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Background: To determine the safety and maximum-tolerated dose of concurrent sunitinib and image-guided radiotherapy (IGRT) followed by maintenance sunitinib in oligometastastic patients.Methods: Eligible patients had 1 to 5 sites of metastatic cancer measuringResults: Twenty-one patients with 36 metastatic lesions were enrolled, with a median follow-up of 10 months. No dose limiting toxicities (DLT) were noted at dose levels 1 or 2 (SU 37.5 mg/RT 40 Gy). One of 10 patients at dose level 3 (SU 37.5 mg/RT 50 Gy) and 2 of 5 patients at dose level 4 (SU 50 mg/RT 50 Gy) experienced DLTs comprising grade 4 myelosuppression and grade 3 nausea. At last follow-up, 8 patients are alive without evidence of progression. The 1-year local, progression-free, and overall survival were 85%, 44%, and 75%, respectively.Conclusions: Addition of SU (25 to 37.5 mg) to IGRT is tolerable in patients with oligometastases, without potentiation of RT toxicity. On the basis of promising antitumor responses observed with this novel combination, a multi-institutional phase 2 trial using SU 37.5 mg/RT 50 Gy is ongoing. [ABSTRACT FROM AUTHOR]

Low-dose rate brachytherapy has become a mainstream treatment option for men diagnosed with prostate cancer because of excellent long-term treatment outcomes in low-, intermediate-, and high-risk patients. Largely due to patient lead advocacy for minimally invasive treatment options, high-quality prostate implants have become widely available in the US, Europe, and Japan. The reason that brachytherapy results are reproducible in several different practice settings is because numerous implant quality factors have been defined over the last 20 years, which can be applied objectively to judge the success of the intervention both during and after the procedure. In addition, recent long-term follow-up studies have clarified that the secondary cancer incidence of brachytherapy is not clinically meaningful. In terms of future directions, the study of radiation repair genetics may allow for the counseling physician to better estimate any given patients risk for side effects, thereby substantially reducing the therapeutic uncertainties faced by patients choosing a prostate cancer intervention. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to characterize the oncologic results and toxicity profile of patients treated with 125I implants using the dose delivered to 90% of the gland from the dose–volume histogram (D90) of greater than 144 Gy. Methods and Materials: From June 1995 to Feb 2005, a total of 643 patients were treated with 125I monotherapy for T1–T2 prostate cancer with a D90 of 180 Gy or greater (median, 197 Gy; range, 180–267 Gy). Implantations were performed using a real-time ultrasound-guided seed-placement method and intraoperative dosimetry to optimize target coverage and homogeneity by using modified peripheral loading. We analyzed biochemical disease-free survival (bDFS) of 435 patients who had a minimum 2-year prostate-specific antigen follow-up (median follow-up, 6.7 years; range, 2.0–11.1 years). Results: Five-year bDFS rates for the entire cohort using the American Society for Therapeutic Radiology and Oncology and Phoenix definitions were 96.9% and 96.5%, respectively. Using the Phoenix definition, 5-year bDFS rates were 97.3% for low-risk patients and 92.8% for intermediate/high-risk patients. The positive biopsy rate was 4.1%. The freedom rate from Grade 2 or higher rectal bleeding at 5 years was 88.5%. Acute urinary retention occurred in 10.7%, more commonly in patients with high pretreatment International Prostate Symptom Scores (p < 0.01). In patients who were potent before treatment, 73.4% remained potent at 5 years after implantation. Conclusions: Patients with a minimum D90 of 180 Gy had outstanding local control based on prostate-specific antigen control and biopsy data. Toxicity profiles, particularly for long-term urinary and sexual function, were excellent and showed that D90 doses of 180 Gy or greater performed using the technique described were feasible and tolerable. [Copyright &y& Elsevier]

Purpose: The risk of developing any cancer in carriers of the I1307K mutation of the adenopolyposis coli (APC) gene is significantly increased (odds ratio 1.5, P = 0.01). One of the cancers associated with the I1307K mutation is prostate cancer (odds ratio 2.0, P = 0.14). Also, there is an association of APC mutations with thyroid cancer. In this study, we measured triiodothyronine (t3) levels in Ashkenazi Jewish prostate cancer patients, with and without the I1307K mutation of the APC gene.Materials and Methods: Participants in our study were found through urology and radiation oncology clinics in 1999 and 2000. All eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. The I1307K allele of the APC gene was detected by amplification of DNA isolated from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Serum t3 level was determined by fluorescent immunoassay with a standard, commercially available instrument.Results: We studied 77 patients. The youngest patient was 46, the oldest 88, average age 67 +/- 7.2 (mean +/- SD). Eleven males carrying the APCI 1307K allele had significantly higher serum t3 levels than 66 males carrying the wild type allele. There were no homozygotes for the I1307K allele. None of the males had a t3 level that was above the normal range for our laboratory (137 ng/dl).Conclusions: Our findings of increased serum t3 level with the APC I1307K allele in prostate cancer patients is not surprising, given the mitogenic potential of t3. Further studies may clarify whether t3 elevation is the mechanism whereby APC gene mutations increase the risk of prostate cancer, or whether other pathophysiologic abnormalities are involved. [ABSTRACT FROM AUTHOR]

Objective: To investigate the safety and cancer control of a novel bioabsorbable, low-dose rate brachytherapy device, CivaSheet ® (CivaTech Oncology Inc., Durham, NC, USA), in combination with radical prostatectomy (RP) with or without adjuvant external beam radiation therapy (EBRT) for the management of prostate cancer (PCa)., Patients and Methods: This is an initial, single-centre experience, two-dose level, two-stage study conducted on patients with intermediate- and high-risk PCa. The CivaSheet was implanted during RP, followed by adjuvant EBRT in patients with adverse pathological features. Toxicities and peri- and postoperative complications were assessed. Biochemical recurrence (BCR) at the 6-month follow-up after EBRT was also evaluated., Results: Six patients were enrolled, with a median (range) age of 56 (53-71) years. No intraoperative complications occurred. No dose-limiting toxicities were observed at a maximum tested dose of 75 Gy. BCR occurred in one patient at 6 months, while another patient had residual disease and metastasis at 6 months. All patients reported having postoperative erectile dysfunction and one patient experienced urinary incontinence after EBRT., Conclusions: This study demonstrated the feasibility and safety of CivaSheet combined with RP and adjuvant EBRT for high-risk PCa. The short-term toxicity profile was well-tolerated, supporting further prospective evaluation with clinical trials., (© 2024 BJU International.)

Purpose/objectives: To characterize the clinical course and prognosis of bladder malignancies associated with prior prostate brachytherapy SUBJECTS/PATIENTS AND METHODS: We queried our institutional database for patients with bladder cancer (BC) diagnosed between January 2005 and April 2019 who had previously undergone low dose rate (LDR) prostate brachytherapy. Patients diagnosed with BC at least 1 year following LDR prostate brachytherapy with or without external beam radiation therapy were included. Clinical and disease-specific characteristics were abstracted from chart review and survival outcomes were estimated using Kaplan-Meier estimates. We compared the pathologic characteristics and prognosis of secondary BCs in our study cohort to those of BCs diagnosed after prostate cancer managed without radiation reported by the Surveillance, Epidemiology, and End Results (SEER) populational database from 2005 to 2018., Results: Three hundred seventy-five patients were identified with combined diagnosis of prostate cancer and BC, 51 of whom met inclusion criteria in the study cohort. Median times from brachytherapy to BC diagnosis for the study and SEER cohort were 9.5 ± 4.5 and 6.3 ± 4.1 years, respectively. Compared to the SEER cohort, significantly greater proportion of BC from the study cohort presented with high-grade (study: 78.4%, SEER: 52.3%, P = 0.0008) and with MIBC (Study BC 35.3%, SEER BC: 17.5%, P = 0.0009). The study and the SEER cohort had similar 5-year overall survival (study: 67.9%, SEER: 58.0%, P = 0.1099), and 5-year cancer-specific survival (study: 81.0%, SEER: 82.8%, P = 0.5559). The 5-year progression-free survival for the study cohort was 43.7% (95% CI: 28.8-57.7)., Conclusion: Compared to bladder cancers following prostate cancer managed without radiation, bladder malignancies following prostate LDR brachytherapy present with higher grade and are more likely to be muscle invasive. Despite the aggressive presenting features of postprostate brachytherapy BC, there were no differences in overall and cancer-specific survival between the groups., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To compare biochemical recurrence free survival (BCRFS) and cancer-specific survival (CSS) after brachytherapy using the AUA and the Phoenix definitions., Methods and Materials: 2634 men with T1-T4N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant hormonal therapy or external beam radiation therapy. Five, 10, and 15- year BCRFS and CSS were estimated with Kaplan-Meier estimates with log rank. Multivariate analysis of survival was performed with Cox regression analysis., Results: Median age was 66, follow-up was 8.6 years, and prostate specific antigen was 6.9. Overall, 11.1% (n = 293) of patients experienced Phoenix BCR and 17.48% (n = 457) experienced AUA BCR. The rates of AUA BCR and Phoenix BCR were significantly different at 5 and 10-years but not at 15 years. Patients treated with BED ≤ 200 Gy were more likely to experience AUA BCR (22.5% vs. 12.4%, OR 1.44, p < 0.001) and Phoenix BCR (14.3% and 8.3%, OR 1.37, p < 0.001) than patients treated with a BED > 200 Gy., Conclusions: Compared to the Phoenix definition, the AUA definition of BCR after brachytherapy is associated with significantly worse BCRFS for the first 15 years after treatment. Receiving a BED > 200, which cannot be achieved without the addition of brachytherapy, is associated with better BCRFS and CSS. Our findings reaffirm the importance of dose in the management of prostate cancer., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The breakthrough of a limited number of clones while on immune checkpoint inhibitors (ICIs), known as oligoprogression, has been previously described. The benefit of ablative radiation therapy (RT) directed at these clones, as opposed to changing systemic therapy, is unclear. We analyzed 30 patients with advanced solid tumors, the majority of whom (23/30, 86.7%) had either hepatocellular or urothelial carcinoma, who experienced oligoprogression on ICIs and were referred for RT. In this study, oligoprogression was defined as having experienced progression at three or fewer metastatic sites outside of the brain after achieving at least stable disease on ICIs for a minimum of three months. The median time to oligoprogression was 11.1 months from the initiation of immunotherapy. 24 patients had one oligoprogressive lesion and six had two. The median radiation dose delivered was 4650 cGy in a median of five fractions. The median progression-free survival (PFS) after RT was 7.1 months, and the time to oligoprogression was not a significant predictor of PFS2. 26 patients continued on ICIs after RT. While 17 patients subsequently progressed, 15 did so at three or fewer metastatic sites and could have theoretically stood to benefit from an additional course of salvage RT to further extend the lifespan of their ICIs. Overall survival at 6, 12, and 24 months was 100.0%, 96.3%, and 82.8%, respectively. These results suggest that RT may provide a PFS benefit and extend the lifespan of ICIs in patients who experience oligoprogression. Regardless of PFS, however, overall survival in this population appears to be excellent.

Background and Purpose: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy., Methods and Materials: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards., Results: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy., Conclusions: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Prostate cancer is a significant cause of morbidity and mortality among men worldwide. Although most patients present with localized or regional disease and experience excellent outcomes with treatment, approximately 10% to 20% of patients develop castrate-resistant prostate cancer (CRPC) within 5 years of diagnosis. Bone metastases, which can cause pain and adversely affect quality of life, are common among this population. Radium-223 has a relatively short half-life and decays via α-decay. Its daughter products, α-particles, have a short path length in tissue and exhibit high linear energy transfer. Together, these properties allow radium-223 to achieve relatively high cell kill in its target tissue while sparing the surrounding normal tissues. Administered in the clinic as radium-223 dichloride (Xofigo), radium-223 acts as a calcium mimetic in the human body, forming complexes with hydroxyapatite. In areas of high bone turnover, such as the osteoblastic bone metastases that are common in patients with CRPC, radium-223 is preferentially incorporated into the bone matrix, where it can exert an antitumor effect. In May 2013, the U.S. Food and Drug Administration approved Xofigo for use in patients with CRPC who have symptomatic bone metastases and no visceral metastases. In this topic discussion, we review the mechanism of action and clinical efficacy of radium-223 in patients with metastatic CRPC. We also discuss its administration and handling, distribution and elimination, and associated toxicities., (Copyright © 2022. Published by Elsevier Inc.)

Background: Radium-223 is used for the treatment of osseous metastases in castrate-resistant prostate cancer, and has been shown to increase time to the first skeletal-related event, reduce the rate of hospitalization, and improve quality of life. It is well tolerated, with hematologic toxicity as the main adverse event. Thus far, no ocular complication has been reported in the literature after initial administration of radium-223 with a single case reported of ocular complications after a patient's second course of radium-223., Case Presentations: We present three cases of ocular complications after the use of radium-223 in patients with metastatic prostatic adenocarcinoma. Ocular complications presented as blurry vision, and formal diagnosis included uveitis and hyphema., Conclusions: Documentation of adverse events is exceedingly important due to the high incidence of metastatic prostate cancer and increasing interest for the use of radium-223 in other osteoblastic disease. The authors postulate that these ocular complications may be a result of radiation's potential effect on neovascularization, polypharmacy, or the biomolecular effects of radium-223 on integral signaling proteins, potentially coupled with poor underlying ocular health., (© 2022. The Author(s).)

Background and Purpose: Genome-wide association studies (GWAS) of late hematuria following prostate cancer radiotherapy identified single nucleotide polymorphisms (SNPs) near AGT, encoding angiotensinogen. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEi) have a reduced risk of late hematuria. We additionally tested genetically-defined hypertension., Materials and Methods: Prostate cancer patients undergoing potentially-curative radiotherapy were enrolled onto two multi-center observational studies, URWCI (N = 256) and REQUITE (N = 1,437). Patients were assessed pre-radiotherapy and followed prospectively for development of toxicity for up to four years. The cumulative probability of hematuria was estimated by the Kaplan-Meier method. Multivariable grouped relative risk models assessed the effect of ACEi on time to hematuria adjusting for clinical factors and stratified by enrollment site. A polygenic risk score (PRS) for blood pressure was tested for association with hematuria in REQUITE and our Radiogenomics Consortium GWAS., Results: Patients taking ACEi during radiotherapy had a reduced risk of hematuria (HR 0.51, 95%CI 0.28 to 0.94, p = 0.030) after adjusting for prior transurethral prostate and/or bladder resection, heart disease, pelvic node radiotherapy, and bladder volume receiving 70 Gy, which are associated with hematuria. A blood pressure PRS was associated with hypertension (odds ratio per standard deviation 1.38, 95%CI 1.31 to 1.46, n = 5,288, p < 0.001) but not hematuria (HR per standard deviation 0.96, 95%CI 0.87 to 1.06, n = 5,126, p = 0.41)., Conclusions: Our study is the first to show a radioprotective effect of ACEi on bladder in an international, multi-site study of patients receiving pelvic radiotherapy. Mechanistic studies are needed to understand how targeting the angiotensin pathway protects the bladder., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

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.

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

Aim: To identify the effect of single nucleotide polymorphism (SNP) interactions on the risk of toxicity following radiotherapy (RT) for prostate cancer (PCa) and propose a new method for polygenic risk score incorporating SNP-SNP interactions (PRSi)., Materials and Methods: Analysis included the REQUITE PCa cohort that received external beam RT and was followed for 2 years. Late toxicity endpoints were: rectal bleeding, urinary frequency, haematuria, nocturia, decreased urinary stream. Among 43 literature-identified SNPs, the 30% most strongly associated with each toxicity were tested. SNP-SNP combinations (named SNP-allele sets) seen in ≥10% of the cohort were condensed into risk (RS) and protection (PS) scores, respectively indicating increased or decreased toxicity risk. Performance of RS and PS was evaluated by logistic regression. RS and PS were then combined into a single PRSi evaluated by area under the receiver operating characteristic curve (AUC)., Results: Among 1,387 analysed patients, toxicity rates were 11.7% (rectal bleeding), 4.0% (urinary frequency), 5.5% (haematuria), 7.8% (nocturia) and 17.1% (decreased urinary stream). RS and PS combined 8 to 15 different SNP-allele sets, depending on the toxicity endpoint. Distributions of PRSi differed significantly in patients with/without toxicity with AUCs ranging from 0.61 to 0.78. PRSi was better than the classical summed PRS, particularly for the urinary frequency, haematuria and decreased urinary stream endpoints., Conclusions: Our method incorporates SNP-SNP interactions when calculating PRS for radiotherapy toxicity. Our approach is better than classical summation in discriminating patients with toxicity and should enable incorporating genetic information to improve normal tissue complication probability models., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Rectal hydrogel spacers have been shown to decrease rectal radiation dose and toxicity. In this study, we compared prostate and rectal dosimetry and acute toxicity outcomes in patients who had and had not received a rectal hydrogel spacer prior to combination therapy with external beam radiotherapy and low-dose-rate brachytherapy., Materials and Methods: All patients with intermediate-risk and high-risk prostate cancer who received combination therapy at our institution were identified between 2014 and 2019. Dosimetric outcomes of brachytherapy implants and quality of life (QOL) outcomes were compared between patients who had and had not received a hydrogel spacer., Results: A Total of 168 patients meeting our inclusion criteria were identified. Twenty-two patients had received a rectal hydrogel spacer, among whom the mean separation between the rectum and prostate was 7.5 mm, and the V100 rectum was reduced by 47% (0.09 cc vs. 0.17 cc, p = 0.04). There was no difference in the percentage of patients achieving a D90 of ≥100 Gy between those who had and had not received a spacer. The mean rate of change in I-PSS and SHIM scores did not differ between the two groups at 2 months after PID., Conclusion: LDR brachytherapy appears feasible after the placement of a rectal hydrogel spacer. While there was a significantly reduced V100 rectum among patients who had received a hydrogel spacer, there was no statistically significant difference in patients achieving a D90 prostate of ≥100 Gy. Although there was no difference appreciated in QOL scores, the length of follow-up was limited in the rectal-spacer group., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT., Materials and Methods: We included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan-Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0., Results: 108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02-1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004-1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up., Conclusions: Salvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

As a single organ distributed diffusely throughout the body, bones represent both a unique challenge and unique opportunity for the treatment of symptomatic metastatic disease. While the multifocality of bone metastases often prevents effective complete treatment with focal radiotherapy, the similar pathophysiology of these diffuse sites of disease opens the door to targeted systemic therapy. The relatively rapid dose fall-off from beta- or alpha-emitting particles, if correctly and reliably targeted to osseous metastases, might reduce tumor burden and enhance pain control or improve survival. Radioisotopes have thus been studied keenly with the first generation of primarily beta-emitting radioisotopes, strontium-89 and samarium-153, which reached early FDA approval based on successful endpoints of pain control. More recently, an alpha-emitting therapy, radium-223, has demonstrated a successful endpoint of improved overall survival in patients with a burden of symptomatic, metastatic castrate-resistant prostate cancer (mCRPC) confined to the bones. With this discovery, an additional survival-improving tool beyond systemic and hormonal agents was added to the treatment arsenal for mCRPC for suitable candidates. With an improved understanding of the optimization of hormonal and systemic therapies in the context of mCRPC, there is lingering uncertainty regarding the safety and efficacy of combinatorial use of alpha and beta-emitting therapies with the current generation of systemic agents. In this narrative review, we will highlight the current understanding of the relative utility and clinical paradigms involving alpha- and beta-emitting radioisotopes. We discuss fundamental mechanisms for antineoplastic activity, initial clinical trials validating their use, the use of concurrent antiresorptive therapies to provide bone protection, and ongoing clinical trials targeted at best utilization of these agents in the broader context of mCRPC treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Education and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician-physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs., Methods: The ABS, in partnership with industry and academia, has held three radiation oncology team-based LDR/HDR workshops composed of physician-physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop., Results: Of the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR)., Conclusions: The ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: REQUITE (validating pREdictive models and biomarkers of radiotherapy toxicity to reduce side effects and improve QUalITy of lifE in cancer survivors) is an international prospective cohort study. The purpose of this project was to analyse a cohort of patients recruited into REQUITE using a deep learning algorithm to identify patient-specific features associated with the development of toxicity, and test the approach by attempting to validate previously published genetic risk factors. Methods: The study involved REQUITE prostate cancer patients treated with external beam radiotherapy who had complete 2-year follow-up. We used five separate late toxicity endpoints: ≥grade 1 late rectal bleeding, ≥grade 2 urinary frequency, ≥grade 1 haematuria, ≥ grade 2 nocturia, ≥ grade 1 decreased urinary stream. Forty-three single nucleotide polymorphisms (SNPs) already reported in the literature to be associated with the toxicity endpoints were included in the analysis. No SNP had been studied before in the REQUITE cohort. Deep Sparse AutoEncoders (DSAE) were trained to recognize features (SNPs) identifying patients with no toxicity and tested on a different independent mixed population including patients without and with toxicity. Results: One thousand, four hundred and one patients were included, and toxicity rates were: rectal bleeding 11.7%, urinary frequency 4%, haematuria 5.5%, nocturia 7.8%, decreased urinary stream 17.1%. Twenty-four of the 43 SNPs that were associated with the toxicity endpoints were validated as identifying patients with toxicity. Twenty of the 24 SNPs were associated with the same toxicity endpoint as reported in the literature: 9 SNPs for urinary symptoms and 11 SNPs for overall toxicity. The other 4 SNPs were associated with a different endpoint. Conclusion: Deep learning algorithms can validate SNPs associated with toxicity after radiotherapy for prostate cancer. The method should be studied further to identify polygenic SNP risk signatures for radiotherapy toxicity. The signatures could then be included in integrated normal tissue complication probability models and tested for their ability to personalize radiotherapy treatment planning., (Copyright © 2020 Massi, Gasperoni, Ieva, Paganoni, Zunino, Manzoni, Franco, Veldeman, Ost, Fonteyne, Talbot, Rattay, Webb, Symonds, Johnson, Lambrecht, Haustermans, De Meerleer, de Ruysscher, Vanneste, Van Limbergen, Choudhury, Elliott, Sperk, Herskind, Veldwijk, Avuzzi, Giandini, Valdagni, Cicchetti, Azria, Jacquet, Rosenstein, Stock, Collado, Vega, Aguado-Barrera, Calvo, Dunning, Fachal, Kerns, Payne, Chang-Claude, Seibold, West and Rancati.)

Background and Purpose: 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)., Methods and Materials: 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 nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS., Results: Median follow-up was 72 months. Median nPSA and nPSA <0.2 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 nPSA <0.4 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., Conclusion: LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Brachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy., Methods and Materials: Of 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ 2 test with survival determined by the Kaplan-Meier method and Cox regression., Results: Men treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150-200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes., Conclusions: Brachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Men with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT)., Methods and Materials: Three hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan-Meier method with associations determined by log rank and Cox regression., Results: Ten-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001)., Conclusions: Survival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: A genetic test predicting susceptibility for the development of toxicities after prostate cancer radiation therapy is in development. This test intends to help physicians with treatment decision making., Methods and Materials: Radiation oncologists were surveyed using a web-based questionnaire to gauge their interest in using a genetic test predictive of increased risk of radiation therapy toxicities as an aid in determining therapy for men with prostate cancer. Responses were summarized using frequencies, and a χ 2 test compared responses among participants. Multivariable ordinal regression identified factors associated with anticipated adoption or nonadoption of such a genetic test by radiation oncologists., Results: Among 204 radiation oncologists (64% from the United States, 36% from other countries), 86.3% would order a genetic test and 80.2% said the test would be useful for treatment discussions. There was wide acceptance (76.7%) to offer a genetic test to all patients considering radiation therapy for prostate cancer. Additionally, 98.1% indicated that patients would be receptive to the test information. There were no significant differences in the likelihood of ordering a genetic test based on practice setting, familiarity with scientific literature, time spent on research, or geographic location (all P > .05)., Conclusions: Radiation oncologists who treat prostate cancer are interested in and willing to order a genetic test predictive of susceptibility to radiation therapy toxicity to aid their treatment decision making., (© 2020 The Authors.)

Purpose: To identify variables that predict persistent hypogonadism and castration in patients with prostate cancer (PCa) treated with brachytherapy (BT)., Materials and Methods: A retrospective analysis was performed on 1,053 patients receiving BT ± external beam radiation therapy (EBRT) ± hormone therapy (HT) for NCCN low, intermediate, or high-risk PCa between 1990 and 2011. Patients were categorized as not receiving HT (n = 438, 41.6%), ≤6 months (n = 317, 31.1%) or > 6 months (n = 298, 28.3%) of HT. 572 (54.3%) received BT alone, and 481 had combination therapy. The five- and 10-year freedom from persistent hypogonadism (T < 280 ng/dL) and castration (T < 50 ng/dL) for each group was evaluated with Kaplan-Meier estimates. Multivariable cox proportional hazards models were used to compare the risk of persistent hypogonadism and castration at a median followup of 6.5 years (posttreatment to final T) (IQR: 4.3-9.1 years; range: 1.0-19.2 years)., Results: The 5-year freedom from hypogonadism rates were 92.4%, 88.9%, and 87.0% for patients with no HT, ≤ 6 months and >6 months of HT, respectively (10-year rates: 66.7%, 55.3%, 40.5%); p < 0.01. The 5-year freedom from castration rates were 99.2%, 98.0%, and 98.4%, respectively (10-year rates: 97.9%, 95.5%, 90.9%); p = 0.078. Number of months of HT (HR = 1.04, p = 0.030) and BT with EBRT vs. BT alone (HR = 1.56, p = 0.010) significantly increased the risk of persistent hypogonadism. Number of months of HT was the only variable which increased the risk of persistent castration (HR = 1.09, p = 0.014)., Conclusions: The addition of EBRT to BT is an independent risk factor for persistent hypogonadism. Prolonged HT additionally increases the risk of persistent hypogonadism and castration., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: While the concept of oligometastatic disease is increasingly recognized as a distinct clinical disease state, the concept of oligoprogression is less well-characterized. Oligoprogression may be particularly relevant in the context of immune checkpoint inhibitors (CPI) given the underlying mechanism of action and insights regarding acquired resistance. In this study, we sought to characterize the incidence of oligoprogression in patients on CPI and explore the impact of local therapy., Materials and Methods: We performed a retrospective analysis of all patients with advanced solid tumors (excluding glioblastoma multiforme) who received a PD-1, PD-L1, or CTLA-4 inhibitor at a single institution between 2011 and 2017. Oligoprogression was defined as progression at ≤3 metastatic lesions outside of the brain after achieving at least stable disease on CPI for 3 months. Progression-free survival (PFS) was calculated using the Kaplan-Meier method., Results: Among 425 patients treated with CPI, 390 had advanced primary solid tumors outside of the central nervous system. 321 of these patients were evaluable for response, among whom 102 achieved at least stable disease. Oligoprogression was observed in 4.1% of the entire cohort and 15.7% of patients achieving at least stable disease on CPI. Among 16 patients experiencing oligoprogression, 15 received local therapy to the oligoprogressive lesions, many of whom continued CPI. At a median follow-up of 25.8 months, the median PFS for patients with oligoprogression after local therapy was 15.4 months., Conclusions: Oligoprogression occurs in a subset of patients after an initial response to CPI. However, patients receiving local therapy to oligoprogressive sites may experience durable disease control. Further study is warranted., Microabstract: Oligoprogression was observed in 4.1% of the entire cohort of patients on immune checkpoint inhibitors in this study and 15.7% of patients achieving at least stable disease. Among 16 patients experiencing oligoprogression, 15 received local therapy. At a median follow-up of 25.8 months, the median progression-free survival for patients with oligoprogression after local therapy was 15.4 months and zero patients had died. Oligoprogression occurs in a subset of patients after an initial response to CPI and local therapy to oligoprogressive sites may result in durable disease control., (Copyright © 2020. Published by Elsevier Ltd.)

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., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the long-term urinary outcomes of men with severe pretreatment lower urinary tract symptoms (LUTS) treated with permanent prostate brachytherapy (PPB) ± external beam radiation therapy for localized prostate cancer., Methods and Materials: A total of 105 men with International Prostate Symptom Score (IPSS) 20-35 before PPB were categorized by IPSS change at last followup: (1) worse = IPSS rise >3; (2) no change = IPSS change within three points of baseline; (3) improved = IPSS fall by >3 points. We then evaluated patients who worsened vs. those who did not (no change or improved) with respect to incontinence outcomes, LUTS medication usage, and predictors of symptom worsening., Results: Mean followup was 80.3 ± 55.8 months. Mean age was 66.3 ± 7.1 years; mean pretreatment IPSS was 23.6 ± 3.0. Overall mean improvement in IPSS was 7.6 ± 9.3. Specifically, 14.3% (15/105) worsened, 21.9% (23/105) had no significant change, and 63.8% (67/105) improved. There were no patient- or treatment-related factors significantly associated with long-term worsening of urinary symptoms. No men required anticholinergic therapy at last followup, whereas 7% (8/105) were using an alpha blocker. Only 2.9% (3/105) of men were using at least one pad daily at last followup. Alternatively, only 7.7% (8/105) reported subjective incontinence., Conclusions: PPB is an acceptable option in the setting of severe baseline LUTS in appropriately selected and counseled patients when performed by a skilled practitioner., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the oncological and functional outcomes of young men treated with low-dose-rate brachytherapy (BT) for prostate cancer (PCa)., Materials and Methods: 423 men aged ≤60 years with clinically localized PCa were treated with BT ± external beam radiation. Biochemical failure was defined by Phoenix criteria. Freedom from biochemical failure (FFbF) and cancer-specific survival (CSS) at 10 and 15 years were estimated by the Kaplan-Meier method with the log-rank test to compare outcomes between National Comprehensive Cancer Network risk groups. The Cox proportional hazards model was used to determine significant predictors for FFbF and CSS., Results: Median followup was 9.9 years (range, 5.1-21.7). Median age was 57 years (range, 39-60), and median prostate-specific antigen was 6.1 ng/mL (range, 0.8-71). Overall, 10- and 15-year FFbF rates were 89% and 88%; 10- and 15-year CSS rates were 99% and 98%. Increasing disease risk was associated with lower FFbF and CSS (p < 0.0001). Biologically effective dose (p < 0.0001) and use of external beam radiation (p = 0.005) were significantly associated with higher FFbF. In men potent before BT, 64% (151/237) had preserved erectile function at a median 10.2 years. There was no significant difference between treatment groups with respect to long-term urinary function (p = 0.56)., Conclusions: Younger men treated with BT experience excellent long-term PCa control with low rates of treatment-related toxicity., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To report the long-term results of prostate brachytherapy followed by external beam radiotherapy (EBRT) in men with a positive seminal vesicle biopsy (+SVB)., Patients and Methods: In all, 1081 men with localised prostate cancer were treated with permanent brachytherapy, of which 615 had staging SVB and 53 (9.4%) were positive. Higher stage, Gleason score and PSA level were associated with a +SVB (P < 0.001). Patients with +SVB and negative laparoscopic pelvic lymph node dissection, bone and CT scans had 3 months of androgen-deprivation therapy (ADT) followed by 103 Pd implant to the prostate (dose 100 Gy) and proximal SVs, and 2 months later 45 Gy EBRT. ADT was continued for a median of 6 months (total ADT 9 months). The mean (range) follow-up was 9 (5-22) years., Results: Biochemical freedom from failure (computed by the Phoenix definition), freedom from metastasis, and cause-specific survival (CSS) for patients with a negative SVB (-SVB) vs +SVB at 15 years, was 76.3% vs 60.6% (P = 0.001), 95.4% vs 78.2% (P < 0.001), and 95% vs 70.4% (P < 0.001), respectively. Prostate cancer death occurred in 45 of 590 (7.6%) men with a -SVB vs eight of 25 (32%) with a +SVB (odds ratio 5.7, 95% confidence interval 2.35-13.9, P < 0.001). Cox proportion hazard rates (HRs) demonstrated Gleason score (P < 0.001, HR 1.9), stage (P = 0.010, HR 1.42), RT dose (P = 0.013, HR 0.991), and +SVB (P = 0.001, HR 4.48), as significantly associated with CSS., Conclusions: Men with a +SVB have inferior CSS compared to those with a -SVB. However, a strategy that included a SVB in high-risk patients and implantation of the SVs in men undergoing combined therapy still yields favourable long-term results., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To determine which patient and treatment-related factors are associated with increased American Urological Association symptom score (AUASS) in men who presented with minimal symptoms before treatment for prostate cancer by permanent seed implantation., Patients and Methods: Of 1842 men with a minimum follow-up of 5 years (mean 9.4), 1110 (60.3%) had an initial AUASS of 0-7 and were treated with brachytherapy (BT) alone (n = 491) or BT with neoadjuvant hormone therapy (NHT) and/or external beam radiation therapy (EBRT, n = 619). The median prostate volume was 37 mL. Data were prospectively collected on comorbidities. Initial AUASS was compared to last using a Student's t-test (two-tailed). Freedom from increasing from minimal to moderate or severe symptoms was determined by the Kaplan-Meier method with comparisons by log-rank and Cox hazard rates (HRs)., Results: The change from pre-treatment score for the minimal, moderate and severe symptom groups was: 3.6-7.3 (P < 0.001), 11.6-11.3 (P = 0.426), and 24.1-16.9 (P < 0.001). For those with minimal symptoms the 10- and 15-year estimates for freedom from worse symptoms were 72.9% and 39.1%, respectively. Cox HRs were significant for EBRT boost (HR 1.45, P = 0.004), RT dose >200 Gy 2 (HR 1.25, P = 0.024), hypertension (HR 1.37, P = 0.006), and alcohol use (HR 1.46, P = 0.001)., Conclusion: A substantial number of men with initial low AUASS treated by BT experience worsening urinary symptoms with long-term follow-up. Use of EBRT, RT dose, hypertension and alcohol use are risk factors for an increase in urinary symptom score., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

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 χ 2 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To examine biochemical control, survival, and late morbidity with definitive low-dose-rate brachytherapy (LDR-BT) for patients with prostate cancer surviving for >10 years after treatment., Patients and Methods: We identified 757 men with localised prostate cancer who underwent definitive LDR-BT in the period 1990-2006 and were followed for >10 years at our institution. Biochemical failure-free survival (BFFS), distant metastases-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were selected as study endpoints. Survival was examined using the log-rank test, Kaplan-Meier method, and Cox regression modelling. Urinary, quality of life (QoL), and potency scores at baseline and last follow-up were recorded., Results: The median follow-up was 12.5 years (range, 10.1-21.8 years). At the time of analysis, 88.6% of patients were alive, 1.5% died from prostate cancer and 13.9% developed biochemical failure, with 82% of failures occurring in the first decade of follow-up. Overall, 2.3% developed distant metastases. On multivariate analyses, stage T3a-T3b, prostate-specific antigen level of >20 ng/mL, intermediate- and high-risk disease predicted worse BFFS; whereas age >70 years at diagnosis and stage T3a-T3b predicted worse OS. A total biologically effective dose of ≥150 Gy and androgen-deprivation therapy were associated with improved BFFS, but not OS. The overall 17-year rates for BFFS, DMFS, PCSS, and OS were 79, 97, 97, and 72%, respectively. Respective 17-year BFFS rates for low-, intermediate- and high-risk patients were 86, 80, and 65% (P < 0.001), whereas OS rates for the same groups were 82, 73, and 60%, respectively (P = 0.09). Amongst those patients who were potent at baseline, 25% remained potent at the last follow-up. Urinary function and QoL were mainly unaffected., Conclusions: LDR-BT yields excellent survival rates, with a 17-year PCSS rate of 97%. In all, 18% of patients with biochemical relapse failed at >10 years after implantation, which justifies their continued follow-up., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate the cancer control outcomes and long-term treatment-related morbidity of brachytherapy as well as combination brachytherapy and external beam radiation therapy (EBRT) in patients with intermediate-risk prostate cancer., Materials and Methods: A retrospective review was conducted in a prospectively collected database of patients with intermediate-risk prostate cancer who were treated either with brachytherapy or brachytherapy and EBRT, with or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary and erectile dysfunction symptoms were measured using the International Prostate Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual Health Inventory for Men (SHIM). Cancer control endpoints included biochemical failure and development of distant metastases. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS). Survival curves were calculated using Kaplan-Meier actuarial methods and compared using log-rank tests. Cox regression multivariate analyses were used to test the effect of multiple variables on treatment outcomes., Results: A total of 902 patients were identified, with a median follow-up of 91 months. Of these, 390 received brachytherapy and 512 received combination therapy with EBRT. In patients with one intermediate-risk factor, the addition of EBRT did not significantly affect freedom from biochemical failure or distant metastases. Among patients with two or three intermediate-risk factors, added EBRT did not improve freedom from biochemical failure. Significant differences in late toxicity between patients treated with brachytherapy vs combination brachytherapy and EBRT were identified including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P < 0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were reported by patients at any point during treatment follow-up. Analysis of patients who were potent before treatment using actuarial methods showed that patients receiving combination therapy more frequently experienced loss of potency, as measured by the Mount Sinai erectile function scale (P = 0.040)., Conclusion: Brachytherapy monotherapy results in equal biochemical and distant control in both patients with one and more than one intermediate-risk features. While no significant benefit was shown, we believe that the addition of EBRT may prevent recurrence in patients with multiple intermediate-risk features and should be considered., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

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.

Purpose: To review outcomes for high-risk prostate cancer treated with combined modality radiation therapy (CMRT) utilizing external beam radiation therapy (EBRT) with a brachytherapy boost., Methods and Materials: The available literature for high-risk prostate cancer treated with combined modality radiation therapy was reviewed and summarized., Results: At this time, the literature suggests that the majority of high-risk cancers are curable with multimodal treatment. Several large retrospective studies and three prospective randomized trials comparing CMRT to dose-escalated EBRT have demonstrated superior biochemical control with CMRT. Longer followup of the randomized trials will be required to determine if this will translate to a benefit in metastasis-free survival, disease-specific survival, and overall survival. Although greater toxicity has been associated with CMRT compared to EBRT, recent studies suggest that technological advances that allow better definition and sparing of critical adjacent structures as well as increasing experience with brachytherapy have improved implant quality and the toxicity profile of brachytherapy. The role of androgen deprivation therapy is well established in the external beam literature for high-risk disease, but there is controversy regarding the applicability of these data in the setting of dose escalation. At this time, there is not sufficient evidence for the omission of androgen deprivation therapy with dose escalation in this population. Comparisons with surgery remain limited by differences in patient selection, but the evidence would suggest better disease control with CMRT compared to surgery alone., Conclusions: Due to a series of technological advances, modern combination series have demonstrated unparalleled rates of disease control in the high-risk population. Given the evidence from recent randomized trials, combination therapy may become the standard of care for high-risk cancers., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To define the incidence, time course, and risk factors associated with the development of urinary incontinence (UI) following prostate brachytherapy., Materials and Methods: A total of 2461 men were identified who underwent permanent interstitial prostate brachytherapy with or without external beam radiation therapy. We examined the relationship between clinical- and treatment-related variables with the onset of UI, defined as leakage requiring pad usage, and further classified as stress (SUI) or urge (UUI) predominant, using univariate and Cox proportional hazards regression models. The changes in International Prostate Symptom Score and quality of life domains were assessed from baseline to last follow, and examined by UI status., Results: Patients were followed for a median of 6.4 years (interquartile range 4.1-9.3). UI was reported in 108 individuals (4.4%), at a median of 1.8 years (interquartile range 5 months-4.4 years): 30 with SUI and 78 with UUI. Seventy-two men (66.7%) reported using 1, 24 (22.2%) using 2, and 12 (11%) using ≥3 pads per day. On multivariate analysis, post-implantation transurethral resection of the prostate, urinary retention, external beam radiation therapy, and higher pretreatment International Prostate Symptom Score were significantly associated with the development of SUI, although transurethral resection of the prostate was the only significant risk factor associated with SUI. Men experiencing UI reported greater declines in urinary quality of life; however, no significant difference was observed between SUI and UUI., Conclusion: UI occurred in 4.4% of patients following prostate brachytherapy and is more commonly urge-predominant in character. Distinct risk factors exist for the development of UUI vs SUI. Urinary leakage requiring pad usage was associated with declines in urinary QOL., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To describe the diagnosis of local failure after prostate brachytherapy (BT) and treatment options when recurrence is present., Methods and Materials: Review of literature for local recurrence after prostate BT and salvage therapy was performed. A total of 6 patients with prostate-specific antigen increase were identified as local failures by transperineal mapping biopsy (TPMB) and treated with targeted focused therapy using cryoablation., Results: Local recurrence after prostate BT occurs in 2-20% and is dose dependent. The biologic effective dose greater than 200 Gy(2) is associated with a less than 2% recurrence rate. Confirmatory biopsy should include both the prostate and seminal vesicles, as prostate cancer can be found in 20% of the latter. The pathologist should be experienced in evaluating post-irradiation tissue because of the difficulty in distinguishing benign irradiated prostate from residual or recurrent tumor. Whole gland salvage, whether by prostatectomy or cryoablation, is associated with high complication rates. Focal therapy has fewer complications but accurate targeting remains a concern. Newer diagnostic and targeting modalities such as multiparametric MRI and TPMB offer improved opportunity to increase lesion identification and ablation. A TPMB approach, which incorporates new biopsy needle design and interactive targeting software, may offer the best avenue to true focused therapy., Conclusion: Local recurrences after prostate BT are uncommon because of high delivered radiation dose. When present, improved lesion identification and targeting may be associated with better cancer control and lower morbidity., (Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: We analyzed factors influencing 15-year cause specific and all-cause survival in men treated with prostate brachytherapy., Materials and Methods: A total of 1,669 men with a median age of 66 years who had T1-T3 prostate cancer were treated with prostate brachytherapy and followed a mean of 10 years. Treatments were implant alone, implant plus hormone therapy, or external beam irradiation or implant plus hormone therapy plus external beam irradiation. Hormone therapy was administered in 898 men (53.8%) for a median of 6 months. Cause specific and all-cause survival were estimated by the Kaplan-Meier method with comparisons made by logistic regression and Cox proportions hazard rates., Results: The 15-year cause specific survival rate was 94.1%. Cause specific survival in the 3 NCCN® risk groups was 96.3%, 97.5% and 85.2% (p <0.001). Hormone therapy did not positively impact cause specific survival. The 15-year all-cause survival rate was 57%. Cox regression revealed age (HR 1.09, p <0.001), hormone therapy (HR 1.04, p = 0.032), diabetes (HR 1.86, p = 0.013), atrial fibrillation (HR 2.90, p = 0.041), smoking (HR 1.42, p = 0.030) and emphysema (HR 8.20, p = 0.040) as significant associations. At 15 years hormone therapy decreased all-cause survival from 60.3% to 54.9% (p = 0.009). All-cause survival was not reduced when hormone therapy was limited to 6 months or less (p = 0.005). This difference was present in men 66 years old or younger (p = 0.017) and in older men (p = 0.05)., Conclusions: Prostate brachytherapy yields favorable 15-year cause specific survival, especially in patients at high risk. All-cause survival is less in patients with preexisting diabetes, atrial fibrillation and emphysema. Hormone therapy for longer than 6 months has a negative effect on all-cause survival even in younger patients without an apparent beneficial effect on cause specific survival., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To characterize cystoscopy findings performed for cause after prostate brachytherapy in men., Materials and Methods: A retrospective review of cystoscopy reports in 2532 men treated with prostate brachytherapy with or without external beam radiation therapy for clinically localized prostate cancer between 1990 and 2011 was performed. We investigated the relationship between relevant clinical and demographic characteristics with the development of particular cystoscopic findings in patients with hematuria or lower urinary tract symptoms., Results: One hundred eighty-five of 2532 men (7.3%) underwent cystoscopy for gross or microscopic hematuria or refractory urinary symptoms at a median time of 2.7 years after implantation and were followed up for a median of 5.9 years after treatment. Most had a negative cystoscopy finding, whereas in 67 of 185 (36.2%), the findings included bladder tumors in 18 (27%), hypervascularity in 18 (27%), radiation cystitis in 13 (19.4%), inflammation in 7 (10.4%), urethral stricture in 5 (7.5%), and calculus disease in 6 (8.9%). Cystoscopic findings did not significantly differ when stratified by cystoscopy indication (P=.515). Bladder tumors were identified in similar proportions among men with gross hematuria (9.6%) and refractory urinary symptoms (10.3%, P=.840)., Conclusion: Cystoscopy after brachytherapy performed for cause demonstrates a relatively low incidence of benign and malignant pathologies. Detection of bladder tumors was uncommon, although equally observed among men with hematuria and urinary symptoms. Low threshold to perform cystoscopy should be considered in men with hematuria or persistent lower urinary tract symptoms after prostate brachytherapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: We investigated whether earlier PSA failure following prostate brachytherapy is associated with increased rates of distant metastases (DM), prostate cancer-specific mortality (PCSM), and overall mortality., Materials and Methods: We retrospectively analyzed 2818 patients who underwent brachytherapy ± external beam radiation therapy (EBRT) ± androgen deprivation therapy (ADT). With median follow-up of 5.52 years, 264 patients experienced PSA failure at a median time of 3.25 years. Patients were stratified to early vs. late PSA failures at cutoffs of 1.5 years, 3 years, or 5 years, and tested in univariate/multivariate analyses for freedom from DM, cause-specific survival (CSS), and overall survival (OS)., Results: Among patients with PSA failures, 69 (26%) patients experienced DM, 47 (18%) PCSM, and 56 (21%) deaths from other causes. Patients with rapid PSA failures demonstrated increased rates of DM, PCSM, and overall mortality, despite higher total BED and longer ADT. In multivariate analysis with a PSA failure interval <3 years, the hazard ratio (HR) for DM was 3.92 (95% CI: 2.34-6.55; p=0.000); HR for PCSM was 2.79 (95% CI: 1.45-5.38; p=0.002); and HR for overall mortality was 2.28 (95% CI: 1.50-3.48; p=0.000)., Conclusion: Early PSA failure following radiation is a poor prognostic factor, as it is associated with increased DM, PCSM, and overall mortality., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)