Search

Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear.This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT + BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT + BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression.Among the entire cohort, 270 underwent EBRT and 101 EBRT + BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT + BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P = .42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P = .45) between EBRT + BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P = .42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P = .38).In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT + BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

Background and Purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. Materials and Methods: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. Results: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2–3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. Conclusion: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

The summary presented herein represents Part II of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing principles of active surveillance and surgery as well as follow-up for patients after primary treatment. Please refer to Parts I and III for discussion of risk assessment, staging, and risk-based management (Part I), and principles of radiation and future directions (Part III).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding active surveillance, surgical management, and patient follow-up are detailed.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

The summary presented herein represents Part I of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing risk assessment, staging, and risk-based management in patients diagnosed with clinically localized prostate cancer. Please refer to Parts II and III for discussion of principles of active surveillance, surgery and follow-up (Part II), and principles of radiation and future directions (Part III).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding risk assessment, staging, and risk-based management are detailed herein.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

Background: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. Patients and Methods: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. Results: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. Conclusions: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

BACKGROUND Elicitation of patients’ preferences is an integral part of shared decision making, the recommended approach for prostate cancer decision making. However, existing decision aids for this population do not specifically focus on patients’ preferences. Healium is a brief interactive web-based decision aid that aims to elicit patient’s treatment preferences and is designed for a low health literate population. OBJECTIVE This study used a randomized controlled trial to evaluate whether Healium (designed to target preference elicitation) is as efficacious as Healing Choices (a comprehensive education and decision tool) in improving outcomes for decision-making and emotional quality of life. METHODS Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, an extensive decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6-weeks and 3-months post-baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy. RESULTS N = 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (96%), White (76%), married (78.4%), and had an average age of 62.4 years old (SD = 6.9). Within both arms, there was a significant decrease in decisional conflict from baseline to 6-weeks post baseline (Healium, P = CONCLUSIONS Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity and the potential for integration into the physician consultation and electronic medical record. CLINICALTRIAL n/a

BACKGROUND: Supply chain disruptions during the COVID-19 pandemic have affected the availability of components for specimen collection kits to detect SARS-CoV-2. Plastic injection molding offers a rapid and cheap method for mass production of swabs for upper respiratory tract sampling. Local production of virus transport medium increases flexibility to assemble sample collection kits if the medium provides appropriate stability for SARS-CoV-2 detection. METHODS: A locally produced virus transport medium and a novel injection molded plastic swab were validated for SARS-CoV-2 detection by reverse-transcription quantitative polymerase chain reaction. Both components were compared to standard counterparts using viral reference material and representative patient samples. RESULTS: Clinical testing showed no significant differences between molded and flocked swabs. Commercial and in-house virus transport media provided stable test results for over 40 days of specimen storage and showed no differences in test results using patient samples. CONCLUSIONS: This collection kit provides new supply chain options for SARS-CoV-2 testing.

Purpose Data comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT. Methods and Materials This multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only). Results A total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008). Conclusions In this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.

To determine if limiting the doses delivered to the penile bulb (PB) and corporal bodies (CB) with IMRT preserves erectile function compared to standard IMRT in men with prostate cancer.117 patients with low-intermediate risk, clinical T1a-T2c prostate adenocarcinoma were enrolled to a single-institution, prospective, single blind, phase III randomized trial. All received definitive IMRT to 74-80 Gy in 37-40 fractions and standard IMRT (s-IMRT) or erectile tissue sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the PB and CB to ≤ 15 Gy and ≤ 7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function (IIEF) and PDE5 medication records.62 patients received ETS-IMRT and 54 received s-IMRT; 1 patient did not receive radiation therapy. Prior to treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, p=0.53). Of 85 evaluable patients with IIEF and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (p=0.86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (p=0.54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-yr 91.8% vs 90.7%, respectively, p=0.77) with a median follow-up of 7.4 years. There were no differences in acute or late GI or GU toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, though power was limited by attrition and unplanned dosimetric crossover.Erectile tissue sparing IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

There is considerable interest in very short (ultrahypofractionated) radiation therapy regimens to treat prostate cancer based on potential radiobiological advantages, patient convenience, and resource allocation benefits. Our objective is to demonstrate that detectable changes in health-related quality of life measured by the bowel and urinary domains of the Expanded Prostate Cancer Index Composite (EPIC-50) were not substantially worse than baseline scores.xxxx is a nonblinded randomized phase 2 study of National Comprehensive Cancer Network low-risk prostate cancer in which each arm is compared with a historical control. Patients were randomized to 5 fractions (7.25Gy in 2 week and a day - twice a week) or 12 fractions (4.3Gy in 2.5 weeks- five times a week). Secondary objectives assessed patient-reported toxicity at 5 years using the Expanded Prostate cancer Index Composite (EPIC). Chi-square tests were used to assess the proportion of patients with a deterioration from baseline of5 points for bowel,2 points for urinary, and11 points for sexual score, RESULTS: The study enrolled 127 patients to 5 fractions (121 eligible) and 128 patients to 12 fractions (125 eligible). Median follow-up for all patients at the time of analysis was 5.38 years. The 5-year frequency for5 point change in bowel score were 38.4% (P=0.27) and 23.4% (= 0.98) for 5 and 12 fractions, respectively. The 5-year frequencies for2 point change in urinary score were 46.6% (P=0.15) and 36.4% (P=0.70) for 5 and 12 fractions, respectively. For 5 fractions, 49.3% (P=0.007) of patients had a drop in 5-year EPIC-50 sexual score of ≥11 points; for 12 fractions, 54% (P0.001) of patients had a drop in 5-year EPIC-50 sexual score of ≥11 points. Disease-free survival at 5 years is 89.6% (95% confidence interval:84.0-95.2) in the 5-fraction arm and 92.3% (95% confidence interval: 87.4- 97.1) in the 12-fraction arm. There was no late grade 4 or 5 treatment-related urinary or bowel toxicity.This study confirms that, based on long-term changes in bowel and urinary domains and toxicity, the 5- and 12-fraction regimens are well tolerated. These ultrahypofractionated approaches need to be compared with current standard radiation therapy regimens.

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.

145 Background: Studies are conflicting regarding the association between statin use and biochemical recurrence after surgery or radiotherapy for localized prostate cancer. A handful of studies have observed favorable associations between statins and prostate cancer-specific (PCSM) and overall mortality (OS), however, this has not been studied in an advanced disease cohort nor has the combination of statins and androgen deprivation therapy (ADT) been specifically studied. Methods: Patients with PSA >3 ng/mL after >1 year following primary or salvage radiotherapy (RT) were enrolled in a randomized trial of intermittent (IAD) vs. continuous (CAD) ADT (NCT00003653). Statin use at baseline and during the study was captured and modeled as a time-dependent covariate. The primary end-point was OS. Models were adjusted for age, time from RT to ADT and PSA at baseline. As results were nearly identical between the IAD and CAD arms they are reported as aggregates unless otherwise indicated. Results: Of 1,364 patients enrolled, 585 (43%) reported statin use during the study. Statin users were younger (72.7 vs. 73.8, p=0.001) and less likely to have PSA >15 (20 vs. 25%, p=0.04). Median follow-up was 6.9 years and 524 deaths occurred. Statin use was associated with a reduced risk of overall death (HR: 0.64; 95% C.I. 0.53 – 0.78, p

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel’s discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.

The summary presented herein represents Part III of the three-part series dedicated to Clinically Localized Prostate Cancer: AUA/ASTRO Guideline, discussing principles of radiation and offering several future directions of further relevant study in patients diagnosed with clinically localized prostate cancer. Please refer to Parts I and II for discussion of risk assessment, staging, and risk-based management (Part I), and principles of active surveillance and surgery and follow-up (Part II).The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.The Clinically Localized Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with clinically localized prostate cancer. Statements regarding management of patients using radiation therapy as well as important future directions of research are detailed herein.This guideline aims to inform clinicians treating patients with clinically localized prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to further improve care for these men.

Key Points Question What is the optimal minimum duration of androgen deprivation therapy (ADT) when treating high-risk prostate cancer with high-dose radiotherapy? Findings This patient-level cohort study of 3 cohorts found a significant interaction between the type of high-dose radiotherapy (external beam radiotherapy with or without a brachytherapy boost) and optimal duration. Prolonging ADT for 18 to 28 months was associated with a 63% reduction in death or metastasis with external beam radiotherapy; when a brachytherapy boost was added, the nonlinear association between ADT and distant metastasis-free survival was broad and spanned 12 months. Meaning The findings of this cohort study suggest that patients receiving external beam radiotherapy alone may benefit from ADT durations of 18 months or more; if a brachytherapy boost is added, a duration of 18 months or possibly less may be optimal., Importance Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. Objective To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). Design, Settings, and Participants This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. Exposures High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). Main Outcomes and Measures The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). Results This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to, This cohort study explores associations between the duration of androgen deprivation therapy and distant metastasis-free survival in men undergoing external beam radiotherapy with and without a brachytherapy boost for treatment of high-risk prostate cancer.

438 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy or chemoradiation is the standard of care for urothelial carcinoma (UC) patients with MIBC. Both cystectomy and chemoradiation have short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients prospectively for a cystectomy or chemoradiation avoidance algorithm. Methods: We conducted a single-arm, phase II, non-inferiority trial (NCT02710734) to evaluate a risk-adapted approach for MIBC. Patients with cT2-T3N0M0 UC underwent NAC with accelerated MVAC. Pre-NAC TURBT specimens were sequenced (Caris) for mutations in ATM, ERCC2, FANCC or RB1. Patients with ≥ 1 mutations and no clinical evidence of disease by restaging TUR, urine cytology and imaging post-NAC began pre-defined active surveillance (AS). Remaining patients underwent bladder-directed therapy. The primary endpoint was metastasis-free survival (MFS) at 2 years for the entire cohort. The risk-adapted approach would be declared non-inferior to the standard of care if the lower bound of an exact 1-sided 95% CI for MFS was > 64%. The study required 70 patients with a 4.5% type I error and 81.6% power. Results: 71 (ITT) patients were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of MVAC with 17% grade 3-4 TRAEs. In the ITT population, 33 (46%) had a relevant mutation and 26 (37%) began AS. With a median follow-up of 41 months, 47 patients (66%) are metastasis-free (CI 54%-77%). The 2-year MFS for the ITT patients (primary endpoint) was 72% (lower bound exact 1-sided 95% CI=62%). On post hoc analysis, the 2-year MFS was 65% in the AS group (CI 44%-83%) and 76% (CI 60%-87%) in the remaining patients (P=0.42). In the AS group, 18 patients (69%) had some UC recurrence, 8 had a cystectomy, 2 chemoradiation, and 13 (50%) are metastasis-free with an intact bladder. Of the 10 patients (38%) on AS who developed metastatic disease, 9 recurred with localized disease first. The 2-year OS is 83% (CI 72%-90%) and 89% (CI 68%-96%) in the ITT and AS groups, respectively. Associations between mutation presence and MFS or UC recurrence were not observed. Conclusions: The 72% 2-year MFS rate in this MIBC cohort treated with a risk-adapted approach did not satisfy the pre-specified non-inferiority condition. 38% of AS patients developed metastatic disease, with most patients first recurring locally in the bladder. With a median follow-up of 41 months, although 50% of AS patients have been able to avoid cystectomy without metastatic disease, further refinement of this approach is necessary. Clinical trial information: NCT02710734 .

PurposeWe report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up.Methods and materialsEligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen

Key Points Question Are external beam radiotherapy, with or without brachytherapy boost, or radical prostatectomy associated with differences in prostate cancer–specific mortality or distant metastasis outcomes in patients with high-risk prostate cancer after accounting for delivery of guideline-concordant multimodality therapy? Findings In this cohort study of 6004 men with high-risk prostate cancer and at least 1 additional adverse clinicopathologic feature, no differences in prostate cancer-specific mortality across treatment modalities were identified among patients who received guideline-concordant multimodality therapy, although differences in time to metastasis were observed. However, significant differences in prostate cancer–specific mortality were identified when guideline-concordant multimodality care was not delivered. Meaning These findings suggest that guideline-concordant multimodality care was associated with better prostate cancer–specific mortality outcomes for patients with high-risk prostate cancer., This cohort study assesses prostate cancer–specific mortality and distant metastasis outcomes among men with high-risk prostate cancer treated with radical prostatectomy or external beam radiotherapy with or without brachytherapy boost., Importance The optimal management strategy for high-risk prostate cancer and additional adverse clinicopathologic features remains unknown. Objective To compare clinical outcomes among patients with high-risk prostate cancer after definitive treatment. Design, Setting, and Participants This retrospective cohort study included patients with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network [NCCN]) and at least 1 adverse clinicopathologic feature (defined as any primary Gleason pattern 5 on biopsy, clinical T3b-4 disease, ≥50% cores with biopsy results positive for prostate cancer, or NCCN ≥2 high-risk features) treated between 2000 and 2014 at 16 tertiary centers. Data were analyzed in November 2020. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy boost (BT) with ADT. Guideline-concordant multimodal treatment was defined as RP with appropriate use of multimodal therapy (optimal RP), EBRT with at least 2 years of ADT (optimal EBRT), or EBRT with BT with at least 1 year ADT (optimal EBRT with BT). Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis was a secondary outcome. Differences were evaluated using inverse probability of treatment weight–adjusted Fine-Gray competing risk regression models. Results A total of 6004 men (median [interquartile range] age, 66.4 [60.9-71.8] years) with high-risk prostate cancer were analyzed, including 3175 patients (52.9%) who underwent RP, 1830 patients (30.5%) who underwent EBRT alone, and 999 patients (16.6%) who underwent EBRT with BT. Compared with RP, treatment with EBRT with BT (subdistribution hazard ratio [sHR] 0.78, [95% CI, 0.63-0.97]; P = .03) or with EBRT alone (sHR, 0.70 [95% CI, 0.53-0.92]; P = .01) was associated with significantly improved prostate cancer–specific mortality; there was no difference in prostate cancer–specific mortality between EBRT with BT and EBRT alone (sHR, 0.89 [95% CI, 0.67-1.18]; P = .43). No significant differences in prostate cancer–specific mortality were found across treatment cohorts among 2940 patients who received guideline-concordant multimodality treatment (eg, optimal EBRT alone vs optimal RP: sHR, 0.76 [95% CI, 0.52-1.09]; P = .14). However, treatment with EBRT alone or EBRT with BT was consistently associated with lower rates of distant metastasis compared with treatment with RP (eg, EBRT vs RP: sHR, 0.50 [95% CI, 0.44-0.58]; P

PURPOSE Radiotherapy (RT) plus long-term androgen suppression (AS) are a standard treatment option for patients with high-risk localized prostate cancer. We hypothesized that docetaxel chemotherapy (CT) could improve overall survival (OS) and clinical outcomes among patients with high-risk prostate cancer. PATIENTS AND METHODS The multicenter randomized NRG Oncology RTOG 0521 study enrolled patients with high-risk nonmetastatic disease between 2005 and 2009. Patients were randomly assigned to receive standard long-term AS plus RT with or without adjuvant CT. RESULTS A total of 612 patients were enrolled; 563 were evaluable. Median prostate-specific antigen was 15.1 ng/mL; 53% had a Gleason score 9 to 10 cancer; 27% had cT3 to cT4 disease. Median follow-up was 5.7 years. Treatment was well tolerated in both arms. Four-year OS rate was 89% (95% CI, 84% to 92%) for AS + RT and 93% (95% CI, 90% to 96%) for AS + RT + CT (hazard ratio [HR], 0.69; 90% CI, 0.49 to 0.97; one-sided P = .034). There were 59 deaths in the AS + RT arm and 43 in the AS + RT + CT arm, with fewer deaths resulting from prostate cancer in the AS + RT + CT arm versus AS + RT (23 v 16 deaths, respectively). Six-year rate of distant metastasis was 14% for AS + RT and 9.1% for AS + RT + CT, (HR, 0.60; 95% CI, 0.37 to 0.99; two-sided P = .044). Six-year disease-free survival rate was 55% for AS + RT and 65% for AS + RT + CT (HR, 0.77; 95% CI, 0.59 to 1.00; two-sided P = .053). CONCLUSION For patients with high-risk nonmetastatic prostate cancer, CT with docetaxel improved OS from 89% to 93% at 4 years, with improved disease-free survival and reduction in the rate of distant metastasis. The trial suggests that docetaxel CT may be an option to be discussed with selected men with high-risk prostate cancer.

The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.

PurposeOnly retrospective data are available for low-dose-rate (LDR) salvage prostate brachytherapy for local recurrence after external beam radiation therapy (EBRT). The primary objective of this prospective phase 2 trial (NCT00450411) was to evaluate late gastrointestinal and genitourinary adverse events (AEs) after salvage LDR brachytherapy.Methods and materialsEligible patients had low- or intermediate-risk prostate cancerbefore EBRT and biopsy-proven recurrence >30months after EBRT, with prostate-specific antigen levels

INTRODUCTION: Distinct PSA kinetics have been reported across the breadth of radiation modalities used to definitively treat prostate cancer. This study uses a patient-specific model to characterize and compare ideal PSA kinetics for low- and intermediate-risk prostate cancer following definitive treatment with conventionally fractionated (CFRT), hypofractionated (HFRT), ultra-hypofractionated or stereotactic body radiation therapy (SbRT), or brachytherapy, both high-dose-rate (HDR) and low-dose-rate (LDR). METHODS: This retrospective analysis includes patients with low- or intermediate-risk prostate cancer treated with definitive radiation between 1998 and 2018 at a single, NCI-designated Comprehensive Cancer Center. Patient demographics, treatment characteristics, and follow-up information were prospectively collected in an institutional database. Eligible patients had at least two PSA measurements within 24-months of treatment and were free from biochemical recurrence and receipt of androgen deprivation therapy. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed by radiation modality. Ideal PSA kinetics were characterized for each modality and compared. RESULTS: Of 1,047 patients included, 45% had low-risk prostate cancer, 37% had favorable intermediate-risk, and 19% had unfavorable intermediate-risk. The majority of patients were treated with CFRT or LDR; the smallest subset was 52 patients (5%) who received SbRT. nPSA measurements within the two-year follow-up period were significantly higher for those treated with ablative modalities, both as absolute nPSA values and relative to initial PSA (iPSA). Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% of those treated with non-ablative therapy (CFRT, HFRT, and LDR) reached a critical nPSA threshold of ≤0.5 ng/mL, while only 23% of SbRT and 33% of HDR cohorts achieved the same threshold. The overall incidence of bPSA was 13.3% and was not affected by treatment modality, Gleason Score, or prostate volume. A piecewise linear regression showed no statistically significant difference in the PSA decay rates between radiation modalities over time, though there was a trend toward faster PSA decay in ablative therapies between the 6–24-month period. CONCLUSION: Ablative therapies, such as HDR and SbRT, are associated with a latent PSA response and higher nPSA when compared to non-ablative therapies. Multivariate logistics modeling revealed younger age, iPSA above the mean, presence of bPSA, and receipt of ablative therapy as significant predictors for not achieving an nPSA ≤0.5 ng/mL. Understanding the different PSA kinetic profiles for the various radiation modalities is critical to assess treatment response and survey for disease recurrence.

PURPOSE/OBJECTIVE(S) The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown. MATERIALS/METHODS A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates. RESULTS Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment. CONCLUSION A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.

Purpose/objective(s) Occult non-localized disease (N1 or M1) at the time of definitive treatment of high-risk prostate cancer (HR-PCa) underlies most treatment failures. We recently developed a nomogram tuned to the identification of non-localized disease on prostate specific membrane antigen PET/CT (PSMA PET/CT) in patients with cN0M0 HR-PCa by conventional imaging, which incorporates iPSA, percent positive core on biopsy, Gleason Grade and cT stage. We systematically compared the prognostic performance of the PSMA nomogram against other validated risk stratification tools for HR-PCa. Materials/methods We identified 5275 men from a multi-institutional database treated with radical prostatectomy (55%), external beam radiation therapy (EBRT, 31%), or EBRT and brachytherapy (14%). The prognostic performance of the PSMA nomogram was compared against the STAR-CAP score, the Cancer of the Prostate Risk Assessment (CAPRA) score, Cambridge Prognostic Groups (CPG) risk group, and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram of 5-year recurrence probability. Accuracy was determined for 5- and 10-year distant metastasis (DM) and prostate cancer specific mortality (PCSM) using the concordance index (C-index). Results Median follow-up was 50.3 months (interquartile range 28.1-84.5 months). Overall, 16.1% developed DM, and 4.6% died from PCa. C-indices for the PSMA nomogram were 0.67 and 0.67 for 5- and 10-year DM, and 0.69 and 0.73 for 5- and 10-year PCSM, respectively. The PSMA nomogram outperformed CAPRA, CPG, and MSKCC for all endpoints, outperformed STAR-CAP for 10-year DM, and performed similarly to STAR-CAP for all other endpoints (see Table). The comparative performance between the tools was generally maintained at different follow-up times and in subgroup analyses stratified by primary treatment modalities. Conclusion A nomogram tuned to the detection of non-localized disease on PSMA/PET in HR-PCa patients is significantly prognostic of important clinical endpoints, with performance comparable to STAR-CAP and superior to other tools. These data strongly suggest that upstaging based on PSMA PET/CT provides clinically relevant information and warrant prospective validation.

Purpose We sought to compare changes in patient-reported quality of life (PRQOL) following stereotactic body radiation therapy (SBRT), high dose rate (HDR), and low dose rate (LDR) brachytherapy for prostate cancer. Materials and methods International Prostate Symptom Score (IPSS), Sexual Health Inventory For Men (SHIM), and Expanded Prostate cancer Index Composite Short Form (EPIC-26) were prospectively collected for men with low/intermediate-risk cancer treated at a single institution. We used Generalized Estimating Equations to identify associations between variables and early (3 to 6 mo) or late (1 to 2 y) PRQOL scores. Minimally important differences (MID) were compared with assess clinical relevance. Results A total of 342 LDR, 159 HDR, and 112 SBRT patients treated from 2001 to 2018 were eligible. Gleason score, PSA, and age were lower among LDR patients compared with HDR/SBRT. Unadjusted baseline IPSS score was similar among all groups. Adjusted IPSS worsened at all time points compared with baseline after LDR/HDR. At early/late time points, rates of IPSS MID after LDR were higher compared to HDR/SBRT. There were no IPSS differences between SBRT and HDR. All modalities showed early and late SHIM worsening. There were no temporal differences in SHIM between SBRT and brachytherapy. There were no differences in EPIC subdomains between HDR and SBRT. Bowel symptoms worsened early after SBRT, whereas urinary irritative/obstructive symptoms worsened late after HDR. Among all domains, MID after SBRT and HDR were similar. Conclusions In a cohort of patients treated with modern radiotherapy techniques, HDR and SBRT resulted in clinically meaningful improved urinary PRQOL compared with LDR.

Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA0.2 ng/mL and0.5 ng/mL, rates of nPSA0.4 ng/mL at 4 years, and BCRFS.Median follow-up was 72 months. Median nPSA and nPSA0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control.LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Background Optimal management of isolated local recurrence of prostate cancer after primary radiotherapy remains to be defined. Up-front androgen deprivation therapy (ADT) is widely used but may adversely affect the quality of life and is essentially a palliative treatment. Local salvage carries a different side-effect profile and is potentially curative, but it has not been compared to ADT. Materials and methods We conducted a propensity-matched analysis of cohorts of men treated with either whole gland cryotherapy (CRYO) or primary ADT following the diagnosis of locally recurrent prostate cancer. Our specific objectives were to compare overall survival (OS) and prostate cancer-specific mortality (PCSM) between CRYO vs. ADT. Results After a one-to-one matching, 169 patients from each cohort were included in comparisons. Median follow-up time was 6.7 years (ADT) vs. 18 years (CRYO). The 10-year PCSM was 18.5% (ADT) vs. 16.2% (CRYO), which was not statistically different [hazard ratioo (HR): 0.69, 95% CI: 0.36-1.34, p=0.27]. The median OS was 12.3 years (CRYO) versus 10.2 years (ADT) (HR: 0.63, 95% CI: 0.42-0.95, p=0.03). Conclusions While PCSM was similar between the two strategies, CRYO was associated with a longer OS compared to primary ADT. Given the retrospective nature of the trial, these results should be considered hypothesis-generating, and phase III trials comparing these two options are required to further explore these findings.

INTRODUCTION AND OBJECTIVE:External beam radiotherapy (EBRT) with androgen deprivation therapy (ADT), EBRT with a brachytherapy boost (EBRT+BT) with ADT, and radical prostatectomy (RP) with or with...

Initial reports suggest that COVID-19 can be particularly lethal in patients with cancer. This commentary discusses how to balance a delay in cancer diagnosis or treatment against the risk for a potential COVID-19 exposure, mitigate the risks for significant care disruptions associated with social distancing behaviors, and manage the appropriate allocation of limited health care resources in this unprecedented time of health care crisis.

PURPOSE The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use ( P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer–specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Importance In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. Objective To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. Design, Setting, and Participants This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. Exposures Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. Main Outcomes and Measures Prostate cancer–specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. Results Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). Conclusions and Relevance Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

Purpose Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. Methods and Materials The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer–specific survival, and distant metastasis–free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. Results The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P Conclusions To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.

Freedom from biochemical failure (FFBF) is a common primary outcome of randomized-controlled trials of prostate cancer (PCa). We aimed to determine how increasing the PCa biologically equivalent dose (BED) of external radiation therapy (RT) is correlated with FFBF and overall patient outcomes: overall survival (OS), distant metastasis (DM), and cancer-specific mortality (CSM); as well as genitourinary (GU), and gastrointestinal toxicities. We performed a meta-analysis of 6884 PCa patients from 12 randomized-controlled trials of external beam RT. Mixed effects regression models were used to estimate weighted linear relationships between BED and observed percentages of 5- and 10-year outcomes. For toxicities, a subset analysis of using 3-dimensional conformal RT (3D-CRT) versus intensity-modulated RT (IMRT) was performed. Increasing BED correlated with improved FFBF: 10-year absolute improvement of 9.6% and 7.2% for low-risk and intermediate-risk patients, respectively (P

Key Points Question Is previously occult, nonlocalized (regional or metastatic) disease detected on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) associated with clinically significant outcomes in patients with high-risk and very high-risk prostate cancer? Findings In this cohort study of 5275 patients, a nomogram estimative of an individual’s risk of nonlocalized disease on PSMA PET/CT was significantly associated with long-term outcomes, including distant metastasis and prostate cancer–specific mortality. The nomogram performed favorably compared with other risk-stratification tools. Meaning These findings suggest that previously occult disease may be associated with outcomes in this patient population., This cohort study evaluates the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and compares its performance with existing risk-stratification tools., Importance Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. Objectives To evaluate the prognostic significance of a nomogram that models an individual’s risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. Design, Setting, and Participants This cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. Exposures Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. Main Outcomes and Measures PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer–specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. Results Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

PURPOSE/OBJECTIVE(S) Limited published data address modifiable risk factors for significant toxicity complicating moderately hypofractionated schedules of intensity-modulated radiation therapy (IMRT) and proton-beam therapy (PBT) in patients with early-stage prostate cancer (PC). This study explored dosimetric predictors of Grade 3+ gastrointestinal (GI) and genitourinary (GU) toxicity following IMRT or PBT in this patient population. MATERIALS/METHODS The study population included patients from five tertiary referral centers treated from 2002-2018 for low- or intermediate-risk biopsy-proven prostate adenocarcinoma. All patients were treated with moderately hypofractionated radiation defined as 250-300 cGY per daily fraction given over 4-6 weeks. Primary outcomes were late GI and GU toxicity as defined by CTCAE v4.0. Dosimetric variables included PTV max dose, PTV volume, bladder V31 Gy, bladder V50 Gy, bladder V70 Gy, bladder max dose, rectum V31 Gy, rectum V50 Gy, rectum V70 Gy, rectum max dose, penile bulb V10 Gy, penile bulb V15 Gy, and the left and right femoral head V40 Gy. The association of dosimetric variables with treatment toxicity was assessed with the Wilcoxon signed-rank test. RESULTS Dosimetric data were obtained for 1139 patients, including 667 treated with IMRT and 472 treated with PBT. Median follow-up for the two groups was 46.0 and 48.5 months, respectively. Late toxicity rates for the total population were 4.7% for Grade 3+ GU toxicity and 1.5% for Grade 3+ GI toxicity. Grade 3+ GU toxicity was associated with prostate volume, bladder V31 Gy and bladder V50 Gy (P = 0.016, P = 0.018, P = 0.028), but not with bladder V70 Gy or maximum dose to the bladder. Grade 3+ GI toxicity was not associated with any of the dosimetric variables. When analyzed by treatment group, Grade 3+ GU toxicity was observed in 3% of the IMRT cohort and 1.7% of the PBT cohort. Grade 3+ GI toxicity was seen only in PBT and was observed in 1.5% of patients. Proton plans were associated with less radiation exposure of rectum and bladder at lower doses (rectum V31 Gy: 13% vs 16%, P < 0.001; bladder V31 Gy: 18% vs 26%, P < 0.001), while IMRT was associated with less radiation exposure of rectum and bladder at higher doses (rectum V70 Gy: 0.4% vs 2%, P < 0.001; bladder V70 Gy: 1% vs 3%, P < 0.001). Photon plans yielded superior V40 Gy to the femoral heads, and superior V10 Gy and V15 Gy to the penile bulb (P < 0.001, P < 0.003, P < 0.002). CONCLUSION In this multi-institutional analysis of 1139 early-stage PC patients treated with moderately hypofractionated IMRT or PBT, risk of serious late GU and GI complications was low for both treatment groups. Analysis of the dosimetric variables identified an association of Grade 3+ GU toxicity with low-dose radiation exposure of the bladder. Grade 3+ GI toxicity was unrelated to dosimetric variables. PBT plans yielded less exposure of non-target organs to lower-dose radiation while IMRT plans yielded less exposure of non-target organs to higher-dose radiation.

Purpose/Objective(s) Prospective data show improved biochemical control—at a cost of worse urinary and overall physical function scores—in patients receiving a low dose rate (LDR) prostate brachytherapy boost when compared to IMRT alone. An HDR prostate boost may cause less toxicity than LDR brachytherapy. We, therefore, compared patient status post an HDR prostate boost or IMRT alone to see if there were any differences in PRO data between groups. Materials/Methods American Urologic Association (AUA) symptom score and Sexual Health Inventory for Men (SHIM) score were prospectively collected for men with intermediate/high risk prostate cancer at a single institution. Genitourinary (GU) and gastrointestinal (GI) toxicity were also obtained and graded using the Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Patients had undergone either IMRT plus an HDR prostate boost (n = 53) or IMRT alone (n = 346). Patients were excluded if they had prior TURP, a history of irritable bowel disease (IBD), or a prostate size greater than 75 cc. PRO were compared at baseline and at 1-2 years. AUA and SHIM scores were compared using a two-sample Wilcoxon rank-sum test. Results We identified 346 patients treated between 2001 and 2018 with IMRT alone (80 Gy median EBRT dose) and 53 patients treated with HDR boost (46 Gy median EBRT dose). Patient characteristics and unadjusted PRO scores are reported below in the table. There was no grade 4 or 5 acute or late GU or GI events. Conclusion Zero grade 3 late GI events occurred in the IMRT plus HDR group, while 1.7% of patients (n = 6) in the IMRT alone group experienced late grade 3 GI toxicity; this difference was not statistically significant. Patients receiving an HDR boost have greater change in AUA score at 1-2 years compared to the IMRT alone patients; this change does not appear clinically significant. SHIM scores are higher in the HDR group before and after treatment, suggesting patients selected for a prostate boost may have better erectile function at baseline. Lastly, clinicians seem more comfortable withholding ADT in patients receiving an HDR prostate boost, possibly due to the higher ablative dose provided by HDR brachytherapy.

Introduction To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa). Methods We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group. Results There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12–185.8). The median NTDR was 31% (range 23–71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR

BACKGROUND The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. METHODS The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. RESULTS A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. CONCLUSIONS In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.