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Abstract Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function. Significance: Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance. See related commentary by Finch and Baena, p. 2132. This article is highlighted in the In This Issue feature, p. 2113

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-17 EXPLORING THE ASSOCIATION OF ANDROGEN MODULATION THERAPY AMONG MEN HOSPITALIZED WITH COVID19: A RETROSPECTIVE OBSERVATIONAL STUDY Albert Ha, Nahid Punjani, Vinson Wang, Joseph Caputo, Brendan K Wallace, Luis Pina, Valary Raup, Philip Li, James McKiernan, and Joseph Alukal Albert HaAlbert Ha , Nahid PunjaniNahid Punjani , Vinson WangVinson Wang , Joseph CaputoJoseph Caputo , Brendan K WallaceBrendan K Wallace , Luis PinaLuis Pina , Valary RaupValary Raup , Philip LiPhilip Li , James McKiernanJames McKiernan , and Joseph AlukalJoseph Alukal View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.17AboutPDF Cite Export CitationSelect Citation formatNLMIEEEACMAPAChicagoMLAHarvardTips on citation downloadDownload citationCopy citation ToolsAdd to favoritesTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While primarily associated with prostate cancer pathogenesis, TMPRSS2 has recently been identified as a co-receptor for ACE2, the target protein used by SARS-CoV2 for viral entry. This protein is primarily regulated by the androgen receptor, and this mechanism may partly explain the disproportionate burden of disease among males. We hypothesized that the use of androgen modulation therapies (AMT) such as 5-a-reductase inhibitors (5-ARI) and androgen deprivation therapy (ADT) may affect inpatient outcomes among hospitalized men with COVID-19. METHODS: In a single-center retrospective analysis in a large urban hospital system, hospitalized males with laboratory-confirmed diagnosis of COVID-19 and a history of benign prostatic hyperplasia (BPH) and/or prostate cancer was identified from February to June 2020. Men were then stratified by use of specific AMT (ADT or 5-ARI). Baseline patient and hospital characteristics were analyzed using descriptive statistics, and multivariable regression models were used to explore the association of AMT with inpatient mortality, length of hospital stay (LOS), and other ICU outcomes (ICU admission, ICU Length of Stay, Non-Invasive Mechanical Ventilation, Intubation, and ARDS). RESULTS: A total of 396 inpatients were identified, with 130 (32.8%) having prior use of AMT. Of these, a large majority used 5-ARI (n=122, 93.8%). Mean (SD) age of patients was higher for those using AMT (76.5 (10.7) vs. 71.1 (11.8) years; p<0.001). No significant differences were identified in AMT use by race, body mass index, smoking status, or Charlson Comorbidity Index. Despite adjustment for these factors, AMT use was not associated with ICU admission, ventilation status, length of ICU stay, or length of hospital stay. However, a non-significant trend of decreased mortality was identified with the use of AMT (adjusted OR: 0.56; 95% CI: 0.29–1.02; p=0.06) (Table 1). CONCLUSIONS: Preliminary analysis suggests that AMT does not appear to improve inpatient outcomes among hospitalized males with COVID-19. The non-significant trend of decreased inpatient mortality, however, may be attributed to insufficient power. Future research with large sample sizes may uncover potential benefits of androgen modulation on COVID19 pathogenesis and outcomes. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e642-e642 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Metrics Author Information Albert Ha More articles by this author Nahid Punjani More articles by this author Vinson Wang More articles by this author Joseph Caputo More articles by this author Brendan K Wallace More articles by this author Luis Pina More articles by this author Valary Raup More articles by this author Philip Li More articles by this author James McKiernan More articles by this author Joseph Alukal More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: Growing evidence suggests a possible sex disparity in COVID-19 disease related outcomes. Objective: To explore the sex disparity in COVID-19 cases and outcomes using New York City (NYC) population level data. Setting: NYC surveillance data from February 29 to June 12, 2020. Participants: Individuals tested for COVID-19 in metropolitan NYC. Outcome Measurements and Statistical Analysis: Outcomes of interest included rates of COVID-19 case positivity, hospitalization and death. Relative risks and case fatality rates were computed for all outcomes based on sex and were stratified by age groups. Results and Limitations: 911,310 individuals were included, of whom 434,273 (4765%) were male and 477,037 (52.35%) were female. Men represented the majority of positive cases (n=106,275, 51.36%), a majority of hospitalizations (n=29,847, 56.44%), and a majority of deaths (n=13,054, 59.23%). Following population level adjustments for age and sex, testing rates of men and women were equivalent. The majority of positive cases and hospitalizations occurred in men for all age groups except age >75 years, and death was more likely in men of all age groups. Men were at a statistically significant greater relative risk of case positivity, hospitalization, and death across all age groups except those <18 years of age. The most significant difference for case positivity was observed in the 65-74 age group (RR 1.22, 95%CI 1.19-1.24), for hospitalization in the 45-65 age group (RR 1.85, 95% 1.80-1.901, and for death in the 18-44 age group (RR 3.30, 95% CI 2.82-3.87). Case fatality rates were greater for men in all age-matched comparisons to women. Limitations include the use of an evolving surveillance data set and absence of further demographic characteristics such as ethnographic data. Conclusion: Men have higher rates of COVID-19 positivity, hospitalization, and death despite greater testing of women; this trend remains after stratification by age.

Background While direct-to-consumer (DTC) medical advertising can provide useful information, it also risks oversimplification and being misleading. For an abbreviated prostate cancer treatment regimen called “ultrahypofractionation” (UHF), advertising has been used for CyberKnife (CK), a common delivery system for stereotactic body radiation therapy. We hypothesized that those viewing an advertisement for CK versus factual information would have inaccurate impressions of effectiveness and safety. Methods 400 men aged 40–80 were randomly assigned to one of four arms: a de-identified CK advertisement, the same advertisement with disclaimers, scientific information obtained from review of contemporary peer-reviewed literature, and a control. Subjects answered questions regarding risks/benefits of CK and likelihood of pursuing CK versus other treatments. Regression analysis was performed to determine factors associated with CK preference. Results 400 men were included. Compared to controls, those who viewed any of the three interventions were more likely to pursue CK over other treatments ( p < 0.01), with a greater increase in the advertisement groups. Respondents who viewed scientific information were less likely to agree CK is superior regarding impotence and urinary dysfunction. Disclaimers decreased positive impressions of CK’s side effects, but not effectiveness. Both advertisement and advertisement with disclaimer respondents were more likely to consider CK superior. Conclusions DTC medical advertisements can be misleading and impact laypersons’ impressions. In this case, viewing an advertisement created inaccurate impressions regarding effectiveness and safety of UHF for prostate cancer.

You have accessJournal of UrologyProstate Cancer: Detection & Screening IV (MP56)1 Apr 2020MP56-08 MPMRI PROSTATE LESION SIZE AS A PREDICTOR OF PROSTATE CANCER DETECTION ON MRI/US FUSION PROSTATE BIOPSY Luis A Pina*, Joseph M Caputo, Elizabeth M Sebesta, Sven Wenske, Hiram Shaish, and Gen Li Luis A Pina*Luis A Pina* More articles by this author , Joseph M CaputoJoseph M Caputo More articles by this author , Elizabeth M SebestaElizabeth M Sebesta More articles by this author , Sven WenskeSven Wenske More articles by this author , Hiram ShaishHiram Shaish More articles by this author , and Gen LiGen Li More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000925.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in prostate cancer (PCa) diagnosis. MRI/ultrasound (US) fusion biopsy (FBx) technology can target suspicious lesions noted on pre-biopsy mpMRI. It seems intuitive that larger lesions on mpMRI would be easier for the urologist to target on and therefore result in an increased PCa detection rate; however this has not been previously reported. Therefore, this study’s objective was to determine whether purely the size of a lesion on mpMRI would be predictive of PCa detection. METHODS: We retrospectively reviewed patients who underwent FBx from 7/2017 to 8/2019. Patient pre-biopsy prostate specific antigen (PSA) and lesion characteristics, including lesion dimensions and Prostate Imaging Reporting and Data System (PI-RADS) v2 score were noted and compared to final lesion biopsy pathology results. Multivariate logistic regression used to determine pre-biopsy factors independently associated with PCa detection on FBx. RESULTS: A total of 349 mpMRI lesions were included. Median PSA at biopsy was 6.0 (1.5-84) ng/ml. Median lesion size was 254 (28.6-5024) mm2. . A total of 40 out of the 349 (11.5%) lesions were reported as PI-RADS 2, 94 (26.9%) PI-RADS 3, 138 (39.5%) PI-RADS 4, and 76 (21.8%) PI-RADS 5. There were 151 (43.3%) lesions positive for PCa on final pathology, including 60 (39.7%) lesions with Grade Group (GG) 2 disease and 60 (39.7%) GG3 disease or higher. On regression analysis, higher pre-biopsy PSA and higher PI-RADS were significant independent predictors of detecting PCa on final pathology of lesion biopsy; with each unit increase in PSA the odds of a positive biopsy increased 1.05 times (p=0.023); with each unit increase in PI-RADS score the odds of a positive biopsy increased 2.18 times (p<0.001). Larger lesion area did not significantly predict positive lesion biopsy result in this cohort. CONCLUSIONS: There was no association between larger lesion area and PCa detection, suggesting small lesions can be accurately targeted on MRI/US fusion biopsy. It remains to be studied though whether larger lesions require higher numbers of biopsy cores due to potential higher chance for heterogeneity within larger lesions (concordance between biopsy cores). Source of Funding: N/A © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e850-e850 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luis A Pina* More articles by this author Joseph M Caputo More articles by this author Elizabeth M Sebesta More articles by this author Sven Wenske More articles by this author Hiram Shaish More articles by this author Gen Li More articles by this author Expand All Advertisement PDF downloadLoading ...

The goal of the current study was to evaluate the effect of a standardized prostate mpMRI reporting template on urologists’ understanding and confidence in counselling a patient on the results of the MRI. To do this we performed a survey study to assess the understanding and confidence of urologists reviewing reports prior to (pre) and after (post) adoption of a standardized mpMRI template. Six urologists reviewed ten pre- and post- mpMRI templated reports and completed a survey to assess the clarity of key elements and the confidence in counseling the patient. The urologists were blinded to the study objective. Nonparametric constrained permutation test for significance was performed to compare the results prior to and after implementation of the template. 29 pre- and 30 post-template mpMRI reports were reviewed. The average score for the post-template reports was significantly higher (10.7 ± 0.6 vs 7.5 ± 2.7 [ p< 0.001]) regardless of the reviewer. Urologists were also overall more confident in counselling patients when the standardized mpMRI reporting template had been used. Implementation of a standardized template for reporting of prostate mpMRI findings resulted in improved clarity and confidence in counselling patients. Radiologists should consider implementing a standardized reporting template to improve clinicians’ understanding and confidence of the report.

You have accessJournal of UrologyInfertility: Epidemiology & Evaluation I (MP26)1 Apr 2020MP26-16 MISMATCH BETWEEN ATTITUDES TOWARDS FERTILITY AND CLINICAL CARE FOR FERTILITY PRESERVATION IN TRANSGENDER WOMEN: DATA FROM PROJECT AFFIRM Denise Asafu-Adjei*, Joseph M. Caputo, Walter O. Bockting, Jonathan Diah, Joseph Alukal, and Peter J. Stahl Denise Asafu-Adjei*Denise Asafu-Adjei* More articles by this author , Joseph M. CaputoJoseph M. Caputo More articles by this author , Walter O. BocktingWalter O. Bockting More articles by this author , Jonathan DiahJonathan Diah More articles by this author , Joseph AlukalJoseph Alukal More articles by this author , and Peter J. StahlPeter J. Stahl More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000865.016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 1.4 million U.S. adults identify as transgender. Attitudes and knowledge about fertility preservation among transgender women (male sex at birth, but the gender identify is woman) have not been rigorously studied. Moreover, it is not clear to what extent healthcare providers follow recommendations from the World Professional Association for Transgender Health (WPATH) to discuss fertility preservation prior to initiation of gender affirming hormonal or surgical therapies that can permanently impact fertility. The objectives of the current study were to describe attitudes towards fertility amongst transgender women, and to explore the extent to which fertility preservation was offered to these patients in their clinical care. METHODS: A non-randomized survey about fertility and clinical experiences with fertility preservation was developed and distributed to transgender women participating at the Columbia University site of Project AFFIRM, an NIH funded multi-institutional study of transgender identity and health in the U.S. When applicable, data was supplemented with patient interviews. Data were analyzed with descriptive statistics. RESULTS: There were 133 participants in this study, average age 34.5 ± 13.6. 37.1% of patients reported a desire to have children in the future, with 15.9% expressing they would possibly like to have children in the future. 21.4% stated it was very important for them to have biological children. 78% of patients were taking gender-affirming hormonal therapy at the time of the survey. 81% of respondents had not taken steps to preserve their fertility. Only 16.5% of transgender women had seen a provider for issues pertaining to reproductive health. Of those who had seen someone, only 6 had been evaluated by a urologist (4.5%). 61% of patients stated that no health care provider discussed sperm banking prior to gender affirming hormone therapy or surgery. 5.5% (7) of patients had undergone sperm retrieval surgery for banking. CONCLUSIONS: This is the first large-scale study examining attitudes towards fertility and clinical practices pertaining to fertility preservation in transgender women. 53% of transgender women indicated that they were definitely or possibly interested in having children, but 61% reported that they had not been offered fertility preservation prior to initiation of gender affirming hormonal or surgical therapies. Efforts to educate providers and patients about fertility preservation in this population could address this clear and important gap in clinical care. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e406-e407 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Denise Asafu-Adjei* More articles by this author Joseph M. Caputo More articles by this author Walter O. Bockting More articles by this author Jonathan Diah More articles by this author Joseph Alukal More articles by this author Peter J. Stahl More articles by this author Expand All Advertisement PDF downloadLoading ...

INTRODUCTION AND OBJECTIVE: In 2012, the United States Preventive Services Task Force (USPSTF) issued guidelines discouraging screening for prostate cancer using prostate specific antigen (PSA). We evaluated trends in our biopsy practices during this time period, with the hypothesis that criteria for biopsy became increasingly stringent, and there was a shift in diagnosis from low risk to higher risk disease. METHODS: We queried our institution’s electronic medical record for transrectal ultrasound-guided prostate biopsies (CPT code 55700) from 2012-2017. Patient and biopsy parameters (age, PSA, standard vs. MRI fusion biopsy, Grade Group [GG]), were recorded. Biopsies for PSA >50 ng/mL or those done for surveillance were excluded. Chi-square correlation assessed differences between % clinically significant prostate cancer (csPCa, defined as GG ≥ 2) and %GG1 diagnosis between 2012 and 2017. Multivariate logistic regression assessed predictors of csPCa as well as clinically insignificant prostate cancer (GG1). RESULTS: A total of 1,031 prostate biopsies were reviewed, and 927 were retained as initial diagnostic biopsies. Overall, PSA increased 0.35 ng/mL/year. The %csPCa increased from 20% in 2012 to 43% in 2017 (p < 0.001) while the %GG1 decreased from 23% to 11% (p = 0.004). On multivariable logistic regression, year was a significant independent predictor of csPCa (OR 1.13, p = 0.016). Year was also an independent predictor of GG1 disease with a 14% decreased odds of GG1 diagnosis with each additional year (OR 0.86, p=0.013). CONCLUSIONS: In the post-2012 era, there has been migration in prostate biopsy outcomes from low risk to higher risk disease. Rising PSA for biopsied patients during this time reflects more stringent criteria for biopsy. While less diagnosis of low grade disease (“overdiagnosis”) is a desirable outcome, increased detection of high grade disease is potentially worrisome. The effects of these shifts on prostate cancer mortality and advanced disease will become evident over time.Source of Funding: None.

INTRODUCTION No-show appointments can weigh heavily on a urology practice's finances and productivity. Our objective was to investigate if a relationship existed between lag time and no-show appointments at the Columbia University Medical Center department of urology. METHODS We queried adult new patient appointments from July 2017 to July 2018 and excluded rescheduled or cancelled visits. We organized appointments by subspecialty training/practice of the urologist (general urology, voiding dysfunction/female urology, male sexual dysfunction/infertility, urological oncology, endourology and reconstructive urology). We performed logistic regression analysis to determine the relationship between lag time and no-show rate. We did the same for age and gender. We also organized lag time into 4 categories (less than 3 days, 3 to 7 days, 8 to 14 days, more than 14 days) and performed a goodness of fit test for no-show rates. RESULTS A total of 6,060 new patient appointments were scheduled from July 2017 to July 2018. The no-show rate was 14.3% (865 patients). Each daily increase in lag time resulted in a 2% rise in the odds of no-shows for the overall practice (OR 1.02). There were similar results for sexual dysfunction (OR 1.03), general urology (OR 1.02), oncology (OR 1.02) and voiding dysfunction (OR 1.01). There was a positive correlation with increasing lag time category and no-show rates for all subspecialties (R2 >0.80) except reconstructive urology (R2=0.68). Each increase in age resulted in a 2% rise in the odds of no-shows (OR 0.98). CONCLUSIONS Lag time for new patient visits is highly correlated with no-show rates, with a 2% rise in the odds of a no-show with each daily increase in lag time. Increasing age also demonstrated a correlation with no-show rates. Practice interventions to reduce lag time will hopefully reduce no-show rates.

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Quality Improvement & Patient Safety III (PD53)1 Apr 2019PD53-01 INCREASED WAIT TIMES FOR NEW PATIENTS MAY RESULT IN DECREASED UROLOGIST PRODUCTIVITY Joseph M. Caputo*, Elisabeth M. Sebesta, Christopher R. Haas, Matthew P. Rutman, and Kimberly L. Cooper Joseph M. Caputo*Joseph M. Caputo* More articles by this author , Elisabeth M. SebestaElisabeth M. Sebesta More articles by this author , Christopher R. HaasChristopher R. Haas More articles by this author , Matthew P. RutmanMatthew P. Rutman More articles by this author , and Kimberly L. CooperKimberly L. Cooper More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556969.54934.43AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: No-show appointments weigh heavily, leading to under-utilized resources and decreased productivity for urologists. There is concern that increased lag-time (time between scheduling date and appointment date) results in higher no-show rates. We sought to investigate if there was a relationship between lag-time and no-show appointments at Columbia University Medical Center Department of Urology. METHODS: We queried new-patient appointments from 7/2017-7/2018 and excluded rescheduled and cancelled visits. We organized the appointments by sub-specialty training/practice of the urologist (general urology, voiding dysfunction/female urology, sexual dysfunction/infertility, uro-oncology, endo-urology, and reconstructive urology). We performed logistic regression analysis using daily increase as the predictor to determine the relationship between lag-time and no-show rate. We also organized lag-time into 4 categories (<3 days, 3-7 days, 8-14 days, >14 days) and calculated percentage of no-show appointments for each sub-specialty within each category and performed a goodness of fit model. RESULTS: A total of 6060 new-patient appointments were scheduled from 7/2017-7/2018. The overall no-show rate was 14.3% (865/6060). Longer lag-time resulted in statistically higher no-show rates on logistic regression for the overall practice (OR=1.02), sexual dysfunction (OR=1.03), general urology (OR=1.02), oncology (OR=1.02), and voiding dysfunction (OR=1.01) (Table). There was a positive correlation with increasing lag-time category and no-show rates for all sub-specialties (Figure). R2>0.80 for each sub-specialty, except reconstructive urology (R2=0.68). CONCLUSIONS: Lag-time for new-patient visits is highly correlated with no-show rates. We detected a difference at the daily level with a 2% increase in the odds of a no-show with each day increase in lag-time. These findings advocate a role for ancillary providers for follow-up visits which may decrease lag-time for new-patient appointments with physicians and decrease overall no-show rates. Source of Funding: None New York, NY© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e930-e930 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph M. Caputo* More articles by this author Elisabeth M. Sebesta More articles by this author Christopher R. Haas More articles by this author Matthew P. Rutman More articles by this author Kimberly L. Cooper More articles by this author Expand All Advertisement PDF downloadLoading ...