ABSTRACT
Growth of prostate cancer cells is dependent upon androgen stimulation of the androgen receptor (AR). Dihydrotestosterone (DHT), the most potent androgen, is usually synthesized in the prostate from testosterone secreted by the testis. Following chemical or surgical castration, prostate cancers usually shrink owing to testosterone deprivation. However, tumors often recur, forming castration-resistant prostate cancer (CRPC). Here, we show that CRPC sometimes expresses a gain-of-stability mutation that leads to a gain-of-function in 3ß-hydroxysteroid dehydrogenase type 1 (3ßHSD1), which catalyzes the initial rate-limiting step in conversion of the adrenal-derived steroid dehydroepiandrosterone to DHT. The mutation (N367T) does not affect catalytic function, but it renders the enzyme resistant to ubiquitination and degradation, leading to profound accumulation. Whereas dehydroepiandrosterone conversion to DHT is usually very limited, expression of 367T accelerates this conversion and provides the DHT necessary to activate the AR. We suggest that 3ßHSD1 is a valid target for the treatment of CRPC.
Subject(s)
3-Hydroxysteroid Dehydrogenases/genetics , Dihydrotestosterone/metabolism , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/genetics , 3-Hydroxysteroid Dehydrogenases/metabolism , Androgens/metabolism , Animals , Humans , Male , Mice , Prostatic Neoplasms/metabolism , Proteolysis , UbiquitinationABSTRACT
Multiparametric MRI-the most accurate imaging technique for detection of prostate cancer-has transformed the landscape of prostate cancer diagnosis by enabling targeted biopsies. In a targeted biopsy, tissue samples are obtained from suspicious regions identified at prebiopsy diagnostic MRI. The authors briefly compare the different strategies available for targeting an MRI-visible suspicious lesion, followed by a step-by-step description of the direct MRI-guided in-bore approach and an illustrated review of its application in challenging clinical scenarios. In this technique, direct visualization of the needle, needle guide, and needle trajectory during the procedure provides a precise and versatile strategy to accurately sample suspicious lesions, improving detection of clinically significant cancers. Published under a CC BY 4.0 license Test Your Knowledge questions for this article are available in the supplemental material.
Subject(s)
Prostate , Prostatic Neoplasms , Male , Humans , Prostate/diagnostic imaging , Image-Guided Biopsy/methods , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Prostate-Specific AntigenABSTRACT
Benign prostatic hyperplasia (BPH) is a progressive expansion of peri-urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5-alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI-treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI-induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF-κB signaling and anti-apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3-1 expression. In addition, club-like cells within regions of 5ARI-induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI-treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell-like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , 5-alpha Reductase Inhibitors/pharmacology , 5-alpha Reductase Inhibitors/therapeutic use , Atrophy/pathology , Dihydrotestosterone/pharmacology , Humans , Lower Urinary Tract Symptoms/drug therapy , Lower Urinary Tract Symptoms/pathology , Male , Prostate/pathology , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/genetics , Prostatic Hyperplasia/pathologyABSTRACT
BACKGROUND: The prostatic apex is the most frequent location of positive surgical margin (PSM) after surgery. Data regarding the ability of multiparametric magnetic resonance imaging (mpMRI) to prospectively identify men at risk for apical PSMs (aPSMs) using a structured report are lacking. OBJECTIVES: The aims of the study are to determine and to compare the rate of aPSM in men with versus without prospectively flagged at-risk prostate lesions during clinical mpMRI interpretation using whole-mount histopathology as the reference standard. METHODS: This single-center, retrospective study of prospectively collected data included treatment-naive men with abnormal 3T mpMRI (PI-RADS v2 score ≥3) between January 2016 and December 2018 followed by surgery. During routine clinical interpretation, radiologists flagged prostate lesions abutting the apical most gland and/or encircling the distal most prostatic urethra using standardized language available as a "pick list" option in the structured report. Logistic regression was used to compare the rate of PSM in 2 groups (flagged vs nonflagged men). Propensity score covariate adjustment corrected for potential selection bias according to age, prostate-specific antigen (PSA), PSA density, grade group, and pT stage. The estimate was further adjusted by including surgeon as a covariate. RESULTS: A total of 428 men were included. A statistically significant higher proportion of aPSMs was noted in flagged (56% [51/91]) compared with nonflagged apical lesions (31% [105/337]; adjusted odds ratio, 2.5; 95% confidence interval, 1.6-4.1; P < 0.01). The difference in aPSM between both groups also varied according to the surgeon performing the RP. Prostate-specific antigen, PSA density, lesion size, apical location, Prostate Imaging Reporting & Data System score, grade group, pT stage, and surgeon's experience were associated with higher PSM rate. Biochemical recurrence, defined as PSA greater than 0.2 ng/mL on 2 measurements after RP, was significantly associated with PSM status (propensity score adjusted odds ratio, 3.1; 95% confidence interval, 1.8-5.3; P < 0.0001); however, patients flagged by radiologists did not have a significant difference in biochemical recurrence rates as compared with nonflagged patients ( P = 0.11). CONCLUSIONS: Standard language built into structured reports for mpMRI of the prostate helps identify preoperatively patients at risk for aPSM. CLINICAL IMPACT: Multiparametric MRI is able to identify patients at increased risk for aPSM, and this information can be conveyed in a structured report to urologists, facilitating patient counseling and treatment decisions.
Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Prostate/diagnostic imaging , Prostate/surgery , Prostate/pathology , Prostate-Specific Antigen , Margins of Excision , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Retrospective Studies , Prostatectomy/methodsABSTRACT
INTRODUCTION: To report the 5-year efficacy and safety of Aquablation compared with transurethral resection of the prostate for the management of lower urinary tract symptoms secondary to benign prostatic hyperplasia in men with prostate volumes 50-80 mL. MATERIALS AND METHODS: In a large double-blinded, multicenter, and prospective randomized controlled trial, 96 randomized men with 50-80 mL prostates who underwent Aquablation or transurethral prostate resection were prospectively identified for subgroup analysis. Follow up was performed for up to 5 years. The primary efficacy endpoint was the reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo (CD) postoperative complications grade 1 persistent and grade 2 or higher at 3 months. RESULTS: Both groups had comparable baseline characteristics. Reduction in IPSS score was significantly higher in the Aquablation group across 5 years of follow up (-14.1 vs. -10.8, p = 0.02). The Aquablation group achieved a significantly lower rate of CD1P and CD2 or higher events at 3 months follow up (risk difference of -23.1%). Among recorded adverse events, de novo postoperative ejaculatory dysfunction was notably lower in Aquablation (risk difference of -21.9%), while the risk of bleeding remained similar after 6 months. The surgical and medical retreatment rate at 6 months was also lower in Aquablation (risk difference of -14.4%). CONCLUSIONS: In the 50-80 mL prostate volume subgroup, Aquablation yields superior long-term symptom relief and lower complication rates than standard transurethral resection, with notably lower rates of ejaculatory dysfunction. This further supports the adoption of Aquablation for men with medium-sized prostates.
Subject(s)
Ablation Techniques , Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Transurethral Resection of Prostate , Humans , Male , Ablation Techniques/adverse effects , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/surgery , Prospective Studies , Prostate/surgery , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/surgery , Prostatic Hyperplasia/diagnosis , Transurethral Resection of Prostate/adverse effects , Treatment Outcome , Water , Double-Blind MethodABSTRACT
BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.
Subject(s)
Prostatic Hyperplasia , 5-alpha Reductase Inhibitors/therapeutic use , Humans , Male , Prostate/pathology , Prostate-Specific Antigen , Prostatic Hyperplasia/pathologyABSTRACT
Stromal-epithelial interactions are critical to the morphogenesis, differentiation, and homeostasis of the prostate, but the molecular identity and anatomy of discrete stromal cell types is poorly understood. Using single-cell RNA sequencing, we identified and validated the in situ localization of three smooth muscle subtypes (prostate smooth muscle, pericytes, and vascular smooth muscle) and two novel fibroblast subtypes in human prostate. Peri-epithelial fibroblasts (APOD+) wrap around epithelial structures, whereas interstitial fibroblasts (C7+) are interspersed in extracellular matrix. In contrast, the mouse displayed three fibroblast subtypes with distinct proximal-distal and lobe-specific distribution patterns. Statistical analysis of mouse and human fibroblasts showed transcriptional correlation between mouse prostate (C3+) and urethral (Lgr5+) fibroblasts and the human interstitial fibroblast subtype. Both urethral fibroblasts (Lgr5+) and ductal fibroblasts (Wnt2+) in the mouse contribute to a proximal Wnt/Tgfb signaling niche that is absent in human prostate. Instead, human peri-epithelial fibroblasts express secreted WNT inhibitors SFRPs and DKK1, which could serve as a buffer against stromal WNT ligands by creating a localized signaling niche around individual prostate glands. We also identified proximal-distal fibroblast density differences in human prostate that could amplify stromal signaling around proximal prostate ducts. In human benign prostatic hyperplasia, fibroblast subtypes upregulate critical immunoregulatory pathways and show distinct distributions in stromal and glandular phenotypes. A detailed taxonomy of leukocytes in benign prostatic hyperplasia reveals an influx of myeloid dendritic cells, T cells and B cells, resembling a mucosal inflammatory disorder. A receptor-ligand interaction analysis of all cell types revealed a central role for fibroblasts in growth factor, morphogen, and chemokine signaling to endothelia, epithelia, and leukocytes. These data are foundational to the development of new therapeutic targets in benign prostatic hyperplasia. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Cellular Microenvironment/physiology , Fibroblasts/cytology , Prostate/cytology , Animals , Extracellular Matrix , Humans , Male , Mice , Prostatic Hyperplasia/pathology , Single-Cell AnalysisABSTRACT
INTRODUCTION: Anticholinergic or ß-3 agonist use following robotic simple prostatectomy (RASP) is not well described. We describe rates of antispasmodic use following RASP and identify potential predictors of medication use. MATERIALS AND METHODS: A retrospective review of all RASP patients from 2/2016 - 1/2020 was conducted. Patients with no preoperative International Prostate Symptom Score (IPSS) were excluded. Demographics, clinical data, and postoperative medication use were collected by electronic medical record review. Multivariable logistic regression analysis using a priori variables was performed to identify independent factors associated with antispasmodic use. RESULTS: A total of 255 patients underwent RASP at a mean age of 70.0 years ± 7.3 and mean body mass index (BMI) of 28.6 kg/m2 ± 5.0. Median preoperative prostate volume was 132.3 cc ± 45.0. Rates of preoperative diabetes, obstructive sleep apnea (OSA), smoking and alcohol use were 19.6%, 6.3%, 3.1%, and 11.8% respectively; 8.6% of patients (n = 22) initiated antispasmodics at a median of 2.5 months (IQR 1.3-4.2) postoperatively. Median duration of antispasmodic use was 6.5 months (IQR 1.7-14.7). Mirabegron was most commonly prescribed (31.8%). On multivariable logistic regression analysis, OSA was independently associated with postoperative antispasmodic use (OR 8.13, 95% CI 2.02-32.67, p = 0.003); 68.8% of OSA patients were treated with continuous positive airway pressure (CPAP). Treatment was not significantly associated with postoperative antispasmodic use (p = 0.61). CONCLUSION: Patients with OSA are over 8 times more likely to require antispasmodic medications following RASP in the short term. These patients may benefit from more tailored preoperative counseling.
Subject(s)
Prostatic Hyperplasia , Robotic Surgical Procedures , Sleep Apnea, Obstructive , Aged , Humans , Male , Parasympatholytics , Prostatectomy/adverse effects , Prostatic Hyperplasia/surgery , Retrospective Studies , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/surgery , Treatment OutcomeABSTRACT
INTRODUCTION: To determine if Aquablation therapy can maintain long term effectiveness in treating men with moderate to severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) with a baseline prostate volume between 30 and 80 mL at 5 years compared to TURP. MATERIALS AND METHODS: In a double-blinded, multicenter prospective randomized controlled trial, 181 patients with moderate to severe LUTS secondary to BPH underwent TURP or Aquablation. The primary efficacy endpoint was reduction in International Prostate Symptom Score (IPSS) at 6 months. The primary safety endpoint was the occurrence of Clavien-Dindo persistent Grade 1 or Grade 2 or higher operative complications at 3 months. The assessments included IPSS, Male Sexual Health Questionnaire (MSHQ), International Index of Erectile Function (IIEF) and uroflow (Qmax). The patients were followed for 5 years. RESULTS: The primary safety endpoint was successfully achieved at 3 months where the Aquablation group had a lower event rate than TURP (26% vs. 42%, p = .0149 for superiority). Procedure-related ejaculatory dysfunction was lower for Aquablation (7% vs. 25%, p = .0004). The primary efficacy endpoint was successfully achieved at 6 months, where the mean IPSS decreased from baseline by 16.9 points for Aquablation and 15.1 points for TURP; the mean difference in change score at 6 months was 1.8 points larger for Aquablation (p < .0001 for non-inferiority, p = .1346 for superiority). At 5 years, IPSS scores improved by 15.1 points in the Aquablation group and 13.2 points in TURP (p = .2764). However, for men with larger prostates (≥ 50 mL), IPSS reduction was 3.5 points greater across all follow up visits in the Aquablation group compared to the TURP group (p = .0123). Improvement in peak urinary flow rate was 125% and 89% compared to baseline for Aquablation and TURP, respectively. The risk of patients needing a secondary BPH therapy, defined as needing BPH medication or surgical intervention, up to 5 years due to recurrent LUTS was 51% less in the Aquablation arm compared to the TURP arm. CONCLUSIONS: The improvement in net health outcomes from Aquablation therapy outweigh those offered by a TURP when considering the efficacy benefit along with the lower risk of needing a secondary BPH therapy and avoiding retrograde ejaculation. Following Aquablation therapy, symptom reduction and uroflow improvement at 5 years have shown to be durable and consistent across all years of follow up compared to TURP. Larger prostates (≥ 50 mL) demonstrated a larger safety and efficacy benefit for Aquablation over TURP.
Subject(s)
Ablation Techniques , Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Transurethral Resection of Prostate , Ablation Techniques/adverse effects , Ablation Techniques/methods , Humans , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/surgery , Male , Prospective Studies , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/methods , Treatment OutcomeABSTRACT
PURPOSE: In men, complaints of nocturia causing poor sleep are often attributed to benign prostatic hyperplasia and treated with benign prostatic hyperplasia medications. We assessed whether treating lower urinary tract symptoms with dutasteride altered either nocturia or sleep quality using data from REDUCE. MATERIALS AND METHODS: REDUCE was a 4-year randomized, multicenter trial comparing dutasteride 0.5 mg/day vs placebo for prostate cancer chemoprevention. Study participants were men considered at increased risk for prostate cancer. Eligibility included age 50-75 years, prostate specific antigen 2.5-10 ng/ml, and 1 negative prostate biopsy. At baseline, 2 years and 4 years, men completed the International Prostate Symptom Score and Medical Outcomes Study Sleep Scale, a 6-item scale assessing sleep. To test differences in nocturia and Medical Outcomes Study Sleep Scale over time, we used linear mixed models adjusted for baseline confounders. Subanalyses were conducted in men symptomatic from lower urinary tract symptoms, nocturia, poor sleep, or combinations thereof. RESULTS: Of 6,914 men with complete baseline data, 80% and 59% were assessed at 2 and 4-year followup, respectively. Baseline characteristics were balanced between treatment arms. Dutasteride improved nocturia at 2 (-0.15, 95% CI -0.21, -0.09) and 4 years (-0.24, 95% CI -0.31, -0.18) but did not improve sleep. When limited to men symptomatic from lower urinary tract symptoms, nocturia, poor sleep or combinations thereof, results mirrored findings from the full cohort. CONCLUSIONS: In men with poor sleep who complain of nocturia, treatment of lower urinary tract symptoms with dutasteride modestly improves nocturia but has no effect on sleep. These results suggest men with poor sleep who complain of nocturia may not benefit from oral benign prostatic hyperplasia treatment.
Subject(s)
5-alpha Reductase Inhibitors/therapeutic use , Dutasteride/therapeutic use , Lower Urinary Tract Symptoms/complications , Lower Urinary Tract Symptoms/drug therapy , Nocturia/drug therapy , Nocturia/etiology , Sleep , Humans , Male , Middle Aged , Nocturia/physiopathology , Treatment OutcomeABSTRACT
PURPOSE: We present final 5-year outcomes of the multicenter randomized sham-controlled trial of a water vapor therapy (Rezum™) for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 subjects >50 years of age with International Prostate Symptom Score ≥13, maximum flow rate ≤15 ml/second and prostate volume 30 to 80 cc were randomized and followed for 5 years. From the control arm of 61 subjects, a subset of 53 subjects requalified and after 3 months received treatment as part of the crossover group and were also followed for 5 years. The total number of vapor treatments to each lobe of the prostate was determined by length of prostatic urethra and included middle lobe treatment per physician discretion. RESULTS: Significant improvement of lower urinary tract symptoms was observed at <3 months post-thermal therapy, remaining durable through 5 years in the treatment group (International Prostate Symptom Score reduced 48%, quality of life increased 45%, maximum flow rate improved 44%, Benign Prostatic Hyperplasia Impact Index decreased 48%). Surgical re-treatment rate was 4.4% with no reports of device or procedure related sexual dysfunction or sustained de novo erectile dysfunction. Results within the crossover group were similar through 5 years. CONCLUSIONS: Minimally invasive treatment with water vapor thermal therapy provides significant and durable symptom relief as well as flow rate improvements through 5 years, with low surgical re-treatment rates and without impacting sexual function. It is a versatile therapy, providing successful treatment to obstructive lateral and middle lobes.
Subject(s)
Hyperthermia, Induced/methods , Lower Urinary Tract Symptoms/therapy , Prostatic Hyperplasia/therapy , Aged , Cross-Over Studies , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Follow-Up Studies , Humans , Hyperthermia, Induced/adverse effects , Hyperthermia, Induced/statistics & numerical data , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/etiology , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prostatic Hyperplasia/complications , Quality of Life , Retreatment/statistics & numerical data , Severity of Illness Index , Sexual Dysfunction, Physiological/epidemiology , Sexual Dysfunction, Physiological/etiology , Steam , United StatesABSTRACT
PURPOSE: Surgical therapies for symptomatic bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) are many, and vary from minimally invasive office based to high-cost operative approaches. This Guideline presents effective evidence-based surgical management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). See accompanying algorithm for a detailed summary of procedures (figure[Figure: see text]). MATERIALS/METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible studies published between January 2007 and September 2020, which includes the initial publication (2018) and amendments (2019, 2020). The Team also reviewed articles identified by Guideline Panel Members. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). RESULTS: Twenty-four guideline statements pertinent to pre-operative and surgical management were developed. Appropriate levels of evidence and supporting text were created to direct urologic providers towards suitable and safe operative interventions for individual patient characteristics. A re-treatment section was created to direct attention to longevity and outcomes with individual approaches to help guide patient counselling and therapeutic decisions. CONCLUSION: Pre-operative and surgical management of BPH requires attention to individual patient characteristics and procedural risk. Clinicians should adhere to recommendations and familiarize themselves with criteria that yields the highest likelihood of surgical success when choosing a particular approach for a particular patient.
Subject(s)
Erectile Dysfunction/surgery , Lower Urinary Tract Symptoms/surgery , Postoperative Complications/prevention & control , Prostatectomy/standards , Prostatic Hyperplasia/surgery , Erectile Dysfunction/diagnosis , Erectile Dysfunction/etiology , Humans , Lower Urinary Tract Symptoms/diagnosis , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/urine , Male , Organ Size , Postoperative Complications/etiology , Prostate/pathology , Prostate/surgery , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/diagnosis , Prostatic Hyperplasia/pathology , Risk Assessment/standards , Severity of Illness Index , Societies, Medical/standards , Treatment Outcome , United States , Urology/methods , Urology/standardsABSTRACT
PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.
Subject(s)
Lower Urinary Tract Symptoms/diagnosis , Prostatic Hyperplasia/diagnosis , Urology/standards , Dietary Supplements , Humans , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/therapy , Lower Urinary Tract Symptoms/urine , Male , Prostate/pathology , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/pathology , Prostatic Hyperplasia/therapy , Societies, Medical/standards , United States , Urological Agents/therapeutic use , Urology/methodsABSTRACT
PURPOSE: To evaluate the effect of delayed start of combination therapy (CT) with dutasteride 0.5 mg and tamsulosin 0.4 mg on the risk of acute urinary retention or benign prostatic hyperplasia (BPH)-related surgery (AUR/S) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) at risk of disease progression. METHODS: Using a time-to-event model based on pooled data from 10,238 patients from Phase III/IV dutasteride trials, clinical trial simulations (CTS) were performed to assess the risk of AUR/S up to 48 months in moderate-to-severe LUTS/BPH patients following immediate and delayed start of CT for those not responding to tamsulosin monotherapy. Simulation scenarios (1300 subjects/arm) were investigated, including immediate start (reference) and alternative delayed start (six scenarios 1-24 months). AUR/S incidence was described by Kaplan-Meier survival curves and analysed using log-rank test. The cumulative incidence of events as well as the relative and attributable risks were summarised stratified by treatment. RESULTS: Survival curves for patients starting CT at month 1 and 3 did not differ from those who initiated CT immediately. By contrast, significant differences (p < 0.001) were observed when switch to CT occurs ≥ 6 months from the initial treatment. At month 48, AUR/S incidence was 4.6% vs 9.5%, 11.0% and 11.3% in patients receiving immediate CT vs. switchers after 6, 12 and 24 months, respectively. CONCLUSIONS: Start of CT before month 6 appears to significantly reduce the risk of AUR/S compared with delayed start by ≥ 6 months. This has implications for the treatment algorithm for men with LUTS/BPH at risk of disease progression.
Subject(s)
5-alpha Reductase Inhibitors/administration & dosage , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Dutasteride/administration & dosage , Lower Urinary Tract Symptoms/drug therapy , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/surgery , Tamsulosin/administration & dosage , Urinary Retention/surgery , Acute Disease , Disease Progression , Drug Combinations , Humans , Male , Risk Assessment , Severity of Illness Index , Symptom Assessment , Time FactorsABSTRACT
PURPOSE: In this review, we will discuss the state of the literature regarding Aquablation, its limitations, and opportunities for its application in the treatment of benign prostatic enlargement (BPE). METHODS: A comprehensive review of original research on Aquablation was conducted. Articles related to transurethral resection of the prostate, holmium laser enucleation of the prostate, greenlight photoselective vaporization of the prostate, and simple prostatectomy were reviewed for discussion. RESULTS: For small-medium prostates (30-80 mL), Aquablation's main advantages include better ejaculatory function and similar functional outcomes compared to TURP. For large prostates (80-150 mL), Aquablation demonstrates shorter operative time and superior ejaculatory function when compared to simple prostatectomy, HoLEP, and Greenlight PVP. In addition, Aquablation displays shorter hospital stays than simple prostatectomy. The integration of software programming and semi-automatic technology increases the reproducibility of the procedure and helps standardize overall outcomes, while also accelerating the learning curve. Its ability to preserve antegrade ejaculation makes Aquablation a very compelling option for sexually active patients. However cost and postoperative bleeding risks remain a concern. CONCLUSION: The current evidence suggests that Aquablation is a safe and effective alternative for BPE for small to large prostates. Further prospective clinical trials, with comparisons to other BPE modalities, and data from longer follow-up periods are still required.
Subject(s)
Ablation Techniques/methods , Prostatectomy/methods , Prostatic Hyperplasia/surgery , Ablation Techniques/instrumentation , Equipment Design , Humans , Male , Transurethral Resection of Prostate , WaterABSTRACT
AIMS: Combination therapy of 5α-reductase inhibitor and α-blocker is a guideline-endorsed therapeutic approach for patients with moderate-to-severe lower urinary tract symptoms or benign prostatic hyperplasia (LUTS/BPH) who are at risk of disease progression. We aimed to disentangle the contribution of clinical and demographic baseline characteristics affecting the risk of acute urinary retention or BPH-related surgery (AUR/S) from the effect of treatment with drugs showing symptomatic and disease-modifying properties. METHODS: A time-to-event model was developed using pooled data from patients (n = 10 238) enrolled into six clinical studies receiving placebo, tamsulosin, dutasteride or tamsulosin-dutasteride combination therapy. A parametric hazard function was used to describe the time to first AUR/S. Covariate model building included the assessment of relevant clinical and demographic factors on baseline hazard. Predictive performance was evaluated by graphical and statistical methods. RESULTS: An exponential hazard model best described the time to first AUR/S in this group of patients. Baseline International Prostate Symptom Score, prostate-specific antigen, prostate volume and maximum urine flow were identified as covariates with hazard ratio estimates of 1.04, 1.08, 1.01 and 0.91, respectively. Dutasteride monotherapy and tamsulosin-dutasteride combination therapy resulted in a significant reduction in the baseline hazard (56.8% and 66.4%, respectively). By contrast, the effect of tamsulosin did not differ from placebo. CONCLUSIONS: Our analysis showed the implications of disease-modifying properties of dutasteride and tamsulosin-dutasteride combination therapy for the risk of AUR/S. It also elucidated the contribution of different baseline characteristics to the risk of these events. The use of tamsulosin monotherapy (symptomatic treatment) has no impact on individual long-term risk.
Subject(s)
Prostatic Hyperplasia , Urinary Retention , Azasteroids/therapeutic use , Drug Therapy, Combination , Humans , Male , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/drug therapy , Sulfonamides/therapeutic use , Treatment Outcome , Urinary Retention/chemically induced , Urinary Retention/drug therapyABSTRACT
INTRODUCTION Minimally invasive surgical therapies for benign prostatic hyperplasia (BPH) are popular alternatives to the gold standard transurethral resection of the prostate (TURP). These procedures have fewer discernable side effects on urinary and sexual function, when compared to TURP, making it a desirable option for many patients. MATERIALS AND METHODS: We provide an updated literature review on the current landscape of minimally invasive modalities, specifically the prostatic urethral lift (UroLift) and water vapor thermal therapy (Rezum), for the surgical treatment of BPH. RESULTS: Both UroLift and Rezum have demonstrated excellent efficacy and durability in relieving lower urinary tract symptoms (LUTS) in the BPH patient. When compared to TURP, these minimally invasive therapies can be performed in an outpatient setting, with decreased hospitalization, operative and catheterization times, which minimizes overall healthcare costs. Moreover, these therapies have no discernable adverse effects on sexual function (both ejaculatory and erectile) or sexual satisfaction, making it a desirable option for many patients. CONCLUSIONS: Both the UroLift and Rezum are office-based, minimally invasive techniques capable of providing durable, and significant relief of LUTS secondary to BPH. In select patients, they demonstrate comparable efficacy to TURP with the added advantage of preserving sexual function and minimizing patient morbidity and healthcare cost. An individualized, shared decision-making approach is essential in selecting the optimal treatment option for each patient.
Subject(s)
Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Transurethral Resection of Prostate , Humans , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/surgery , Male , Minimally Invasive Surgical Procedures , Prostatic Hyperplasia/complications , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/adverse effects , Treatment Outcome , UrethraABSTRACT
INTRODUCTION Historically, transurethral resection of the prostate (TURP) was considered the endoscopic "gold standard" surgical treatment of benign prostatic hyperplasia (BPH). Over the years, several other endoscopic procedures emerged, including the size-independent holmium laser enucleation of the prostate (HoLEP). In an effort to reduce the cost and morbidity associated with traditional endoscopic techniques, novel minimally invasive techniques have been developed, one of which is Aquablation. This review is an update of a previously published review article looking at the most recently published available data on Aquablation. MATERIALS AND METHODS: This review article covers the technical aspects of Aquablation and provides an update on the recently published literature regarding Aquablation compared to TURP and HoLEP. RESULTS: At up to 3 years of follow up, Aquablation performs favorably when compared to TURP in terms of alleviation of lower urinary tract symptoms (LUTS) and preservation of sexual function compared to TURP. Safety profile was similar between Aquablation and TURP. CONCLUSIONS: Aquablation is a safe and effective method of treating LUTS associated with BPH. At up to 3 years of follow up, it has shown a durable with efficacy similar to TURP.
Subject(s)
Laser Therapy , Lower Urinary Tract Symptoms , Prostatic Hyperplasia , Transurethral Resection of Prostate , Humans , Lower Urinary Tract Symptoms/etiology , Lower Urinary Tract Symptoms/surgery , Male , Prostate , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Castration-insensitive epithelial progenitors capable of regenerating the prostate have been proposed to be concentrated in the proximal region based on facultative assays. Functional characterization of prostate epithelial populations isolated with individual cell surface markers has failed to provide a consensus on the anatomical and transcriptional identity of proximal prostate progenitors. METHODS: Here, we use single-cell RNA sequencing to obtain a complete transcriptomic profile of all epithelial cells in the mouse prostate and urethra to objectively identify cellular subtypes. Pan-transcriptomic comparison to human prostate cell types identified a mouse equivalent of human urethral luminal cells, which highly expressed putative prostate progenitor markers. Validation of the urethral luminal cell cluster was performed using immunostaining and flow cytometry. RESULTS: Our data reveal that previously identified facultative progenitors marked by Trop2, Sca-1, KRT4, and PSCA are actually luminal epithelial cells of the urethra that extend into the proximal region of the prostate, and are resistant to castration-induced androgen deprivation. Mouse urethral luminal cells were identified to be the equivalent of previously identified human club and hillock cells that similarly extend into proximal prostate ducts. Benign prostatic hyperplasia (BPH) has long been considered an "embryonic reawakening," but the cellular origin of the hyperplastic growth concentrated in the periurethral region is unclear. We demonstrate an increase in urethral luminal cells within glandular nodules from BPH patients. Urethral luminal cells are further increased in patients treated with a 5-α reductase inhibitor. CONCLUSIONS: Our data demonstrate that cells of the proximal prostate that express putative progenitor markers, and are enriched by castration in the proximal prostate, are urethral luminal cells and that these cells may play an important role in the etiology of human BPH.
Subject(s)
Prostate/cytology , Stem Cells/cytology , Urethra/cytology , Adolescent , Adult , Animals , Antigens, Neoplasm/metabolism , Cell Adhesion Molecules/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Humans , Male , Mice , Mice, Inbred C57BL , Prostate/metabolism , Stem Cells/metabolism , Urethra/metabolism , Young AdultABSTRACT
OBJECTIVES: To provide an update on novel minimally invasive lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) treatments in a non-systematic review. To define potential target populations for the various new minimally invasive treatments. METHODS: Recent literature, meta-analyses and guideline recommendations for aquablation (AquaBeam® ; PROCEPT BioRobotics, Redwood City, CA, USA), water vapour thermal therapy (Rezum® ; Boston Scientific, Natick, MA, USA), prostate artery embolisation (PAE), prostatic urethral lift (UroLift® ; NeoTract-Teleflex, Pleasanton, CA, USA) and the temporary implantable nitinol device [i-TIND® (nitinol butterfly-like stent ); Medi-Tate Ltd., Or-Akiva, Israel] were reviewed. RESULTS: Procedures that can be performed on an outpatient basis (Rezum, PAE, UroLift and i-TIND) are not an alternative for the standard patient requiring BPH surgery. Their effect on urinary flow, post-void residual urine volume or bladder outlet obstruction is less pronounced than that of transurethral resection of the prostate (TURP). Yet, these options appear to be valuable for those patients unfit for surgery, men who want to avoid medical therapy in general, or those who want to avoid sexual side-effects associated with medical therapy or standard BPH surgery (e.g. TURP). Aquablation is the first successfully operationalised robotic resection system, especially for patients with prostates >50 g. Nevertheless, long-term data are necessary for all novel, minimally invasive treatments. CONCLUSIONS: Better designed clinical trials, a clearer definition of target populations and a more realistic marketing allow a better characterisation of novel minimally invasive therapies for LUTS/BPH. It is hoped that some of these novel devices will stand the test of time, in contrast to the vast majority of their predecessors.