Major Complications and Adverse Events Related to Use of SpaceOAR Hydrogel for Prostate Cancer Radiotherapy.

OBJECTIVE: To determine the prevalence and severity of SpaceOAR-related adverse events using the Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: We analyzed SpaceOAR-related adverse event reports in the Manufacturer and User Facility Device Experience (MAUDE) database from January 2015 to May 2023. For each report, the event type, associated device and patient problems, event description, event timing, and event severity stratified by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE) grading system were recorded. RESULTS: From 2015 to 2022, 206,619 SpaceOAR devices were sold. From January 2015 to May 2023, we identified 981 reports describing 990 SpaceOAR-related adverse events. Malfunctions were the most common event type (N = 626), followed by patient injuries (N = 350) with few reported deaths (N = 5). Device positioning problems were the most frequent device issue (N = 686). Pain was the most reported patient problem (N = 216). Abscesses and fistulas related to the device were each reported in 91 events. A noteworthy portion of relevant adverse events occurred before the initiation of radiation (N = 35, 22.4%), suggesting the device, rather than the radiation, was responsible. In total, 470 (50.2%) and 344 (36.7%) of the adverse events were CTCAE grade 1 and 2, respectively. There were 123 (13.1%) events that were CTCAE grade ≥3. CONCLUSION: We identified multiple reports of SpaceOAR-related adverse events, many of which are more serious than have been reported in clinical trials. While SpaceOAR use is common, suggesting these events are rare, these data highlight the need for continued postmarket surveillance.

PI-RADS Upgrading Rules: Impact on Prostate Cancer Detection and Biopsy Avoidance of MRI-Directed Diagnostic Pathways.

Background: PI-RADS incorporate rules by which ancillary sequence findings upgrade a dominant score to a higher final category. Evidence on the upgrading rules' impact on diagnostic pathways remains scarce. Objective: To evaluate the clinical net benefit of the PI-RADS upgrading rules in MRI-directed diagnostic pathways. Methods: This study was a retrospective analysis of a prospectively maintained clinical registry. The study included patients without known prostate cancer who underwent prostate MRI followed by prostate biopsy from January 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as International Society of Urological Pathology (ISUP) grade group ≥2. csPCa detection was compared between dominant (i.e., no upgrade rule applied) and upgraded lesions. Decision curve analysis was used to compare the net benefit, considering the tradeoff of csPCa detection and biopsy avoidance, of MRI-directed pathways in scenarios considering and disregarding PI-RADS upgrading rules. These included biopsy-all pathway, MRI-focused pathway (no biopsy for PI-RADS ≤2), and risk-based pathway (use of PSA density ≥0.15 to select patients with PI-RADS ≤3 for biopsy). Results: The sample comprised 716 patients (mean age, 64.9 years; 93 with a PI-RADS ≤2 examination, 623 with total of 780 PI-RADS ≥3 lesions). Frequencies of csPCa were not significantly different between dominant and upgraded PI-RADS 3 transition zone lesions (20% vs 19%), dominant and upgraded PI-RADS 4 transition zone lesions (33% vs 26%), and dominant and upgraded PI-RADS 4 peripheral zone lesions (58% vs 45%) (p>.05). In the biopsy-all, per-guideline MRI-focused, MRI-focused disregarding upgrading rules, per-guideline risk-based, and risk-based disregarding upgrading rules pathways, csPCa frequency was 53%, 52%, 51%, 52%, and 48%, and biopsy avoidance was 0%, 13%, 16%, 19%, and 25%, respectively. Disregarding upgrading rules yielded 5.5 and 1.9 biopsies avoided per missed csPca for MRI-focused and risk-based pathways, respectively. At probability thresholds for biopsy selection of 7.5-30%, net benefit was highest for the per-guideline risk-based pathway. Conclusion: Disregarding PI-RADS upgrading rules reduced net clinical benefit of the risk-based MRI-directed diagnostic pathway when considering tradeoffs between csPCa detection and biopsy avoidance. Clinical Impact: This study supports the application of PI-RADS upgrading rules to optimize biopsy selection, particularly in risk-based pathways.

Novel reference range values for serum testosterone: a cross-sectional study of 200,000 males.

PURPOSE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency. METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels. RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01). CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms.

The association between frailty, hypogonadism, and postoperative outcomes among men undergoing radical cystectomy.

INTRODUCTION: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes. MATERIALS AND METHODS: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT. CONCLUSIONS: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial.

BACKGROUND AND OBJECTIVE: The transrectal biopsy approach is traditionally used to detect prostate cancer. An alternative transperineal approach is historically performed under general anesthesia, but recent advances enable transperineal biopsy to be performed under local anesthesia. We sought to compare infectious complications of transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis. METHODS: We assigned biopsy-naïve participants to undergo transperineal biopsy without antibiotic prophylaxis versus transrectal biopsy with targeted prophylaxis (rectal culture screening for fluoroquinolone-resistant bacteria and antibiotic targeting to culture and sensitivity results) through a multicenter, randomized trial. The primary outcome was post-biopsy infection captured by a prospective medical review and patient report on a 7-d survey. The secondary outcomes included cancer detection, noninfectious complications, and a numerical rating scale (0-10) for biopsy-related pain and discomfort during and 7-d after biopsy. KEY FINDINGS AND LIMITATIONS: A total of 658 participants were randomized, with zero transperineal versus four (1.4%) transrectal biopsy infections (difference -1.4%; 95% confidence interval [CI] -3.2%, 0.3%; p = 0.059). The rates of other complications were very low and similar. Importantly, detection of clinically significant cancer was similar (53% transperineal vs 50% transrectal, adjusted difference 2.0%; 95% CI -6.0, 10). Participants in the transperineal arm experienced worse periprocedural pain (0.6 adjusted difference [0-10 scale], 95% CI 0.2, 0.9), but the effect was small and resolved by 7-d. CONCLUSIONS AND CLINICAL IMPLICATIONS: Office-based transperineal biopsy is tolerable, does not compromise cancer detection, and did not result in infectious complications. Transrectal biopsy with targeted prophylaxis achieved similar infection rates, but requires rectal cultures and careful attention to antibiotic selection and administration. Consideration of these factors and antibiotic stewardship should guide clinical decision-making. PATIENT SUMMARY: In this multicenter randomized trial, we compare prostate biopsy infectious complications for the transperineal versus transrectal approach. The absence of infectious complications with transperineal biopsy without the use of preventative antibiotics is noteworthy, but not significantly different from transrectal biopsy with targeted antibiotic prophylaxis.

Artificial intelligence applications in prostate cancer.

Artificial intelligence (AI) applications have enabled remarkable advancements in healthcare delivery. These AI tools are often aimed to improve accuracy and efficiency of histopathology assessment and diagnostic imaging interpretation, risk stratification (i.e., prognostication), and prediction of therapeutic benefit for personalized treatment recommendations. To date, multiple AI algorithms have been explored for prostate cancer to address automation of clinical workflow, integration of data from multiple domains in the decision-making process, and the generation of diagnostic, prognostic, and predictive biomarkers. While many studies remain within the pre-clinical space or lack validation, the last few years have witnessed the emergence of robust AI-based biomarkers validated on thousands of patients, and the prospective deployment of clinically-integrated workflows for automated radiation therapy design. To advance the field forward, multi-institutional and multi-disciplinary collaborations are needed in order to prospectively implement interoperable and accountable AI technology routinely in clinic.

Antibiotic Use in Hospital Urinary Tract Infections After FDA Regulation.

BACKGROUND: The FDA issued a "black box" warning regarding risks of fluoroquinolones in 2008 with updates in 2011, 2013, and 2016. OBJECTIVE: To examine antimicrobial use in hospital-treated UTIs from 2000 to 2020. DESIGN: Cross-sectional study with interrupted time series analysis. PARTICIPANTS: Patient encounters with a diagnosis of UTI from January 2000 to March 2020, excluding diagnoses of renal abscess, chronic cystitis, and infection of the gastrointestinal tract, lungs, or prostate. MAIN MEASURES: Monthly use of fluoroquinolone and non-fluoroquinolone antibiotics were assessed. Fluoroquinolone resistance was assessed in available cultures. Interrupted time series analysis examined level and trend changes of antimicrobial use with each FDA label change. KEY RESULTS: A total of 9,950,790 patient encounters were included. From July 2008 to March 2020, fluoroquinolone use declined from 61.7% to 11.7%, with similar negative trends observed in inpatients and outpatients, age ≥ 60 and < 60 years, males and females, patients with and without pyelonephritis, and across physician specialties. Ceftriaxone use increased from 26.4% encounters in July 2008 to 63.6% of encounters in March 2020. Among encounters with available culture data, fluoroquinolone resistance declined by 28.9% from 2009 to 2020. On interrupted time series analysis, the July 2008 FDA warning was associated with a trend change (-0.32%, < 0.001) and level change (-5.02%, p < 0.001) in monthly fluoroquinolone use. CONCLUSIONS: During this era of "black box" warnings, there was a decline in fluoroquinolone use for hospital-treated UTI with a concomitant decline in fluoroquinolone resistance and rise in ceftriaxone use. Efforts to restrict use of a medication class may lead to compensatory increases in use of a single alternative agent with changes in antimicrobial resistance profiles.

Immune approaches beyond traditional immune checkpoint inhibitors for advanced renal cell carcinoma.

Renal cell carcinoma (RCC), especially clear cell RCC, is generally considered an immunotherapy-responsive cancer. Recently, the prognosis for patients with locally advanced and metastatic RCC has significantly improved with the regulatory approvals of anti-PD-1/PD-L1/CTLA-4 immune checkpoint inhibitor (ICI)-based regimens. Yet in most cases, RCC will remain initially unresponsive to treatment or will develop resistance over time. Hence, there remains an unmet need to understand what leads to ICI resistance and to develop novel immune and nonimmune treatments to enhance the response to ICIs. In this review, we highlight recently published studies and the latest clinical studies investigating the next generation of immune approaches to locally advanced and metastatic RCC beyond traditional ICIs. These trials include cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These agents are being evaluated as monotherapy or in combination with traditional ICIs and will hopefully provide improved outcomes to patients with RCC soon.

Racial disparities in prostate cancer mortality: a model-based decomposition of contributing factors.

To investigate the relative contributions of natural history and clinical interventions to racial disparities in prostate cancer mortality in the United States, we extended a model that was previously calibrated to Surveillance, Epidemiology, and End Results (SEER) incidence rates for the general population and for Black men. The extended model integrated SEER data on curative treatment frequencies and cancer-specific survival. Starting with the model for all men, we replaced up to 9 components with corresponding components for Black men, projecting age-standardized mortality rates for ages 40-84 years at each step. Based on projections in 2019, the increased frequency of developing disease, more aggressive tumor features, and worse cancer-specific survival in Black men diagnosed at local-regional and distant stages explained 38%, 34%, 22%, and 8% of the modeled disparity in mortality. Our results point to intensified screening and improved care in Black men as priority areas to achieve greater equity.

Increasing Use of Shorter-Course Radiotherapy for Prostate Cancer.

Importance: Randomized clinical trials have demonstrated the noninferiority of shorter radiotherapy (RT) courses (termed hypofractionation) compared with longer RT courses in patients with localized prostate cancer. Although shorter courses are associated with cost-effectiveness, convenience, and expanded RT access, their adoption remains variable. Objective: To identify the current practice patterns of external beam RT for prostate cancer in the US. Design, Setting, and Participants: This cohort study obtained data from the National Cancer Database, which collects hospital registry data from more than 1500 accredited US facilities on approximately 72% of US patients with cancer. Patients were included in the sample if they had localized prostate adenocarcinoma that was diagnosed between 2004 and 2020 and underwent external beam RT with curative intent. Analyses were conducted between February and March 2023. Exposures: Radiotherapy schedules, which were categorized as ultrahypofractionation (≤7 fractions), moderate hypofractionation (20-30 fractions), and conventional fractionation (31-50 fractions). Main Outcomes and Measures: Longitudinal pattern in RT fractionation schedule was the primary outcome. Multivariable logistic regression was performed to evaluate the variables associated with shorter RT courses. Covariables included age, National Comprehensive Cancer Network risk group, rurality, race, facility location, facility type, median income, insurance type or status, and Charlson-Deyo Comorbidity Index. Results: A total of 313 062 patients with localized prostate cancer (mean [SD] age, 68.8 [7.7] years) were included in the analysis. There was a temporal pattern of decline in the proportion of patients who received conventional fractionation, from 76.0% in 2004 to 36.6% in 2020 (P for trend <.001). From 2004 to 2020, use of moderate hypofractionation increased from 22.0% to 45.0% (P for trend <.001), and use of ultrahypofractionation increased from 2.0% to 18.3% (P for trend <.001). By 2020, the most common RT schedule was ultrahypofractionation for patients in the low-risk group and moderate hypofractionation for patients in the intermediate-risk group. On multivariable analysis, treatment at a community cancer program (compared with academic or research program; odds ratio [OR], 0.54 [95% CI, 0.52-0.56]; P < .001), Medicaid insurance (compared with Medicare; OR, 1.49 [95% CI, 1.41-1.57]; P < .001), Black race (compared with White race; OR, 0.90 [95% CI, 0.87-0.92]; P < .001), and higher median income (compared with lower median income; OR, 1.28 [95% CI, 1.25-1.31]; P < .001) were associated with receipt of shorter courses of RT. Conclusions and Relevance: Results of this cohort study showed an increase in the use of shorter courses of RT for prostate cancer from 2004 to 2020; a number of social determinants of health appeared to be associated with reduced adoption of shorter treatment courses. Realignment of reimbursement models may be necessary to enable broader adoption of ultrahypofractionation to support technology acquisition costs.

Individual-level home values and cancer mortality in a statewide registry.

BACKGROUND: Prior work assessing disparities in cancer outcomes has relied on regional socioeconomic metrics. These metrics average data across many individuals, resulting in a loss of granularity and confounding with other regional factors. METHODS: Using patients' addresses at the time of diagnosis from the Ohio Cancer Incidence Surveillance System, we retrieved individual home price estimates from an online real estate marketplace. This individual-level estimate was compared with the Area Deprivation Index (ADI) at the census block group level. Multivariable Cox proportional hazards models were used to determine the relationship between home price estimates and all-cause and cancer-specific mortality. RESULTS: A total of 667 277 patients in Ohio Cancer Incidence Surveillance System were linked to individual home prices across 16 cancers. Increasing home prices, adjusted for age, stage at diagnosis, and ADI, were associated with a decrease in the hazard of all-cause and cancer-specific mortality (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.92 to 0.93, and HR = 0.95, 95% CI = 0.94 to 0.95, respectively). Following a cancer diagnosis, individuals with home prices 2 standard deviations above the mean had an estimated 10-year survival probability (7.8%, 95% CI = 7.2% to 8.3%) higher than those with home prices 2 standard deviations below the mean. The association between home price and mortality was substantially more prominent for patients living in less deprived census block groups (Pinteraction < .001) than for those living in more deprived census block groups. CONCLUSION: Higher individual home prices were associated with improved all-cause and cancer-specific mortality, even after accounting for regional measures of deprivation.

Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Trends, Cost, and Predictors of Local Hemostatics Use in Major Urological Surgery.

INTRODUCTION: The national usage and cost trends associated with hemostatic agents in major urologic procedures remain unknown. This study aims to describe the trends, costs, and predictors of local hemostatic use in major urologic surgeries. METHODS: We utilized the Premier Healthcare Database to analyze 385,261 patient encounters between 2000 and 2020. Our primary objective was to describe the usage patterns of topical hemostatic agents in open and laparoscopic/robotic major urological surgeries. The data from the last 5 years (2015-2020) were used to characterize specific cost trends, and multivariable regression analysis was performed to identify predictors of hemostatic agent use in relation to surgical approach, patient, and hospital characteristics. RESULTS: By 2020, at least 1 topical hemostatic agent was used in 37.3% (95% CI: 35.5-39.1) of laparoscopic/robotic prostatectomies and 30.7% (95% CI: 24.2-37.1) of open prostatectomies; 60.8% (95% CI: 57.6-64.1) of laparoscopic/robotic partial nephrectomies and 55.9% (95% CI: 47.3-64.5) of open partial nephrectomies; 40.7% (95% CI: 36.9-44.3) of laparoscopic/robotic radical nephrectomies and 43.2% (95% CI: 38.8-47.6) of open radical nephrectomies; and 40.52% (95% CI: 35.02-46.02) of open radical cystectomies. For the 2015-2020 cohort, predictors for hemostatic agent use varied by surgery type and included gender, race, surgical approach, insurance coverage, geographical location, urbanicity, and attending volume. The cost of the hemostatic agent accounted for less than 1.6% of the total cost of hospitalization for each procedure. CONCLUSIONS: The use of hemostatic agents in major urologic surgeries has grown over the past 2 decades. For all procedures, the specific cost of using a hemostatic agent constitutes a small fraction of the total hospitalization cost and does not vary significantly between open and laparoscopic/robotic approaches. Some patient, surgeon, and hospital characteristics are highly correlated with their use.

Prostate cancer genetic alterations in Hispanic men.

BACKGROUND: Differences in DNA alterations in prostate cancer among White, Black, and Asian men have been widely described. This is the first description of the frequency of DNA alterations in primary and metastatic prostate cancer samples of self-reported Hispanic men. METHODS: We utilized targeted next-generation sequencing tumor genomic profiles from prostate cancer tissues that underwent clinical sequencing at academic centers (GENIE 11th). We decided to restrict our analysis to the samples from Memorial Sloan Kettering Cancer Center as it was by far the main contributor of Hispanic samples. The numbers of men by self-reported ethnicity and racial categories were analyzed via Fisher's exact test between Hispanic-White versus non-Hispanic White. RESULTS AND LIMITATIONS: Our cohort consisted of 1412 primary and 818 metastatic adenocarcinomas. In primary adenocarcinomas, TMPRSS2 and ERG gene alterations were less common in non-Hispanic White men than Hispanic White (31.86% vs. 51.28%, p = 0.0007, odds ratio [OR] = 0.44 [0.27-0.72] and 25.34% vs. 42.31%, p = 0.002, OR = 0.46 [0.28-0.76]). In metastatic tumors, KRAS and CCNE1 alterations were less prevalent in non-Hispanic White men (1.03% vs. 7.50%, p = 0.014, OR = 0.13 [0.03, 0.78] and 1.29% vs. 10.00%, p = 0.003, OR = 0.12 [0.03, 0.54]). No significant differences were found in actionable alterations and androgen receptor mutations between the groups. Due to the lack of clinical characteristics and genetic ancestry in this dataset, correlation with these could not be explored. CONCLUSION: DNA alteration frequencies in primary and metastatic prostate cancer tumors differ among Hispanic-White and non-Hispanic White men. Notably, we found no significant differences in the prevalence of actionable genetic alterations between the groups, suggesting that a significant number of Hispanic men could benefit from the development of targeted therapies.

Protocol of a multicentre randomised controlled trial assessing transperineal prostate biopsy to reduce infectiouscomplications.

INTRODUCTION: Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer. METHODS AND ANALYSIS: We will perform a multicentre, prospective randomised clinical trial to compare transperineal versus transrectal prostate biopsy for elevated prostate-specific antigen in the first biopsy, prior negative biopsy and active surveillance biopsy setting. Prostate MRI will be performed prior to biopsy, and targeted biopsy will be conducted for suspicious MRI lesions in addition to systematic biopsy (12 cores). Approximately 1700 men will be recruited and randomised in a 1:1 ratio to transperineal versus transrectal biopsy. A streamlined design to collect data and to determine trial eligibility along with the two-stage consent process will be used to facilitate subject recruitment and retention. The primary outcome is postbiopsy infection, and secondary outcomes include other adverse events (bleeding, urinary retention), pain/discomfort/anxiety and critically, detection of non-low-grade (grade group ≥2) prostate cancer. ETHICS AND DISSEMINATION: The Institutional Review Board of the Biomedical Research Alliance of New York approved the research protocol (protocol number #18-02-365, approved 20 April 2020). The results of the trial will be presented at scientific conferences and published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT04815876.