Apalutamide for High-Risk Localized Prostate Cancer Following Radical Prostatectomy (Apa-RP).

PURPOSE: Approximately 25% to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence (BCR) within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy (ADT) in high-risk patients who have undergone radical prostatectomy improved BCR-free survival. MATERIALS AND METHODS: Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the US. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus ADT. The primary end point was BCR-free survival. Secondary end points included testosterone recovery (≥150 ng/dL) and safety. RESULTS: One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0 years). Median preoperative PSA and baseline testosterone were 7.6 ng/mL (range 2.2-62.7 ng/mL) and 340.0 ng/dL (range 43.0-939.0 ng/dL), respectively. The BCR-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events. CONCLUSIONS: In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04523207.

Clinician-Reported Management Recommendations in Response to Universal Germline Genetic Testing in Patients With Prostate Cancer.

PURPOSE: Identification of pathogenic germline variants in patients with prostate cancer can help inform treatment selection, screening for secondary malignancies, and cascade testing. Limited real-world data are available on clinician recommendations following germline genetic testing in patients with prostate cancer. MATERIALS AND METHODS: Patient data and clinician recommendations were collected from unselected patients with prostate cancer who underwent germline testing through the PROCLAIM trial. Differences among groups of patients were determined by 2-tailed Fisher's exact test with significance set at P < .05. Logistic regression was performed to assess the influence of test results in clinical decision-making while controlling for time of diagnosis (newly vs previously diagnosed). RESULTS: Among 982 patients, 100 (10%) were positive (>1 pathogenic germline variant), 482 (49%) had uncertain results (>1 variant of uncertain significance), and 400 (41%) were negative. Patients with positive results were significantly more likely than those with negative or uncertain results to receive recommendations for treatment changes (18% vs 1.4%, P < .001), follow-up changes (64% vs 11%, P < .001), and cascade testing (71% vs 5.4%, P < .001). Logistic regression demonstrated that positive and uncertain results were significantly associated with both changes to treatment and follow-up (P < .001) when controlling for new or previous diagnosis. CONCLUSIONS: Germline genetic testing results informed clinical recommendations for patients with prostate cancer, especially in patients with positive results. Higher than anticipated rates of clinical management changes in patients with uncertain results highlight the need for increased genetic education of clinicians treating patients with prostate cancer.

Hereditary cancer risk assessment and genetic testing in the community urology practice setting.

OBJECTIVES: To evaluate the feasibility of integrating a hereditary cancer risk assessment (HCRA) process in the community urology practice setting for patients with prostate cancer (PCa). METHODS: In this prospective intervention, an HCRA process was implemented across six different community urology clinics between May 2019 and April 2020. The intervention included a process integration during which the workflow at each site was refined, a post-integration period during which HCRA was conducted in all patients with PCa, and a follow-up period during which healthcare providers and patients reported their satisfaction with the HCRA and genetic testing process. RESULTS: Among patients who completed a family history assessment during the post-integration period, 23.6% met guideline criteria for genetic testing. Of all patients seen at the clinic during the post-integration period, 8.7% completed genetic testing; this was a twofold increase over the period immediately preceding process integration (4.2%), and a sevenfold increase over the same period 1 year prior (1.2%). The majority of providers reported that the HCRA was as important as other regularly performed assessments (61.0%) and planned to continue using the process in their practice (68.3%). Most patients believed that the genetic test results were important for their future cancer care (84.7%) and had already shared their test results with at least one family member (63.2%). CONCLUSIONS: This study demonstrated that implementing an HCRA process in the community urology practice setting was feasible, generally favored by providers and patients, and resulted in an increase in the number of patients with PCa who completed genetic testing.

Efficacy and safety of darolutamide in Black/African-American patients from the phase III ARAMIS study.

Aim: Darolutamide significantly improved metastasis-free survival (MFS) and overall survival (OS) versus placebo in the phase III ARAMIS study. We evaluated outcomes in Black/African-American patients in ARAMIS. Materials & methods: Patients with nonmetastatic castration-resistant prostate cancer were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554) plus androgen-deprivation therapy. The primary end point was MFS. Secondary end points included OS and safety. Results: In 52 (3.4%) Black/African-American patients, darolutamide improved MFS (median: not reached vs 12.4 months) and OS (3-year survival rates: 100 vs 71%) versus placebo. The safety profile of darolutamide in Black/African-American patients was consistent with that of all ARAMIS patients. Conclusion: In Black/African-American patients, darolutamide improved MFS and OS and was well tolerated, consistent with the overall ARAMIS population.

In patients with prostate cancer that has stopped responding to androgen-deprivation therapy, or 'ADT,' and has not spread to other parts of the body (known as nonmetastatic castration-resistant prostate cancer, or 'nmCRPC'), darolutamide is an oral treatment option. Darolutamide added to ADT was tested in patients with nmCRPC in a large international study called ARAMIS and was found to prolong the time that patients were free from their cancer spreading compared with patients who received ADT alone. This report provides information on the effect of darolutamide in the 52 Black/African­American patients who took part in ARAMIS. In these patients, darolutamide showed similar effects on lowering the risk of their cancer spreading and was well tolerated.

Socio-Environmental Conditions Associated with Geospatial Clusters of Urothelial Carcinoma: A Multi-Institutional Analysis.

PURPOSE: The interaction between sources of industrial byproducts and environmental pollutants (IBP/EP) and the prevalence of urothelial carcinoma (UC) in surrounding communities has been infrequently explored. The purpose of this research is to identify microregional UC hotspots and associated industrial and environmental risk factors. MATERIALS AND METHODS: We retrospectively queried a multi-institutional database for UC patients diagnosed between 2008 and 2018. Addresses were geocoded and used to perform hotspot analysis on the census block level. Demographic and clinicopathological characteristics, census data and proximity to sources of IBP/EP were compared between patients who did vs did not reside in a hotspot. Associations were tested using multilevel logistic regression models using 95% confidence intervals. RESULTS: A total of 5,080 patients met inclusion criteria and 148 (2.9%) were identified as living in 1 of 3 UC hotspots. In univariate analyses, race, tobacco and alcohol use, household income, IBP/EP exposure and proximity to traffic, industrial discharge and airports were significantly associated with UC hotspots. Multivariable analysis demonstrated that polycyclic aromatic hydrocarbon exposure (OR: 48.09, p ≤0.001) and proximity to high-density traffic (OR: >999, p ≤0.001) increased the odds of living in a hotspot. Patients living in a hotspot were significantly less likely to be white (OR: 0.06, p ≤0.001) or tobacco users (OR: 0.39, p=0.031) on multivariate analysis. CONCLUSIONS: Spatially related clusters of UC may be associated with locoregional environmental exposures rather than tobacco exposure and may also be correlated with socioeconomic disparities. Geospatial analysis can help to identify at-risk populations, offering the opportunity to better focus preventive and diagnostic interventions.

EFFICACY AND SAFETY OF A NEW TOPICAL TESTOSTERONE REPLACEMENT GEL THERAPY FOR THE TREATMENT OF MALE HYPOGONADISM.

OBJECTIVE: Testosterone replacement therapy is indicated for male hypogonadism. This study aimed to evaluate the efficacy and safety of testosterone gel 2% (Tgel) over 90 days. METHODS: This phase 3, open-label, noncomparator study was conducted in adult hypogonadal men (2 consecutive fasting serum testosterone values <300 ng/dL and >86% subjects with symptoms consistent with testosterone deficiency). Subjects applied Tgel 23 mg/day (single pump-actuation using a hands-free cap applicator). The dose was uptitrated to 46 mg/day after 2 weeks if the 4-hour serum total testosterone level was <500 ng/dL. The dose could be further up- or downtitrated to 23, 46, and 69 mg on Days 21, 42, and 63. The primary endpoint included the percentage of subjects with average testosterone concentration (Cave (0-24)) between 300 and 1,050 ng/dL on Day 90. Safety endpoints were adverse events (AEs), laboratory parameters, and vital signs. RESULTS: Of the 159 who enrolled, 139 men completed the study. Approximately three-quarters (76.1%) of subjects met Cave criteria on Day 90. Most AEs were mild to moderate. There were 5 serious AEs, and 1 (myocardial infarction) was judged as possibly related to Tgel. Confirmed excessive increases in prostate-specific antigen or hematocrit levels were rare. Tgel had a favorable local skin tolerability profile. CONCLUSION: Overall, 76% of subjects achieved Cave between 300 and 1,050 ng/dL with Tgel. Symptoms of testosterone deficiency improved with few safety concerns. ABBREVIATIONS: AE = adverse event Cave(0-24) = average testosterone concentration CI = confidence interval Cmax = maximum concentration IIEF = International Index of Erectile Function MAF = Multidimensional Assessment of Fatigue PK = pharmacokinetic PSA = prostate-specific antigen SAE = serious adverse event SF-12 = Short Form 12 Health Survey Tgel = testosterone gel 2% Tmax = time to achieve maximum concentration TRT = testosterone replacement therapy.

A randomized, double-blind, solifenacin succinate versus placebo control, phase 4, multicenter study evaluating urinary continence after robotic assisted radical prostatectomy.

PURPOSE: Bladder dysfunction influences recovery of urinary continence after radical prostatectomy. We performed a multicenter, randomized, double-blind study evaluating solifenacin vs placebo on return to continence in patients who were still incontinent 7 to 21 days after catheter removal after robot-assisted radical prostatectomy. MATERIALS AND METHODS: A wireless personal digital assistant was given to patients the day of catheter removal. Encrypted answers were transmitted daily to dedicated servers. After a 7 to 21-day treatment-free washout period, patients requiring 2 to 10 pads per day for 7 consecutive days were randomized (1:1) to 5 mg solifenacin daily or placebo. The primary end point was time from first dose to continence defined as 0 pads per day or a dry security pad for 3 consecutive days. Secondary end points included proportion of patients continent at end of study, average change in pads per day number and quality of life assessments. RESULTS: A total of 1,086 screened patients recorded personal digital assistant information. Overall 640 patients were randomized to solifenacin vs placebo and 17 failed to take medication. There was no difference in time to continence (p=0.17). Continence was achieved by study end in 91 of 313 (29%) vs 66 of 309 (21%), respectively (p=0.04). Pads per day change from baseline was -3.2 and -2.9, respectively (p=0.03). Dry mouth was the only common adverse event seen in 6.1% and 0.6%, respectively. Constipation rates were similar. The overall rate of continence in the entire population from screening to end of study was 73%. CONCLUSIONS: There was no effect on primary outcome but some secondary end points benefited the solifenacin arm. The study provides level 1B clinical evidence for continence outcomes after robot-assisted radical prostatectomy.

Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study.

PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction. MATERIALS AND METHODS: This randomized, double-blind, placebo controlled, 12-week study (4-week run-in and 8-week treatment) randomized 145 men to placebo, 147 to avanafil 100 mg and 148 to avanafil 200 mg on demand. The primary efficacy variable was the per subject proportion of sexual attempts during the treatment period in which subjects achieved erection sufficient for vaginal penetration within approximately 15 minutes after dosing as measured by a stopwatch. The attempt had to enable successful completion of sexual intercourse according to SEP question 3. RESULTS: Significantly greater mean per subject percentages of successful intercourse attempts within approximately 15 minutes after dosing were observed for avanafil 100 mg (mean 25.9%, LS mean ± SE 24.7% ± 2.9%) and 200 mg (mean 29.1%, LS mean 28.2% ± 2.9%) vs placebo (mean 14.9%, LS mean 13.8% ± 2.9%, p = 0.001 and <0.001, respectively). After treatment we noted a statistically significant difference between avanafil and placebo in the average per subject proportion of successful intercourse attempts according to SEP question 3 as early as 10 minutes in the 200 mg group and 12 minutes in the 100 mg group. Treatment emergent adverse events included headache, upper respiratory tract infection and nasal congestion, and most such events were mild or moderate in severity. CONCLUSIONS: Avanafil was efficacious within approximately 15 minutes of dosing compared to placebo. A statistically significant treatment difference in the percentage of successful sexual attempts was demonstrated as early as 10 minutes after treatment.

Appropriateness of Imaging for Low-Risk Prostate Cancer-Real World Data from the Pennsylvania Urologic Regional Collaboration (PURC).

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) high-risk prostate cancer, based on the AUA guidelines. Amongst the low-risk patients, imaging utilization included pelvic MRI (59.7%), bone scan (17.8%), CT (16.0%), and PET-based imaging (0.5%). Redundant imaging occurred in 1022 patients (29.2%). There was variability among the PURC sites for imaging used in the low-risk patients, and iterative education reduced the need for CT and bone scans. Approximately 15% of low-risk patients had staging imaging performed using either a CT or bone scan, and redundant imaging occurred in almost one-third of men. Such data underscore the need for continued guideline-based education to optimize the stewardship of resources and reduce unnecessary costs to the healthcare system.

Deep and Durable Prostate-specific Antigen Response to Darolutamide with Androgen Deprivation Therapy and Docetaxel, and Association with Clinical Outcomes for Patients with High- or Low-volume Metastatic Hormone-sensitive Prostate Cancer: Analyses of the Randomized Phase 3 ARASENS Study.

BACKGROUND AND OBJECTIVE: Addition of darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (OS) in ARASENS (NCT02799602). Here we report on prostate-specific antigen (PSA) responses and their association with outcomes. METHODS: ARASENS is an international, double-blind, phase 3 study in patients with metastatic hormone-sensitive prostate cancer (mHSPC) randomized to darolutamide 600 mg orally twice daily (n = 651) or placebo (n = 654), both with ADT + docetaxel. The proportion of patients with undetectable PSA (<0.2 ng/ml) and time to PSA progression (≥25% relative and ≥2 ng/ml absolute increase from nadir) were compared between groups in prespecified exploratory analyses. PSA outcomes by disease volume and the association of undetectable PSA with OS and times to castration-resistant prostate cancer (CRPC) and PSA progression were assessed in post hoc analyses. KEY FINDINGS AND LIMITATIONS: The proportion of patients with undetectable PSA at any time was more than doubled with darolutamide versus placebo, at 67% versus 29% in the overall population, 62% versus 26% in the high-volume subgroup, and 84% versus 38% in the low-volume subgroup. Darolutamide delayed time to PSA progression versus placebo, with hazard ratios of 0.26 (95% confidence interval [CI] 0.21-0.31) in the overall population, 0.30 (95% CI 0.24-0.37) in the high-volume subgroup, and 0.093 (95% CI 0.047-0.18) in the low-volume subgroup. Undetectable PSA at 24 wk was associated with longer OS, with a hazard ratio of 0.49 (95% CI 0.37-0.65) in the darolutamide group, as well as longer times to CRPC and PSA progression, with similar findings in the disease volume subgroups. CONCLUSIONS AND CLINICAL IMPLICATIONS: Darolutamide + ADT + docetaxel led to deep and durable PSA responses in patients with high- or low-volume mHSPC. Achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes.

Coadministration of Apalutamide and Relugolix in Patients with Localized Prostate Cancer at High Risk for Metastases.

BACKGROUND: The single-arm, open-label, multicenter, phase II Apa-RP study evaluates the biochemical recurrence (confirmed prostate-specific antigen [PSA] > 0.2 ng/mL)-free rate in patients with high-risk localized prostate cancer (HR-LPC) after radical prostatectomy following adjuvant apalutamide and androgen-deprivation therapy. In this substudy, relugolix, an oral gonadotropin-releasing hormone antagonist, was evaluated in combination with apalutamide. OBJECTIVE: The aim of this study was to evaluate whether the approved standard maintenance dose of relugolix in combination with apalutamide sustains castrate testosterone levels (< 50 ng/dL). PATIENTS AND METHODS: Twelve patients with HR-LPC who met all the main study criteria were included in the substudy. Patients received relugolix monotherapy for 2 weeks (loading dose [360 mg] at Day - 14 then 120 mg/day daily until Day - 1), then daily relugolix (120 mg) with apalutamide (240 mg) from Day 1 to Day 28. Endpoints were rate of maintained castration (testosterone < 50 ng/dL) through Day 28 (primary) and safety (secondary). RESULTS: All 12 patients received relugolix and apalutamide and achieved castrate testosterone levels after 2-week relugolix monotherapy (median testosterone 348.5 ng/dL and 8.7 ng/dL at Days - 14 and - 1). All 11 patients who had testosterone measured at Day 28 maintained castrate testosterone (median 10.0 ng/dL) without relugolix dose adjustment. Treatment-emergent adverse events (TEAEs) occurred in nine patients during relugolix monotherapy and in eight patients during relugolix + apalutamide coadministration. Hot flush was the most common TEAE reported, in six and four patients, respectively. CONCLUSIONS: Relugolix administered at approved standard doses concurrently with apalutamide was effective in maintaining castrate testosterone levels in HR-LPC without new safety signals. TRIAL REGISTRATION NUMBER AND DATE: NCT04523207, 21 August 2020.

The Apa-RP study evaluates the combination of apalutamide with drugs that lower male sex hormones for reducing the risk of prostate cancer recurrence. Patients in this study had their prostate gland surgically removed and were at high risk for disease recurrence. Relugolix, a newly approved oral drug for advanced prostate cancer, lowers blood testosterone (the primary male sex hormone) and, in combination with apalutamide, may reduce the risk of prostate cancer recurrence. The Apa-RP substudy goal was to test whether relugolix lowers blood testosterone and maintains these low levels when administered with apalutamide. Researchers looked at the testosterone levels of 12 patients with early prostate cancer who received standard doses of relugolix alone for 2 weeks followed by apalutamide and relugolix for an additional 28 days. Testosterone was measured before and after 2 weeks of relugolix treatment, and then again 28 days after apalutamide was added. All 12 substudy patients achieved low testosterone levels (< 50 ng/dL) after 2 weeks of relugolix treatment. Testosterone was measured at Day 28 of relugolix + apalutamide treatment in 11 patients, all of whom maintained low testosterone without adjustment of their relugolix dose. Adverse effects were consistent with those previously reported for each drug when administered alone. All 12 patients completed the substudy and moved onto the main study, the longer-term results of which will be reported in the future. In summary, relugolix administered at the same time as apalutamide was effective in maintaining low testosterone levels in patients with prostate cancer, without any new safety concerns.

Model risk scores may underestimate rate of biochemical recurrence in African American men with localized prostate cancer: a cohort analysis of over 3000 men.

INTRODUCTION: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP). METHODS: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores. RESULTS: Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007). CONCLUSION: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies.

A Phase I Clinical Trial Evaluating the Safety and Dosing of Relugolix with Novel Hormonal Therapy for the Treatment of Advanced Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, is commonly co-prescribed as combination therapy. OBJECTIVE: To better understand the safety and tolerability profile of relugolix, an oral non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, in combination with abiraterone acetate (abiraterone) and apalutamide, a phase I study was undertaken. PATIENTS AND METHODS: This is an ongoing, 52-week, open-label, parallel cohort study of relugolix in combination with abiraterone in men with metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC) [Part 1] and apalutamide in men with mCSPC or non-metastatic castration-resistant prostate cancer (nmCRPC) [Part 2]. Eligible patients treated with leuprolide acetate or degarelix with abiraterone or apalutamide prior to baseline, at which time they were transitioned to relugolix. Assessments included reporting of adverse events, clinical laboratory tests, vital sign measurements, electrocardiogram (ECG) parameters, and testosterone serum concentrations. In this interim report, patients completing ≥12 weeks were included. RESULTS: Overall, 15 men were enrolled in Part 1 and 10 in Part 2. Adverse events were mostly mild-to-moderate in intensity and were consistent with the known safety profiles of the individual medications. No transition (from prior ADT treatment)- or time-related trends in clinical laboratory tests, vital sign measurements, or ECG parameters were observed. Mean testosterone concentrations remained below castration levels. CONCLUSIONS: Combination therapy of relugolix and abiraterone or apalutamide was associated with a favorable safety and tolerability profile consistent with the known profiles of the individual medications. Castration levels of testosterone were maintained after transitioning to relugolix from other ADTs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04666129.

Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial.

BACKGROUND: Prostate cancer (PCa) patients with pathogenic/likely pathogenic germline variants (PGVs) in cancer predisposition genes may be eligible for U.S. Food and Drug Administration-approved targeted therapies, clinical trials, or enhanced screening. Studies suggest that eligible patients are missing genetics-informed care due to restrictive testing criteria. OBJECTIVE: To establish the prevalence of actionable PGVs among prospectively accrued, unselected PCa patients, stratified by their guideline eligibility. DESIGN, SETTING, AND PARTICIPANTS: Consecutive, unselected PCa patients were enrolled at 15 sites in the USA from October 2019 to August 2021, and had multigene cancer panel testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correlates between the prevalence of PGVs and clinician-reported demographic and clinical characteristics were examined. RESULTS AND LIMITATIONS: Among 958 patients (median [quartiles] age at diagnosis 65 [60, 71] yr), 627 (65%) had low- or intermediate-risk disease (grade group 1, 2, or 3). A total of 77 PGVs in 17 genes were identified in 74 patients (7.7%, 95% confidence interval [CI] 6.2-9.6%). No significant difference was found in the prevalence of PGVs among patients who met the 2019 National Comprehensive Cancer Network Prostate criteria (8.8%, 43/486, 95% CI 6.6-12%) versus those who did not (6.6%, 31/472, 95% CI 4.6-9.2%; odds ratio 1.38, 95% CI 0.85-2.23), indicating that these criteria would miss 42% of patients (31/74, 95% CI 31-53%) with PGVs. The criteria were less effective at predicting PGVs in patients from under-represented populations. Most PGVs (81%, 60/74) were potentially clinically actionable. Limitations include the inability to stratify analyses based on individual ethnicity due to low numbers of non-White patients with PGVs. CONCLUSIONS: Our results indicate that almost half of PCa patients with PGVs are missed by current testing guidelines. Comprehensive germline genetic testing should be offered to all patients with PCa. PATIENT SUMMARY: One in 13 patients with prostate cancer carries an inherited variant that may be actionable for the patient's current care or prevention of future cancer, and could benefit from expanded testing criteria.

Metastatic esophageal cancer presenting as bladder mass, a case report.

Metastatic esophageal cancer to urinary bladder is extremely rare and presents as an extremely poor prognosis. Herein, we describe the case of a 68 year-old female with history of resected adenocarcinoma of gastroesophageal junction in remission, who presented with gross hematuria and a bladder lesion. The patient underwent resection of the mass with final pathology consistent with metastatic adenocarcinoma of gastroesophageal junction.

Factors Influencing Fluoroscopy Use During Ureteroscopy at a Residency Training Program.

Introduction: Ionizing radiation is used throughout urologic surgery and is known to cause a greater cancer risk with increasing exposure. The International Commission on Radiological Protection states that "it is the control of radiation dose that is important, no matter the source." However, there are few reports on the amount of radiation used by urology residents during ureteroscopy (URS). We present the largest database evaluating fluoroscopy (fluoro) use during URS at a resident training program. Our objective is to assess the amount of fluoro use at varying levels of experience and to identify factors that lead to increased fluoro use. Methods: Retrospective data from 242 URSs performed at two resident training sites were collected. In total, 105 surgeries were done by two attending physicians without and 137 surgeries with residents (Uro1-Uro3). Patient data were collected from the electronic medical record. Statistical analyses included analysis of variance, Spearman correlations, and multiple linear regression (MLR). Results: Comparisons between years 1 and 2 revealed significantly (p < 0.05) decreased fluoro time (20.0 seconds) and operative time (OT) (12.2 minutes) for the year 2 resident. Total OT was significantly (p < 0.05) decreased (11.1 minutes) for attending physicians operating on their own compared with a year 1 resident. Significant (p < 0.05) correlations with fluoro time were demonstrated for OT, stone size, ureteral dilation, ureteral access sheath use, presence of a preoperative stent, resident year, and resident month. OT, ureteral dilation, and a preoperative stent placement were significant predictors of fluoro time on MLR (p < 0.05). Conclusion: Fluoro time during retrograde URS was significantly reduced as residents gained more experience in the operating room. An increase in fluoro time was also associated with ureteral dilation, access sheath use, increasing stone size, and lack of prestenting. With knowledge of these factors, emphasis can be placed on using and teaching techniques that limit radiation exposure.

Impact of COVID-19 on Initial Management and Evaluation of Prostate Cancer.

INTRODUCTION: The COVID-19 pandemic starkly affected all aspects of health care, forcing many to divert resources towards emergent patient needs while decreasing emphasis on routine cancer care. We compared prostate cancer care before and during the pandemic in a multi-institutional cohort. METHODS: A prospective regional collaborative was queried to assess practice pattern variations relative to the initial COVID-19 lockdown (March 16 to May 15, 2020). The preceding 10 months were selected for comparison. The impact of the lockdown was evaluated on the basis of 1) weekly trends in biopsy and radical prostatectomy volumes, 2) comparisons between those undergoing prostate biopsy, and 3) clinicopathological characteristics within radical prostatectomy patients. Categorical variables were compared using Fisher's exact and Pearson's chi-square tests, and Wilcoxon rank sum test to evaluate continuous covariates. RESULTS: Overall, there was a 55% and 39% decline in biopsy and prostatectomy volumes, respectively. During the pandemic, biopsy patients were younger with fewer COVID-19 severity risk factors (17.0% vs 9.7% no risk factors, p=0.023) and prostatectomy patients had higher grade group (GG; 45.6% >GG 4 vs 28%, p=0.01). Large variation in the change in procedural volume was noted across practice sites. CONCLUSION: In a multi-institutional assessment of surgical and diagnostic delay for prostate cancer, we found a non-uniform decline in procedural volume across sites. Future analyses within this cohort are needed to further discern the effects of care delays related to COVID-19.

Assessment of Prostate Cancer Treatment Among Black and White Patients During the COVID-19 Pandemic.

Importance: Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown. Objective: To assess the association between race and PCa care delivery for Black and White patients during the first wave of the COVID-19 pandemic. Design, Setting, and Participants: This multicenter, regional, collaborative, retrospective cohort study compared prostatectomy rates between Black and White patients with untreated nonmetastatic PCa during the COVID-19 pandemic (269 patients from March 16 to May 15, 2020) and prior (378 patients from March 11 to May 10, 2019). Main Outcomes and Measures: Prostatectomy rates. Results: Of the 647 men with nonmetastatic PCa, 172 (26.6%) were non-Hispanic Black men, and 475 (73.4%) were non-Hispanic White men. Black men were significantly less likely to undergo prostatectomy during the pandemic compared with White patients (1 of 76 [1.3%] vs 50 of 193 [25.9%]; P < .001), despite similar COVID-19 risk factors, biopsy Gleason grade groups, and comparable prostatectomy rates prior to the pandemic (17 of 96 [17.7%] vs 54 of 282 [19.1%]; P = .75). Black men had higher median prostate-specific antigen levels prior to biopsy (8.8 ng/mL [interquartile range, 5.3-15.2 ng/mL] vs 7.2 ng/mL [interquartile range, 5.1-11.1 ng/mL]; P = .04). A linear combination of regression coefficients with an interaction term for year demonstrated an odds ratio for likelihood of surgery of 0.06 (95% CI, 0.01-0.35; P = .002) for Black patients and 1.41 (95% CI, 0.81-2.44; P = .23) for White patients during the pandemic compared with prior to the pandemic. Changes in surgical volume varied by site (from a 33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery caring for a greater proportion of Black patients. Conclusions and Relevance: In this large multi-institutional regional collaborative cohort study, the odds of PCa surgery were lower among Black patients compared with White patients during the initial wave of the COVID-19 pandemic. Although localized PCa does not require immediate treatment, the lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.