External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.

ACR-ABS-ASTRO Practice Parameter for Transperineal Permanent Brachytherapy of Prostate Cancer.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR), American Brachytherapy Society (ABS), and American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for transperineal permanent brachytherapy of prostate cancer. Transperineal permanent brachytherapy of prostate cancer is the interstitial implantation of low-dose rate radioactive seeds into the prostate gland for the purpose of treating localized prostate cancer. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. RESULTS: This practice parameter provides a framework for the appropriate use of low-dose rate brachytherapy in the treatment of prostate cancer either as monotherapy or as part of a treatment regimen combined with external-beam radiation therapy. The practice parameter defines the qualifications and responsibilities of all involved radiation oncology personnel, including the radiation oncologist, medical physicist, dosimetrist, radiation therapist, and nursing staff. Patient selection criteria and the utilization of supplemental therapies such as external-beam radiation therapy and androgen deprivation therapy are discussed. The logistics of the implant procedure, postimplant dosimetry assessment, and best practices with regard to safety and quality control are presented. CONCLUSIONS: Adherence to established standards can help to ensure that permanent prostate brachytherapy is delivered in a safe and efficacious manner.

Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts.

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 <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01). CONCLUSIONS AND RELEVANCE: These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.

Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer.

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 < .001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database. Conclusions and Relevance: These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement.

PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

Comparison of Multimodal Therapies and Outcomes Among Patients With High-Risk Prostate Cancer With Adverse Clinicopathologic Features.

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 < .001). Conclusions and Relevance: These findings suggest that among patients with high-risk prostate cancer and additional unfavorable clinicopathologic features receiving guideline-concordant multimodal therapy, prostate cancer-specific mortality outcomes were equivalent among those treated with RP, EBRT, and EBRT with BT, although distant metastasis outcomes were more favorable among patients treated with EBRT and EBRT with BT. Optimal multimodality treatment is critical for improving outcomes in patients with high-risk prostate cancer.

The Impact of Body Mass Index on Freedom From Therapeutic Intervention and Quality of Life in Active Surveillance Prostate Cancer Patients.

OBJECTIVE: The objective of this study was to evaluate the impact of body mass index (BMI) on overall survival, freedom from distant metastases, rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. MATERIALS AND METHODS: Three hundred forty consecutive, prospectively evaluated AS patients underwent a staging transperineal template-guided mapping biopsy before AS enrollment and were stratified by BMI (<25, 25 to 29.9, 30 to 34.9, and >35 kg/m2). Evaluated outcomes included overall survival, freedom from distant metastases, TI, QOL to include urinary, bowel, sexual function and depression and serial postvoid residual urine measurements. The relationship between BMI and anterior prostate cancer distribution was evaluated. Repeat biopsy was based on prostate specific antigen kinetics, abnormal digital rectal examination and patient preference. RESULTS: Of the 340 patients, 323 (95%) were Gleason 3+3 and 17 patients (5.0%) were Gleason 3+4. The median follow-up was 5.2 years (range: 1 to 14 y). At 10 years, TI was instituted in 4.7%, 2.2%, 9.5%, and 25.0% of patients in BMI cohorts <25, 25 to 29.9, 30 to 34.9, and ≥35 (P=0.075). No patient has developed distant metastases. The median time to TI was 4.86 years. In multivariate analysis, TI was most closely predicted by prostate specific antigen density (P=0.071). At 8 years, no statistical differences in urinary function, bowel function, depression or postvoid residual were noted. However, a trend for erectile dysfunction was identified (P=0.106). CONCLUSION: At 10 years, BMI did not statistically predict for TI, geographic distribution of prostate cancer or QOL parameters.

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer.

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.

Effect of the timing of hydrogel spacer placement on prostate and rectal dosimetry of low-dose-rate brachytherapy implants.

PURPOSE: To verify the dose sparing effect of hydrogel spacer (SpaceOAR™) on rectal dosimetry for prostate brachytherapy, and to determine whether prostate and rectal dosimetry was affected by the time gap between hydrogel spacer injection and brachytherapy dosimetry. MATERIAL AND METHODS: The 103Pd brachytherapy dosimetry of 174 consecutive intermediate- and high-risk patients injected with hydrogel was compared with a dosimetry of 174 contemporaneous patients without hydrogel injections. Of the SpaceOAR™ patients, 91 had hydrogel injected upon completion of brachytherapy implant, while the remaining 83 patients had hydrogel placed prior to external beam radiation therapy (EBRT), followed 2-10 weeks later by brachytherapy. Brachytherapy implants were either planned with the prostate undistorted by any hydrogel or planned with hydrogel in place. Dosimetry of the prostate and tissues at risk was determined from CT imaging on the day of brachytherapy implant. RESULTS: SpaceOAR™ significantly reduced mean and maximum rectal doses as well as rectal wall V50, but there was a statistically significant reduction of planning target volume (PTV) D90 to 121.1% of the prescribed dose in hydrogel patients compared to 123.3% in the non-hydrogel patients. Rectal dosimetry was similar between patients injected with hydrogel after brachytherapy and those with spacer injected prior to EBRT. However, patients who had hydrogel placed prior to EBRT had statistically significantly higher dosimetry indices of PTV and urethra relative to those with spacer placed at the completion of brachytherapy. CONCLUSIONS: There was a significant rectal dose sparing in the cohort with hydrogel spacer compared to a reference group without spacer injection. The rectal dose sparing effect was similar in the sub-group of patients injected with hydrogel prior to EBRT and the sub-group injected with hydrogel at the conclusion of brachytherapy.

The impact of age on prostate cancer progression and quality of life in active surveillance patients.

Objectives: To evaluate the impact of age on overall survival (OS), freedom from distant metastasis (FDM), rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients. Materials and methods: Three hundred and five consecutive, prospectively evaluated AS patients who underwent a staging transperineal template-guided mapping biopsy (TTMB) prior to enrollment on AS were evaluated and stratified by age. Evaluated outcomes included OS, FDM, TI, and QOL to include urinary, bowel, sexual function, and depression. Post void residual (PVR) urine measurements were also followed. Repeat biopsy was based on PSA kinetics, abnormal digital rectal examination or patient preference. Results: Of the 305 patients, 290 (95.1%) were Gleason 3 + 3 and 15 patients (4.9%) were Gleason 3 + 4. The median follow-up was 5.5 years (range 1-14 years). At 10 years, TI was 0%, 1.0%, and 11.4% for patients ≤59, 60-69, and ≥70 years of age (P < .001). No patient has developed distant metastasis. The median time to TI was 4.71 years. No statistical differences in urinary function, bowel function, or depression were noted. Potency preservation was dependent on patient age. Conclusion: Within the confines of the follow-up of our series, younger patients were less likely to proceed to therapeutic intervention. In addition, patient age did not adversely impact QOL outcomes.

CT-PLANNED transperineal prostate BIOPSY IN patients without a rectum.

A patient at risk of harboring prostate cancer with a history of ulcerative colitis surgically managed with total colectomy (including the distal rectum and anal canal) underwent CT-planned transperineal prostate biopsy with fluoroscopic guidance. We describe the planning and intraoperative technique to obtain prostate biopsy cores.

Associations of multimorbidity and patient-reported experiences of care with conservative management among elderly patients with localized prostate cancer.

BACKGROUND: Many elderly localized prostate cancer patients could benefit from conservative management (CM). This retrospective cohort study examined the associations of patient-reported access to care and multimorbidity on CM use patterns among Medicare Fee-for-Service (FFS) beneficiaries with localized prostate cancer. METHODS: We used linked Surveillance, Epidemiology, and End Results cancer Registry, Medicare Claims, and the Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey files. We identified FFS Medicare Beneficiaries (age ≥ 66; continuous enrollment in Parts A & B) with incident localized prostate cancer from 2003 to 2013 and a completed MCAHPS survey measuring patient-reported experiences of care within 24 months after diagnosis (n = 496). We used multivariable models to examine MCAHPS measures (getting needed care, timeliness of care, and doctor communication) and multimorbidity on CM use. RESULTS: Localized prostate cancer patients with multimorbidity were less likely to use CM (adjusted odds ratio (AOR)=0.42 (0.27- 0.66), P < .001); those with higher scores on timeliness of care (AOR = 1.21 (1.09, 1.35), P < .001), higher education attainment (3.21 = AOR (1.50,6.89), P = .003), and impaired mental health status (4.32 = AOR (1.86, 10.1) P < .001) were more likely to use CM. CONCLUSION(S): Patient-reported experience with timely care was significantly and positively associated with CM use. Multimorbidity was significantly and inversely associated with CM use. Addressing specific modifiable barriers to timely care along the cancer continuum for elderly localized prostate cancer patients with limited life expectancy could reduce the adverse effects of overtreatment on health outcomes and costs.

Prostate-only Versus Whole-pelvis Radiation with or Without a Brachytherapy Boost for Gleason Grade Group 5 Prostate Cancer: A Retrospective Analysis.

BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

Active surveillance outcomes in prostate cancer patients: the use of transperineal template-guided mapping biopsy for patient selection.

PURPOSE: To evaluate active surveillance (AS) outcomes including overall survival (OS), freedom from distant metastases (FDM), freedom from therapeutic intervention (FTI), and quality of life (QOL) outcomes in prostate cancer patients using transperineal template-guided mapping biopsy (TTMB) for patient selection. METHODS: From April 2005-January 2016, 226 consecutive, prospectively evaluated prostate cancer patients underwent TTMB for either low-grade prostate cancer or persistently elevated prostate-specific antigen (PSA) and/or the presence of ASAP. Evaluated outcomes included OS, FDM, FTI and QOL including urinary, bowel, sexual function and depression. Repeat biopsy was based on PSA kinetics and/or abnormal digital rectal examination. RESULTS: Of the 226 patients, 212 (93.8%) were Gleason 3 + 3 and 14 (6.2%) were Gleason 3 + 4. The median follow-up was 5.0 years (range 0.8-13.0 years). The mean prostate volume was 61.3 cm3 with a mean of 59.5 TTMB cores/patient. At the time of AS enrollment, an average of 72.9 cores (TRUS + TTMB) had been obtained for each patient. At 8 years, OS, FTI and FDM were 92.5, 96.8 and 100%. Two hundred and twenty-two patients (98.2%) had a PSA doubling time of more than 3 years. No statistical changes in urinary function, bowel function or depression were noted. At 8 years, 73% of the patients maintained erectile function. CONCLUSION: Within the confines of the follow-up of this study, the use of TTMB for patient selection identifies a cohort of patients unlikely to develop biochemical or clinical progression and maintain a favorable quality of life.

Clinical Outcomes for Patients With Gleason Score 10 Prostate Adenocarcinoma: Results From a Multi-institutional Consortium Study.

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 < .01 by χ2 test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048). 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.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

Importance: The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective: To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants: Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures: Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures: The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results: Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance: Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Impact of Androgen Deprivation Therapy on Overall Mortality in Prostate Brachytherapy Patients With Low Pretreatment Testosterone Levels.

OBJECTIVES: To evaluate whether the use of androgen deprivation therapy (ADT) in prostate brachytherapy patients impacts overall mortality (OM) in patients with lower pretreatment serum testosterone levels compared with those with normal or high baseline serum testosterone. MATERIALS AND METHODS: From October 2001 to May 2014, 1916 patients underwent brachytherapy and had a pretreatment serum testosterone. Baseline serum testosterone values were collected prospectively before initiation of therapy. Median follow-up was 7.2 years. In total, 26% of the patients received ADT, primarily men with higher risk disease. OM and prostate cancer-specific mortality were examined to determine whether men with lower baseline serum testosterone were at increased risk of mortality when ADT was used, compared with men with baseline normal or higher testosterone. RESULTS: Prostate cancer-specific mortality and OM at 10 years was 0.8% and 22.0%. Age, tobacco use, diabetes, cardiovascular disease, and percent positive biopsies were the strongest predictors of OM. ADT use by itself was not associated with an increased risk of OM on multivariate analysis (P=0.695). However, ADT use in men with lower baseline testosterone was associated with a significantly higher risk of OM (P<0.01). ADT use in men with normal or higher baseline testosterone was not associated with an increased OM risk (P=0.924). CONCLUSIONS: Men with lower baseline testosterone may be at increased risk of premature death when ADT is utilized compared with men with baseline normal or higher testosterone. Further analysis of this potential risk factor is warranted to further identify subsets of men who may be at higher risk of long-term adverse sequelae from ADT.

Does supplemental external beam radiation therapy impact urinary, bowel, and erectile function following permanent prostate brachytherapy?: results of two prospective randomized trials.

PURPOSE: To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function. MATERIAL AND METHODS: Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes. RESULTS: The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age. CONCLUSIONS: Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

Prostate cancer-specific death in brachytherapy treated high-risk patients stratified by pre-treatment PSA.

PURPOSE: To evaluate prostate-cancer specific mortality (PCSM) in a cohort of high-risk patients treated with a permanent prostate brachytherapy approach, stratified by pre-treatment PSA. MATERIAL AND METHODS: 448 high-risk patients (NCCN criteria) underwent permanent prostate brachytherapy. High risk patients were stratified by pre-treatment PSA (≤ 10.0, 10.1-20, and > 20 ng/ml). Biochemical failure (BF), prostate cancer-specific mortality (PCSM), distant failure (DM), and overall mortality (OM) were assessed as a function of prognostic group. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on outcome. RESULTS: The 10-year OM, BF, and PCSM for the entire cohort were 28.5%, 13.3%, and 4.9%, respectively. At 10 years, PCSM was 2.5%, 10.7%, and 4.5% in the PSA ≤ 10, 10.1-20, and > 20 ng/ml groups, respectively. No statistically significant differences in BF or overall survival (OS) were noted when stratified by pre-treatment PSA. DF was the most common in the 10.1-20 ng/ml cohort (8.6% at 10 years). In multivariate analysis, PCSM was most closely related to percent positive biopsies (p = 0.001) and tobacco (p = 0.042). CONCLUSIONS: High-risk prostate cancer treated with permanent prostate brachytherapy and supplemental external beam radiotherapy resulted in excellent long-term biochemical control and PCSM. Overall, PCSM was low in all cohorts but highest in the intermediate PSA group (10.1-20 ng/ml).