Enzalutamide at standard doses (160 mg/day) is effective in advanced prostate cancer (PCa) but is associated with considerable adverse events (AEs) and high financial costs. Preliminary reports suggest that low/intermediate doses (≤80 mg/day) retain efficacy while reducing toxicity. This study evaluates the efficacy and safety of low/intermediate dose vs standard-dose enzalutamide in a real-world cohort. This retrospective observational study included 140 assessable patients treated with enzalutamide for metastatic castration resistant (80

Importance Due to the often indolent nature of prostate cancer (PCA), treatment decisions must weigh the risks and benefits of cancer control with those of treatment-associated morbidities. Objective To characterize long-term treatment-related adverse effects and complications in patients treated for PCA compared to a general population of older males. Design, Setting, and Participants This cohort study used a novel approach linking data from 2 large PCA prevention clinical trials (the Prostate Cancer Prevention Trial and the Selenium and Vitamin-E Cancer Prevention Trial) with Medicare claims records. This analysis included patients with PCA who had been treated with prostatectomy or radiotherapy compared with an untreated control group. Multivariable Cox regression was used, with a time-varying covariate for the occurrence of PCA treatment, adjusted for age, race, and year of time-at-risk initiation, and stratified by study and intervention arm. Data analyses were performed from September 21, 2022, to March 18, 2024. Exposure Prostatectomy and radiotherapy occurring after a PCA diagnosis, identified from trial data or Medicare claims records. Main Outcomes and Measures Ten potential PCA treatment-related complications identified from Medicare claims data. Results The study sample comprised 29 196 participants (mean [SD] age at time-at-risk initiation, 68.7 [4.8] years). Of these, 3946 participants had PCA, among whom 655 were treated with prostatectomy and 1056 with radiotherapy. The 12-year hazard risk of urinary or sexual complications was 7.23 times greater for those with prostatectomy (95% CI, 5.96-8.78; P < .001) and 2.76 times greater for radiotherapy (95% CI, 2.26-3.37; P < .001) compared to untreated participants. Moreover, among participants treated with radiotherapy, there was a nearly 3-fold greater hazard risk of bladder cancer than in the untreated (hazard ratio [HR], 2.78; 95% CI, 1.92-4.02; P < .001), as well as an approximately 100-fold increased hazard risk of radiation-specific outcomes including radiation cystitis (HR, 131.47; 95% CI, 52.48-329.35; P < .001) and radiation proctitis (HR, 87.91; 95% CI, 48.12-160.61; P < .001). The incidence per 1000 person-years of any 1 of the 10 treatment-related complications was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants. Conclusions and Relevance This cohort study found that, even after accounting for age-related symptoms and disease, PCA treatment was associated with higher rates of complications in the 12 years after treatment. Given the uncertain benefit of PCA treatment for most patients, these findings highlight the importance of patient counseling before PCA screening and treatment and provide a rationale for pursuing opportunities for cancer prevention.

3 Background: CaboNivo and CaboNivoIpi showed promising efficacy and safety in a dose-escalation phase I study in patients (pts) with metastatic genitourinary (mGU) tumors. We now report the final results from a pooled analysis of the phase I dose-finding and 7 subsequent expansion cohorts. Methods: Pts with mGU tumors in the phase I cohort received 8 escalating doses of CaboNivo or CaboNivoIpi. In the 7 expansion cohorts, pts received the recommended phase II dose for CaboNivo (cabo 40mg qd + nivo 3mg/kg q2wks in 28-day cycles) and for CaboNivoIpi (CaboNivo same dose + ipi 1mg/kg q3wks in 21-day cycles x 4 cycles followed by CaboNivo). The CaboNivo expansion cohorts included pts with urothelial carcinoma (UC); clear cell renal cell carcinoma (RCC), bladder adenocarcinoma (BlaAdeno), and other rare mGU tumors. The CaboNivoIpi expansion cohorts included, UC, RCC, and penile carcinoma (penile). The objectives of the study were to determine the clinical activity, safety and tolerability of both combinations. A secondary objective was the detection of EpCAM+ circulating tumor cells (CTCs). Biomarker correlatives of plasma VEGFA/VEGFR2, PIGF, and inflammatory cytokines will be presented. Results: A total of 120 pts (median age 59; range 20-82) were enrolled: 54 in the phase I and 66 in the dose expansion cohorts. 64 pts received CaboNivo and 56 CaboNivoIpi. Median follow-up was 40.4 months (range 2.2-62.2 months). The ORR for 108 evaluable pts was 38% (95% CI: 28.8-47.8%) with 12 complete responses (CRs) (11.1%) and 29 partial responses (26.9%). The ORRs for the following mGU tumors were: UC 42.4% (n=33) with CR=21.2%; RCC 62.5% (n=16); prostate cancer 11.1% (n=9); germ cell tumor no responses (n=6); BlaAdeno 20% (n=15); penile 44.4% (n=9); bladder squamous 85.7 (n=7); renal medullary 50% (n=2); bladder small cell 33.1 (n=3). The median overall survival for the entire population was 15.9 months (95% CI: 11.6-23.9); 24.9 months (95% CI: 11.8-41.6) for pts with UC (n=39); and 38.6 months (95% CI: 19.4-not estimable) for RCC (n=16). Median duration of response was 22.8 months (95% CI: 18.3-40.1 months) for all pts, 32.1 months [95% CI: 20.3-NE)] for the UC pts and 20.1 months (95% CI: 5.8-NE) for RCC pts. Grade 3 or 4 treatment related adverse events (AEs) occurred in 84% and 80% of pts treated with CaboNivo and CaboNivoIpi pts respectively, and included hypophosphatemia (25% and 16%), lipase elevation (20% and 20%), fatigue (20% and 18%), ALT elevation (5% and 14%), AST elevation (9% and 11%), diarrhea (9% and 11%), and thromboembolic event (11% and 4%). One pt had Grade 5 pneumonitis on CaboNivoIpi. Baseline EpCAM+ CTC count of < 5 vs. > 5, was associated with longer median OS (24.3 vs. 12.3 months p=0.037). Conclusions: CaboNivo and CaboNivoIpi demonstrated promising clinical activity and manageable safety in many mGU histologies including rare tumors. Clinical trial information: NCT02496208.

Introduction Multiparametric magnetic resonance imaging (mpMRI) has led to improved diagnosis and risk stratification of prostate cancer. The Prostate Imaging Reporting and Data System (PI-RADS) is a widely-adopted standardized interpretation scheme for prostate mpMRI. Lesions are scored 1-5 based on suspicion for clinically significant prostate (csPCa), defined as Grade Group ≥ 2, with increasing positive predictive value indicated by higher score. Multiple studies have demonstrated the positive predictive value of a PI-RADS 5 lesion for csPCa to cluster around 70-80%. Since nearly 80% of those with PI-RADS 5 lesions harbor clinically significant disease on biopsy, many receive upfront therapy. There is limited understanding of what happens to remaining patients with PI-RADS 5 lesions in whom biopsies reveal less aggressive disease. The purpose of this study is to evaluate the clinical course of those with PI-RADS 5 lesions with Grade Group 1 disease who were placed on Active Surveillance (AS). Methods This analysis was limited to AS patients with GG1 prostate cancer on targeted biopsy of a solitary PI-RADS 5 index lesion performed from 2007 to 2022. Each scan was read by a high-volume genitourinary radiologist (BT or PC). These patients underwent systematic and targeted biopsy by physicians experienced with MRI-fusion biopsies (PP, BW, SG). Repeat biopsies were performed based on clinicopathologic concern for progression (rising PSA, MRI changes) or local AS protocols. For MRIs preceding PI-RADS scoring, an internal Likert suspicion scoring system that has been validated in the literature was used and converted into PI-RADS scores. Beginning in 2015, internal mpMRI readings were reported using PI-RADS v2.0 and in 2019 transitioned to PI-RADS v2.1. Biopsy specimens were reviewed by dedicated genitourinary pathologists. Descriptive statistics were performed. Univariate analyses, including independent samples t-test, chi-squared analysis, and Fisher's exact test, were performed to evaluate for factors associated with disease upgrading. Results 21 patients met inclusion criteria. The mean PSA was 7.9 ng/ml (range 2.4-14.5) (Table 1). At median follow up of 4.3 years, 15/21 (71%) patients progressed to GG≥2 disease, 5 of whom (24% of initial cohort) progressed to GG≥3 (Figure 1). Median time to progression to GG≥2 and GG≥3 was 3.3 years and 4.4 years, respectively. Of the 6 who did not progress, 1 underwent prostatectomy (upgraded to GG2 on final pathology) and 5 were maintained on AS. Of the 16 who progressed to GG≥2, 6/21 (29%) were continued on AS. 5 of these patients remained on AS (median follow-up 3.3 years after progression) and one underwent prostatectomy. Overall, 11 (52%) received definitive therapy. On univariate analysis, only mean maximum cancer core length was associated with progression to radical therapy (4.8 vs 8.0 mm, p=0.048). Conclusions Patients with PI-RADS 5 lesions and GG1 PCa on AS demonstrate a rate of upgrading to GG≥2 of >70% and nearly a quarter were upgraded to GG≥3. Nearly 50% of patients progressed to radical treatment at 4 years. This represents a high rate of upgrading in a short period of time relative to larger AS series, which place pathologic upgrading at 25-50%. Further studies, including longer-term follow-up, will be necessary. Genomic classification of these initially indolent lesions may provide clarity regarding the best management. The question of how our findings should affect practice is important. With half of patients suitable for AS at follow-up, it is reasonable to continue AS as the preferred management. However, there is a higher risk of requiring intervention and these patients should be counseled and monitored accordingly. While focal therapy is not guideline-endorsed for GG1 disease, this may be a population that could benefit.

Introduction The advent of multiparametric magnetic resonance imaging (mpMRI) has helped to localize clinically significant prostate cancer (csPCA). Focal Therapy (FT) has emerged in the mpMRI era, which can treat MRI-visible lesions while avoiding side effects of whole-gland treatment. However, FT remains an investigational treatment option for PCa patients with intermediate-risk disease. Little is known about how many patients on active surveillance (AS) with Gleason grade group (GG) 2 disease retain eligibility for FT over time, or risk factors for loss of eligibility. The objective of this study is to evaluate initial and long-term FT eligibility (FTE) of patients with GG2 disease. Methods A prospectively maintained cohort was retrospectively queried for patients initiated on AS between 2007;and 2020 with GG2 PCa. Patients with biopsy-concordant GG2, unilateral, MRI-visible PIRADS 2-5 lesions amenable to hemiablation were considered FT candidates. Those with PSA>20 ng/mL, >4 MRI lesions, bilateral (BL) MRI-visible/biopsy-concordant lesions, or contralateral GG≥2 PCa or MRI-invisible lesions were excluded. Patients were considered to progress if they developed BL GG≥2 disease or unilateral GG≥3 PCa. Patients without GG progression maintained FTE and those with GG progression maintained FTE if they had unilateral biopsy-concordant/MRI-visible GG≤3, no contralateral GG≥2 disease, and PSA<20 ng/mL. Univariate and multivariate analyses were conducted to compare patients who maintained and lost FTE. Results 252 PCa patients were identified as eligible for FT with an average follow-up of 3.4 years, 83 of whom (33%) had GG2 disease and were FT candidates. 29/83 (35%) lost FT eligibility, 19/83 (23%) with progression to high-risk disease, 6/83 (7.2%) due to development of BL GG≥2 disease, and 4/83 (4.8%) with development of MRI-invisible csPCA. Baseline characteristics are shown in Table 1. Univariate analysis demonstrated that those who lost FTE had smaller prostates than those who maintained it (44.9 mL vs. 56.2mL, respectively, p=0.018). PSA density was similar between the groups. No significant differences were noted in initial imaging and pathologic parameters. No factors significantly associated with loss of FTE were identified on logistic regression (Table 2). Conclusions 33% of the patients on AS had GG2 disease and were initially eligible for FT. 65% of patients with GG2 disease were still eligible for FT after a median follow up of 3.4 years; over one third of these patients lose FTE. This data regarding the loss of a FT therapeutic window could prove useful in counseling GG2 patients considering AS, FT, or radical treatment.

Screening for Prostate Cancer Prostate cancer is the most diagnosed cancer (excluding nonmelanoma skin cancer) and is the cancer with the second highest mortality among men in the United States. Prostate cancer-specific survival at 10 years is 95% among men with localized disease. Prostate-specific antigen (PSA) screening should involve shared decision making with consideration of the risks and benefits of screening and patient preferences. Findings from randomized trials support a modest reduction in prostate cancer mortality with PSA screening; screening 1000 men may prevent deaths from prostate cancer in 1.3 men in the 13 years after initial screening. Persons with elevated PSA levels on screening may choose to undergo further tests to inform the need for biopsy, multiparametric magnetic resonance imaging (MRI) to identify biopsy targets, or both. Persons with low-risk or favorable intermediate-risk prostate cancer may choose to undergo active surveillance (periodic PSA tests and biopsies) over immediate curative treatment (surgery or radiation therapy). Surgery and radiation therapy generally provide excellent outcomes in prostate cancer but may result in harms, including urinary incontinence and erectile dysfunction with surgery, and bowel dysfunction and erectile dysfunction with radiation therapy. Screening for Prostate Cancer PSA screening for prostate cancer should involve consideration of benefits and risks. Screening is associated with a small reduction in prostate cancer deaths; risks include overdiagnosis and unnecessary biopsy and treatment.

muscle mass. This might be related to urinary incontinence.

Supplementary Tables 1-3. Supplementary Table 1. Characteristics1 of cases2 with and without inflammation in prostate biopsy cores, in the placebo arm of the Prostate Cancer Prevention Trial. Supplementary Table 2. Distribution of serum phospholipid fatty acids by percent of total among cases with and without inflammation in prostate biopsy cores, in the placebo arm of the Prostate Cancer Prevention Trial. Supplementary Table 3. Multivariable-adjusted associations of serum phospholipid fatty acids in relation to inflammation in prostate biopsy cores, among cases from the placebo arm of the Prostate Cancer Prevention Trial.

Finasteride and Prostate Cancer: New York Times Article from Estimating Rates of True High-Grade Disease in the Prostate Cancer Prevention Trial

You have accessJournal of UrologyCME1 Apr 2023MP19-19 PRIORITIZED RESEARCH QUESTIONS ON THE USE OF ACTIVE SURVEILLANCE FOR THE MANAGEMENT OF PROSTATE CANCER: RESULTS FROM PCASRI CONFERENCE Shu Wang, Michelle Medeiros, Michael Rothberg, Ryan Russell, Zach Kozel, Tony Crispino, Joseph Gallo, Mark Lichty, Alexandra Scholz, Jimmie Slade, Judi Wolinsky, Howard Wolinsky, Arvin George, Jim Hu, Howard Parnes, Christian Pavlovich, Peter Pinto, Sanoj Punnen, Christopher Saigal, Samuel Washington, Kara Watts, Caroline Moore, Daniel Mullins, Michael Scott, and M. Minhaj Siddiqui Shu WangShu Wang More articles by this author , Michelle MedeirosMichelle Medeiros More articles by this author , Michael RothbergMichael Rothberg More articles by this author , Ryan RussellRyan Russell More articles by this author , Zach KozelZach Kozel More articles by this author , Tony CrispinoTony Crispino More articles by this author , Joseph GalloJoseph Gallo More articles by this author , Mark LichtyMark Lichty More articles by this author , Alexandra ScholzAlexandra Scholz More articles by this author , Jimmie SladeJimmie Slade More articles by this author , Judi WolinskyJudi Wolinsky More articles by this author , Howard WolinskyHoward Wolinsky More articles by this author , Arvin GeorgeArvin George More articles by this author , Jim HuJim Hu More articles by this author , Howard ParnesHoward Parnes More articles by this author , Christian PavlovichChristian Pavlovich More articles by this author , Peter PintoPeter Pinto More articles by this author , Sanoj PunnenSanoj Punnen More articles by this author , Christopher SaigalChristopher Saigal More articles by this author , Samuel WashingtonSamuel Washington More articles by this author , Kara WattsKara Watts More articles by this author , Caroline MooreCaroline Moore More articles by this author , Daniel MullinsDaniel Mullins More articles by this author , Michael ScottMichael Scott More articles by this author , and M. Minhaj SiddiquiM. Minhaj Siddiqui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003244.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is recommended for the management of favorable-risk prostate cancer (PCa) to avoid the harmful effects of overtreatment. Rates of utilization of AS in the US however remain suboptimal due to multi-factorial issues. We sought to engage a diverse group of patients, patient advocates, researchers and clinicians to better understand the current shortcomings in AS implementation, as well as develop a patient-engaged list of research priorities for PCa AS. METHODS: We organized a 2-day conference, Developing Provocative Questions-PCa AS Research Initiative (PCASRI). Through small groups consisting of physicians, patients and families, researchers, and advocates we discussed twelve selected topics in four domains following the PICOTS criteria (Population, Intervention, Outcome, and Setting). Through an iterative process, we generated and then ranked meaningful PCa AS research questions from all participants. Ultimately, eight prioritized questions were selected and ranked through voting. RESULTS: A total of 152 people participated over the 2-day conference with 45.5% patients with PCa, 29.5% urologists, and the remainder a mix of supporters, advocates, and researchers. Eight questions were prioritized out of 22 initially generated. The number one research priority that emerged after this process was “How do we incorporate imaging for improved AS of favorable-risk PCa patients”. The remainder of the 8 research priority topics in order of priority were 2: use of focal therapy to augment AS, 3: risk-specific personalized follow-up intensity for AS, 4: use of telemedicine vs in-person support groups to address disparities in PCa AS utilization, 5: impact of micro-ultrasound vs MRI for AS of PCa, 6: optimal integration of imaging and genomic biomarkers for AS, 7: integration of health educators to improve uptake of AS, and 8: impact of HIIT exercise on PCa AS. CONCLUSIONS: We generated a multi-stakeholder engaged process to identify research priorities in improving uptake of AS in the appropriate risk PCa population. The top priority identified was optimal integration of MRI in AS follow-up processes. Continued research in these priority areas combined with continued patient and multi-stakeholder engagement may provide meaningful patient-centered impact on the use of AS. Source of Funding: This project was funded through a Patient-Centered Outcomes Research Institute (PCORI) Eugene Washington PCORI Engagement Award (EAIN-19842). © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e273 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shu Wang More articles by this author Michelle Medeiros More articles by this author Michael Rothberg More articles by this author Ryan Russell More articles by this author Zach Kozel More articles by this author Tony Crispino More articles by this author Joseph Gallo More articles by this author Mark Lichty More articles by this author Alexandra Scholz More articles by this author Jimmie Slade More articles by this author Judi Wolinsky More articles by this author Howard Wolinsky More articles by this author Arvin George More articles by this author Jim Hu More articles by this author Howard Parnes More articles by this author Christian Pavlovich More articles by this author Peter Pinto More articles by this author Sanoj Punnen More articles by this author Christopher Saigal More articles by this author Samuel Washington More articles by this author Kara Watts More articles by this author Caroline Moore More articles by this author Daniel Mullins More articles by this author Michael Scott More articles by this author M. Minhaj Siddiqui More articles by this author Expand All Advertisement PDF downloadLoading ...

4571 Background: Bintrafusp alfa is a novel bifunctional fusion protein targeting PD-L1 and TGF-β which has demonstrated clinical efficacy in some tumor types and a manageable safety profile. M9241 is an immunocytokine that allows targeting of the pro-inflammatory IL-12 cytokine to exposed DNA in necrotic portions of tumors. SBRT can help promote anti-tumor responses and may potentially synergize with immunotherapy by inducing DNA damage. Methods: This is an open label, non-randomized, three arm phase I trial of bintrafusp alfa and M9241 combination therapy administered alone (Arm 1), or with either sequential (Arm 2), or concurrent (Arm 3) SBRT. Eligible patients must have metastatic non-prostate GU cancers with measurable disease. Bintrafusp alfa was used at a flat dose of 1200mg (q2w) for arms 1-3 and a fixed dose of SBRT (24Gy in 3 fractions) was used for arms 2-3. M9241 was administered at 16.8mcg/kg (q4w) for Arm 1 and decreased if side effects occur. Arm 1 used bintrafusp alfa and M9241 alone, with the maximum tolerated dose (MTD) of M9241 being dose level 1 (DL1) for Arm 2. Arm 2 used SBRT followed by bintrafusp alfa and M9241, with the MTD of M9241 being DL1 for Arm 3. Arm 3 used concurrent SBRT with bintrafusp alfa and M9241. The primary objective was to determine the safety and highest tolerable doses of each arm. Secondary objectives include objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: Study enrollment began in 12/2019, with interim safety analyses performed quarterly. A total of 16 patients have enrolled, 12 in Arm 1, three in Arm 2, and one in Arm 3 at data cutoff 1/2/23. The first six patients enrolled in Arm 1 had no DLTs allowing Arm 2 to open, Arm 2 had no DLTs after 3 patients enrolled allowing Arm 3 to open. At data cut off four of 16 patients remained on treatment. The median age was 63 and 19% were female. The most frequent TRAEs were fatigue (grade 2, 38%), lipase increase (grade 2+3, 31%), and anemia (grade 2+3, 31%). Grade 3 hematuria occurred in 2 patients (13%); a grade 4 creatinine increase occurred in one (8%). There were no grade 5 TRAEs. Two (13%) patients had treatment discontinued and 5 (31%) had dose reductions due to AEs. Of the 16 patients enrolled on study, 11 were evaluable at data cutoff. Currently three patients (38%) on Arm 1 and one patient (50%) in Arm 2 had objective responses, corresponding to an ORR of 36.4% (4/11). All responses have been partial responses. On Arm 1 the responding patients included one with small cell carcinoma of the renal pelvis, one with Leydig cell tumor, and one with urothelial carcinoma. On Arm 2 the responding patient had a Sertoli cell tumor. Conclusions: The use of bintrafusp alfa and M9241 either alone or in combination with sequential or concurrent SBRT has shown clinical activity in pts with GU tumors and has not been associated with any DLTs. Clinical trial information: NCT04235777 .

Perspective from Estimating Rates of True High-Grade Disease in the Prostate Cancer Prevention Trial

BACKGROUND. Precise risk stratification through MRI/ultrasound (US) fusion-guided targeted biopsy (TBx) can guide optimal prostate cancer (PCa) management. OBJECTIVE. The purpose of this study was to compare PI- RADS version 2.0 (v2.0) and PI- RADS version 2.1 (v2.1) in terms of the rates of International Society of Urological Pathology (ISUP) grade group (GG) upgrade and downgrade from TBx to radical prostatectomy (RP). METHODS. This study entailed a retrospective post hoc analysis of patients who underwent 3-T prostate MRI at a single institution from May 2015 to March 2023 as part of three prospective clinical trials. Trial participants who underwent MRI followed by MRI/US fusion-guided TBx and RP within a 1-year interval were identified. A single genitourinary radiologist performed clinical interpretations of the MRI examinations using PI-RADS v2.0 from May 2015 to March 2019 and PI-RADS v2.1 from April 2019 to March 2023. Upgrade and downgrade rates from TBx to RP were compared using chi-square tests. Clinically significant cancer was defined as ISUP GG2 or greater. RESULTS. The final analysis included 308 patients (median age, 65 years; median PSA density, 0.16 ng/mL2). The v2.0 group (n = 177) and v2.1 group (n = 131) showed no significant difference in terms of upgrade rate (29% vs 22%, respectively; p =.15), downgrade rate (19% vs 21%, p =.76), clinically significant upgrade rate (14% vs 10%, p =.27), or clinically significant downgrade rate (1% vs 1%, p >.99). The upgrade rate and downgrade rate were also not significantly different between the v2.0 and v2.1 groups when stratifying by index lesion PI-RADS category or index lesion zone, as well as when assessed only in patients without a prior PCa diagnosis (all p >.01). Among patients with GG2 or GG3 at RP (n = 121 for v2.0; n = 103 for v2.1), the concordance rate between TBx and RP was not significantly different between the v2.0 and v2.1 groups (53% vs 57%, p =.51). CONCLUSION. Upgrade and downgrade rates from TBx to RP were not significantly different between patients whose MRI examinations were clinically interpreted using v2.0 or v2.1. CLINICAL IMPACT. Implementation of the most recent PI- RADS update did not improve the incongruence in PCa grade assessment between TBx and surgery.

PSA screening for prostate cancer should involve consideration of benefits and risks. Screening is associated with a small reduction in prostate cancer deaths; risks include overdiagnosis and unnecessary biopsy and treatment.

Background: There is an unmet clinical need for interventions to prevent disease progression in patients with localized prostate cancer on active surveillance (AS).Objective: To determine the immunologic response to the PROSTVAC vaccine and the clinical indicators of disease progression in patients with localized prostate cancer on AS.Design, setting, and participants: This was a phase 2, double-blind, randomized controlled trial in 154 men with low-or intermediate-risk prostate cancer on AS.Intervention: Participants were randomized (2:1) to receive seven doses of subcutaneous PROSTVAC, a vaccinia/fowlpox viral vector-based immunotherapy containing a prostate-specific antigen (PSA) transgene and three T-cell co-stimulatory molecules, or an empty fowlpox vector (EV) over 140 d.Outcome measurements and statistical analysis: The primary outcome was the change from baseline in CD4 and CD8 T-cell infiltration in biopsy tumor tissue. Key secondary outcomes were safety and changes in prostate biopsy tumor pathology, peripheral antigen-specific T cells, and serum PSA. Continuous variables were compared using non parametric tests. Categorical variables were compared using Fisher's exact test.Results and limitations: The PROSTVAC/EV vaccination was well tolerated. All except one participant completed the vaccination series. Changes in CD4 or CD8 density in biopsy tumor tissue did not differ between the PROSTVAC and EV arms. The proportions of patients with Gleason upgrading to grade group 3 after treatment was similar between the arms. There were no differences in postvaccination peripheral T-cell responses or the PSA change from baseline to 6-mo post-treatment follow-up between the groups.Conclusions: In this first-of-kind trial of immunotherapy in patients on AS for prostate cancer, PROSTVAC did not elicit more favorable prostate tissue or peripheral T-cell responses than the EV. There was no difference between the arms in clinicopathologic effects. Despite the null findings, this is the first study reporting the feasibility and acceptability of an immunotherapy intervention in the AS setting.Patient summary: We looked at responses after an experimental prostate cancer vaccine in patients with prostate cancer on active surveillance (AS). Participants who received the vaccine did not show more favorable outcomes than those receiving the control. Despite these findings, this is the first report showing the feasibility and acceptability of immunotherapy for prostate cancer in patients on AS. & COPY; 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Finasteride and Prostate Cancer: New York Times Article from Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention

e16506 Background: Peripheral blood markers (PBM) have been demonstrated to be prognostic and/or predictive for cancer patients (pts) treated with immune checkpoint inhibitors (ICI). Initial evidence has shown their potential role in predicting the occurrence of immune-related adverse events (IrAE) in pts treated with single-agent ICI. We explored the potential role of different PBM in predicting IrAE in metastatic genitourinary cancer (mGU) pts treated with an ICI-based combination. Methods: We retrospectively evaluated 60 mGU pts treated with Cabozantinib + Nivolumab +/- Ipilimumab (CaboNivo +/- Ipi) in a phase I study at the National Cancer Institute. We retrieved their demographics, the occurrence of IrAE, and the baseline values of different PBM (neutrophil/lymphocyte ratio [NLR], neutrophil/eosinophil ratio [NER], lymphocyte/monocyte ratio [LMR], monocyte/lymphocyte ratio [MLR], platelet/lymphocyte ratio [PLR], systemic immune-inflammation index [SII] [N/L*P], and HALP score [albumin*hemoglobin*L/P]). We evaluated PBM based on the presence or absence of IrAE using the Wilcoxon rank sum test followed by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve analyses were used to investigate an optimal cut-off for PBM suitable for prediction. Results: The median age of pts was 58.5 years (interquartile range [IQR] 46 - 67), and 13 (21.7%) were female. Twenty (33.3%) pts developed at least one IrAE. Baseline median values of PMB are summarized in the Table. A multivariable logistic regression model showed after backward elimination that only NER had the potential to predict IrAE (p = 0.033; Odds Ratio = 0.989 per unit [95% Confidence Interval 0.979 - 0.999]) and thus, we further investigated the predictive potential of NER for the development of IrAE following CaboNivo +/- Ipi. The ROC curve suggested that an optimal cut-off value for NER was 30.647 (area under the ROC = 0.6351). Accordingly, we classified pts with high NER ( > 30.647) as not having IrAE vs low NER (≤ 30.647) as having IrAE. Using this classification, 24/37 (64.9%) of those without (w/o) IrAE and 14/20 (80%) of those with an IrAE could simultaneously be correctly predicted by NER alone. Conclusions: A baseline low NER value was an independent factor associated with a higher probability of developing IrAE in mGU pts treated with CaboNivo +/- Ipi. Prospective validation on a larger cohort of pts is needed. [Table: see text]

249 Background: Immunotherapy could potentially prevent disease progression for early-stage prostate cancer. In this randomized Phase 2 clinical trial, we evaluated the clinical effects of PROSTVAC, a vaccinia/fowlpox viral vector-based immunotherapy that contains PSA and three T-cell costimulatory molecules, in patients with localized prostate cancer. Methods:154 patients with clinically localized, low- or favorable intermediate-risk prostate cancer active surveillance were randomized (2:1) to receive 7 doses of subcutaneous PROSTVAC or placebo (empty fowlpox vector) over 140 days. Post-intervention prostate biopsy was performed 7-14 days after the last dose. Participants were followed for 6 months post-treatment. The primary outcome was change from baseline to post-vaccination in CD4 and CD8 T cell infiltration in biopsy tumor tissue. Secondary outcomes included changes in prostate biopsy Gleason grade (Grade Group) and serum PSA. Results: There were no differences in CD4 and CD8 densities (count of cells/mm 2 ) in post-treatment biopsy tumor tissue between groups ( p = 0.63 and p = 0.75, respectively). Compared to placebo, patients who received PROSTVAC were less likely to demonstrate upgrading at follow-up biopsy, but this difference did not attain significance (22% vs. 40%, p= 0.08). There was no difference in the change of PSA from baseline to 6 months post-treatment between arms ( p= 0.30). Conclusions: In this first-of-kind trial of immunotherapy for localized prostate cancer, PROSTVAC was well tolerated but did not elicit significant prostate tissue T-cell responses compared to placebo. The favorable post-treatment biopsy grade findings in PROSTVAC patients merit further evaluation and longer-term clinical follow-up. Clinical trial information: NCT02326805.

Background: Five-alpha reductase inhibitors (5-ARIs), specifically finasteride and dutasteride, have been shown to significantly reduce prostate cancer incidence. However, these agents were also associated with a significant increase in the detection of high-grade prostate cancer leading to an FDA black box warning in 2011. Little is known about the effect of this warning on the subsequent use of these 5-ARIs. The purpose of this analysis was to assess use patterns of finasteride and dutasteride before and after the black box warning. Methods: This cohort study evaluated men enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial who had ≥12 months of Medicare Part D coverage from 2008 to 2015, and had not been diagnosed with prostate cancer through 2007. Socio-demographic factors and benign prostatic hyperplasia (BPH) status were ascertained from follow-up questionnaires, while medication use was ascertained from linkage to Medicare Part D claims data. Results: Of 14,833 eligible men, 88.7% identified as non-Hispanic white, 1.7% as African-American, 5.2% as Asian/Pacific Islander and 1.7% as Hispanic. The median age was 72 years; 41.8% reported a BPH diagnosis. Only 13.6% and 4% of the population took finasteride or dutasteride, respectively, at any time from 2008 to 2015. During this period, finasteride use significantly increased from 3.6% to 9.7% and was highest among men with BPH; dutasteride use remained low and decreased from 2.8% to 1.9%. Conclusions: Finasteride use significantly increased after the FDA’s 2011 black box warning, while dutasteride use remained low and steady throughout the study period.