bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (DEAR).
Authors: George Daniel J. , Khan Nasreen , Constantinovici Niculae , Khan Javeed , Chen Guifang , Xu Julie , Ortiz Jorge A. , Morgans Alicia K. 
Published: March 2023

332 Background: Second-generation androgen receptor inhibitors (ARIs) are the preferred treatment for patients (pts) with non-metastatic castration-resistant prostate cancer (nmCRPC). In this setting, an important therapeutic goal is to minimize adverse events (AEs) and prolong time on ARI treatment. This is the first study to assess real-world (RW) utilization and outcomes of all currently available ARIs, darolutamide (daro), enzalutamide (enza), and apalutamide (apa) in pts with nmCRPC. Methods: DEAR (NCT05362149) is a retrospective observational chart review using electronic medical records from the Precision Point Specialty network of US urology practices. Eligibility criteria included nmCRPC diagnosis, no previous treatment with a novel hormonal agent, and ARI treatment initiation for the first time from August 2019 to March 2022. Pts were classified into 3 cohorts based on the first prescribed ARI in the nmCRPC stage. We present an interim report including the primary composite endpoint (DIS/MET): proportion of pts who discontinued initial ARI treatment (DIS) or progressed to metastasis (MET); and secondary endpoints: time to DIS/MET and underlying reasons. Results: In total, 666 pts were included (daro/enza/apa, n=276/280/110). The proportion of pts starting treatment with daro increased during the study period relative to enza or apa, which declined or remained stable, respectively. Median age (80/79/80 years), White race (68%/69%/74%) and median PSA doubling time (6.7/6.0/7.8 months) at baseline were similar in the daro/enza/apa cohorts, respectively. Median length of follow-up was similar. Fewer pts had a DIS/MET event during the study in the daro cohort (35.9%), compared with enza or apa (52.1%/50.9%); this trend was seen within 6 to 18 months after ARI start. Median time to DIS/MET was 33.4/20.8/18.5 months for daro/enza/apa, respectively. Most common reasons for DIS/MET in the daro/enza/apa cohorts were AEs (8.3%/15.0%/12.7%), death (3.3%/5.4%/2.7%), and MET (14.9%/22.9%/18.2%). Conclusions: This RW study in the US shows that, despite similar baseline characteristics, fewer nmCRPC pts treated with daro had DIS/MET (especially due to AEs/MET) versus enza and apa, and the time to this event was longer in the daro cohort. These findings may be attributed to daro being a structurally distinct ARI with low potential for blood–brain barrier penetration. [Table: see text]
Pelvic clinical node-positive prostate cancer: Impact of radiotherapy and nodal disease burden.
Authors: Felefly Tony , Jooya Alborz , Laprade Selena , Roy Soumyajit , Malone Shawn , Morgan Scott C. 
Published: March 2023

338 Background: The optimal management of pelvic clinical node-positive (cN1) prostate cancer remains controversial and randomized evidence for local therapy is lacking. Recent data suggests that common iliac nodal metastases (CIM), while technically constituting M1a disease, are more common than previously recognized and might carry a prognosis similar to that of cN1 disease when treated radically. In this context, we reviewed the experience at our center of treating cN1 prostate cancer, with or without CIM, focusing on the role of radiotherapy (RT) and measures of nodal disease burden. Methods: The study population consisted of men diagnosed between 2002 and 2018 with prostate cancer with cN1 disease and/or CIM and treated with androgen deprivation therapy and/or definitive local therapy. Outcomes of interest included overall survival (OS) and castration resistance-free survival (CRFS), which were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression were used to identify factors associated with OS and CRFS. In the subgroup of patients treated with RT, the association between a number of RT characteristics – including biologically effective dose (BED) to the prostate, use of elective pelvic nodal RT, and escalated dose (RT boost) to positive nodes – and OS was studied. Results: A total of 87 patients were included, of whom 14 had CIM and 68 received RT. Median follow-up was 110 months. On univariate analysis, RT was associated with improved OS (hazard ratio [HR] 0.28, 95% CI 0.14-0.55, p<0.0005) and CRFS (HR 0.22, 95% CI 0.12-0.41, p<0.0005). Median OS in patients receiving RT was 134.9 months versus 63.1 months in those not receiving RT. Receipt of RT remained significantly associated with OS on multivariate analysis (HR 0.12, 95% CI 0.05-0.31, p<0.001). Biopsy Gleason score 10 and presence of >2 positive lymph nodes were associated with worse OS while presence of CIM was not associated with OS. In patients treated with RT, increasing BED to the prostate was associated with improved OS (HR 0.73 per 10 Gy increase, 95% CI 0.54-0.97, p=0.03) while use of elective pelvic nodal RT and use of an RT boost to positive nodes were not associated with OS. Conclusions: This is the first cohort to evaluate the impact of RT in pelvic clinical node-positive prostate cancer that includes CIM. Receipt of RT was associated with improved oncologic outcomes. The number of positive pelvic nodes, but not their common iliac location, was prognostic and warrants further investigation in a larger dataset.
Effect of prostate brachytherapy case volume in the community setting on oncologic outcomes.
Authors: Chang Kevin , Wang Lufan , Cowan Janet E. , Carroll Peter , Cooperberg Matthew R. 
Published: March 2023

339 Background: A volume-outcome relationship has not yet been comprehensively established for prostate cancer brachytherapy, a treatment modality that is declining in usage, with regard to cancer-specific outcomes. The goal of this study is to describe the relationship between facility brachytherapy case volume and cancer-specific outcomes in patients with localized prostate cancer. Methods: We identified patients in CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) diagnosed with localized prostate cancer between 1999-2007 and treated with brachytherapy. Only community hospital settings had sufficient documented cases for inclusion. The brachytherapy case volume of each facility was based on its total number of brachytherapy-treated prostate cancer patients with facilities above the 75th percentile categorized as high-volume facilities. The primary outcome was biochemical failure based on the Phoenix definition or receipt of salvage treatment after primary brachytherapy. We used logistic regression to compute a propensity score for on high vs low volume facility based on demographic, clinical, and treatment variables. Cumulative incidence of biochemical failure and prostate cancer specific mortality of patients were assessed with lifetable estimates, log-rank test, and Cox proportional hazards regression, adjusted for propensity score and case volume. Secondary outcomes included patient-reported UCLA Prostate Cancer scores for urinary, sexual, and bowel function and bother. Results: We identified 1,282 patients with localized prostate cancer treated with brachytherapy between 1999-2007 across 18 community facilities with median follow-up of 9 years. The median number of brachytherapy cases over the 8 study years was 210. 722 patients (56.3%) received brachytherapy at high-volume (>210 cases) community facilities and 560 patients (43.7%) at low-volume (10-210 cases) facilities. High-volume facilities predominantly used Pd-103 seeds while low-volume facilities predominantly used I-125 seeds. A greater proportion of patients at low-volume facilities had pre-brachytherapy hormone therapy (47% vs 26%; p<0.01). Cumulative incidence of biochemical failure at 10 years was 10.3% for high-volume facilities and 12.5% for low-volume facilities (p=0.27). Cumulative incidence of prostate cancer specific mortality at 10 years was 4.0% for high-volume facilities and 4.5% for low-volume facilities (p=0.62). Patient-reported scores of urinary, sexual, and bowel bother at 6 months following brachytherapy were comparable between the two groups. Conclusions: Patients with localized prostate cancer treated with brachytherapy at high-volume community facilities have similar rates of biochemical failure, prostate cancer specific mortality, and trends in quality of life outcomes compared to those treated at low-volume community facilities.
Evaluation of eligibility criteria in advanced prostate cancer clinical trials based on ASCO-FCR recommendations.
Authors: Feng Matthew I. , Prajapati Sweta R. , Castro Daniela V. , Lee Kyle O. , Chan Elyse H. , Sehgal Ishaan , Patel Jalen , O'Dell Anna , Zengin Zeynep Busra , Li Xiaochen , Chehrazi-Raffle Alex , Dizman Nazli , Tripathi Abhishek , Rock Adam , Liu Sandy , Mercier Benjamin D. , Meza Luis A , Philip Errol James , Dorff Tanya B. , Pal Sumanta Monty 
Published: March 2023

34 Background: The American Society of Clinical Oncology (ASCO) and the Friends of Cancer Research (FCR) published a joint statement addressing clinical eligibility for characteristics lacking adequate representation in recent studies (Kim et al., Clin Cancer Res 2021). Herein, we aimed to identify the frequency of other potentially excessive exclusion criteria in the context of metastatic prostate cancer. Methods: The eligibility criteria of advanced prostate cancer studies with start dates between June 30, 2012 and June 30, 2022 were identified through Clinicaltrials.gov. MeSH (Medical Subject Headings) terms in our query were “(metastatic OR advanced OR stage IV OR unresectable) AND (prostate cancer OR prostate adenocarcinoma)”. Our study included trials conducted worldwide and examined patients aged 18 and over in phase I-III trials. To narrow the scope of study, trials including more than one cancer type (basket trials) as well as those focusing on radiation therapy were not included in the study. Descriptive statistics were used to determine the frequency of eligibility criteria while the Fisher’s exact test or chi-square test were performed to demonstrate association between type of treatment and exclusion criteria. Results: 265 of 699 (37.9%) clinical trials within the specified search had sufficiently available data for evaluation. Of these, 136 (51.3%), 51 (19.2%), 26 (9.8%), 20 (7.5%), 19 (7.2%), and 7 (2.6%) of trials investigated treatment with combination therapy, hormone therapy, targeted therapy, immunotherapy, radioligand therapy, and chemotherapy, respectively. The most common ASCO-FCR-cited exclusion criteria in the studies were brain metastases (161/265, 60.8 %), HIV positivity (123/265, 46.4%), HBV/HCV positivity (122/265, 46.0%), and concurrent malignancies (41/265, 16.6%). Statistically significant relationships were identified between type of treatment along with status of brain metastases, HIV, and HBV/HCV (p=0.011, <0.001, and 0.001, respectively. Conclusions: This study represents the first effort to analyze this specific subset of exclusion criteria in relation to type of treatment in advanced prostate cancer. Attention to the ASCO-FCR consensus statement may maximize patient representation in future studies and increase generalizability of data. [Table: see text]
Cardiovascular and thromboembolic events associated with intense neoadjuvant androgen deprivation therapy followed by prostatectomy in patients with localized prostate cancer: A meta-analysis of clinical trials.
Authors: Campos Eduardo Felicio , Xavier Camila Bragança , Queiroz Marcello Moro , Lima Nildevande Firmino , Jardim Denis L. , Bastos Diogo Assed , Ilario Eder Nisi , Coelho Rafael Ferreira , Nahas William Carlos 
Published: March 2023

341 Background: Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients (pts). However, data regarding complications of the intense hormone therapy and surgical complications are scarce. The phase III trial PROTEUS testing ARSIs plus ADT added an amendment for thrombotic prophylaxis in the perioperative setting. We conducted a systematic review and meta-analysis to evaluate cardiovascular (CV) and thromboembolic (TE) adverse events (AEs) during neoadjuvant and perioperative intervals. Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with PROSPERO (CRD42022344104). A comprehensive search of PubMed, Embase, and Scopus databases and conference abstracts was performed from January 2010 to June 2022. Eligible studies include randomized and single-arm trials testing ARSIs prior to prostatectomy which adequately reported safety data regarding TE and CV AEs, peri-operative complications, and mortality during therapy. DerSimon and Laird method for random effects model was performed to estimate the pooled incidence (PI) of events with 95% confidence interval (95% CI). Heterogeneity was tested with I2 value. Results: 8 RCTs and 3 single-arm phase II trials comprising 674 pts were included (674 pts for CV and TE AEs and 499 for perioperative complications). Neoadjuvant regimen was classified as monotherapy with ADT (21 pts), ARSIs (100 pts), combination therapy with ADT + ARSI (338 pts), or ADT + ARSI + ARSI (215 pts). PI of all grade TE was 3.2% (95% CI, 1.6% – 4.8%, I2 = 0.0%, p = 0.92); TE incidence during perioperative period was 3.9% (95% CI, 1.6 – 6.1%, I2 = 0.0%, p = 0.67). 7 deaths were reported, with a PI of 3.0% (95% CI, 0.7–5.3%, I2 = 0.0%, p = 0.98). 2 of the mortality AE were considered treatment-related within perioperative interval. Incidence of hypertension grade 3-5 was 8.9% (95% CI, 5.2–12.7%, I2= 51.6%, p = 0.02). Incidence measures per regimen are described. Conclusions: CV and TE events associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 3.9% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting. [Table: see text]
Urinary proteome as a prognostic factor in the deterioration of the quality of life of patients with localized prostate cancer during radiotherapy: Radiotoxicity Bladder Biomarkers (RABBIO) prospective trial.
Authors: Helissey Carole , Cavallero Sophie , Guitard Nathalie , Thery Hélène , Parnot Charles , Schernberg Antoine , Mondot Stanislas , Christopoulos Christos , Malek Karim , Malaurie Emmanuelle , Chargari Cyrus , Francois Sabine 
Published: March 2023

344 Background: Despite improvements in radiation techniques, pelvic radiotherapy is responsible for acute and delayed bladder adverse events, defined as radiation cystitis (CysR). About 50% of irradiated patients present acute symptoms and experience a significant decrease in their quality of life (QOL). The pathophysiology of CysR is not well understood, which limits our ability to study this process and develop treatments. The RABBIO study evaluates the correlation of urinary biomarkers with the intensity of acute CysR and the QOL of patients, assessed with the digital telemonitoring platform Cureety. Methods: Patients with intermediate-risk localized prostate cancer eligible for localized radiotherapy were included. Urinary biomarkers were analyzed before the start of radiotherapy, and at weeks (W) 4, 12 and 48 of irradiation. Between sample collection visits, patients completed various questionnaires related to radiation cystitis symptoms and QOL using a digital remote monitoring platform. Upon receipt of the questionnaires, an algorithm processed the information and classify patients according to the severity of symptoms and adverse events reported according to CTCAE. We also collected FACT-P questionnaires at baseline, W4 and W12. We correlated the levels of urinary biomarkers with the severity of acute CysR symptoms and patient-reported QOL. Results: The study started in March 2022, with 15 patients included to date. The median age was 76 (range 65-99). 80% (15/17) presented a localized prostate cancer de novo and 20% presented a biochemical recurrence. The compliance was 100% at baseline, 93% at W4 and 100% at W12. We collected a total of 172 AE questionnaires over the duration of the study so far, of which 61.0% (105/172) indicated a correct health status and 31.4% (54/172) a compromised status. The mean (range) FACT-P score at baseline for all patients was 33.9 (24 – 40), which changed to 29.8 (20 – 35) at W4, and 38.7 (37 – 42) at W12. Elevated SHBG (p=0.019, r=-0.93) and decreased IL8 (p=0.034, r=0.91) at baseline correlated with worse FACT-P score at W4. Conclusions: This prospective study is the first to explore the overexpression of inflammatory proteins in fluid biopsies from patients with symptoms of acute CysR. Our first results revealed that an elevated SHBG and a decreased IL8 in urine at baseline were a prognostic factor in the deterioration of QOL for localized prostate cancer patients during radiotherapy. The results of this study will allow us to develop strategies to limit radiation damage to the bladder and improve the QOL of patients. Clinical trial information: NCT05246774 .
Determining the impact of genomic classifier testing on patient-reported quality of life after prostatectomy: Results from the G-MINOR randomized trial.
Authors: Singhal Udit , Daignault-Newton Stephanie , Dunn Rodney , Spratt Daniel Eidelberg , Okoth Linda , Feng Felix Y , Johnson Anna , Lane Brian R , Linsell Susan , Khurshid Ghani , Mehra Rohit , Davicioni Elai , Maatman Thomas , Burks Frank , Rodriguez Paul , Kleer Eduardo , Sarle Richard , Miller David Christopher , Cher Michael L. , Morgan Todd Matthew 
Published: March 2023

345 Background: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting to help guide adjuvant treatment decisions for prostate cancer (PCa). We conducted the first prospective, randomized trial assessing the impact of GC testing on adjuvant therapy use. Here, we determine the impact of GC testing on patient reported (PRO) quality of life outcomes (QoL) in men at high-risk of post-RP recurrence. Methods: The G-MINOR trial is a prospective, unblinded, randomized trial which enrolled 356 patients from 12 centers in the Michigan Urological Surgery Improvement Collaborative (MUSIC). Patients were enrolled between Aug 2016-July 2018. Eligible patients had undergone RP within 9 months of enrollment, had pT3-4 disease and/or positive surgical margins, and a post-RP PSA <0.1ng/mL. Patients were assigned to either the GC or usual-care (UC) group using cluster-crossover block randomization assignments. Evaluable patients (338) were followed for at least 18 months. PROs were obtained using the Expanded Prostate Cancer Index Composite (EPIC-26) survey at baseline (before RP), 3, 6, 12, and 24 months after RP. Results: A total of 226/338 evaluable men (67%) had PRO data for this analysis (116 UC arm/110 GC arm). Median age was 65 years. Of the 226 men included in the PRO analysis, a total of 23 (9 UC arm/14 GC arm) had adjuvant treatment (p = 0.22). At 12 months follow-up, those in the GC arm had no significant change in adjusted mean difference in domain score from baseline compared to those in the UC arm for urinary irritative (UIR) function (1.0, 95% CI [-2.9– 4.9], p=0.6), urinary incontinence (UI) (0.8, 95% CI [-5.1– 6.7], p=0.8), or sexual function (SF) (0.5, 95% CI [-6.9– 7.9], p=0.9). This remained true at 24 months for all three domains [UIR; (2.3, 95% CI [-2.1– 6.6], p=0.3)], [UI; (-0.3, 95% CI [-7.3– 6.7], p=0.9)], [SF; (1.5, 95% CI [-6.8– 9.7], p=0.7)]. Conclusions: In the first ever randomized trial testing the clinical utility of a GC test in localized PCa, longitudinal patient reported QOL outcomes were not significantly different between men who underwent risk stratification with or without Decipher. Clinical trial information: NCT02783950 .
Longitudinal analysis of persistent stress urinary incontinence after radical prostatectomy and time to definitive surgical treatment: Data from CaPSURE.
Authors: Braun Avery , Washington Samuel L. , Cowan Janet E. , Cooperberg Matthew R. , Carroll Peter 
Published: March 2023

347 Background: Persistent urinary incontinence (UI) after radical prostatectomy (RP) can have significant impact on quality of life, return to work and need for additional surgery. We aim to characterize the long-term cumulative incidence of incontinence procedure and report changes in urinary function (UF), urinary bother (UB), and work status from time of RP to 1 year postop. Methods: Participants treated by primary RP (1990-2020) for prostate cancer enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry of 43 US urologic practices. UI was defined as self-reported use of >1 pad per day at 1 year after RP. UI procedure was tracked with CPT codes for urinary sling and artificial urinary sphincter (AUS). Participants reported work status (full-time paid, part-time paid, unpaid) and urinary scores (0-100) using UCLA Prostate Cancer Index. Associations of incontinence with changes in urinary scores (t-test) were assessed. Lifetable estimates and Cox proportional hazards regression were used to evaluate the risk of undergoing a UI surgical procedure, with model adjustment for pre-treatment age and urinary dysfunction, surgical characteristics, and post-surgical radiation. Results: Of 5742 men treated with primary RP, 641 (11%) reported UI as defined above at 1 year post-RP. Mean age was 61 years. A larger proportion of individuals with UI underwent open RP (93% vs 7%) and non-nerve sparing (62% vs 38%). At 1 year post RP, score decline in UF (-42.6 vs -11.7) and UB (-25.5 vs -2.7) were significantly worse in the incontinent group (all p<0.01). Cumulative incidence of incontinence procedures was 1.4% at 10 years with median time to UI-redirected procedure of 36 months (IQR 12, 74) after RP. Incontinence procedures comprised 52.4% AUS, 15.8% sling, 6.3% both, and 25.4% unspecified. UI (HR 10.6,95%CI 6.3-17.9), older age (per decade, HR 2.0, 95% CI1.3-3.0), history of voiding dysfunction (HR 6.1,95% CI 2.9-12.8) and receipt of radiation (adjuvant or salvage) (HR 2.4, 95% CI1.2-4.8)) were associated with undergoing incontinence procedure. Conclusions: UI at 1 year after RP may occur in up to 11% of surgical recipients. However, the rate of intervention remained low with 1.4% of the total cohort undergoing an incontinence procedure within 10 years. Incontinence affected urinary quality of life. Median time to UI procedure was 36 months. This information suggests that a significant number of men may have long – term, untreated incontinence and even those who undergo procedures to manage it may not have it in a timely fashion.