Transperineal vs Transrectal Prostate Biopsy-The PREVENT Randomized Clinical Trial.

This randomized clinical trial compares the effect of transperineal vs transrectal prostate biopsy on infection rates after biopsy.

Outcomes and Cost of Donor Nephrectomy Across Surgical Specialties and Operative Approaches.

INTRODUCTION: Live donor nephrectomy (LDN) is performed by various specialty surgeons, including urologists, general surgeons, and transplant surgeons. However, national practice patterns and outcomes associated with surgeon specialty have not been previously explored. Here, we investigate surgeon specialty trends, perioperative complications, hospital length of stay, cost, and charge for LDN according to surgeon specialty. METHODS: Patients who underwent LDN from 2000 to quarter 1 of 2020 were identified in the Premier Healthcare Database. Associations between physician specialty and 3-month complications, hospital length of stay, institutional cost, and patient charge for LDN procedures were examined using multivariable regression. RESULTS: We identified 11,418 patients who underwent LDN. Of these cases, 3387 (29.7%) were performed by urologists, 3127 (27.4%) by transplant surgeons, 3928 (34.4%) by general surgeons, and 976 (8.5%) by other specialties. In 2000, urologists performed 35.92% of LDNs, decreasing to 18.91% by 2019 (P < .001 for trend). In the last 5 years, we found no significant difference in complications or length of stay according to surgeon specialty. LDNs performed by a urologist ($57,289, 95% CI $49,292-$66,582) were associated with lower patient charges than those performed by a general surgeon ($68,501, 95% CI $59,090-$79,412) or transplant surgeon ($62,639, 95% CI $53,993-$72,670). CONCLUSIONS: From 2000 to 2019, the proportion of LDNs performed by urologists significantly decreased, while the proportion for transplant surgeons significantly increased, with no significant differences in complications or length of stay across specialties. However, surgeries performed by urologists cost hospitals less and had lower charges for patients.

DNA mismatch and damage patterns revealed by single-molecule sequencing.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases1,2. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired3,4. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination-a common type of DNA damage-with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing.

Trends in hospital price transparency after implementation of the CMS Final Rule.

OBJECTIVE: To assess trends in hospital price disclosures after the Centers for Medicare & Medicaid Services (CMS) Final Rule went into effect. DATA SOURCES AND STUDY SETTING: The Turquoise Health Price Transparency Dataset was used to identify all US hospitals that publicly displayed pricing from 2021 to 2023. STUDY DESIGN: Price-disclosing versus nondisclosing hospitals were compared using Pearson's Chi-squared and Wilcoxon rank sum tests. Bayesian structural time-series modeling was used to determine if enforcement of increased penalties for nondisclosure was associated with a change in the trend of hospital disclosures. DATA COLLECTION/EXTRACTION METHODS: Not applicable. PRINCIPAL FINDINGS: As of January 2023, 5162 of 6692 (77.1%) US hospitals disclosed pricing of their services, with the majority (2794 of 5162 [54.1%]) reporting their pricing within the first 6 months of the final rule going into effect in January 2021. An increase in hospital disclosures was observed after penalties for nondisclosure were enforced in January 2022 (relative effect size 20%, p = 0.002). Compared with nondisclosing hospitals, disclosing hospitals had higher annual revenue, bed number, and were more likely to be have nonprofit ownership, academic affiliation, provide emergency services, and be in highly concentrated markets (p < 0.001). CONCLUSIONS: Hospital pricing disclosures are continuously in flux and influenced by regulatory and market factors.

High variability in self-pay pricing for vasectomy and vasectomy reversal in the United States.

CONTEXT: In the United States (US) men who undergo vasectomy and/or vasectomy reversal (vasovasotomy) are likely to pay out-of-pocket for these procedures. We characterized the publicly disclosed pricing of both procedures with a focus on variability in self-pay prices. METHODS: We queried all US hospitals for publicly disclosed prices of vasectomy and vasovasotomy. We assessed interhospital variability in self-pay pricing and compared hospitals charging high (≥75th percentile) and low (≤25th percentile) self-pay prices for either procedure. We also examined trends in pricing after the 2022 US Supreme Court decision that allowed individual states to ban abortion. RESULTS: Of 6692 hospitals, 1375 (20.5%) and 281 (4.2%) disclosed self-pay prices for vasectomy and vasovasotomy, respectively. There was a 17-fold difference between the 10th and 90th percentile self-pay prices for vasectomy ($421-$7147) and a 39-fold difference for vasovasotomy ($446-$17,249). Compared with hospitals charging low (≤25th percentile) self-pay prices for vasectomy or vasovasotomy, hospitals charging high (≥75th percentile) prices were larger (median 150 vs. 59 beds, p < 0.001) and more likely to be for-profit (31.2% vs. 7.8%, p < 0.001), academic-affiliated (52.7% vs. 23.1%, p < 0.001), and located in an urban zip code (70.1% vs. 41.3%, p < 0.001). From October 2022 to April 2023, the median self-pay price of vasectomy increased by 10% (from $1667 to $1832) while the median self-pay price of vasovasotomy decreased by 16% (from $3309 to $2786). CONCLUSION: We found large variability in self-pay pricing for vasectomy and vasectomy reversal, which may serve as a barrier to the accessibility of male reproductive care.

Hypogonadism, frailty, and postoperative outcomes among men undergoing radical nephrectomy.

BACKGROUND AND OBJECTIVE: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes. METHODS: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes. CONCLUSIONS: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes.

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 incorporates 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. The purpose of this article was 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 and higher. 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 trade-off of csPCa detection and biopsy avoidance, of MRI-directed pathways in scenarios considering and disregarding PI-RADS upgrading rules. These included a biopsy-all pathway, MRI-focused pathway (no biopsy for PI-RADS ≤ 2), and risk-based pathway (use of PSA density ≥ 0.15 ng/mL2 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%, respectively), 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 7.5-30.0%, net benefit was highest for the per-guideline risk-based pathway. CONCLUSION. Disregarding PI-RADS upgrading rules reduced net clinical bene fit of the risk-based MRI-directed diagnostic pathway when considering trade-offs 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.

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.

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.

Risk of postoperative mesh exposure following sacrocolpopexy with supracervical versus total concomitant laparoscopic hysterectomy.

INTRODUCTION AND HYPOTHESIS: The primary objective was to compare rates of mesh exposure in women undergoing minimally invasive sacrocolpopexy with concurrent supracervical vs total hysterectomy. We hypothesized there would be a lower risk of mesh exposure for supracervical hysterectomy. METHODS: This was a retrospective cohort study using the Premier Healthcare Database. Women undergoing sacrocolpopexy with supracervical or total hysterectomy between 2010 and 2018 were identified using Current Procedural (CPT) codes. Complications were identified using CPT and diagnosis codes; reoperations were identified using CPT codes. Mesh exposures were measured over a 2-year period. A multivariable logistic regression was performed with a priori defined predictors of mesh exposure. RESULTS: This study includes 17,111 women who underwent minimally invasive sacrocolpopexy with concomitant supracervical or total hysterectomy (6708 (39%) vs 10,403 (61%)). Women who underwent supracervical hysterectomy were older (age 60 ± 11 vs 53 ± 13, p < 0.01) and less likely to be obese (4% vs 7%, p < 0.01). Postoperative mesh exposures within 2 years were similar (supracervical n = 47, 0.7% vs total n = 65, 0.62%, p = 0.61). On logistic regression, obesity significantly reduced the odds of mesh exposure (OR 0.2, 95% CI 0.01, 0.8); concomitant slings increased odds (OR 1.91, 95% CI 1.28, 2.83). Supracervical hysterectomy was associated with higher rates of port site hernias (1.3% vs 0.65%, p < 0.01), but lower surgical site infections within 3 months (0.81% vs 1.2%, p = 0.03). Reoperation for recurrent prolapse within 24 months was similar (supracervical n = 94, 1.4% vs total n = 150, 1.4%, p = 0.88). CONCLUSIONS: Postoperative mesh exposure rates do not significantly differ based on type of concomitant hysterectomy in this dataset.

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.