NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation.

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.

Innovative standardized reporting template for prostate mpMRI improves clarity and confidence in the report.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Exposure to direct-to-consumer advertising is associated with overestimation of benefits regarding ultrahypofractionated radiation therapy for prostate cancer.

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.

Increased Time between Scheduling Date and Appointment Date Results in Increased No-Show Rates in the Academic Urology Practice.

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.

The Management of Newly-Diagnosed Non-muscle Invasive Bladder Cancer in Veterans Integrated Services Network 02 of the Veterans Health Administration.

INTRODUCTION: Over 1,500 bladder cancers were diagnosed among US Veterans in 2010, the majority of which were non-muscle invasive bladder cancer (NMIBC). Little is known about NMIBC treatment within the Veterans Health Administration. The objective of the study was to assess the quality of care for Veterans with newly-diagnosed NMIBC within Veterans Integrated Service Network (VISN) 02. MATERIALS AND METHODS: We used ICD-9 and ICD-10 codes to identify patients with newly-diagnosed bladder cancer from 1/2016-8/2017. We risk-stratified the patients into low, intermediate, and high-risk based on the 2016 American Urological Association Guidelines on NMIBC. Our primary objectives were percentages of transurethral resection of bladder tumors (TURBTs) with detrusor, repeat TURBT in high-risk and T1 disease, high-risk NMIBC treated with induction intravesical therapy (IVT), and responders treated with maintenance IVT. We performed logistic regression for association between distance to diagnosing hospital and receipt of induction IVT in high-risk patients. RESULTS: There were 121 newly-diagnosed NMIBC patients; 16% low-risk, 28% intermediate-risk, and 56% high-risk. Detrusor was present in 80% of all initial TURBTs and 84% of high-risk patients. Repeat TURBT was performed in 56% of high-risk NMIBC and 60% of T1. Induction IVT was given to 66% of high-risk patients and maintenance IVT was given to 59% of responders. On multivariate logistic regression, distance to medical center was not associated with receipt of induction IVT (OR = 0.99, 95% CI [0.97,1.01], p = 0.52). CONCLUSIONS: We observed high rates of sampling of detrusor in the first TURBT specimen, utilization of repeat TURBT, and administration of induction and maintenance intravesical BCG for high-risk patients among a regional cohort of US Veterans with NMIBC. While not a comparative study, our findings suggest high quality NMIBC care in VA VISN 02.