bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of transperineal and transrectal biopsy approaches to detect clinically significant prostate cancer in patients undergoing MRI fusion prostate biopsy: A lesion level analysis.
Authors: Wood Andrew , Khooblall Prajit , Benidir Tarik , Bullen Jennifer , Ward Ryan , Purysko Andrei , Weight Christopher J.
Published: March 2023

320

Background: The use of transperineal (TP) prostate biopsy has gained in popularity due to reduced risk of infectious events, however evidence regarding cancer detection rates versus transrectal (TR) prostate biopsy is lacking. Our objective was to examine whether transperineal (TP) MRI-fusion targeted prostate biopsy (MRI-TBx) resulted in improved detection of clinically significant prostate cancer (csPCa), defined as International Society of Urological Pathology (ISUP) grade group ≥2, as compared to TR MRI-TBx. Methods: Retrospective review of all patients who underwent MRI-TBx at a tertiary care academic center. A cohort of patients who underwent TP MRI-TBx was compared to a second cohort of patients who underwent TR MRI-TBx. The primary outcome of interest was detection of csPCa, however detection of ISUP grade group 1 prostate cancer (GG1 PCa) was also examined. Analyses were performed on a lesion level basis. Multivariable logistic regression analyses were performed to assess for predictors of csPCa detection. Results: A total of 389 and 1144 lesions from 303 and 836 patients who underwent TP MRI-TBx vs TR MRI-TBx respectively were included in the analysis. The detection of both csPCa (39.6% vs 29.6%, p <0.001) and GG1 PCa (34.4% vs 21.1%, p <0.001) was higher for TP MRI-TBx vs. TR MRI-TBx. On multivariable analysis adjusted for age, prior biopsy status, Prostate Imaging–Reporting and Data System (PIRADS) score, prostate volume, PSA, size of PIRADS lesion, and zone of PIRADS lesion, TP MRI-TBx remained an independent predictor of csPCa (odds ratio [OR] 1.49, 95% CI 1.13-1.98). Surprisingly, transperineal biopsy was not a significant predictor of csPCa for Transition zone lesions (OR 1.24, p = 0.35), but was for Peripheral zone lesions (OR = 1.84, p < 0.001). Conclusions: Performance of TP MRI-TBx demonstrates improved detection of both csPCa and GG1 PCa. This difference is not dependent on anterior/transition zone location. This has important implications in risk assessment for localized prostate cancer, including counseling for active surveillance and definitive management strategies. [Table: see text]
The impact of focal therapy tumor boards, including prostate magnetic resonance imaging overreads, in refining the selection candidacy for focal therapy patients: A prospective study.
Authors: Benidir Tarik , Lone Zaeem M , Wood Andrew , Abdallah Nour , Nguyen Jane , Kaouk Jihad , Stein Robert , Haywood Samuel , Abouassaly Robert , Almassi Nima , Weight Christopher J. , Olivares Ruben , Purysko Andrei
Published: March 2023

324

Background: Focal therapy (FT) for prostate cancer is increasingly recognized as an adequate therapeutic option in well selected men. Nevertheless, in-field and out-of-field recurrences at one year from treatment are notable. A multidisciplinary tumor board geared towards improving focal therapy (FTTB) patient selection is a novel concept which has not been explored. The impact of conducting prostate MRI-overreads during FTTB may also help refine FT candidacy and potentially reduce failure rates. We aimed to explore the value of a dedicated FTTB. Therein, we also evaluated the impact of prostate MRI overreads and its overall influence on FT candidacy. Methods: Single center, prospective study, incorporating a multidisciplinary bi-weekly FTTB (2021-2022) on patients being considered for FT. All prostate MRIs were re-reviewed by a single GU radiologist with >10 years prostate MR imaging experience. Outside pathology, when requested, was also re-reviewed. The impact of such tumor boards, and specifically MRI overreads on patient candidacy are presented. Results: Forty-five patients were presented at our FTTB over the span of one year. Patient demographics are presented. Thirty-nine patients were treatment naïve while six had prior radiation +/- ADT. MRI overread was performed on all treatment naïve patients (39/45, 87%) while pathology overreads on 11/45 (24.4%) Four patients were excluded upfront due to not meeting safety criteria for FT (Urolift device (n=1), J-pouch (n=1), suspicions of metastasis at time of consideration (n=2). Among those with MRI overreads 44.7% (17/39) were found to have findings that negatively impacted eligibility for FT like lesion crossing anteriorly to the urethra occurred in (9/17), multifocal disease (8/17), discordance of lesion on prior MRI (3/17) and lesion abutting rectal wall (1/17). Pathology re-review changed management for 3/11 patients with 2/3 being downgraded to GG1 disease and opting for active surveillance. Following multidisciplinary tumor boards, twelve patients (26.7%) were deemed candidates for FT. Conclusions: FTTB increases the selection scrutiny for FT candidates. MRI overreads are a meaningful part of FT tumor boards and can change candidacy based on new or meaningful findings. FTTB with prostate MR overreads should be considered as part of the selection process in FT decision making. [Table: see text]
The natural progression of patients with an IsoPSA value and its predictive ability of clinically significant prostate cancer on biopsy.
Authors: Abdallah Nour , Benidir Tarik , Lone Zaeem M , Zhang Ao , Wood Andrew , Curry Caleb , Haywood Samuel , Kaouk Jihad , Abouassaly Robert , Klein Eric A. , Weight Christopher J.
Published: March 2023

325

Background: IsoPSA is a structure-based serum assay exploring the spectrum of possible prostate-specific antigen (PSA) isoforms. It was shown to outperform total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (grade group (GG) ≥2 on biopsy). IsoPSA reduced unnecessary biopsies and magnetic resonance imaging (MRI). We sought to compare the outcomes of eventual biopsy and imaging of surveilled patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients who underwent IsoPSA testing from 2017-present. Data was dichotomized into patients with normal (≤6) and high IsoPSA (>6). We collected the outcomes of any consequent IsoPSA and PSA test, prostate biopsy and MRI. We calculated the statistical IsoPSA’s characteristics for the prediction of csPCa on biopsy. Results: The median follow-up time of 811 patients who underwent IsoPSA testing was 18 months (IQR, 16.5-20). Among 443 patients with initial low IsoPSA, 5 (1.1%) had a csPCa on a subsequent biopsy, 19 (4.3%) subsequent high IsoPSA, 122 (27.5%) rising PSA, and 22 (5%) csPCa on MRI. Among 368 patients with initial high IsoPSA, 105 (28.5%) had a csPCa on a subsequent biopsy and 106 (28.8%) on an MRI. The sensitivity of IsoPSA to predict csPCa was 95.5%, and the NPV was 94.8%. Among 124 patients with high IsoPSA and initial negative biopsy, 110 had a subsequent negative and 14 a positive biopsy (10GG1 (8.1%), 4 ≥GG2 (3.2%)), with a respective median IsoPSA of 7.2 and 9.6 (p=0.007). An IsoPSA>10 generated an OR of csPCa of 7.2 (95%CI 2.1-25.2, p=0.0005). Conclusions: In 18-month follow-up, 1.1% of patients with normal IsoPSA developed csPCa compared to 28.5% of patients with high IsoPSA. In the cohort of patients with high IsoPSA and initially negative biopsy, 3.2% eventually developed csPCa, however, having a significantly higher IsoPSA than those who remained negative. The odds of having csPCa were 7 times higher with IsoPSA>10. [Table: see text]
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.
Two-fraction stereotactic MRI-guided ablative radiotherapy with simultaneous boost to dominant intraprostatic lesion: Results from the 2SMART phase 2 trial.
Authors: Ong Wee Loon , Cheung Patrick , Chung Hans T. , Chu William , Detsky Jay , Liu Stanley K. , Morton Gerard , Szumacher Ewa , Tseng Chia-Lin , Vesprini Danny , Davidson Melanie , Ravi Ananth , McGuffin Merrylee , Zhang Liying , Mamedov Alexandre , Deabreu Andrea , Poon Meghan , Loblaw Andrew
Published: March 2023

349

Background: Prostate stereotactic ablative radiotherapy (SABR) for localised prostate cancer is commonly delivered over 5 fractions. Focal boost to the dominant intraprostatic lesion (DIL) seen on multiparametric magnetic resonance imaging (mpMRI) is an approach for dose-escalation in prostate SABR. This is the first report of the outcomes of the 2SMART trial, a phase 2 single-arm study using 2-fraction prostate SABR with DIL boost. Methods: Men with low to intermediate risk prostate cancer were enrolled in the study. Three gold fiducial markers were inserted for image guidance. The clinical target volume (CTV) included the prostate gland, and the planning target volume (PTV) was a 2mm expansion antero-posterior and laterally, and 2.5mm supero-inferiorly. The DIL was contoured on fused mpMRI. The prescribed dose was 26Gy in 2 fractions (EQD2 110Gy, α/β of 1.4) to the CTV, and up to 32Gy in 2 fractions (EQD2 164Gy) to the DIL as long as the dose constraints for the organs at risks were not exceeded. Each fraction was delivered 1 week apart. Daily image guidance with cone-beam computed tomography was used pre- and post-treatment. The primary endpoint was acute (≤3 months) changes in quality of life (QOL), assessed using the EPIC questionnaire. Minimal clinically important change (MCIC) in QOL was defined as an EPIC score decrease of >0.5 standard deviation of the baseline EPIC score for each domain. Secondary endpoints were acute and late toxicities (assessed using CTCAEv4), and biochemical failure (based on Phoenix criteria). Results: 30 men were enrolled in the study, of which 2 (7%) had low risk and 28 (93%) had intermediate risk prostate cancer. The median follow-up was 44 months (range: 39-49 months). The median PSA nadir was 0.2ng/mL, with median time to nadir of 37 months. One patient (3%) had biochemical failure at 44 months post-treatment. 1 (3%) and 17 (57%) had acute Grade 2 GU and GI toxicities, while 3 (10%) and 15 (50%) had late (>6 months) Grade 2 GU and GI toxicities. No acute or late Grade ≥3 GU or GI was reported. 10 (33%), 6 (20%), and 3 (10%) men had acute MCIC in urinary, bowel and sexual domains respectively. 15 (50%), 9 (30%) and 13 (43%) had late MCIC in urinary, bowel and sexual domain respectively. Conclusions: Two-fraction prostate SABR with DIL boost is a safe approach for dose-escalation for localised prostate cancer, with minimal impact on acute QOL, and no grade 3-4 toxicities. Clinical trial information: NCT03588819 .
Comparison of ctDNA between African American and Caucasian patients with CRPC post abiraterone and/or enzalutamide.
Authors: Jang Albert , Huang Minqi , Casado Crystal , Caputo Sydney , Sweeney Patrick L , Lanka Sree M , Gupta Kanika , Pocha Olivia , Habibian Nicholas , Hawkins Maddie , Lieberman Alexandra , Schwartz Jennifer , Jaeger Ellen B. , Miller Patrick , Layton Jodi Lyn , Barata Pedro C. , Lewis Brian E. , Ledet Elisa M. , Sartor A. Oliver
Published: March 2023

35

Background: Genetic differences between African American and Caucasian patients with advanced prostate cancer may contribute to racial disparities in terms of treatment outcomes and survival, hence further exploration is warranted. We assessed ctDNA differences between African American and Caucasian men in the setting of CRPC post treatment with abiraterone and/or enzalutamide. Methods: From 2015 through 2022 at Tulane Cancer Center, 250 patients with CRPC including 50 African Americans and 200 Caucasian with prior abiraterone and/or enzalutamide treatment were included. All patients had ctDNA assessed via Guardant360. Data including both gene mutations and types of mutations were for between 73-80 genes. Clinical annotation including initial staging, treatment history, and genetic testing were obtained. Statistical analyses included Fisher’s exact test and Wilcoxon rank-sum test. Results: The most common pathogenic/likely pathogenic (P/LP) alterations in both African Americans and Caucasians were TP53 (44% and 46%, respectively), AR (50% and 39%), and PIK3CA (14% and 9%). CDK12 (OR= 8.955, 95% C.I. [2.156, 37.192], p=0.003) and KIT (OR= 5.710, 95% C.I. [1.235, 26.397]. p=0.031) alterations were more frequently detected in African Americans. In terms of pathologic mutation type, frameshift mutations were significantly more frequent in African Americans (OR= 2.293, 95% C.I. [1.103, 4.769], p=0.035). All patients were CRPC at the time of testing and had prior abiraterone and/or enzalutamide, but there were no significant differences between African American and Caucasian patients with regards to prior life-extending therapies. Conclusions: African Americans with CRPC post treatment with abiraterone and/or enzalutamide had a higher frequency of P/LP CDK12 and KIT mutations, which have both been shown to lead to aggressive clinical features and treatment resistance. African Americans also had a higher incidence of frameshift mutations, a finding not previously noted. [Table: see text]
Planned interim analysis of perioperative safety of fluzoparib combined with abiraterone in the neoadjuvant treatment of locoregional high-risk prostate cancer: Results from multicenter, phase 2 FAST-PC trial.
Authors: Zhu Yao , Zhang Tingwei , Wang Beihe , Li Huajun , Ye Dingwei
Published: March 2023

356

Background: Previous studies confirmed that the combination of PARP inhibitors and abiraterone might bring survival benefits to prostate cancer (PC) patients (pts) regardless of HRR mutation status. Hence, we conducted a single-arm, multicenter, phase II trial (FAST-PC, NCT05223582) to investigate safety and efficacy of fluzoparib combined with abiraterone and androgen deprivation therapy (ADT) in the neoadjuvant treatment of locoregional high-risk PC. Herein, a planned interim analysis of safety outcome of this study was reported. Methods: FAST-PC trial enrolled pts with only pelvic lymph node metastasis or high-risk localized (cT3-4 or prostate specific antigen (PSA) >20 ng/mL or Grade Group ≥4) PC. Eligible pts received fluzoparib (150mg PO BID), abiraterone (1000mg PO QD), prednisone (5mg PO BID), and ADT for 24 weeks followed by minimally invasive radical prostatectomy (RP). Perioperative outcomes were collected and evaluated during treatment period and follow-up period which was three months after surgery. Post-surgery AEs within 90 days were classified by Clavien-Dindo. Results: As of Sep 2022, 31 pts were recruited. All the 12 pts (patient No.1 to No.12) who have completed both the 24-week neoadjuvant regimen and surgery were analyzed. Baseline characteristics were shown in table. None of them were lost to follow-up or discontinued the protocol due to adverse events (AEs). The common AEs related to medication including anemia (4, 33.3%), hypokalemia (3, 25.0%), and liver dysfunction (3, 25.0%). As for post-surgery outcomes, median days of hospitalization, surgical time, and blood loss were 8.5 days (6-12.8), 144 minutes (16.5-171.3), and 100ml (50-200), respectively. Overall, 7 (58.3%) pts experienced post-surgery AEs of any grade, in which 4 (33.3%) were grade 1 and 3 (25.0%) were grade 2. 6 (50.0%) experienced fever, and 2 (16.7%) had urinary tract infections. Of note, pulmonary thrombosis (grade 2) was diagnosed in one patient after RP. Conclusions: Our data represent the first prospective evidence supporting the perioperative safety in locoregional high-risk PC pts who received neoadjuvant fluzoparib combined with abiraterone and ADT. The combined regimen is generally safe and reliable, while special vigilance should be paid to the occurrence of anemia, hypokalemia and liver dysfunction. Clinical trial information: NCT05223582 . [Table: see text]
Effect of undetectable PSA following SRT for biochemical recurrence on BPFS, FFM, and OS.
Authors: Scharl Sophia , Gartner Luca , Boehmer Dirk Heinz Gerhard , Siegmann Alessandra , Zips Daniel , Thamm Reinhard , Wiegel Thomas
Published: March 2023

367

Background: Salvage radiotherapy (SRT) alone or in combination with androgen deprivation therapy (ADT) is the only curative treatment option for patients with biochemical recurrence after radical prostatectomy (RP) for prostate cancer. An undetectable post SRT PSA in patients without ADT (<0.1 ng/ml) has been shown retrospectively to correlate significantly with long-term freedom from progression, metastasis free survival and overall survival. The aim of this study was to investigate whether the predictive power of a post SRT-nadir <0.1 ng/ml extends to all subgroups of SRT patients. Methods: Between 1998 and 2018, 698 patients (all pN0/cN0) with persisting PSA or increasing PSA out of the undetectable range (<0.1 ng/ ml) of two German university hospitals received SRT alone without ADT. Exclusion criteria were distant metastases and/or ADT in the interval between RP and/or in combination with SRT. ADT before RP was allowed. All patients received 3D-conformal or intensity-modulated SRT to a median dose of 70.2 Gy. The impact of post-SRT nadir <0.1 ng/ml on biochemical progression free survival (BPFS), freedom from metastases (FFM) and on overall survival (OS) was analyzed by Kaplan-Meier analysis and multivariate Cox regression analysis. 9 subgroups with at least 30 patients per group were analyzed separately (pT2 + R0, pT3 + R0, pT3 + R1, pT2 + Gleason Score ≤ 7, pT3 + Gleason Score ≤ 7, pT3 + Gleason Score ≥ 8, pT3 + Gleason Score ≥ 7 + R1, pT3 + Gleason Score ≥ 7 + pre-SRT-PSA-Wert ≤1,0 ng/ ml and pT2/3 + Gleason Score ≥ 8 + pre-SRT-PSA-Wert ≤1,0 ng/ ml). Results: Median follow-up was 5.6 years. Median PSA before SRT was 0.30 ng/ ml. A post SRT PSA <0.1ng/ml was achieved by 76.6% of patients. In univariate analysis of the entire cohort, post SRT PSA <0.1 ng/ ml was a significant predictor of BPFS (p<0.001), FFM (p<0.001) and OS (p=0.01). Regarding univariate analysis of the subgroups, post SRT PSA <0.1ng/ml was a significant predictor of BPFS in all subgroups (p<0.001), FFM in 6 subgroups (p<0.001 to p=0.03) and for OS in 3 subgroups (p<0.001 to p=0.02). In multivariate analysis of the entire cohort, post-SRT PSA <0.1ng/ml was an independent predictor for BPFS (HR: 7.25, 95%-CI: 5.36-9.81, p<0.001), FFM (HR: 4.21, 95%-CI: 2.00-8.84, p=0.002) and OS (HR: 2.59, 95%-CI: 1.28-5.23, p=0.008). Conclusions: Achieving an undetectable PSA after SRT is an independent predictor of BPFS, FFM and OS. This effect is present in subgroups with favorable (pT2+Gleason score ≤ 7) as well as in those with unfavorable characteristics (pT3+ Gleason score >8). Our findings indicate that ADT could be withheld in a proportion of patients that are candidates for ADT based on their risk factors but achieve an undetectable PSA after SRT. Prospective studies are needed to confirm these results.
Partial gland ablation outcomes for localized prostate cancer in patients with MRI-visible and MRI-invisible lesions.
Authors: Zhu Alec , Gereta Sofia , Stangl-Kremser Judith , Margolis Daniel , Borregales Leonardo Daniel , Basourakos Spyridon P. , McClure Timothy D , Hu Jim C.
Published: March 2023

368

Background: Partial gland ablation (PGA) for MRI-invisible prostate cancer (PCa) remains controversial, and we compared treatment failure rates, adverse events, and health-related quality-of-life outcomes (HRQoL) following PGA in subjects with MRI-visible vs. MRI-invisible lesions. Methods: Retrospective review was done of primary PGA therapy (cryoablation, irreversible electroporation, and high-intensity focused ultrasound) performed between January 2017 and 2022 at Weill Cornell Medical Center. Analysis was restricted to men with at least one post-PGA prostate biopsy. Men with PCa on systematic biopsy outside of the MRI-targeted zone were categorized as having MRI-invisible lesions. Failure of PGA was defined as persistence or recurrence of Gleason grade group (GGG) ≥2 on surveillance biopsy for subjects diagnosed with GGG ≥2 PCa. For patients treated for GGG 1 PCa, failure was defined by the detection of GGG ≥1 PCa. Adverse events were captured by the Clavien-Dindo classification and HRQoL outcomes were captured by the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP). Groups were compared using Pearson’s chi-squared test and the 2-sided Wilcoxon-Mann-Whitney test. Results: Out of 115 men were treated for primary prostate cancer, 89 men had at least one surveillance biopsy performed, and 87 men had available pre-treatment MRI data. Out 79 subjects treated with MRI-visible lesions and 34 subjects treated with MRI-invisible lesions, 59 and 28 subjects, respectively, had surveillance biopsy data. Median (IQR) follow-up was 15.5 months (7.7-25.5) in the overall cohort; median follow-up was not significantly different between the MRI-visible and MRI-invisible groups (15 vs. 15 months, p-value=0.766). Failure of PGA occurred in 43 (48.3%) of total subjects. Failure of PGA was not significantly different between the MRI-visible and MRI-invisible groups (50.9% vs. 42.9%, p-value=0.502). Mean total EPIC-CP scores were not significantly different between both groups at baseline, 3, 6, and 12 months after PGA. Additionally, rates of 30-day complications were not significantly different between both groups. Conclusions: Failure is evident in almost half of patients treated with PGA therapy. Oncologic and functional treatment outcomes after focal therapy are similar between patients with MRI-visible and MRI-invisible lesions. [Table: see text]
Short term pathologic outcomes and biochemical recurrence rates of single port transvesical retzius-sparing radical prostatectomy as compared to multiport radical prostatectomy.
Authors: Benidir Tarik , Ferguson Ethan , Lone Zaeem M , Campbell Rebecca , Weight Christopher J. , Kaouk Jihad
Published: March 2023

369

Background: Single port radical prostatectomy with a transvesical Retzius-sparing approach (SPRP) has shown technical feasibility and early evidence of improved time to urinary continence. How this novel approach leads to differences in pathologic outcomes and biochemical recurrence rates (BCR) as compared to multiport radical prostatectomy (MPRP) has yet to be investigated. Our goal was thus to study the pathologic and short term survival outcomes of patients undergoing SPRP as compared to those undergoing MPRP. Methods: Single center, single surgeon retrospective review of prospectively collected data on 169 patients with low and intermediate risk prostate cancer, whom either underwent SPRP or MRPR (2017-2022). Preoperative clinicopathologic and radiographic characteristics were compared. Following RP, pathologic outcomes, including T stage, grade group (GG), margin status, extraprostatic extension (EPE), seminal vesical invasion (SVI), node retrieval rates, lymph node invasion (LNI) and other adverse histopathologic features were compared between both groups. Cox proportional hazards univariate analysis was used to evaluate the impact of SPRP on biochemical recurrence free survival as compared to MPRP with a three year follow up. Results: A total of 84 patients underwent MPRP and 85 patients underwent SPRP. The SPRP cohort had a higher proportion of clinical T stage one as compared to the MPRP cohort (99% vs 85%, p=0.04), however both groups did not differ preoperatively in terms of median total PSA (6.9 MPRP vs 6.2 SPRP, p=0.24), PI-RADS score (p=0.60) or biopsy GG (p=0.52). Following RP, both groups had similar pathologic outcomes including final grade group, T stage, EPE rates, SVI and Cribriform/intraductal rates (p>0.05). SPRP did yield a lower median number of nodes as compared to MPRP (2 (0-5) vs 6(4-9), p<0.001), but this did not translate to differences in LNI (p=0.08). At a median of approximately 12 months of follow up, there were no differences in the biochemical recurrence-free survival rates among both groups (p=0.38). Cox proportional hazards univariate analysis did not consider SPRP to be an independent predictor of biochemical recurrence (HR 0.53, 95% CI 0.13-2.23, p=0.39). Conclusions: In well selected men, SPRP yields similar short term oncologic control as MPRP with equal rates of margin status, EPE/SVI invasion rates and rates of biochemical recurrence at 1 year. In this small, early, single surgeon experience, SPRP appears to be oncologically safe for low and intermediate risk prostate cancer patients, however longer follow up is necessary, larger numbers and multi- institutional comparisons are needed.