range) PSA level of 7.1 (4.7-8.9) ng/mL, 1334 patients (51.5%) with a Gleason score 6 disease, and 1706 patients (65.8%) with T1 disease. Rates of BF from time of treatment were 1.63% (95% CI, 1.20%-2.18%) at 1 year, 7.04% (95% CI, 6.09%-8.08%) at 3 years, 12.54% (95% CI, 11.28%-13.88%) at 5 years, and 22.32% (95% CI, 20.46%-24.24%) at 8 years. For patients surviving 1, 3, and 5 years without BF, the rates of BF in the next 5 years were 14.20% (95% CI, 12.80%-15.66%), 17.19% (95% CI, 15.34%-19.14%), and 18.85% (95% CI, 16.21%-21.64%), respectively. At the initial time point, the rate of PCSD in the next 5 years was 0.66% (95% CI, 0.39%-1.04%). For patients who achieved 1, 3, 5, and 8 years of survivorship, the rates of PCSD in the next 5 years were 1.16% (95% CI, 0.77-1.67) at 1 year, 2.42% (95% CI, 1.74%-3.27%) at 3 years, 2.88% (95% CI, 2.01%-3.99%) at 5 years, and 3.49% (95% CI, 0.98%-8.73%) at 8 years., Conclusions and Relevance: In this secondary analysis of 2 randomized clinical trials of patients undergoing external beam radiotherapy for prostate cancer, the conditional risks of BF and death from prostate cancer increased with time for patients with low- and intermediate-risk prostate cancer treated with radiotherapy alone. These results could inform optimal trial design and may be helpful information for patients evaluated in follow-up., Trial Registration: ClinicalTrials.gov Identifier: NCT00033631; NCT00331773.

Purpose: Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa., Methods: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ 2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure., Results: One hundred and sixty-seven patients were included in the analysis (Black: n = 81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P = .011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = .114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P = .42). Overall survival was comparable between racial groups (P = .972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001)., Conclusions: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality., Materials and Methods: Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death., Results: Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area., Conclusions: This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa., (© 2022 American Cancer Society.)

Our ability to prognosticate the clinical course of patients with cancer has historically been limited to clinical, histopathological, and radiographic features. It has long been clear however, that these data alone do not adequately capture the heterogeneity and breadth of disease trajectories experienced by patients. The advent of efficient genomic sequencing has led to a revolution in cancer care as we try to understand and personalize treatment specific to patient clinico-genomic phenotypes. Within prostate cancer, emerging evidence suggests that tumor genomics (e.g., DNA, RNA, and epigenetics) can be utilized to inform clinical decision making. In addition to providing discriminatory information about prognosis, it is likely tumor genomics also hold a key in predicting response to oncologic therapies which could be used to further tailor treatment recommendations. Herein we review select literature surrounding the use of tumor genomics within the management of prostate cancer, specifically leaning toward analytically validated and clinically tested genomic biomarkers utilized in radiotherapy and/or adjunctive therapies given with radiotherapy., (© 2022 Wiley Periodicals LLC.)

Purpose: To compare the predictive ability of mapping algorithms derived using cross-sectional and longitudinal data., Methods: This methodological assessment used data from a randomized controlled noninferiority trial of patients with low-risk prostate cancer, conducted by NRG Oncology (ClinicalTrials.gov identifier: NCT00331773), which examined the efficacy of conventional schedule versus hypofractionated radiation therapy (three-dimensional conformal external beam radiation therapy/IMRT). Health-related quality-of-life data were collected using the Expanded Prostate Cancer Index Composite (EPIC), and health utilities were obtained using EuroQOL-5D-3L (EQ-5D) at baseline and 6, 12, 24, and 60 months postintervention. Mapping algorithms were estimated using ordinary least squares regression models through five-fold cross-validation in baseline cross-sectional data and combined longitudinal data from all assessment periods; random effects specifications were also estimated in longitudinal data. Predictive performance was compared using root mean square error. Longitudinal predictive ability of models obtained using baseline data was examined using mean absolute differences in the reported and predicted utilities., Results: A total of 267 (and 199) patients in the estimation sample had complete EQ-5D and EPIC domain (and subdomain) data at baseline and at all subsequent assessments. Ordinary least squares models using combined data showed better predictive ability (lowest root mean square error) in the validation phase for algorithms with EPIC domain/subdomain data alone, whereas models using baseline data outperformed other specifications in the validation phase when patient covariates were also modeled. The mean absolute differences were lower for models using EPIC subdomain data compared with EPIC domain data and generally decreased as the time of assessment increased., Conclusion: Overall, mapping algorithms obtained using baseline cross-sectional data showed the best predictive performance. Furthermore, these models demonstrated satisfactory longitudinal predictive ability.

Purpose of Review: Although a standard of care in the treatment of organ-confined prostate cancer, use of radiation for treatment in the high-risk, metastatic and salvage settings is evolving rapidly., Recent Findings: Recent clinical trials have explored the role of increased treatment for high-risk disease with the addition of adjuvant chemotherapy and expanded the role of radiation in settings previously reserved for systemic therapy. Addition of adjuvant chemotherapy for high-risk prostate cancer is controversial and recent evidence is discussed that continues to refine the patient population for further evaluation. Evidence recently published demonstrates that for patients with low burden metastatic disease and those with oligometastatic disease may have a survival benefit with radiation treatment to all sites of known disease. Finally, reirradiation after prior radiotherapy-based treatment offers a potential salvage option for patients with locally recurrent prostate cancer., Summary: As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities., Methods and Materials: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE)., Results: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462., Conclusions: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations., Competing Interests: Drs. Khairnar, Albert, Bentzen, Bruner, Chen, Currey, Dayes, DeNittis, Horwitz, Lee, Michalski, Mullins, Palumbo, Pisansky, Seaward, Shah, Shaya, and Villalonga have nothing to disclose. Dr. Feng reports personal fees from Janssen Oncology, Sanofi, Bayer, Celgene, and Blue Earth Diagnostics, grants from Zenith Epigenetics, and other from PFS Genomics, outside the submitted work; Dr. Malone reports personal fees from Sanofi, and honoraria from Amgen, Abbvie, Astellas, Janssen, Tersara, Astra Zeneca, Knight Therapeutics, and Bayer, outside the submitted work; Dr. Mishra reports grants from American Society of Radiation Oncology (ASTRO), during the conduct of the study and other from Varian Medical Systems, outside the submitted work; Dr. Sandler reports grants from ACR/NRG Oncology, during the conduct of the study; personal fees from Janssen, other from Radiogel, outside the submitted work; Dr. Pugh reports other from Millennium, other from Pfizer, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The Extended Prostate Cancer Index Composite (EPIC) instrument is a commonly used patient reported outcome (PRO) tool in prostate cancer clinical trials. Summary scores for EPIC subscales are calculated by averaging patient scores for attributes (e.g., side effects), implying equal weighting of the attributes in the absence of evidence showing otherwise., Methods: We estimated patient preferences for each of the attributes included in the bowel subscale of the EPIC instrument using best-worst (B-W) scaling among a cohort of men with prostate cancer. Patients were presented with multiple tasks in which they were asked to indicate which attribute they would find most and least bothersome at different levels of severity. Analysis utilized both (simple) B-W counts and scores to estimate patient preferences for each attribute as well as attribute levels., Results: A total of 174 respondents from two institutions participated in the survey. Preference estimates for each of the five attributes included in the EPIC-26 bowel subscale showed wide variation preferences: 'losing control of bowel movements' was found to be the most bothersome attribute, with a B-W score of -0.48, followed by bowel urgency which also had negative B-W score (-0.04). Increased frequency of bowel movements was the least bothersome attribute, with a B-W score of +0.33, followed by bloody stools (+0.12), and pelvic/rectal pain (+0.06). Analysis of preference weights for attribute bother levels showed preference estimates be linear., Conclusions: We provide novel evidence on patient preferences for side effect reduction following prostate radiotherapy. Within the bowel sub-scale of the EPIC-26 short form, we found that bowel incontinence was perceived to be the most bothersome treatment effect, while increased bowel frequency was least bothersome to patients., Competing Interests: Dr. Mishra reports receiving an honorarium from Varian Medical Systems, outside of the scope and unrelated to the content of this manuscript. All other authors have declared that no competing interests exist.

Purpose: A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT)., Methods and Materials: A multistate Markov model was constructed from the U.S. payer perspective to examine the cost-effectiveness of HRS in men with localized PC receiving EBRT (EBRT alone vs EBRT + HRS). The subgroups analyzed included site of HRS placement (hospital outpatient, physician office, ambulatory surgery center) and proportion of patients with good baseline erectile function (EF). Data on EF, gastrointestinal and genitourinary toxicities incidence, and potential risks associated with HRS implantation were obtained from a recently published randomized clinical trial. Health utilities and costs were derived from the literature and the 2018 Physician Fee Schedule and were discounted 3% annually. Quality-adjusted life years (QALYs) and costs were modeled for a 5-year period from receipt of RT. Probabilistic sensitivity analysis and value-based threshold analyses were conducted., Results: The per-patient 5-year incremental cost for spacers administered in a hospital outpatient setting was $3578, and the incremental effectiveness was 0.0371 QALYs. The incremental cost-effectiveness ratio was $96,440/QALY for patients with PC undergoing HRS insertion in a hospital and $39,286/QALY for patients undergoing HRS insertion in an ambulatory facility. For men with good baseline EF, the incremental cost-effectiveness ratio was $35,548/QALY and $9627/QALY in hospital outpatient and ambulatory facility settings, respectively., Conclusions: Based on the current Medicare Physician Fee Schedule, HRS is cost-effective at a willingness to pay threshold of $100,000. These results contain substantial uncertainty, suggesting more evidence is needed to refine future decision-making., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: To compare long-term outcomes of men with adverse pathologic features after adjuvant radiation therapy (ART) versus salvage radiation therapy (SRT) after radical prostatectomy at our institution., Methods: Patients treated with postprostatectomy radiation therapy with pT3 tumors, or pT2 with positive surgical margins, were identified. Cumulative freedom from biochemical failure (FFBF), freedom from metastatic failure (FFMF), and overall survival rates were estimated utilizing the Kaplan-Meier method. Multivariate analyses were performed to determine independent prognostic factors correlated with study endpoints. Propensity score analyses were performed to adjust for confounding because of nonrandom treatment allocation., Results: A total of 186 patients with adverse pathologic features treated with ART or SRT were identified. The median follow-up time after radical prostatectomy was 103 and 88 months after completion of radiation therapy. The Kaplan-Meier estimates for 10-year FFBF was 73% and 41% after ART and SRT, respectively (log-rank, P=0.0001). Ten-year FFMF was higher for patients who received ART versus SRT (98.6% vs. 80.9%, P=0.0028). On multivariate analyses there was no significant difference with respect to treatment group in terms of FFBF, FFMF, and overall survival after adjusting for propensity score., Conclusions: Although unadjusted analyses showed improved FFBF with ART, the propensity score-adjusted analyses demonstrated that long-term outcomes of patients treated with ART and SRT do not differ significantly. These results, with decreased effect size of ART after adjusting for propensity score, demonstrate the potential impact of confounding on observational research.

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP)., Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms., Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups., Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: With the widespread use of prostate-specific antigen testing, an increasing number of men are diagnosed with favorable-risk prostate cancer (PC). Recently, emphasis has been placed on active surveillance for selected men with favorable-risk PC to avoid unnecessary treatment for tumors that may be clinically insignificant. We performed a population-based analysis to assess patterns of initial treatment (IT) for a contemporary cohort of elderly men diagnosed with a favorable-risk PC in the United States., Methods: We used the Surveillance, Epidemiology, and End Results database to identify men aged more than or equal to 70 years diagnosed with a favorable-risk PC from 2004 to 2008. Multivariable logistic regression analyses were performed to determine patient, tumor, and socioeconomic factors associated with IT., Results: A total of 15,108 men more than or equal to 70 years with a favorable-risk PC were identified. Prostatectomy was performed in 2.6% of patients. Fifty-nine percent of patients were recommended to undergo radiation therapy (RT). Among patients 70 to 74 years, 66.45% were recommended to undergo RT. Fifty-nine percent, 36.6%, and 15.8% of patients between 75 and 79, 80 and 84, and more than or equal to 85 years were recommended to receive RT, respectively. Factors significantly associated with IT on multivariable logistic regression analysis included: younger age, white race, Gleason Score 6 (vs.≤5), married marital status, and no history of prior malignancy. We also identified significant geographic variations in patterns of IT., Conclusions: A large percentage of elderly men diagnosed with favorable-risk PC undergo IT, most commonly with RT. Future research should be performed to identify barriers to patient and physician acceptance of active surveillance.

Objectives: Qualitative research aimed at identifying patient acceptance of active surveillance (AS) has been identified as a public health research priority. The primary objective of this study was to determine if analysis of a large-sample of anonymous internet conversations (ICs) could be utilized to identify unmet public needs regarding AS., Methods: English-language ICs regarding prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel internet search methodology. Web spiders were developed to mine, aggregate, and analyze content from the world-wide-web for ICs centered on AS. Collection of ICs was not restricted to any specific geographic region of origin. NLP was used to evaluate content and perform a sentiment analysis. Conversations were scored as positive, negative, or neutral. A sentiment index (SI) was subsequently calculated according to the following formula to compare temporal trends in public sentiment towards AS: [(# Positive IC/#Total IC)-(#Negative IC/#Total IC) x 100]., Results: A total of 464 ICs were identified. Sentiment increased from -13 to +2 over the study period. The increase sentiment has been driven by increased patient emphasis on quality-of-life factors and endorsement of AS by national medical organizations. Unmet needs identified in these ICs include: a gap between quantitative data regarding long-term outcomes with AS vs. conventional treatments, desire for treatment information from an unbiased specialist, and absence of public role models managed with AS., Conclusions: This study demonstrates the potential utility of online patient communications to provide insight into patient preferences and decision-making. Based on our findings, we recommend that multidisciplinary clinics consider including an unbiased specialist to present treatment options and that future decision tools for AS include quantitative data regarding outcomes after AS.

There have been significant advancements in the quality and precision of radiation therapy (RT) for prostate cancer over the past two decades. The development and implementation of intensity-modulated radiation therapy has allowed for RT dose-escalation without parallel increases in treatment morbidity. Moreover, integration of androgen deprivation therapy with definitive RT has led to improvements in outcomes for certain subgroups of prostate cancer patients. In this review, we highlight several ongoing and developing technical advances that hold promise for further optimizing RT care, including proton beam therapy, inter- and intra-fractional image-guided dose-delivery, methods for improved target volume definition, and development of techniques for safely performing hypofractionation and stereotactic body radiotherapy. We also discuss the importance of investigating the potential benefit of integrating novel systemic therapies with prostate RT to further improve outcomes for patients with locally advanced prostate cancer., (Copyright © 2013. Published by Elsevier Inc.)

Purpose: This population-based analysis compared prostate cancer-specific mortality (PCSM) in a cohort of patients with high-risk prostate cancer after nonsurgical treatment with external beam radiation therapy (EBRT), brachytherapy (BT), or combination (BT + EBRT)., Methods and Materials: We identified from the Surveillance, Epidemiology and End Results database patients diagnosed from 1988 through 2002 with T1-T3N0M0 prostate adenocarcinoma of poorly differentiated grade and treated with BT, EBRT, or BT + EBRT. During this time frame, the database defined high grade as prostate cancers with Gleason score 8-10, or Gleason grade 4-5 if the score was not recorded. This corresponds to a cohort primarily with high-risk prostate cancer, although some cases where only Gleason grade was recorded may have included intermediate-risk cancer. We used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on PCSM., Results: There were 12,745 patients treated with EBRT (73.5%), BT (7.1%), or BT + EBRT (19.4%) included in the analysis. The median follow-up time for all patients was 6.4 years. The use of BT or BT + EBRT increased from 5.1% in 1988-1992 to 31.4% in 1998-2002. Significant predictors of use of BT or BT + EBRT were younger age, later year of diagnosis, urban residence, and earlier T-stage. On multivariate analysis, treatment with either BT (hazard ratio, 0.66; 95% confidence interval, 0.49-0.86) or BT + EBRT (hazard ratio, 0.77; 95% confidence ratio, 0.66-0.90) was associated with significant reduction in PCSM compared with EBRT alone., Conclusion: In patients with high-grade prostate cancer, treatment with brachytherapy is associated with reduced PCSM compared with EBRT alone. Our results suggest that brachytherapy should be investigated as a component of definitive treatment strategies for patients with high-risk prostate cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Comparative effectiveness research aims to help clinicians, patients and policymakers make informed treatment decisions under real-world conditions. Prostate cancer patients have multiple treatment options, including active surveillance, androgen deprivation therapy, surgery and multiple modalities of radiation therapy. Technological innovations in radiation therapy for prostate cancer have been rapidly adopted into clinical practice despite relatively limited evidence for effectiveness showing the benefit for one modality over another. Comparative effectiveness research has become an essential component of prostate cancer research to help define the benefits, risks and effectiveness of the different radiation therapy modalities currently in use for prostate cancer treatment.

While the majority of men with localized prostate cancer who undergo a radical prostatectomy will remain disease free, men with certain clinical and pathological features are known to be at an increased risk for developing a biochemical recurrence and, ultimately, distant metastatic disease. The optimal management of these patients continues to be a source of controversy. To date, three randomized Phase III trials have demonstrated that adjuvant radiation therapy (ART) for patients with certain adverse pathological features results in an improvement in several clinically-relevant end points, including biochemical recurrence-free survival and overall survival. Despite the evidence from these trials showing a benefit for ART, many believe that ART results in overtreatment and unwarranted treatment morbidity for a significant number of patients. Many physicians, therefore, instead advocate for close observation followed by early salvage radiation therapy (SRT) at the time of a biochemical recurrence. The purpose of this review is to evaluate the evidence for and to distinguish between ART and early SRT. We will also highlight current and future areas of research for this patient population, including radiation treatment dose escalation, hypofractionation and androgen deprivation therapy. We will also discuss the cost-effectiveness of ART and early SRT.

Purpose: Hemorrhagic radiation proctitis (HRP) is a potential complication of prostate brachytherapy. We sought to determine the incidence and clinical course of hemorrhagic radiation proctitis after iodine-125 (125I) prostate brachytherapy., Patients and Methods: Between 1995 and 2003, 221 consecutive patients were treated at the Barrett Cancer Center with permanent 125I seed implantation for presumed localized adenocarcinoma of the prostate. No patients received EBRT. All cases of HRP were confirmed by colonoscopy. Median follow-up was 52 months. All patients were evaluated for HRP using a 5-grade rectal bleeding scale developed by the Radiation Therapeutic Oncology Group., Results: Thirty-three patients experienced grade>or=1 toxicity at some point after treatment. Twenty patients developed grade 2 toxicity, 9 developed grade 3, and 2 developed grade 4. The median time to onset of symptoms of HRP was 14 months. The incidence of HRP had a bimodal temporal onset, with a peak seen at 4 months and a second larger peak at 16 months. Peak toxicity occurred at 18 months after the onset of rectal bleeding, after which there was a sharp decline in toxicity., Conclusion: This study demonstrates tolerable rectal morbidity after transperineal prostate brachytherapy of the prostate. Hemorrhagic radiation proctitis occurring after brachytherapy for prostate cancer is usually self-limiting and frequently resolves without treatment or with minor medical treatment. Patients develop HRP soon after treatment or after a delay in treatment. Symptoms appear to peak 18 months after the onset of HRP.

A 63-year-old man with a T1c adenocarcinoma of the prostate, Gleason score of 7 (4+3), and a pretreatment prostate-specific antigen (PSA) level of 9.5 ng/mL was treated with external-beam radiation therapy (45 Gy) and 2 magnetic resonance imaging-guided high-dose rate brachytherapy boosts (10 Gy each.) The patient also received neoadjuvant, concurrent, and adjuvant hormonal treatment with leuprolide for 7 months total. Without any further intervention the patient had 2 separate and prolonged PSA increases and decreases 12-35 months after therapy. His PSA nadir was <0.2 ng/mL and rose slowly over several months to 4.2 ng/mL, resolved, and then rose 2.3 ng/mL before again slowly resolving. After prostate irradiation, many patients experience a transient rise in serum PSA levels and a subsequent decline without any treatment. This is known as a PSA "bounce" or "bump." Some patients experience a second transient rise in PSA levels after irradiation. To our knowledge, this case report is the first documentation of a second PSA bump in a patient treated with external-beam radiation therapy and high-dose rate boost therapy and provides context to address concerns and therapeutic decisions confronting physicians and patients.