Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Mechanism of action of nadofaragene firadenovec-vncg.

Effective bladder-preserving therapeutic options are needed for patients with bacillus Calmette-Guérin unresponsive non-muscle-invasive bladder cancer. Nadofaragene firadenovec-vncg (Adstiladrin®) was approved by the US Food and Drug Administration as the first gene therapy in urology and the first intravesical gene therapy indicated for the treatment of adult patients with high-risk bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors. The proposed mechanism of action underlying nadofaragene firadenovec efficacy is likely due to the pleiotropic nature of interferon-α and its direct and indirect antitumor activities. Direct activities include cell death and the mediation of an antiangiogenic effect, and indirect activities are those initiated through immunomodulation of the innate and adaptive immune responses. The sustained expression of interferon-α that results from this treatment modality contributes to a durable response. This review provides insight into potential mechanisms of action underlying nadofaragene firadenovec efficacy.

Dissemination of Circulating Tumor Cells in Breast and Prostate Cancer: Implications for Early Detection.

Burgeoning evidence suggests that circulating tumor cells (CTCs) may disseminate into blood vessels at an early stage, seeding metastases in various cancers such as breast and prostate cancer. Simultaneously, the early-stage CTCs that settle in metastatic sites [termed disseminated tumor cells (DTCs)] can enter dormancy, marking a potential source of late recurrence and therapy resistance. Thus, the presence of these early CTCs poses risks to patients but also holds potential benefits for early detection and treatment and opportunities for possibly curative interventions. This review delves into the role of early DTCs in driving latent metastasis within breast and prostate cancer, emphasizing the importance of early CTC detection in these diseases. We further explore the correlation between early CTC detection and poor prognoses, which contribute significantly to increased cancer mortality. Consequently, the detection of CTCs at an early stage emerges as a critical imperative for enhancing clinical diagnostics and allowing for early interventions.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part II: Considerations for a Prostate Biopsy.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part II of a two-part series focusing on initial and repeat biopsies, and biopsy technique. Please refer to Part I for discussion of initial prostate cancer screening recommendations. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsies, and biopsy technique. CONCLUSIONS: The evaluation of prostate cancer risk should be focused on the detection of clinically significant prostate cancer (Grade Group 2 or higher [GG2+]). The use of laboratory biomarkers, prostate MRI, and biopsy techniques described herein may improve detection and safety when a prostate biopsy is deemed necessary following prostate cancer screening.

Early Detection of Prostate Cancer: AUA/SUO Guideline Part I: Prostate Cancer Screening.

PURPOSE: The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. RESULTS: The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique. CONCLUSIONS: Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.

Discrimination of Sexual and Gender Minority Patients in Prostate Cancer Treatment: Results from the Restore-1 Study.

This study is the first to quantify experiences of discrimination in treatment undertaken by sexual and gender minority prostate cancer patients. Participants were 192 gay and bisexual and one transgender prostate cancer patients living in the US recruited from North America's largest online cancer support group. In this online survey, discrimination in treatment was measured using the Everyday Discrimination Scale (EDS), adapted for medical settings. Almost half (46%) endorsed at least one item, including 43% that the provider did not listen, 25% that they were talked down to, 20% that they received poorer care than other patients, 19% that the provider acted as superior, and 10% that the provider appeared afraid of them. While most (26.3%) rated the discrimination as "rare" or "sometimes" (EDS=1-3), 20% reported it as more common (EDS≥4). Most attributed the discrimination to their sexual orientation, or to providers being arrogant or too pushed for time. Discrimination was significantly associated with poorer urinary, bowel, and hormonal (but not sexual) EPIC function and bother scores, and with poorer mental health (SF-12). Those who had systemic/combined treatment (versus either radiation only or surgery only) were more likely to report discrimination. This study provides the first evidence that discrimination in prostate cancer treatment, including micro-aggressions, appear a common experience for gay and bisexual patients, and may result in poorer health outcomes.

Unrecognized sexual dysfunction in gay and bisexual men after prostate cancer treatment: the antecedents and impact of anodyspareunia.

BACKGROUND: Anodyspareunia may be an adverse outcome of prostate cancer (PCa) treatment for gay, bisexual, and other men who have sex with men (GBM). AIM: The aims of this study were to (1) describe the clinical symptoms of painful receptive anal intercourse (RAI) in GBM following PCa treatment, (2) estimate the prevalence of anodyspareunia, and (3) identify clinical and psychosocial correlates. METHODS: This was a secondary analysis of baseline and 24-month follow-up data from the Restore-2 randomized clinical trial of 401 GBM treated for PCa. The analytic sample included only those participants who attempted RAI during or since their PCa treatment (N = 195). OUTCOMES: Anodyspareunia was operationalized as moderate to severe pain during RAI for ≥6 months that resulted in mild to severe distress. Additional quality-of-life outcomes included the Expanded Prostate Cancer Index Composite (bowel function and bother subscales), the Brief Symptom Inventory-18, and the Functional Assessment of Cancer Therapy-Prostate. RESULTS: Overall 82 (42.1%) participants reported pain during RAI since completing PCa treatment. Of these, 45.1% experienced painful RAI sometimes or frequently, and 63.0% indicated that the pain was persistent. The pain at its worst was moderate to very severe for 79.0%. The experience of pain was at least mildly distressing for 63.5%. Painful RAI worsened for a third (33.4%) of participants after completing PCa treatment. Of the 82 GBM, 15.4% were classified as meeting criteria for anodyspareunia. Antecedents of anodyspareunia included a lifelong history of painful RAI and bowel dysfunction following PCa treatment. Those reporting symptoms of anodyspareunia were more likely to avoid RAI due to pain (adjusted odds ratio, 4.37), which was negatively associated with sexual satisfaction (mean difference, -2.77) and self-esteem (mean difference, -3.33). The model explained 37.2% of the variance in overall quality of life. CLINICAL IMPLICATIONS: Culturally responsive PCa care should include the assessment of anodyspareunia among GBM and explore treatment options. STRENGTHS AND LIMITATIONS: This is the largest study to date focused on anodyspareunia among GBM treated for PCa. Anodyspareunia was assessed with multiple items characterizing the intensity, duration, and distress related to painful RAI. The external validity of the findings is limited by the nonprobability sample. Furthermore, the cause-and-effect relationships between the reported associations cannot be established by the research design. CONCLUSIONS: Anodyspareunia should be considered a sexual dysfunction in GBM and investigated as an adverse outcome of PCa treatment.

The Effects of Prostate Cancer Treatment on Role-In-Sex in Gay and Bisexual Men: Mixed Methods Results from the Restore-1 and Restore-2 Studies.

Gay and bisexual men (GBM) with prostate cancer experience worse sexual and mental health outcomes following prostate cancer treatment than heterosexual men. Emerging evidence suggests that GBM may change their role-in-sex in response to treatment effects. The purpose of this study was to describe the impact of prostate cancer treatment on role-in-sex, to estimate the prevalence of such changes, and to determine the impact on quality of life and mental health. We conducted semi-structured interviews with 30 sexual minority prostate cancer patients. Then, we recruited 401 gay and bisexual prostate cancer patients into a study assessing the effects of rehabilitation. Qualitative data were analyzed using descriptive thematic analysis. Differences in quality of life and mental health outcomes were analyzed using multivariate analyses of variance. Prostate cancer treatment resulted in loss of role-in-sex for many patients. When changes in role-in-sex occurred, the shifts were predominantly from tops to bottoms. Those with a current top role-in-sex had significantly better sexual and mental health outcomes than either versatiles or bottoms. Clinical implications include the need for providers to ask about role-in-sex in order to address disparities in health outcomes by sexual orientation and to provide culturally appropriate care to sexual minority patients.

Race reporting and disparities regarding clinical trials in bladder cancer: a systematic review.

PURPOSE: To systematically review the literature to investigate racial disparities among bladder cancer clinical trial enrollees. METHODS: A systematic review was conducted using Ovid, MEDLINE® to identify clinical trials between 1970 and 2020. Articles were reviewed and were included if they assessed race in their outcomes reporting among bladder cancer patients enrolled in clinical trials. The review was conducted in accordance with the PRISMA statement. RESULTS: We identified 544 clinical trials meeting our initial search criteria, with only 24 (4.4%) studies reporting racial demographic data. Enrollees were largely Caucasian (81-98%), with a strikingly small proportion of enrolled patients consisting of African-Americans (2-8%) and Hispanics (2-5%). Only one of the studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups and performed analyses stratified by race. CONCLUSION: Race is poorly studied in bladder cancer clinical trials. Trial cohorts may not reflect multicultural populations. The potential association between race and efficacy, safety or tolerability of the tested interventions is unknown. Given the up to twofold increase in bladder cancer-specific death among African-Americans, further research is needed to address the impact of race in clinical trials, while encompassing socioeconomic factors and disease risk factor exposures.

Racial/Ethnic Differences in Health-Related Quality of Life Among Gay and Bisexual Prostate Cancer Survivors.

Introduction: Prostate cancer treatment has established effects on the health-related quality of life (HRQOL) of patients. While racial/ethnic differences in HRQOL have been explored in heterosexual patients, this is the first study to examine racial/ethnic differences in a cohort of sexual minority prostate cancer survivors. Methods: We used data from the Restore-1 study, an online cross-sectional survey of sexual and gender minority (SGM) prostate cancer survivors in North America, to explore the association between race/ethnicity and HRQOL. General mental and physical HRQOL was assessed using the Short-Form Health Survey version 2 (SF-12). The frequency and distress of prostate cancer specific symptoms was assessed using the Expanded Prostate Cancer Composite (EPIC) scale. Multivariable linear regression was used to estimate mean differences in HRQOL between sexual minority men of color and their white, non-Hispanic counterparts after adjustment for pertinent demographic and medical characteristics. Results: Among 190 participants, 23 (12%) self-identified as non-white and/or Hispanic. In unadjusted analysis, sexual minority men of color compared to their white counterparts reported worse HRQOL scores in the EPIC hormonal summary (73.8 vs. 81.8) and hormonal function (70.9 vs 80.5) domains. Clinically important differences between men of color and their white counterparts were seen in the EPIC bowel function (mean difference (MD): -4.5, 95% CI: -9.9, 0.8), hormonal summary (MD: -8.0, 95% CI: -15.6, -0.4), hormonal function (MD: -9.6, 95% CI: -17.6, -1.6), and hormonal bother (MD: -6.7, 95% CI: -14.4, 1.1) domains. After adjustment for covariates, clinically important differences persisted between men of color and white, non-Hispanic men on the hormonal summary (74.4 vs. 81.7), hormonal function (71.3 vs. 80.3), and hormonal bother (77.0 vs. 82.7) domains. Conclusions: This exploratory study provides the first evidence that sexual minority men of color may have worse HRQOL outcomes compared to white, non-Hispanic sexual minority men following prostate cancer treatment.

Prevalence and Risk Factors for Sexually Transmitted Infections in Gay and Bisexual Prostate Cancer Survivors: Results From the Restore-2 Study.

Background: Equitable cancer survivorship care for gay and bisexual male (GBM) prostate cancer survivors should be responsive to their sexual health needs. Rates of sexually transmitted infections (STIs) are higher among GBM compared to heterosexual men across the lifespan. In addition, evidence suggests that GBM will use a variety of strategies to cope with sexual dysfunction that may increase risk for STIs. The purpose of this study was to determine the prevalence of STIs following prostate cancer treatment among GBM and identify risk factors. Methods: In 2019, 401 GBM previously treated for prostate cancer were recruited into the Restore-2 Study. They completed a baseline online questionnaire with items assessing STIs diagnosed since being treated for prostate cancer. Any STI diagnoses was regressed on demographic, clinical, and relationship related variables using binary logistic regression. Results: Forty-five participants (11.4%) were diagnosed with an STI during or following their prostate cancer treatment. The mostly commonly diagnosed STI was syphilis (4.3%), followed by gonorrhoea (2.8%), and chlamydia (2.5%). Four participants were infected with HIV following their prostate cancer treatment. Independent risk factors for STI diagnosis included time since prostate cancer diagnosis (aOR = 1.18; 95% CI: 1.10-1.26), nonmonogamous sexual relationship (aOR = 11.23; 95% CI: 2.11-59.73), better sexual function (aOR = 1.02; 95% CI: 1.01-1.04), penile injection treatment (aOR = 3.28; 95% CI: 1.48-7.29), and multiple sex partners (aOR = 5.57; 95% CI: 1.64-18.96). Conclusions: GBM prostate cancer survivors are at risk for STIs. Culturally responsive STI prevention should be incorporated into cancer survivorship plans, particularly as men are treated for and regain sexual function over time.

The monetary costs of pediatric upper urinary tract stone disease: Analysis in a contemporary United States cohort.

INTRODUCTION: The prevalence of upper urinary tract stone disease (USD) in the United States is rising among both adults and children. Studies on the contemporary economic burden of USD management in the pediatric population are lacking. OBJECTIVE: To comprehensively analyze the economic impact of USD in a contemporary United States pediatric cohort, and to evaluate drivers of cost. STUDY DESIGN: A retrospective cohort study of pediatric patients (aged 0-17), diagnosed with USD between 2011 and 2018 were identified from PearlDiver-Mariner, an all-payer claims database containing diagnostic, treatment and prescription data provided in all treatment settings. Relevant International Classification of Disease (ICD-9 and ICD-10) and Current Procedural Terminology (CPT) codes were used for identification, and only patients with claims recorded for at least one year before and after entry of a diagnosis code for USD were selected (N = 10,045). Patients were stratified into those undergoing operative vs. non-operative management and for each patient, total 1-year healthcare costs following USD diagnosis, including same day and non-same day encounters, were analyzed. Factors associated with increased spending, as well as economic trends were analyzed. RESULTS: Overall, 8498 (85%) patients were managed non-operatively, while 1547 (15%) underwent a total of 1880 procedural interventions. Total overall cost was $117.1 million, while median annual expenditure was $15.8 million. Proportion of spending for outpatient, inpatient and prescription services was 52%, 32% and 16%, respectively (Table). Outpatient management accounted for 67% of overall spending. The proportion of patients managed non-operatively increased significantly over time, in parallel with spending for non-operative care. Comorbidity burden, treatment year and geographic region were among predictors of costs. DISCUSSION: Our study is the first to report actual insurance reimbursements for pediatric USD management using actual reimbursement data, examined across all treatment settings. We found that majority of the costs were for outpatient services and for non-operative management, with a rising tendency toward non-operative management over time. Regional variation in expenditures was evident. Specific reasons underlying these observed patterns could not directly be discerned from our dataset, but merit further investigation. CONCLUSION: Non-operative and outpatient management for pediatric USD are increasingly common, resulting in parallel shifts in spending. Notably, 52% of overall spending was for outpatient care. These insights into the contemporary economic burden of pediatric USD could provide value in shaping future healthcare policy.

Recruiting an underserved, difficult to reach population into a cancer trial: Strategies from the Restore-2 Rehabilitation Trial for gay and bisexual prostate cancer patients.

BACKGROUND/AIMS: Sexual minorities are small and under-researched populations that are at disproportionate risk for cancer and poor cancer outcomes. Described as a "hidden population," the principal research challenge has been to develop effective methods to identify and recruit such cancer patients into cancer studies. Online recruitment strategies, as well as targeted clinic recruitment using patient-entered sexual orientation and gender identity data from electronic medical records have potential to transform recruitment, but studies testing the effects of how to recruit using these have not been published. METHODS: In 2019, we conducted a naturalistic, three-arm, stratified prospective study to compare three recruitment strategies: (a) clinic based recruitment of prostate cancer patients from gay health and urology clinics; (b) directly from the gay community; and (c) online recruitment (through cancer support, sex/dating, and social sites). For each strategy, we estimated time, workload, and direct costs involved. To study how recruitment strategy may affect sampling, we tested for retention rates, demographic and outcome differences across sites. Using these methods, we successfully recruited 401 gay and bisexual prostate cancer patients into a randomized, controlled, 24-month trial testing an online sexual and urinary rehabilitation curriculum tailored for this population. RESULTS: There were seven key results. First, it is possible to recruit substantial numbers of sexual minority men into prostate cancer studies provided online recruitment methods are used. Second, we observed big differences in dropout during study onboarding by recruitment source. Third, within online recruitment, the online sex/dating application (app) was the most successful and efficient, followed by the cancer support site, and then the social networking site. Fourth, while clinics were the cheapest source of recruitment, they were time intensive and low in yield. Fifth, the cancer support site and sex/dating app recruits differed by several characteristics, with the former being more rehabilitation-focused while the latter were younger and more sexually active. Sixth, we found almost no differences in outcomes across the three online recruitment sites. Seventh, because retention in online studies has been a concern, we confirm very low attrition at 3- and 6 months into the trial. CONCLUSION: For sexual minority cancer research, more research on how to use sexual orientation and gender identity electronic medical record data for clinic-based recruitment is needed. For other small or hard-to-reach populations, researchers should compare and publish online versus offline recruitment strategies.

Health Disparities of Sexual Minority Patients Following Prostate Cancer Treatment: Results From the Restore-2 Study.

PURPOSE: The NIH has identified sexual and gender minority persons as a health disparity population but little is known about cancer outcomes in these populations. The purpose of this study was to identify disparities in sexual minority prostate cancer patient-reported outcomes, to examine within group differences, and to test for alternative explanations for identified differences. MATERIALS AND METHODS: In 2019, we recruited 401 gay and bisexual prostate cancer patients into the Restore-2 study, a randomized controlled trial of rehabilitation program tailored for sexual minority men. RESULTS: Compared to the normative (heterosexual) EPIC sample, participants had significantly worse urinary, bowel and hormonal function, better sexual function, and no difference on bother scores. They also had worse depression and overall mental health, and worse physical, social/family, functional, prostate specific and overall well-being quality of life outcomes. Across measures, no differences by age, gay versus bisexual orientation, race/ethnicity, and relationship status were observed. Those who had hormonal treatment had worse sexual and hormonal function than those who had radiation or surgery only. Those with a longer time since treatment had better urinary function. Differences remained when participants were matched to normative samples on cancer stage and time since treatment. CONCLUSIONS: This, the largest study of sexual minority prostate cancer patients to date, confirms health disparities in prostate cancer quality of life outcomes. Findings appear reliable and robust. To improve the clinical care of prostate cancer, it will be important to address the health disparities experienced by sexual minority prostate cancer patients.

Creation and Psychometric Validation of the Sexual Minorities and Prostate Cancer Scale (SMACS) in Sexual Minority Patients-The Restore-2 Study.

BACKGROUND: Existing measures of sexual functioning in prostate cancer survivors focus primarily on erectile function and do not adequately measure the experiences of sexual minority men. AIM: To develop and psychometrically evaluate a new scale to measure sexual functioning among sexual minority men with prostate cancer. METHODS: Sexual minority prostate cancer patients (n = 401) completed an online battery of urinary and sexual functioning tests in 2019, including a new 37-item instrument about their sexual functioning post-treatment for prostate cancer. OUTCOMES: We used confirmatory factor analysis to determine the construct validity of a new scale including five subscales: a four-factor model for all participants (n = 401) evaluated Sexual Satisfaction, Sexual Confidence, Frequency of Sexual Problems, and Urinary Incontinence in Sex. A single-factor model completed only by participants who had attempted or desired receptive anal sex (n = 255) was evaluated in the fifth subscale: Problematic Receptive Anal Sex. To evaluate criterion validity, we calculated the intercorrelations between each Sexual Minorities and Prostate Cancer Scale (SMACS) subscale and four related scales: the Expanded Prostate Cancer Index Composite-50 (EPIC), the Functional Assessment of Cancer Therapy-Prostate, the Brief Symptom Inventory-18, and the International Consultation on incontinence questionnaire. Cronbach's alphas were calculated to measure internal consistency (ie, reliability). RESULTS: Cronbach's alpha values ranged from 0.64 to 0.89. Loadings (0.479-0.926) and model fit indices were strong (Root Mean Square Error of Approximation: 0.085, Standardized root mean squared residual: 0.063, comparative fit index: 0.927, Tucker-Lewis Index: 0.907). For criterion validity, Sexual Satisfaction, Sexual Confidence, and Frequency of Sexual Problems were moderately correlated with EPIC function and bother scores (r = 0.50-0.72) and Urinary incontinence in sex correlated moderately with EPIC Urinary Function and International Consultation on incontinence questionnaire scores (0.45-0.56). CLINICAL IMPLICATIONS: The SMACS can be used by clinicians and researchers to comprehensively measure sexual functioning in sexual minority men, in conjunction with existing scales. STRENGTHS AND LIMITATIONS: This new scale is validated in a large, geographically diverse cohort of sexual minority cancer survivors and fills an important gap in existing measures of sexual functioning. Limitations include a lack of a validation sample. CONCLUSION: The SMACS is a valid and reliable new scale that measures sexual minority men's experience of urinary incontinence in sex, problematic receptive anal sex, and sexual distress. Polter EJ, Kohli N, Rosser BRS, et al. Creation and Psychometric Validation of the Sexual Minorities and Prostate Cancer Scale (SMACS) in Sexual Minority Patients-The Restore-2 Study. J Sex Med 2022;19:529-540.

Comparison of Robot-Assisted and Open Radical Cystectomy in Recovery of Patient-Reported and Performance-Related Measures of Independence: A Secondary Analysis of a Randomized Clinical Trial.

Importance: No data exist on time to recovery of patient-reported and performance-related measures of functional independence after radical cystectomy (open or robotic). Objective: To determine recovery of functional independence after radical cystectomy and whether robot-assisted radical cystectomy (RARC) is associated with any advantage over open procedures. Design, Setting, and Participants: Data for this secondary analysis from the RAZOR (Randomized Open vs Robotic Cystectomy) trial were used. RAZOR was a phase 3 multicenter noninferiority trial across 15 academic medical centers in the US from July 1, 2011, to November 18, 2014, with a median follow-up of 2 years. Participants included the per-protocol population (n = 302). Data were analyzed from February 1, 2017, to May 1, 2021. Interventions: Robot-assisted radical cystectomy or open radical cystectomy (ORC). Main Outcomes and Measures: Patient-reported (activities of daily living [ADL] and independent ADL [iADL]) and performance-related (hand grip strength [HGS] and Timed Up & Go walking test [TUGWT]) measures of independence were assessed. Patterns of postoperative recovery for the entire cohort and comparisons between RARC and ORC were performed. Exploratory analyses to assess measures of independence across diversion type and to determine whether baseline impairments were associated with 90-day complications or 1-year mortality were performed. Findings: Of the 302 patients included in the analysis (254 men [84.1%]; mean [SD] age at consent, 68.0 [9.7] years), 150 underwent RARC and 152 underwent ORC. Baseline characteristics were similar in both groups. For the entire cohort, ADL, iADL, and TUGWT recovered to baseline by 3 postoperative months, whereas HGS recovered by 6 months. There was no difference between RARC and ORC for ADL, iADL, TUGWT, or HGS scores at any time. Activities of daily living recovered 1 month after RARC (mean estimated score, 7.7 [95% CI, 7.3-8.0]) vs 3 months after ORC (mean estimated score, 7.5 [95% CI, 7.2-7.8]). Hand grip strength recovered by 3 months after RARC (mean estimated HGS, 29.0 [95% CI, 26.3-31.7] kg) vs 6 months after ORC (mean estimated HGS, 31.2 [95% CI, 28.8-34.2] kg). In the RARC group, 32 of 90 patients (35.6%) showed a recovery in HGS at 3 months vs 32 of 88 (36.4%) in the ORC group (P = .91), indicating a rejection of the primary study hypothesis for HGS. Independent ADL and TUGWT recovered in 3 months for both approaches. Hand grip strength showed earlier recovery in patients undergoing continent urinary diversion (mean HGS at 3 months, 31.3 [95% CI, 27.7-34.8] vs 33.9 [95% CI, 30.5-37.3] at baseline; P = .09) than noncontinent urinary diversion (mean HGS at 6 months, 27.4 [95% CI, 24.9-30.0] vs 29.5 [95% CI, 27.2-31.9] kg at baseline; P = .02), with no differences in other parameters. Baseline impairments in any parameter were not associated with 90-day complications or 1-year mortality. Conclusions and Relevance: The results of this secondary analysis suggest that patients require 3 to 6 months to recover baseline levels after radical cystectomy irrespective of surgical approach. These data will be invaluable in patient counseling and preparation. Hand grip strength and ADL tended to recover to baseline earlier after RARC; however, there was no difference in the percentage of patients recovering when compared with ORC. Further study is needed to assess the clinical significance of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT01157676.

Diagnosing Prostate Cancer: The Role of Intravesical Prostatic Gland Protrusion on Accuracy of Prostate Biopsies.

PURPOSE: We evaluated the association between intravesical prostate protrusion (IPP) and the detection rate of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion targeted biopsy (TB). MATERIALS AND METHODS: A total of 538 consecutive men who underwent MRI-TRUS fusion TB and concomitant systematic biopsy were evaluated. IPP on MRI was independently measured by 4 blinded reviewers. The primary outcome was per-lesion detection of csPCa on TB. We assessed the association between IPP and csPCa detection on TB, controlling for age, prostate specific antigen, Prostate Imaging Reporting and Data System® (PI-RADS®) score, prostate volume, targeted cores sampled and previous biopsy experience. RESULTS: A total of 847 PI-RADS 3 or greater lesions were targeted across 570 biopsies. Intra- and interrater reliability for measuring IPP was strong. A total of 81 (14.2%), 127 (22.3%), 237 (41.6%) and 125 (21.9%) men had 0, small, medium and large IPP, respectively. A total of 230, 392 and 196 lesions were PI-RADS 3, 4 and 5, respectively. Of the lesions 198 (34.7%) had csPCa on TB. The overall relationship between IPP size and csPCa found on TB was not significant; however, large IPP is associated with a significantly lower rate of csPCa detection than 0 IPP (p=0.007). Every mm increase in IPP is associated with a 5.6% decrease in the odds of csPCa detection on TB (p=0.004) and a 66.5% decrease in odds of detection in large IPP compared to 0 IPP (p=0.003). CONCLUSIONS: As the size of the IPP and volume increase, there is a decrease in the detection rate of csPCa on MRI-guided TB. These findings may be driven by poor MRI-TRUS co-registration and prostate asymmetry.

Contemporary Assessment of the Economic Burden of Upper Urinary Tract Stone Disease in the United States: Analysis of One-Year Health Care Costs, 2011-2018.

Background: The U.S. health care landscape has witnessed numerous changes since implementation of the Affordable Care Act coupled with rising prevalence of upper urinary tract stone disease (SD). Data on the economic burden of SD during this period are lacking, providing the objective of our study. Materials and Methods: Adults diagnosed as having SD from 2011 to 2018 were identified from PearlDiver Mariner, a national all-payer database reporting reimbursements and prescription costs for all health care encounters. Patients undergoing operative and nonoperative care were identified. Time trends in annual expenditures were evaluated. Multivariable analysis evaluated determinants of spending. Results: A total of $10 billion were spent on SD management between 2011 and 2018 (median overall annual expenditure = $1.4 billion) among 786,756 patients. Inpatient, prescription, and outpatient costs accounted for 34.7%, 20.7%, and 44.6% of expenditures, respectively. Seventy-eight percent of patients were managed nonoperatively (total cost = $6.9 billion). The average overall cost per encounter was $13,587 ($17,102 for surgical vs $11,174 for nonsurgical care). Expenditures on inpatient care decreased significantly over time, while expenditures on prescriptions and outpatient care increased significantly. On multivariable analysis, a higher Charlson Comorbidity Index (CCI) was associated with higher spending, while associations for age, insurance, and region varied by treatment modality. Conclusions: The economic burden of SD management is substantial, dominated by expenditure on nonoperative management and outpatient care. Expenditures for prescription and outpatient care are rising, with the only consistent predictor of higher spending being CCI. Spending variation according to demographic, clinical, and geographic factors was evident.

Pain and Loss of Pleasure in Receptive Anal Sex for Gay and Bisexual Men following Prostate Cancer Treatment: Results from the Restore-1 Study.

Prostate cancer treatments disrupt receptive anal intercourse (RAI) for gay and bisexual men (GBM). Sexual dysfunction following prostate cancer treatment may include severe pain in the anorectum during RAI (i.e., anodyspareunia). The purpose of this study was to explore the impact of prostate cancer and its treatments on RAI among GBM. Data were from a cross-sectional online survey of 100 GBM prostate cancer survivors who reported pleasurable RAI prior to treatment. Approximately 47% of the sample reported recent RAI, which was more common among GBM in long-term relationships. RAI was also associated with engagement in other sexual behaviors (e.g., oral and insertive anal sex). Anodyspareunia was reported by 23% of the men who had attempted recent RAI. Anodyspareunia was negatively associated with mental health, performing oral sex on a partner, and bowel function. The overwhelming majority received no information from their healthcare providers about loss of RAI function prior to prostate cancer treatment. Culturally responsive cancer survivorship care may need to address the loss of RAI function for GBM prostate cancer survivors.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.