5α-reductase Inhibitors Research Articles

(119) The Effect of Tadalafil and Dutasteride Combination on Lower Urinary System Symptoms and Erectile Functions in Patients with and without Prostate Median Lobe

Abstract Introduction Alpha blockers, 5 alpha reductase inhibitors, anticholinergics and tadalafil are used in the treatment of LUTS due to BPH. Objective The aim of this study was to evaluate the effect of daily tadalafil+dutasteride treatment on lower urinary tract symptoms (LUTS) and erectile functions in male patients with and without a median prostate lobe. Methods Male patients over the age of 40 who applied to the Urology Outpatient Clinic due to LUTS/ED between January 2018 and December 2022 were included in the study. Ethics committee approval was obtained for the study. Detailed medical and sexual histories of the patients were taken. The International Prostate Symptom Index was used for the LUTS, and the International Erectile Function Index-Erectile Function section was used for the erectile function. PSA and total testosterone levels of the patients were recorded. Maximum urine flow rate (Qmax) was measured by uroflowmetry. Prostate volume, presence of median lobe, median lobe volume and post-void residual urine volume (PMR) were measured by transabdominal ultrasound. Then, patients with moderate and severe LUTS and prostate volume over 40 cc were divided into 2 groups as those with and without middle lobe. The patients were started on tadalafil 5mg and dutasteride 0.5mg daily. IPSS, IIEF-EF, Qmax, PV and PMR changes of the patients were compared after 24 weeks of treatment. Results A total of 96 patients were included in the study (42 with a median lobe (group-1), 54 without a median lobe (group-2). The mean age of the patients was 56.25±13.47, and the mean BMI was 29.12±7.76. The mean IPSS value of the patients was 14.25±6.69, and the IIEF-EF value was 12.11±9.93. Mean PSA value 2.25±1.36 ng/ml, total testosterone value 345.67±123.21 ng/ml, mean PV 46.71±23.22 ml, Qmax value 8.24±3.36 m/s, PVR 54.32±25.52 was ml. There was no significant difference between the baseline IPSS, IIEF-EF, PSA and Qmax values between the two groups (p>0.05). After daily tadalafil+dutasteride treatment, mean IPSS value of the patients at the 24th week controls was 5.42±4.09 (p<0.001), IIEF-EF score was 20.97±3.67p<0.001), PV was 38.20±10.68 ml (p= 0.021), the Qmax value was found to be 12.45±7.68 m/s (p<0.001). Significant improvements were observed in IPSS, IIEF-EF and Qmax values in both groups compared to the beginning of treatment when the parameters of the groups were changed at the beginning and at the 24th week. When the 24th week data of the two groups were compared, it was found that the IPSS decrease in group-2 was higher than in group-1 (p=0.012). IIEF-EF scores (p=0.034) and Qmax (p=0.001) values were found to be higher than group-1. Conclusions Daily tadalafil+dutasteride treatment is an effective and safe treatment combination in male patients with LUTS/ED. In the presence of the median lobe, the response from tadalafil+dutasteride treatment decreases. The 24-week preliminary results of the study allowed us to have an idea of the long-term results. Further studies are needed to evaluate the effect of tadalafil+dutasteride combination in the treatment of LUTS/ED. Disclosure No

(146) Rezum Water Vapor Therapy for Patients with Mild, Moderate, or Severe Lower Urinary Tract Symptoms: A Retrospective Study in a Multiethnic Population

Abstract Introduction Benign prostatic hyperplasia (BPH) is a common chronic condition that is associated with the development of lower urinary tract symptoms (LUTS). Symptom severity of LUTS secondary to BPH can range from mild, moderate, to severe and can be assessed utilizing the International Prostate Symptom Score (IPSS). The Rezum System (Rezum; Boston Scientific, Marlborough, MA, USA) is a minimally invasive surgical therapy that utilizes convective radiofrequency water vapor thermal energy to ablate obstructive lobes of the prostate, resulting in cell necrosis and improvement in LUTS. Objective To evaluate the safety and efficacy of Rezum in patients with mild, moderate, or severe LUTS secondary to BPH. Methods A single office, retrospective study was conducted on patients from a multiethnic population treated with Rezum between 2017 and 2019. Patients were categorized into three cohorts based on baseline IPSS LUTS severity: mild LUTS (IPSS ≤ 7), moderate LUTS (IPSS 8-19), or severe LUTS (IPSS ≥ 20) cohorts. Outcome measures, including IPSS, quality of life (QoL), maximum urinary flow rate (Qmax), postvoid residual (PVR), alpha blockers and 5-alpha reductase inhibitors usage, and adverse events (AEs) were collected and analyzed at baseline, 1-, 3-, 6-, and/or 12-months postoperatively. Results A total of 238 patients were included: 33 with mild LUTS, 109 with moderate LUTS, and 96 with severe LUTS. At 1-month follow-up, the moderate and severe LUTS cohorts saw significant improvements in IPSS (moderate LUTS: -3.0 [-6.0, 1.5], p<0.001; severe LUTS: -10.0 [-16.0, -5.0], p<0.001) and QoL (moderate LUTS: -1.0 [-3.0, 0.0], p<0.001; severe LUTS: -1.0 [-3.0, 0.0], p<0.001) and improvements remained durable up to 12-months (p<0.001). The mild LUTS cohort saw significant worsening in IPSS by 2.0 (0.0, 12.0) at 1-month (p=0.002) but returned to baseline at 3-months (p=0.114). However, the mild LUTS cohort experienced significant improvements in QoL by -0.5 (-3.0, 0.0) at 3-months (p=0.035) and nocturia by 0.0 (-1.0, 0.0) at 6-months (p=0.002), both of which remained durable to 12-months (p<0.05). Most AEs were transient and non-serious, with gross hematuria (66.5%) being most common. There were no significant differences in QoL point reduction, Qmax improvement, PVR reduction, and AE occurrence between the cohorts at 12-months (p>0.05). At 12-months, 80.0%, 87.5%, and 66.0% of the patients in the mild, moderate, and severe LUTS cohorts discontinued their BPH medications, respectively. Conclusions Rezum provides rapid and durable relief in LUTS in patients with moderate or severe LUTS and can be offered to patients with mild LUTS who have bothersome nocturia and wish to discontinue their BPH medications. Disclosure No

Association of 5α-Reductase Inhibitor Prescription With Bladder Cancer Progression in Males in South Korea

The antiandrogenic effect of the 5α-reductase inhibitor (5-ARI) has been investigated for its role in preventing male-predominant cancers. Although 5-ARI has been widely associated with prostate cancer, its association with urothelial bladder cancer (BC), another cancer experienced predominantly by males, has been less explored. To assess the association between 5-ARI prescription prior to BC diagnosis and reduced risk of BC progression. This cohort study analyzed patient claims data from the Korean National Health Insurance Service database. The nationwide cohort included all male patients with BC diagnosis in this database from January 1, 2008, to December 31, 2019. Propensity score matching was conducted to balance the covariates between 2 treatment groups: α-blocker only group and 5-ARI plus α-blocker group. Data were analyzed from April 2021 to March 2023. Newly dispensed prescriptions of 5-ARIs at least 12 months prior to cohort entry (BC diagnosis), with a minimum of 2 prescriptions filled. The primary outcomes were the risks of bladder instillation and radical cystectomy, and the secondary outcome was all-cause mortality. To compare the risk of outcomes, the hazard ratio (HR) was estimated using a Cox proportional hazards regression model and difference in restricted mean survival time analysis. The study cohort initially included 22 845 males with BC. After propensity score matching, 5300 patients each were assigned to the α-blocker only group (mean [SD] age, 68.3 [8.8] years) and 5-ARI plus α-blocker group (mean [SD] age, 67.8 [8.6] years). Compared with the α-blocker only group, the 5-ARI plus α-blocker group had a lower risk of mortality (adjusted HR [AHR], 0.83; 95% CI, 0.75-0.91), bladder instillation (crude HR, 0.84; 95% CI, 0.77-0.92), and radical cystectomy (AHR, 0.74; 95% CI, 0.62-0.88). The differences in restricted mean survival time were 92.6 (95% CI, 25.7-159.4) days for all-cause mortality, 88.1 (95% CI, 25.2-150.9) days for bladder instillation, and 68.0 (95% CI, 31.6-104.3) days for radical cystectomy. The incidence rates per 1000 person-years were 85.59 (95% CI, 80.53-90.88) for bladder instillation and 19.57 (95% CI, 17.41-21.91) for radical cystectomy in the α-blocker only group and 66.43 (95% CI, 62.22-70.84) for bladder instillation and 13.56 (95% CI, 11.86-15.45) for radical cystectomy in the 5-ARI plus α-blocker group. Results of this study suggest an association between prediagnostic prescription of 5-ARI and reduced risk of BC progression.

Use of 5α-reductase inhibitors and survival of oesophageal and gastric cancer in a nationwide Swedish cohort study

Background We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. Methods This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. Results Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). Conclusion This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer.

Abstract A12: Androgen receptor inhibition is involved in Finasteride-reduced AML cell proliferation

Abstract Acute myeloid leukemia (AML) is a top priority type of hematological malignancies to be studied and treated. Androgen receptor (AR) plays important roles in various cancers, such as types of the prostate, breast, liver, and lung. However, the role of AR in leukemia is so far uncertain. Finasteride is a 5 alpha-reductase inhibitor for reduction of cellular 5 alpha-dihydrotestosterone production and commonly used to treat benign prostatic hyperplasia for decades. Here, the data showed that Finasteride treatment significantly decreased the proliferation of AML cell lines, including KG-1 and HL-60. More specific to its impact on androgen’s actions, the authors found that Finasteride inhibited the phosphorylation and activation of AR, while the cell cycle-related proteins such as CDK1, Cyclin A, and p21 were unaffected. Interestingly, the increase of AKT phosphorylation was observed after Finasteride treatment, which is correspondent to the previous findings of mutual correlations between AR inhibition and AKT activation in prostate cancer cells. It implies that AR might play a physiological role in AML cells for proliferation, in which AR closely collaborates with AKT for a balance of regulation. In summary, these results suggest that Finasteride might reduce the proliferation of AML cell lines through AR inhibition. These findings could be helpful to uncover novel AML treatments in the future. Citation Format: Pang-Ting Cheng, Chieh-Lin Jerry Teng, Yu-Chiao Cheng, Mei-Chih Chen, Ho Lin. Androgen receptor inhibition is involved in Finasteride-reduced AML cell proliferation [abstract]. In: Proceedings of the AACR Special Conference: Acute Myeloid Leukemia and Myelodysplastic Syndrome; 2023 Jan 23-25; Austin, TX. Philadelphia (PA): AACR; Blood Cancer Discov 2023;4(3_Suppl):Abstract nr A12.

Preferred methods of Diagnosis and Treatment of Benign Prostatic Hyperplasia adopted by Ayurveda practitioners - A Survey Study

Introduction: Benign Prostatic Hyperplasia (BPH) refers to the nonmalignant growth of prostate gland. In Ayurveda, it can be correlated with Mutraaghata or Mutradosha. Currently used common oral medications such as 5α-reductase inhibitors, α1-Blockers as well as surgical treatment methods such as Transurethral Resection of the Prostate (TURP) have well-known side effects. Ayurveda case studies on BPH show evidence of a potential alternative to these current methods. Objectives: To conduct a survey to know the diagnostic methods and treatment modalities used by different Ayurveda Practitioners in BPH treatment. Materials & Methods: A survey comprising 7 questions in the form of multiple-choice questions on the diagnosis and treatment methods of BPH adopted by Ayurveda Physicians was done. The answers were recorded and interpreted in the form of graphs and pie charts. Results: A total of 57 different Ayurveda practitioners participated in the survey. Prevalence of BPH was seen more in the age group of 60-70 years. Ultrasonography (USG) and Prostate Specific Antigen (PSA) were among the most commonly used diagnostic methods for BPH. Most common symptoms observed were increased frequency of urine, urine incontinence and urine urgency. Uttara Basti (administration of medicine through the urethra) was the most recommended type of treatment procedure preferred, followed by Matra Basti (enema). Avagaha Swedana (Sitz bath) was recommended by most practitioners. The course duration of treatment is advised to be around half to one month. Around 40-60% relief was claimed in patients with BPH by the participants. Conclusion: BPH is a condition that is currently being treated by various Ayurveda practitioners using classical treatment methods such as Uttara Basti, Matra Basti etc. with claimed relief of about 40-60% by the participants.

Smoking and lower urinary tract symptoms in Reduction by Dutasteride of Prostate Cancer EventsTrial.

Benign prostatic hyperplasia is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Smoking has many well-established adverse effects, but its effects on benign prostatic hypertrophy(BPH) and associated LUTS are unclear. We sought to determine if smoking is a risk factor for the incidence of LUTS in asymptomatic men and for the progression of LUTS in symptomatic men. We performed a post-hoc analysis of Reduction by Dutasteride of Prostate Cancer Events in 3060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) < 8 and in 2198 symptomatic men with baseline IPSS ≥ 8 not taking 5α-reductase inhibitors or α-blockers. We used multivariable Cox regression models to assess associations between smoking status at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical or surgical treatment for BPH, or sustained clinically significant LUTS (two reports of IPSS > 14). Among symptomatic men, LUTS progression was defined as IPSS increase of ≥4 points from baseline, surgical intervention for BPH, or starting a new BPH drug. Of 3060 asymptomatic men, 15% (n = 467) were current, 40% (n = 1231) former, and 45% (n = 1362) never-smokers. Of 2198 symptomatic men, 14% (n = 320) were current, 39% (n = 850) former, and 47% (n = 1028) never-smokers. In asymptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with LUTS incidence (adjusted hazard ratio [adj-HR] = 1.08; 95% confidence interval [95%CI]: 0.78-1.48 and adj-HR = 1.01; 95% CI: 0.80-1.30). In symptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with the progression of LUTS (adj-HR = 1.11; 95% CI: 0.92-1.33 and adj-HR = 1.03; 95% CI: 0.90-1.18). In REDUCE, smoking status was not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men.

5-alpha reductase inhibitors and MRI prostates: actively reducing prostate sizes and ambiguity

BackgroundMagnetic resonance imaging (MRI) scans are increasingly first-line investigations for suspected prostate cancer, and essential in the decision for biopsy. 5-alpha reductase inhibitor (5-ARI) use has been shown to reduce prostate size and prostate cancer risk. However, insufficient data exists on how 5-ARI use affects MRI findings and yield of biopsy. This study explores the differences in imaging and prostate cancer diagnoses between patients receiving and not receiving 5-ARI therapy.MethodsFrom 2015 to 2020, we collected retrospective data of consecutive patients undergoing prostate biopsy at one centre. We included patients who were biopsy-naïve, had prior negative biopsies, or on active surveillance for low-grade prostate cancer. Clinical and pathological data was collected, including 5-ARI use, Prostate Imaging Reporting and Data System (PIRADS) classification and biopsy results.Results351 men underwent saturation biopsy with or without targeted biopsies. 54 (15.3%) had a history of 5-ARI use. On mpMRI, there was no significant difference between the 5ARI and non-5-ARI groups in PIRADS distribution, number of lesions, and lesion location. Significantly fewer cancers were detected in the 5-ARI group (46.3% vs. 68.0%; p < 0.01). There were no significant differences in PIRADS distribution in 5-ARI patients with positive and negative biopsy.ConclusionOur study found significant differences in biochemical, imaging and biopsy characteristics between 5-ARI and non-5-ARI groups. While both groups had similar PIRADS distribution, 5-ARI patients had a lower rate of positive biopsies across all PIRADS categories, which may suggest that the use of 5ARI may confound MRI findings. Further studies on how 5-ARI therapy affects the imaging characteristics of prostate cancer should be performed.

Long-term risk of benign prostatic hyperplasia-related surgery and acute urinary retention in men treated with 5-alpha reductase inhibitor versus alpha-blocker monotherapy in routine clinical care.

To assess the risk of benign prostatic hyperplasia (BPH)-related surgery and acute urinary retention (AUR) in men treated with 5-alpha-reductase inhibitor (5-ARI) versus alpha-blocker monotherapy in routine clinical care over 15 years of follow-up. Using population-based Danish Health registries, we identified all new-users of 5-ARI or alpha-blocker monotherapy in Denmark, 1997-2017. We defined an index date 180 days after the date of first prescription and included men who redeemed at least one additional prescription before the index date. We used multiple imputation to replace missing prostate-specific antigen values. We performed propensity score-weighted Cox regression to estimate weighted hazard ratios (wHRs) and cumulative incidence function to estimate weighted cumulative risks of BPH-related surgery and AUR in intention to treat (ITT) and per protocol (PP) analyses. We included 18,421 and 95,984 men treated with 5-ARI and alpha-blocker monotherapy, respectively. Overall, treatment with 5-ARI monotherapy was associated with a reduced risk of BPH-related surgery (ITT wHR = 0.73 (95% confidence interval [CI]: 0.68-0.78), PP wHR = 0.77 (95% CI: 0.70-0.84) and AUR (ITT wHR = 0.73 (95% CI: 0.67-0.78), PP wHR = 0.75 (95% CI: 0.66-0.84). The 15-year risk of BPH-related surgery in men treated with 5-ARI versus alpha-blocker monotherapy was 14.8% (95% CI: 14.1%-15.5%) versus 19.1% (95% CI: 18.7%-19.5%) in the ITT analysis and 13.8% (95% CI: 12.6%-14.9%) versus 17.5% (95% CI: 16.9%-18.0%) in the PP analysis. The 15-year risk of AUR in men treated with 5-ARI versus alpha-blocker was 13.0% (95% CI: 12.3%-13.6%) versus 16.6% (95% CI: 16.3%-17.0%) in the ITT analysis and 12.6% (95%: 11.3%-14.0%) versus 16.9% (95% CI: 16.3%-17.6%) in the PP analysis. Treatment with 5-ARI versus alpha-blocker monotherapy in routine clinical care was associated with a reduced risk of BPH-related surgery and AUR for up to 15 years of follow-up. After 15 years of follow-up, the relative risk reduction was 21%-25% and the absolute risk reduction was 4%.

How Would You Manage This Patient With Benign Prostatic Hyperplasia? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) are common in older patients assigned male sex at birth, regardless of gender identity, and treatment of these symptoms is therefore common in primary care practice. In 2021, the American Urological Association published guidelines for management of BPH. They recommend using a standardized scoring system such as the International Prostate Symptom Score to help establish a diagnosis and to monitor the efficacy of interventions, α-blockers as the first-choice pharmacotherapy option, and 5α-reductase inhibitors for patients with prostate size estimated to be at least 30 cc. Tadalafil is another option regardless of erectile dysfunction. Combination therapies with α-blockers and 5α-reductase inhibitors, anticholinergic agents, or β3-agonists are effective options. A surgical referral is warranted if the BPH results in chronic kidney disease, refractory urinary retention, or recurrent urinary tract infections; if there is concern for bladder or prostate cancer; or if symptoms do not respond to medical therapy. In this article, a general internal medicine physician and a urologist discuss the treatment options and how they would apply their recommendations to a patient who wishes to learn more about his options.

MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS

You have accessJournal of UrologyCME1 Apr 2023MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS Jason Scovell, Mark Stovsky, Aimee Kestranek, and Eric Klein Jason ScovellJason Scovell More articles by this author , Mark StovskyMark Stovsky More articles by this author , Aimee KestranekAimee Kestranek More articles by this author , and Eric KleinEric Klein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: IsoPSA is a structure-based test linked to tumor biology that has demonstrated improved performance characteristics over PSA and percent free PSA to identify clinically actionable prostate cancer (GG2+). Medications for benign prostatic hyperplasia (BPH) including 5-α reductase inhibitors (5ARIs) and α-blockers are commonly used in the patient population undergoing prostate cancer screening. The relationship between 5-ARIs and PSA levels is well established. We sought to determine the impact that common BPH medications have on IsoPSA performance. METHODS: This is a secondary analysis of data from an institutional review board (IRB) approved, prospective, multicenter study evaluating IsoPSA in men≥50 years of age with a total PSA ≥ 4ng/ml with planned prostate biopsy who met previously described inclusion/exclusion criteria. Analytic groups included (i) all subjects, (ii-iii) +/- 5-ARI use, (iv-v) +/- α-blocker use. Sensitivity and specificity analysis were performed and receiver operating curves (ROC) were evaluated. RESULTS: A total of 1,385 men were recruited from a multi-center (8 sites), prospective, nonrandomized cohort with 888 men included in final analysis. Actionable prostate cancer, defined as GG2 or greater, was identified in a total of 316 patients (35.6%). In this cohort, 40 patients reported 5-ARI use and 217 reported α-blocker use. At the pre-determined IsoPSA threshold (5.25 all cancer; 6.0 GG2+) sensitivity to detect both all prostate cancer and actionable cancer was similar between all patients enrolled and patients on either 5-ARIs or α-blockers (All: 0.90 vs 5-ARI: 0.94 vs α-blocker: 0.85; p>0.05). Specificity was similar between patients regardless of 5-ARI (No 5-ARI: 0.46 vs 5-ARI: 0.45, p>0.05). Increased specificity was noted in patients on α-blockers (No α-blocker: 0.40 vs α-blocker: 0.61, p<0.05). There were no additional differences in FP, FN, FP, FN, LR (+/-), PPV, or NPV rates between all sub-cohorts. ROC analysis demonstrates excellent performance of IsoPSA regardless of 5-ARI or α-blocker use for both the detection of all prostate cancer and for actionable cancer (Figure 1). CONCLUSIONS: Common BPH medications (5-ARI and α-blockers) do not negatively impact IsoPSA performance characteristics for the detection of prostate cancer including clinically actionable prostate cancer. Source of Funding: Cleveland Diagnostics funded the initial study of IsoPSA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e769 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Scovell More articles by this author Mark Stovsky More articles by this author Aimee Kestranek More articles by this author Eric Klein More articles by this author Expand All Advertisement PDF downloadLoading ...

PD02-08 ESR1+ LUMINAL EPITHELIAL CELLS DRIVE THE PROSTATE GROWTH AND SURVIVAL IN THE ABSENCE OF SRD5A2

You have accessJournal of UrologyCME1 Apr 2023PD02-08 ESR1+ LUMINAL EPITHELIAL CELLS DRIVE THE PROSTATE GROWTH AND SURVIVAL IN THE ABSENCE OF SRD5A2 Christina Sharkey, Xingbo Long, Ra'ad Al-Faouri, Aria F. Olumi, and Zongwei Wang Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Aria F. OlumiAria F. Olumi More articles by this author , and Zongwei WangZongwei Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. 5α reductase inhibitors (5ARI) are the only class of benign prostate hyperplasia-related medications that reduce prostate size. However, why the patients respond variably to 5ARI therapies is still largely unknown. We previously demonstrated that 30% of adult human prostatic tissues do not express the SRD5A2 gene and protein via epigenetic modifications. We established a SRD5A2 null (Srd5a2-/-) mouse model and through single cell RNA sequencing, we identified LE2, a sub-cell population of ESR1+ luminal epithelial that is upregulated in Srd5a2-/- mice. Our goal in this study is to characterize the spatial expression of LE2 markers and its functional phenotype when SRD5A2 is absent. METHODS: Homozygous Srd5a2-/- mice and littermate control heterozygous SRD5A2+/- mice were generated and differentially expressed gene profiles of LE2 were obtained from single-cell RNA sequencing (scRNA seq). Spatial expression of LE2 markers was evaluated by RNA fluorescence in-situ hybridization (RNA-FISH). Cell proliferation was detected by Ki67 and BrdU staining. The Cell Death and ER signaling pathways were evaluated with RT2 PCR profiler arrays (84 genes per array) and downstream signaling pathways were analyzed by western blot. Prostate biopsies from the clinical trial of 5ARI for Medical Therapy of Prostatic Symptoms (MTOPS) were used for immunohistochemistry. RESULTS: The prostate weight of Srd5a2-/- mice was significantly decreased compared to Srd5a2+/- littermate control mice (p<0.001). The prostate cell proliferation was suppressed in Srd5a2-/- mice (p=0.05). The cell death signaling akt1, caspase 7, caspase 9, and ER target genes cyp1a1 and vegfa were downregulated (p<0.05). On the other hand, in the anterior lobe of prostate of Srd5a2-/- mice, the cell proliferation was higher than that in control. scRNA seq showed that ESR1 was expressed mainly in the prostate anterior lobe and the number of ESR1+ LE2 cells was significantly increased upon SRD5A2 absence. This was confirmed by RNA-FISH using the probes of LE2 cell markers ESR1 and PVT1. Co-staining of LE2 cell markers ESR1 and PKCa in prostate biopsies of MTOPS further confirmed the existence of an equivalent LE2 cell population in the human prostate with BPH. CONCLUSIONS: Our data demonstrate that LE2, the subpopulation of prostate cells may play an important role in alternative pathways for prostate growth and survival in absence of SRD5A2 and androgen deprivation. Understanding the underlying androgen-independent pathways contributing to prostate growth can help identify novel therapeutic targets for the management of prostatic diseases. Source of Funding: NIH/R01 DK124502 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e71 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Ra'ad Al-Faouri More articles by this author Aria F. Olumi More articles by this author Zongwei Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

Initial management of lower urinary tract symptoms and bladder outlet obstruction

Lower urinary tract symptoms (LUTS) are a common presenting complaint for both men and women, affecting >60% of men and women aged >40 years. They encompass a wide range of aetiologies and can be an indicator of covert underlying pathologies such as obesity and metabolic syndrome. The initial assessment should focus on identifying the underlying cause and assessing the impact on quality of life aided by validated objective questionnaires. Risk factors have been identified that can predict the likelihood of progression of LUTS (e.g. urinary retention), such as age, moderately elevated prostate-specific antigen and prostate size. Initial management includes conservative and medical management, and not all patients require surgery. Identifying those at high risk of acute urinary retention helps in counselling and subsequent management decisions. Aside from lifestyle modification, medications include selective α-adrenoceptor blockers, 5α-reductase inhibitors, antimuscarinics, β3-agonists and phosphodiesterase-5 inhibitors, either as monotherapy or combination therapy.

PD23-09 LUTS, ED, AND QOL IMPROVE UNDER LONG-TERM TESTOSTERONE THERAPY IN OBESE MEN WITH FUNCTIONAL HYPOGONADISM

You have accessJournal of UrologyCME1 Apr 2023PD23-09 LUTS, ED, AND QOL IMPROVE UNDER LONG-TERM TESTOSTERONE THERAPY IN OBESE MEN WITH FUNCTIONAL HYPOGONADISM Ahmad Haider, Karim Sultan Haider, Gheorghe Doros, and Abdulmaged Traish Ahmad HaiderAhmad Haider More articles by this author , Karim Sultan HaiderKarim Sultan Haider More articles by this author , Gheorghe DorosGheorghe Doros More articles by this author , and Abdulmaged TraishAbdulmaged Traish More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in elderly men are closely associated with quality of life (QoL). We aimed to assess long-term effects of testosterone therapy (TTh) in hypogonadal men in a registry study. METHODS: 898 men with hypogonadism, 481 men chose TTh by means of testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group). 417 men opted against TTh and served as controls (CTRL). 14-year data are presented. Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the groups. Means and standard deviations of absolute measures over 14 years are reported. RESULTS: Baseline age was 56.5±8.0 years in the T-group and 62.7±5.3 years in CTRL (p<0.0001). Mean follow-up was 11.0±3.2 years in the T-group and 11.1±3.3 in CTRL. Median follow-up was 12 years in the T-group and 12 years in CTRL. At baseline, alpha-blockers were used by 36.6% (T-group) and 50.2% (CTRL) (p<0.0001), 5α-reductase inhibitors by 2.1% and 8.6% (p<0.0001), and PDE5-Inhibitors by 26.4% and 22.1% (p=0.1308). IPSS (baseline: 6.4±3.7) decreased to 1.5±0.7 (p<0.0001) in the T-group in year 14. In CTRL, IPSS (baseline: 4.9±1.9) increased to 11.4±5.1 (p<0.0001). Estimated adjusted difference between groups: -11.0 (p<0.0001). Residual bladder volume (RBV) in the T-group (baseline: 50.7±25.9) decreased by 39.3±1.4 mL (p<0.0001) in year 14. In CTRL, RBV (baseline: 51.7±16.7) increased by 58.8±1.5 mL (p<0.0001). Estimated adjusted difference between groups: -94.4 mL [95% CI: -98.2;-90.7] (p<0.0001). IIEF-EF in the T-group increased from 17.3±5.9 (mild to moderate) by 11.1±0.2 to 29.5±0.9 (no ED) in year 14. In CTRL, IIEF-EF decreased from 19.7±3.5 (mild to moderate) by 14.5±0.2 to 6.8±0.9 (severe). Estimated adjusted difference between groups: 23.5 (95% CI: 23.0;24.1) (p<0.0001). QoL, assessed by the Aging Males’ Symptoms scale (AMS), improved from 53.0±9.8 (severe symptoms) by 29.8 points in the T-group to 17.2 (no symptoms) and worsened from 40.4±5.6 (moderate symptoms) by 24.7 points to 66.7 (severe symptoms) in CTRL. CONCLUSIONS: In men with functional hypogonadism, long-term TTh improves LUTS and ED sustainably over 14 years. This may have contributed to improvements in QoL. In the untreated control group, LUTS, ED, and QoL deteriorated. Source of Funding: Data entry was compensated by Bayer AG © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e675 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ahmad Haider More articles by this author Karim Sultan Haider More articles by this author Gheorghe Doros More articles by this author Abdulmaged Traish More articles by this author Expand All Advertisement PDF downloadLoading ...

Benign Prostate Hyperplasia - Current Medical Therapy, New Developments, and Side Effects

Benign Prostate Hyperplasia - Current Medical Therapy, New Developments, and Side Effects Abstract: Lower urinary tract symptoms (LUTS) consist of both voiding and storage symptoms. Urethral obstruction leading to voiding symptoms is most commonly attributed to benign prostatic hyperplasia (BPH), where hyperplastic growth and increased smooth muscle tone in the hyperplastic prostate may lead to benign prostate obstruction (BPO). Spontaneous contractions of the detrusor muscle may cause storage symptoms, which are referred to as overactive bladder (OAB). With a considerable proportion of patients suffering from "mixed LUTS", a combination of voiding and storage symptoms, LUTS affect a large portion of the population worldwide, with major impact on quality of life (QoL). A demographic shift in society, will lead to higher incidence and prevalence of LUTS, with a growing economic burden. Standard-of-care medical treatment for LUTS/BPO includes α1-adrenoceptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors, for reduction of prostate smooth muscle tone, and 5α-reductase inhibitors (5-ARI) to slow down disease progression. Medical therapy for LUTS/OAB includes muscarinic receptor antagonists, and β3-agonists for relief of spontaneous bladder contractions. When left untreated, LUTS may cause considerable adverse events, ranging from acute urinary retention with kidney failure, and recurring infections, to social withdrawal, and depression.

TCTAP A-084 The Risk of Cardiovascular Disease in Patients With Benign Prostate Hyperplasia on 5-Alpha Reductase Inhibitors Treatment: A Meta-Analysis

TCTAP A-084 The Risk of Cardiovascular Disease in Patients With Benign Prostate Hyperplasia on 5-Alpha Reductase Inhibitors Treatment: A Meta-Analysis

MP76-13 PROSTATE ARTERY EMBOLIZATION - MULTICENTER RETROSPECTIVE EXPERIENCE OF 1000 PATIENTS WITH SHORT, MID, AND LONG TERM FOLLOW UP

You have accessJournal of UrologyCME1 Apr 2023MP76-13 PROSTATE ARTERY EMBOLIZATION - MULTICENTER RETROSPECTIVE EXPERIENCE OF 1000 PATIENTS WITH SHORT, MID, AND LONG TERM FOLLOW UP Shivank Bhatia, Andrew Richardson, Aneesha Maini, Hamed Jalaeian, Rohit Reddy, Kenneth Richardson, Ansh Bhatia, Hemendra Shah, and Bruce Kava Shivank BhatiaShivank Bhatia More articles by this author , Andrew RichardsonAndrew Richardson More articles by this author , Aneesha MainiAneesha Maini More articles by this author , Hamed JalaeianHamed Jalaeian More articles by this author , Rohit ReddyRohit Reddy More articles by this author , Kenneth RichardsonKenneth Richardson More articles by this author , Ansh BhatiaAnsh Bhatia More articles by this author , Hemendra ShahHemendra Shah More articles by this author , and Bruce KavaBruce Kava More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003350.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To evaluate and expand upon the effectiveness and safety profile of PAE in treating BPH with LUTS or urinary retention. METHODS: 1000 patients underwent PAE for either BPH with LUTS or urinary retention from January 2014 to September 2022. Mean patient age was 70.2±9.5 years, mean prostate volume was 107.2±65.1 g, median pre-procedure IPSS, SHIM and QoL scores were 23 (IQR 18-28), 17 (IQR 10-21) and 5 (IQR 4-6), respectively. Mean PVR was 195.6±232 cc, mean PSA was 6.6±6.9 ng/dl, and mean Qmax 8.0±4.2 cc/s. 100 individuals were indwelling catheter dependent at time of PAE with an average of 127.6 days of catheter dependence prior to PAE. 781 individuals reported BPH medication usage. Patient evaluation occurred at 3-6, 12, 24, 60 and 72-month (mo) intervals post PAE. Adverse events were recorded using the Clavien-Dindo (CD) classification. Two-tailed p<0.05 was considered significant. RESULTS: Median follow up was 1027 days. 63.4% of patients had 3 months or greater follow up. Median IPSS of baseline catheter independent individuals decreased to 5, 6, 7, 3, and 6 at 3-6, 12-, 24-, 60- and 72-months post PAE, respectively (all p<0.01). Percent of non-responders (IPSS>13) are included in the Table 1. Median SHIM, mean prostate size, mean PVR, mean PSA and mean Qmax data is displayed in the Table 1. Average time to indwelling catheter independence was 25.9 days following PAE. At 3 months post PAE 29% (21/73) of individuals were catheter dependent who ultimately achieved catheter independence. 67 patients (6.7%) have required a second procedure for recurrent LUTS; 10 underwent a second PAE. BPH medication cessation, decreased medication burden, and # of individuals on α-blockers of 5α reductase inhibitors is reported in the Table 1. Self-limited frequency, urgency, and dysuria (CD grade I) postoperative symptoms occurred in 33.5% of patients. Complications of non-target embolization, urosepsis, and TIAs were seen in 3 patients each. CONCLUSIONS: PAE is a clinically effective procedure for patients LUTS and urinary retention secondary to BPH with great short-term to midterm results. Long-term outcomes including maintained LUTS relief and significant improvement in QoL continue to be promising. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1096 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shivank Bhatia More articles by this author Andrew Richardson More articles by this author Aneesha Maini More articles by this author Hamed Jalaeian More articles by this author Rohit Reddy More articles by this author Kenneth Richardson More articles by this author Ansh Bhatia More articles by this author Hemendra Shah More articles by this author Bruce Kava More articles by this author Expand All Advertisement PDF downloadLoading ...

PD02-06 SERUM TESTOSTERONE AND DIHYDROTESTOSTERONE AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS IN REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD02-06 SERUM TESTOSTERONE AND DIHYDROTESTOSTERONE AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS IN REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS TRIAL James Daniels, James Mirocha, Daniel Moreira, Gerald Andriole, and Stephen Freedland James DanielsJames Daniels More articles by this author , James MirochaJames Mirocha More articles by this author , Daniel MoreiraDaniel Moreira More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Though the pathogenesis of BPH is unclear, it was previously believed that increasing androgen levels had a role, though not all data support this idea. We tested if elevated serum testosterone and elevated serum DHT are risk factors for LUTS incidence in asymptomatic men and for LUTS progression in symptomatic men. METHODS: A post-hoc analysis of REDUCE was carried out in 3009 asymptomatic men with baseline International Prostate Symptom Score (IPSS) <8 and in 2145 symptomatic men with baseline IPSS≥8 not taking α-blockers or 5α-reductase inhibitor medications. The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated PSA and negative pre-study biopsy. IPSS was measured every 6 months over the 4-year study. We estimated multivariable adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) using Cox models to test the association between quintiles of serum testosterone and quintiles of serum dihydrotestosterone (DHT) at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical treatment, surgery or sustained clinically significant LUTS (i.e., 2 reports of IPSS>14). Among symptomatic men, LUTS progression was defined as an IPSS increase of ≥4 points from baseline, any surgical procedure for BPH, or the start of a new BPH medication. RESULTS: In asymptomatic men, relative to the lowest quantile, all quintiles of serum testosterone and all quintiles of DHT were unrelated to LUTS incidence (all p≥0.25). In symptomatic men, relative to the lowest quantile, all quintiles of serum testosterone and all quintiles of DHT were unrelated to LUTS progression (all p≥0.17). There was no significant interaction between treatment with dutasteride and serum testosterone or DHT when predicting LUTS; as such, data were not stratified by treatment assignment. CONCLUSIONS: In the REDUCE study, higher serum testosterone and higher serum DHT were not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men. These data do not support the hypothesis that serum androgen levels in middle-aged men are associated with LUTS. Source of Funding: Dr. Daniels is funded by the NIH grants TL1 DK132768 and U2C DK129496 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e71 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Daniels More articles by this author James Mirocha More articles by this author Daniel Moreira More articles by this author Gerald Andriole More articles by this author Stephen Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...

PD02-07 ALTERNATE ANDROGEN-INDEPENDENT PATHWAYS FOR PROSTATE GROWTH IN THE ABSENCE OF SRD5A2

You have accessJournal of UrologyCME1 Apr 2023PD02-07 ALTERNATE ANDROGEN-INDEPENDENT PATHWAYS FOR PROSTATE GROWTH IN THE ABSENCE OF SRD5A2 Christina Sharkey, Xingbo Long, Ra'ad Al-Faouri, Aria F. Olumi, and Zongwei Wang Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Aria F. OlumiAria F. Olumi More articles by this author , and Zongwei WangZongwei Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is a heterogeneous disease that results from the nonmalignant proliferation of both the prostate epithelial and stromal compartments. Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. Despite the introduction of steroid 5α-reductase inhibitors (5ARI) for benign prostatic hyperplasia (BPH), the progression of LUTS is only slowed by 34% with 5ARI-response. Therefore, we hypothesize that there are alternative pathways driving prostate growth and development when SRD5A2 is absent. To address this question we generated SRD5A2 null (Srd5a2-/-) mouse model and demonstrated that luminal cells with lineage signature and progenitor signature diminished, whereas luminal cells with estrogen response genetic signature stably survived when SRD5A2 is absent. Here we further aim to identify whether the cell-cell interactions between stromal cells and luminal cells with WNT5A are the critical modulators in absence of SRD5A2. METHODS: Single cell RNA sequencing (scRNA seq) and bulk RNA seq was performed with prostate tissues from Srd5a2-/- and Srd5a2+/- littermate control mice. Unbiased scRNA seq with 10x genomics platform, followed by unsupervised clustering, was utilized to generate cell clusters based on differentially expressed (DE) gene profiles. The heterotypic cell-cell communication was analyzed using CellphoneDB2. Identified ligand-receptor pairs were validated by qPCR in BHPrS1 human prostatic stromal cell line and human prostatic tissues with BPH. RNAscope was performed to identify the transcription expression of target genes. RESULTS: The expression of SRD5A2 was exclusively identified in fibroblasts and myofibroblasts. The absence of SRD5A2 induced the increase of stromal cells (11.3% vs. 18.0%) but decrease of luminal cells (53.2% vs. 31.8%). Analysis of ligand-receptor pairs indicated that stromal cells were the most prolific interactors, and myofibroblasts were the most "outbound" cells. Meanwhile, in Srd5a2-/- mice the fibroblasts had the most significantly increased weighted value (366 vs. 493), and LE1, one subset of luminal cells had most significantly decreased weighted value (205 vs. 96). Myofibroblast and muscle system processes were most significantly upregulated in Srd5a2-/- mice as assessed by bulk RNA-seq analysis. Nine highly significant interactions were identified which regulate stromal–luminal cell communication, including WNT5A/PTPRK, TGFB2/TGFBR1, and (NRP1, NRP2, FLT1)/VEGFA. RNAscope data showed a significant upregulation of WNT5A in the anterior prostate of Srd5a2-/- mice (p<0.0001). CONCLUSIONS: Our data suggest that the heterotypic cell-cell communication is substantially changed in the absence of SRD5A2. The stroma-niched signaling, particularly WNT5A and WNT signaling pathway might serve as a therapeutic target for managing BPH patients who lack SRD5A2 expression and may be unresponsive to 5ARI therapies. Source of Funding: NIH/R01 DK124502 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e71 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Ra'ad Al-Faouri More articles by this author Aria F. Olumi More articles by this author Zongwei Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

The Use of 5-Alpha Reductase Inhibitors Improves the Detection of Prostate Cancer by Increasing Opportunities for Repeated Prostate-Specific Antigen Testing: A Decade-Long (2007–2016) Nationwide Observational Study in Korea

Purpose: The aim of this study was to investigate the influence of taking 5-alpha reductase inhibitors (5ARIs) on the detection of prostate cancer (PCa), considering the reported low uptake of prostate-specific antigen (PSA) testing among Korean men.Materials and Methods: From Korean National Health Insurance Sharing Service data, the number of men older than 40 years who were prescribed 5ARIs from 2007 through 2016 was identified. The association of 5ARI prescriptions with newly registered PCa was analyzed.Results: In total, 1,528,128 men who took 5ARIs for a mean of 1.523±2.221 years were identified. Among 138,614 patients with PCa, 68,529 (49.4%) took 5ARIs and 70,085 did not. The incidence of PCa was significantly higher in the 5ARI group than in the non-5ARI group during all study years (p&lt;0.001) except for 2007. Adjusted for age, the non-5ARI group had a significantly lower likelihood of PCa detection (hazard ratio [HR], 0.854; p&lt;0.001) and radical prostatectomy, including robot-assisted procedures (HR, 0.834, p&lt;0.001). The mean number of PSA tests was about 2 times higher in the 5ARI group than in the non-5ARI group (3.98 vs. 2.18, p&lt;0.001). Among the subjects who took 5ARIs, the incidence of PCa increased up to 3 years of administration, followed by a decreasing trend thereafter (p&lt;0.001).Conclusions: From this observational study in a country with limited PSA testing uptake, the prescription of 5ARIs, for which repeated PSA testing is encouraged to select suitable patients, enhances the detection of PCa, but does not prevent its development.