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.

Current Practice Patterns in the Surgical Management of Benign Prostatic Hyperplasia.

OBJECTIVE: To use American Board of Urology (ABU) case log data to elucidate practice patterns for benign prostatic hyperplasia (BPH) surgery. Several surgical modalities have been introduced in recent decades causing significant practice variation. MATERIALS AND METHODS: We retrospectively analyzed ABU case logs from 2008-2021 to assess trends in BPH surgery. We created logistic regression models to identify surgeon-sided factors associated with utilization of each surgical modality. RESULTS: We identified 6,632 urologists who logged 73,884 surgeries for BPH. Transurethral resection of the prostate (TURP) was the most commonly performed BPH surgery in all but 1 year, and odds of performing a TURP increased year-over-year (OR 1.055, 95% CI [1.013,1.098], P = .010). The use of holmium laser enucleation of the prostate (HoLEP) did not change over time. HoLEP was more likely to be performed by urologists with higher BPH surgical volume (OR 1.017, CI [1.013, 1.021], P < .001) and with endourology subspecialization (OR 2.410, CI [1.45, 4.01], P = .001). Prostatic urethral lift (PUL) utilization increased significantly since its introduction in 2015 (OR 1.663, CI [1.540, 1.796], P < .001). PUL currently comprises over one third of all BPH surgeries logged. CONCLUSION: In the face of newer technologies, TURP remains the most common surgery for BPH in the United States. PUL has been rapidly adopted while HoLEP comprises a consistent minority of cases. Surgeon age, patient age, and urologist subspecialization were associated with use of certain BPH surgical approaches.

Comparative Effectiveness and Tolerability of Transperineal MRI-Targeted Prostate Biopsy under Local versus Sedation.

OBJECTIVES: To assess the prostate cancer diagnostic yield, complications, and costs of transperineal prostate biopsies when performed with local anesthesia versus sedation. METHODS: Data were prospectively collected for men undergoing transperineal MRI-targeted biopsy at the outpatient clinic and tertiary hospital of a single center between October 2017 to February 2020. These data included demographic, procedural, and pathologic variables and complications. Time-driven activity-based costing was performed to compare procedural costs. RESULTS: 126 men were included. Age, BMI and PSA were similar for local (n = 45) vs sedation (n = 81), all P>0.05. Detection of clinically significant prostate cancer (CSPC) on combined systematic and targeted biopsy was similar for local vs sedation (24% vs 36%; P = 0.2). Local had lower detection on targeted biopsies alone (8.9% vs 25%; P = 0.03). However, fewer targeted cores were obtained per region of interest with local vs sedation (median 3 vs 4 cores; P<0.01). For local vs sedation, the complication rate was 2.6% and 6.1% (P = 0.6). The median visual analog pain score for local vs sedation was 3/10 vs 0/10 (P<0.01). The mean procedure time for local vs sedation was 22.5 vs 17.5 minutes (48.3 minutes when including anesthesia time). Time-driven activity-based costs for local vs sedation were $961.64 vs $2208.16 (P<0.01). CONCLUSION: Transperineal biopsy with local anesthesia is safe with comparable outcomes to sedation. While the number of cores taken differed, there was no statistical difference in the detection of clinically significant cancer.

Robot-Assisted Radical Prostatectomy Maneuvers to Attenuate Erectile Dysfunction: Technical Description and Video Compilation.

Erectile dysfunction (ED) remains a significant problem in up to 63% of men after robot-assisted radical prostatectomy (RARP). After the discovery of the neurovascular bundle (NVB), additional anatomic description and variation in nerve-sparing (NS) techniques have been described to improve post-RARP ED. However, it remains questionable whether ED rates have improved over time, and this is concerning as competing treatments are introduced that have better ED outcomes. In this review, we describe RARP NS technical modifications that improve erectile function recovery. We focused on reports that included detailed anatomical descriptions as well as video illustrations to disseminate technique. We found that the alternative RARP NS surgical techniques provide better outcomes compared with standard NS RARP. The use of validated quality of life questionnaires is necessary for the appropriate comparison of outcomes. However, the retrospective character and inherent weaknesses of the included studies do not allow one to conclude which is the best NS approach. Overall, there is significant variation in RARP NS techniques and outcomes, and the ideal technical maneuvers to optimize outcomes remains subject to debate. However, there is a consensus on the importance of anatomically dissecting the NVB, minimizing traction and thermal injury as well as preserving the periprostatic fascia. Well-designed randomized controlled trials with videos describing details of different surgical techniques for generalizability are needed to consistently and objectively evaluate sexual function outcomes after RARP to optimize postoperative potency.

Active Surveillance for Men with Intermediate Risk Prostate Cancer.

PURPOSE: Optimal treatment of intermediate risk prostate cancer remains unclear. National Comprehensive Cancer Network® guidelines recommend active surveillance, prostatectomy or radiotherapy. Recent trials demonstrated no difference in prostate cancer specific mortality for men undergoing active surveillance for low risk prostate cancer compared to prostatectomy or radiotherapy. The use of active surveillance for intermediate risk prostate cancer is less clear. In this study we characterize U.S. national trends for demographic, clinical and socioeconomic factors associated with active surveillance for men with intermediate risk prostate cancer. MATERIALS AND METHODS: This retrospective cohort study examined 176,122 men diagnosed with intermediate risk prostate cancer from 2010 to 2016 in the National Cancer Database. Temporal trends in demographic, clinical and socioeconomic factors among men with intermediate risk prostate cancer and association with the use of active surveillance were characterized. The analysis was performed in April 2020. RESULTS: In total, 176,122 men were identified with intermediate risk prostate cancer from 2010 to 2016. Of these men 57.3% underwent prostatectomy, 36.4% underwent radiotherapy and 3.2% underwent active surveillance. Active surveillance nearly tripled from 1.6% in 2010 to 4.6% in 2016 (p <0.001). On multivariate analysis use of active surveillance was associated with older age, diagnosis in recent years, lower Gleason score and tumor stage, type of insurance, treatment at an academic center and proximity to facility, and attaining higher education (p <0.05). Race and comorbidities were not associated with active surveillance. CONCLUSIONS: Our findings highlight increasing active surveillance use for men with intermediate risk prostate cancer demonstrating clinical and socioeconomic disparities. Prospective data and improved risk stratification are needed to guide optimal treatment for men with intermediate risk prostate cancer.

Persistent Discordance in Grade, Stage, and NCCN Risk Stratification in Men Undergoing Targeted Biopsy and Radical Prostatectomy.

OBJECTIVE: To elucidate the accuracy of MRI and MRI-ultrasound fusion guided targeted biopsy (TBx) on risk stratification in men who underwent subsequent radical prostatectomy (RP). MATERIALS AND METHODS: A single-center, retrospective study was performed in men at risk for prostate cancer who (n = 140) underwent TBx and RP between November 2012 and August 2018. Comparisons were made between patients clinically staged by preoperative MRI and TBx Gleason grade group (GGG) and stage after RP. Multivariable regression was performed to identify factors associated with MRI and TBx compared to RP grading, staging, and consistency with National Comprehensive Cancer Network (NCCN) risk stratification. RESULTS: There was an increase in NCCN risk stratification in 47 men (33.6%) and a decrease in 17 men (12.1%) compared to the resected prostate. GGG upgrading and downgrading occurred in 35 (25.0%) and 31 men (22.1%), respectively. Upstaging occurred in 41 men (29.3%). In adjusted analysis for age, BMI, PSA Density (PSAD), median maximal diameter of the regions of interest, and PIRADS, men with PIRADS 4 were less likely to be upgraded (OR 0.26, 95% CI 0.08-0.81, P = .020) than PIRADS 3. PSAD ≥ 0.15 ng/mL/cc was associated with upstaging (OR 3.92, 95% CI 1.60-9.62, P = .003). CONCLUSION: Accurate risk stratification is critical for disease management, mandated by the increasing use of active surveillance, partial gland ablation, and androgen deprivation therapy with radiation therapy for men with unfavorable intermediate and high-risk prostate cancer. This study confirms the need for advances in imaging and biomarker to increase the accuracy of pretreatment staging.

Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies.

PURPOSE: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. MATERIALS AND METHODS: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. RESULTS: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. CONCLUSIONS: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

PURPOSE: Guidelines from the NCCN® (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. MATERIALS AND METHODS: We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. RESULTS: A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examination. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). CONCLUSIONS: Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity.

Vouchers for Future Kidney Transplants to Overcome "Chronological Incompatibility" Between Living Donors and Recipients.

BACKGROUND: The waiting list for kidney transplantation is long. The creation of "vouchers" for future kidney transplants enables living donation to occur when optimal for the donor and transplantation to occur later, when and if needed by the recipient. METHODS: The donation of a kidney at a time that is optimal for the donor generates a "voucher" that only a specified recipient may redeem later when needed. The voucher provides the recipient with priority in being matched with a living donor from the end of a future transplantation chain. Besides its use in persons of advancing age with a limited window for donation, vouchers remove a disincentive to kidney donation, namely, a reluctance to donate now lest one's family member should need a transplant in the future. RESULTS: We describe the first three voucher cases, in which advancing age might otherwise have deprived the donors the opportunity to provide a kidney to a family member. These 3 voucher donations functioned in a nondirected fashion and triggered 25 transplants through kidney paired donation across the United States. CONCLUSIONS: The provision of a voucher to potential recipients whose need for a transplant makes them "chronologically incompatible" with their donors may increase the number of living donor transplants.

Trends in disparate treatment of African American men with localized prostate cancer across National Comprehensive Cancer Network risk groups.

OBJECTIVE: To determine whether African Americans (AAs) with intermediate- to high-risk prostate cancer (PCa) receive similar treatment as white patients and whether any observed disparities are narrowing with time. METHODS: We used Surveillance, Epidemiology, and End Results to identify 128,189 men with localized intermediate- to high-risk PCa (prostate-specific antigen ≥10 ng/mL, Gleason score ≥7, or T stage ≥T2b) diagnosed from 2004 to 2010. We used multivariate logistic regression analyses to determine the impact of race on the receipt of definitive treatment. RESULTS: AA men were significantly less likely to receive curative-intent treatment than white men (adjusted odds ratio [AOR], 0.82; 95% confidence interval [CI], 0.79-0.86; P <.001). There was no evidence of this disparity narrowing over time (Pinteraction 2010 vs 2004 = .490). Disparities in the receipt of treatment between AA and white men were significantly larger in high-risk (AOR, 0.60; 95% CI, 0.56-0.64; P <.001) than in intermediate-risk disease (AOR, 0.92; 95% CI, 0.88-0.97; P = .04; Pinteraction <.001). After adjusting for treatment, demographics, and prognostic factors, AA men had a higher risk of prostate cancer-specific mortality (adjusted hazard ratio, 1.12; 95% CI, 1.01-1.25; P = .03). CONCLUSION: AA men with intermediate- to high-risk PCa are less likely to be treated with curative intent than white men. This disparity is worse in high-risk disease and is not improving over time. Factors underlying this treatment disparity should be urgently studied as it is a potentially correctable contributor to excess PCa mortality among AA patients.

Comparative effectiveness of minimally invasive vs open radical prostatectomy.

CONTEXT: Minimally invasive radical prostatectomy (MIRP) has diffused rapidly despite limited data on outcomes and greater costs compared with open retropubic radical prostatectomy (RRP). OBJECTIVE: To determine the comparative effectiveness of MIRP vs RRP. DESIGN, SETTING, AND PATIENTS: Population-based observational cohort study using US Surveillance, Epidemiology, and End Results Medicare linked data from 2003 through 2007. We identified men with prostate cancer who underwent MIRP (n = 1938) vs RRP (n = 6899). MAIN OUTCOME MEASURES: We compared postoperative 30-day complications, anastomotic stricture 31 to 365 days postoperatively, long-term incontinence and erectile dysfunction more than 18 months postoperatively, and postoperative use of additional cancer therapies, a surrogate for cancer control. RESULTS: Among men undergoing prostatectomy, use of MIRP increased from 9.2% (95% confidence interval [CI], 8.1%-10.5%) in 2003 to 43.2% (95% CI, 39.6%-46.9%) in 2006-2007. Men undergoing MIRP vs RRP were more likely to be recorded as Asian (6.1% vs 3.2%), less likely to be recorded as black (6.2% vs 7.8%) or Hispanic (5.6% vs 7.9%), and more likely to live in areas with at least 90% high school graduation rates (50.2% vs 41.0%) and with median incomes of at least $60,000 (35.8% vs 21.5%) (all P < .001). In propensity score-adjusted analyses, MIRP vs RRP was associated with shorter length of stay (median, 2.0 vs 3.0 days; P<.001) and lower rates of blood transfusions (2.7% vs 20.8%; P < .001), postoperative respiratory complications (4.3% vs 6.6%; P = .004), miscellaneous surgical complications (4.3% vs 5.6%; P = .03), and anastomotic stricture (5.8% vs 14.0%; P < .001). However, MIRP vs RRP was associated with an increased risk of genitourinary complications (4.7% vs 2.1%; P = .001) and diagnoses of incontinence (15.9 vs 12.2 per 100 person-years; P = .02) and erectile dysfunction (26.8 vs 19.2 per 100 person-years; P = .009). Rates of use of additional cancer therapies did not differ by surgical procedure (8.2 vs 6.9 per 100 person-years; P = .35). CONCLUSION: Men undergoing MIRP vs RRP experienced shorter length of stay, fewer respiratory and miscellaneous surgical complications and strictures, and similar postoperative use of additional cancer therapies but experienced more genitourinary complications, incontinence, and erectile dysfunction.

Patterns of care for radical prostatectomy in the United States from 2003 to 2005.

PURPOSE: The demand for minimally invasive radical prostatectomy is increasing, although population based outcomes remain unclear. We assessed use and outcomes in American men undergoing radical prostatectomy. MATERIALS AND METHODS: We identified 14,727 men undergoing minimally invasive, perineal and retropubic radical prostatectomy during 2003 to 2005 using nationally representative, employer based administrative data. We assessed the association between surgical approach and outcomes, adjusting for age, race, comorbidity and geographic region. RESULTS: Minimally invasive radical prostatectomy use increased from 5.4% to 24.4%, while conversion to open surgery decreased from 28.6% to 4.5% in the 3-year study. Men undergoing minimally invasive and perineal radical prostatectomy vs retropubic radical prostatectomy experienced fewer 30-day complications (14.2% and 14.9% vs 17.5%, p = 0.001), blood transfusions (2.2% and 3.6% vs 9.1%, p <0.001) and anastomotic strictures (6.8% and 8.5% vs 12.9%, p <0.001), and shorter median length of stay (1 and 2 days, respectively, vs 4, p <0.001). On adjusted analysis minimally invasive vs retropubic radical prostatectomy was associated with fewer 30-day complications (OR 0.78, 95% CI 0.66, 0.92), transfusions (OR 0.24, 95% CI 0.16, 0.34) and anastomotic strictures (OR 0.50, 95% CI 0.40, 0.62), and shorter length of stay (parameter estimate -0.53, 95% CI -0.58, -0.49). Similarly perineal vs retropubic radical prostatectomy was associated with fewer transfusions (OR 0.50, 95% CI 0.31, 0.82) and anastomotic strictures (OR 0.65, 95% CI 0.47, 0.90), and shorter length of stay (parameter estimate -0.53, 95% CI -0.42, -0.29). CONCLUSIONS: While the use of minimally invasive radical prostatectomy surged, men undergoing minimally invasive vs perineal radical prostatectomy experienced a lower risk of 30-day complications, blood transfusions and anastomotic strictures, and a shorter length of stay. Furthermore, perineal vs retropubic radical prostatectomy was also associated with relatively favorable outcomes. Further study is needed to assess continence, potency and cancer control.