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The treatment landscape for advanced urothelial cancer has changed dramatically owing to the US Food and Drug Administration approval and introduction of antibody-drug conjugates (ADCs), including enfortumab vedotin and sacituzumab govitecan. Efforts have begun to use these therapies in earlier disease states, specifically bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). We assessed gene expression associated with these newly approved therapies in a novel cohort of treatment-naïve NMIBC tumors before and after BCG therapy. Multiple genes, including Nectin-4, Trop-2, and Her-2, exhibited increased expression after BCG therapy compared to baseline. However, few of the tumors with increased expression of ADC targets also exhibited increased PD-L1/PD-1 expression. Taken together, these data demonstrate the heterogeneous genomic landscape of BCG-exposed NMIBC, and provide evidence supporting the evaluation of ADCs in NMIBC. PATIENT SUMMARY: We evaluated the potential role of targeted therapies that have been approved in the USA for advanced non-muscle-invasive bladder cancer (NMIBC) that has recurred after treatment with bacillus Calmette-Guérin (BCG). By assessing levels of specific genes and proteins linked to the targeted therapies, we demonstrate that there is rationale for further evaluation of these therapies in NMIBC.

To assess the risk of new persistent opioid use in opioid-naïve men undergoing male fertility procedures DESIGN: Retrospective cohort study using a claims database SETTING: TriNetX Diamond Network - a database linking electronic medical record data and claims - assessing men undergoing fertility procedure between 2010 and 2021.Opioid-naïve men undergoing fertility procedures (open or laparoscopic varicocelectomy, spermatocele excision, testicular excisional or incisional biopsy) without further surgical intervention requiring anesthesia in the two years after the index procedure. Those with and without perioperative opioid prescriptions were propensity score matched on age, race/ethnicity, smoking status, mental health diagnoses, and preoperative pain diagnoses.Perioperative opioid prescription MAIN OUTCOME: Incidence of new persistent opioid use (opioid prescription 3 to 9 months after index fertility procedure). Secondary outcome was prolonged opioid use (opioid prescription 9 to 24 months after index fertility procedure).387,565 men undergoing fertility procedures were identified; of whom 25.1% received an opioid prescription. After propensity score matching, 97,215 men were included. 4.7% of men who received a perioperative opioid prescription developed new persistent opioid use compared with 2.2% of men without a perioperative opioid prescription (RR 2.16, 95% CI 2.05-2.27, Number Needed to Harm 39). When assessing each unique fertility procedure independently, men receiving perioperative opioids had statistically higher odds of developing new persistent opioid use for all procedure types. Men with new persistent opioid use were much more likely to go on and develop prolonged opioid use compared to men without new persistent opioid use.Opioid prescription after male fertility procedures is associated with significant risk of new persistent opioid use, emphasizing the importance of judicious opioid prescribing for male fertility procedures.

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome type III (CP/CPPS) is associated with pelvic pain, sexual dysfunction and irritative voiding. Sustained symptom relief has proven difficult with alpha blockers, antibiotics, and nonsteroidal anti-inflammatory drugs (NSAIDs). Phosphodiesterase type 5 (PDE5) inhibitors (PDE5is) have the potential to alleviate bladder urgency, relax the pelvic floor, and correct underlying erectile dysfunction; however, few studies have investigated the application of PDE5i’s to CP/CPPS. The purpose of this study was to assess the effect of long-term PDE5i therapy on symptoms among patients with diagnosed CP/CPPS. METHODS: A group of patients older than 18 years diagnosed with CP/CPPS presenting from 2009 to 2018 were followed prospectively while they were being prescribed off-label PDE5i therapy for symptoms. National Institute of Health chronic prostatitis symptom index (CPSI) scores before PDE5i therapy initiation and after at least 3 months were utilized to assess impact on symptoms. RESULTS: A total of 25 patients (mean age 44.4±12.9 years) met study criteria. The mean duration of PDE5i therapy was 1.3±1.6 years. Continued use of daily PDE5is was associated with significant decreases in total CPSI, pain, urinary symptom and quality of life scores [total CPSI: −12.8, standard deviation (SD) 9.5; pain: −6.1, SD 4.1; urinary symptoms: −2.4, SD 2.1; quality of life: −4.5, SD 3.9; P

INTRODUCTION AND OBJECTIVE:There remains little guidance on how to transition men with prostate cancer from active surveillance (AS) to watchful waiting (WW). We evaluated the predicted prostate ca...

INTRODUCTION AND OBJECTIVE: It was hypothesized that restrictions caused by COVID-19 (virtual interviewing, loss of away rotations) may cause a clustering of applicants matching in regions closer to where they were raised or attended medical school. We utilized data from the urology match to compare dispersal patterns between applicants matching during the COVID-19 cycle (2021) and those matching in the 5 prior application cycles (2016-2020). METHODS: Publicly available data was retrospectively collected on applicants who matched to urology residencies. Variables included longitude/latitude data for each home state, undergraduate institution, medical school, and residency. The primary endpoint was distance (miles, as the crow flies) between medical school and residency. Distances were calculated using haversine formula. Analyses were conducted using R statistics v4.04. Institutional review board approval was not required as data was public information (CFR 45x46.104). RESULTS: Of the 1,965 applicants matching between 2016- 2021, medical school was identified for 1,956 (99.7%) applicants, undergraduate program for 1,551 (79%) applicants, and home state for 1,351 (69%) applicants. Comparing the COVID-19 cycle to the 5 prior cycles (Table 1), there was no significant difference in the median distance between medical school and residency, undergraduate university and residency, or home state and residency. Similarly, there was no significant difference in the proportion of applicants matching at their home institution, matching from medical schools without a home urology program, matching from medical schools with a historically low volume of urology applicants (

INTRODUCTION AND OBJECTIVE:Muscle invasive bladder cancer (MIBC) surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine and...

Introduction Current non-invasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Though these therapies work well for many, a subset of patients have contraindications or are unsatisfied with these options. Restorative therapies for ED are a new frontier of treatments focused on regenerating diseased tissue and providing a potential “cure” for ED. Aim The aim of this position statement is to examine existing clinical trial data for restorative therapies and identify elements that require further research before widespread adoption. Methods A literature review was performed to identify all clinical trials performed with regenerative therapy for ED. This includes treatments such as stem cell therapy (SCT), platelet rich plasma (PRP), and restorative related technologies like low-intensity shockwave therapy (LiSWT). Main Outcome Measures Most clinical trials in restorative therapies were assessed for safety, feasibility, or efficacy. This included recording adverse events, changes in sexual function and erectile function questionnaires, and diagnostics measures. Results To date there is an absence of robust clinical data supporting the efficacy of restorative therapies regarding ED, though technologies such as LiSWT have established relative safety. Conclusions Restorative therapies are a promising technology that represents a new frontier of treatment geared towards reversing disease pathology rather than just treating symptoms. However, current published clinical studies are limited. Future work needs to be adequately powered, multi-center, randomized, sham/placebo-controlled trials in well-characterized patient populations to ensure safety and demonstrate efficacy. Until these studies are done, restorative therapies should be reserved for clinical trials and not offered in routine clinical practice.

Low-intensity extracorporeal shockwave therapy (LI-ESWT) to the penis has recently emerged as novel therapeutic option in the treatment of erectile dysfunction (ED). Randomized-controlled studies investigating the effect of this new treatment modality revealed promising results in men with vasculogenic ED. However, the efficacy of LI-ESWT in men who develop ED following radical prostatectomy (RP) remains obscure due to the exclusion of this group in nearly all clinical trials. In this review, the authors synthesize the findings from available preclinical and clinical studies that examine the potential utility of LI-ESWT in men with post-RP ED.

Coated urethral catheters were introduced in clinical practice to reduce the risk of catheter-acquired urinary tract infection (CAUTI). We aimed to systematically review the incidence of CAUTI and adverse effects in randomized clinical trials of patients requiring indwelling bladder catheterization by comparing coated vs. non-coated catheters. This review was performed according to the 2020 PRISMA framework. The incidence of CAUTI and catheter-related adverse events was evaluated using the Cochran–Mantel–Haenszel method with a random-effects model and reported as the risk ratio (RR), 95% CI, and p-values. Significance was set at p < 0.05 and a 95% CI. Twelve studies including 36,783 patients were included for meta-analysis. There was no significant difference in the CAUTI rate between coated and non-coated catheters (RR 0.87 95% CI 0.75–1.00, p = 0.06). Subgroup analysis demonstrated that the risk of CAUTI was significantly lower in the coated group compared with the non-coated group among patients requiring long-term catheterization (>14 days) (RR 0.82 95% CI 0.68–0.99, p = 0.04). There was no difference between the two groups in the incidence of the need for catheter exchange or the incidence of lower urinary tract symptoms after catheter removal. The benefit of coated catheters in reducing CAUTI risk among patients requiring long-term catheterization should be balanced against the increased direct costs to health care systems when compared to non-coated catheters.

Sexual dysfunction, specifically erectile dysfunction (ED), premature ejaculation (PE), and delayed ejaculation (DE), are debilitating diseases, especially in young men. The past decade has seen an increase in the number of young men (under 40 years of age) presenting to their physician with sexual dysfunction. Traditionally, sexual dysfunction in young men was viewed as a strictly psychosomatic problem stemming from underlying psychogenic causes such as anxiety or insecurity. While this is true in some cases, the advent of new diagnostic tools and pharmacotherapy have revealed that the prevalence of organic causes for these diseases is much higher than previously thought. In reality, many patients present with primarily organic sexual dysfunction that then triggers concomitant psychogenic stressors such as anxiety and depression which exacerbate their problem. This review focuses on the common etiologies of sexual dysfunction experienced by young men in order to help educate clinicians so that they may better understand, identify, and serve this growing patient population.

► Persistent dry cough ► Frequent sinus congestion ► Hemoptysis.

Background Postorgasmic illness syndrome (POIS) is a rare syndrome of unknown etiology where patients experience distressing physical and psychological after ejaculatory sequelae. Aim To better characterize the epidemiology, symptomatology, disease course, and treatment of POIS, with specific interest placed on examining relationships between disease presentation and measures of disease burden. Methods A 30-item questionnaire was distributed to an online community of patients with POIS from June 2019 to January 2020. We assessed diagnostic criteria and clusters of symptomatology described in prior studies. Outcome measures include self-reported measures of symptom severity, disease burden, and behavioral changes. Statistical correlations were assessed with Pearson's chi-squared (χ2) and ordinal regression analyses. Outcomes The main outcome measures of this study are self-reported measures of symptom severity, disease burden, and behavioral changes. Results The sample consisted of 302 men (mean age: 32.6 ± 11.4 years, mean age of onset: 19.1 ± 7.8 years) with 89% satisfying ≥3 diagnostic criteria. Common symptoms were difficulty concentrating (254, 84%), extreme fatigue (250, 83%), irritability (225, 74%), and muscle weakness (212, 70%). Common symptom clusters were general (219, 72%), muscle (137, 45%), and head (93, 31%). Common behavioral modifications were avoiding masturbation (215, 71%), schedule changes (213, 71%), and abstinence (186, 62%). Head and throat symptom clusters demonstrated worse disease burden outcomes. Professional medical advice was sought by 51% of participants. Attempted treatments included pharmacotherapy, vitamins, supplements, and herbs with variable efficacy. Clinical Implications This study further characterizes POIS, including how patients respond to the condition, how it is treated in the community, and presentations that may be associated with more severe disease. Strengths & Limitations This is the largest study to date that concerns patients suffering from POIS and includes a diverse, global population. Limitations include that the survey was only administered in English and within 1 online community, that results were self-reported, and that the response rate was low (32%). Conclusions Characterizing symptom cluster, but not number of diagnostic criteria, may offer prognostic value, and investigation to elucidate pathophysiology and potential treatments for POIS is necessary.

The COVID-19 pandemic has brought unique challenges to the delivery of undergraduate medical education, particularly for current third-year medical students who are preparing to apply to residency. In mid-March, medical schools suspended all clinical rotations for the remainder of the 2019–2020 academic year. As such, third-year medical students may not be able to complete sufficient clinical experiences to make important career choices before they have to submit their residency applications. While the decision to suspend clinical rotations was necessary to protect students, specialty organizations and residency programs must mitigate the deficits in students’ clinical education caused by the COVID-19 pandemic. In this Perspective, the authors identify potential challenges for third-year medical students and advocate for solutions to improve the residency application process for students and programs. First, they propose delaying the date that programs can access applicant data through the Electronic Residency Application Service, thereby affording students more time to complete clinical experiences, solidify their specialty decision, and strengthen their residency application. Second, the authors recommend a restriction on the number of visiting rotations that students are expected to complete to allow for a more equitable distribution of these important experiences. Third, they suggest that program directors from each specialty agree on a maximum number of applications per applicant (based on historical data) to curb an upsurge in applications that may stem from the unique circumstances created by COVID-19 without causing applicants undue stress. Lastly, the authors advocate that residency programs develop infrastructure to conduct video-based interviews and engage students through virtual networking events. Amidst the unique environment created by COVID-19, the authors urge governing bodies, specialty organizations, and residency programs to consider these recommendations to improve the efficiency and reduce the stress surrounding the 2021 Match.

Active surveillance (AS) is a treatment modality for prostate cancer that aims to simultaneously avoid overtreatment and allow for the timely intervention of localized disease. AS has become the de facto standard of care for most men with low-risk prostate cancer. However, few African American (AA) men were included in the prospective observational cohorts that resulted in a paradigm shift in treatment recommendations from active intervention toward AS. It has been established that AA men have an increased prostate cancer incidence, higher baseline prostate-specific antigen (PSA) values, more aggressive prostate cancer features, greater frequency of biochemical recurrence after treatment, and higher overall cancer-specific mortality compared to their Caucasian counterparts. As such, this has given many physicians pause before initiating AS for AA patients. In the following manuscript, we will review the available literature regarding AS, with a particular focus on AA men. The preponderance of evidence demonstrates that AS is as viable a management method for AA with low-risk prostate cancer as it is with other racial groups.

Ischemic priapism is a urological emergency that has been associated with long-standing and irreversible adverse effects on erectile function. Studies have demonstrated a linear relationship between the duration of critically ischemic episodes and the subsequent development of corporal fibrosis and irreversible erectile function loss. Placement of a penile prosthesis is a well-established therapeutic option for the management of erectile dysfunction secondary to ischemic priapism, and will be the focus of this review. Review of the current literature demonstrates a growing utilization of penile prostheses in the treatment of erectile dysfunction secondary to ischemic priapism. Unfortunately, there is a paucity of randomized-controlled trials describing the use of prosthesis in ischemic priapism. As a result, there is a lack of consensus regarding the type of prosthesis (malleable vs. inflatable), timing of surgery (acute vs. delayed), and anticipated complications for each approach. Both types of prostheses yielded comparable complication rates, but the inflatable penile prosthesis have higher satisfaction rates. Acute treatment of priapism was associated with increased risk of prosthetic infection, and could potentially cause psychological trauma, whereas delayed implantation was associated with greater corporal fibrosis, loss of penile length, and increased technical difficulty of implantation. The paucity of high-level evidence fuels the ongoing discussion of optimal use and timing of penile prosthesis implantation. Current guidance is based on consensus expert opinion derived from small, retrospective studies. Until more robust data is available, a patient-centered approach and joint decision-making between the patient and his urologist is recommended.

Objective To present a novel imaging technique used for rapid, nondestructive histological assessment of renal neoplasias using a dual-component fluorescence stain and structured illumination microscopy (SIM). Materials and Methods After Institutional Review Board approval, 65 total biopsies were obtained from 19 patients undergoing partial or radical nephrectomy. Biopsies were stained with a dual-component fluorescent, and optically sectioned SIM images were obtained from the surface of the intact biopsies. Specimens were subsequently fixed and analyzed using hematoxylin and eosin (H&E) histopathologic methods and compared with SIM images. A single, board-certified pathologist blinded to specimens reviewed all SIM images and H&E slides, and determined the presence or absence of neoplasias. Results of blinded diagnosis of SIM were validated against traditional pathology. Results Of the 19 patients, 15 underwent robotic partial nephrectomies and 4 underwent laparoscopic nephrectomies. Indications included clinical suspicion of renal cell carcinoma. In total, 65 biopsy specimens were available for review. Twenty-one specimens were determined to be neoplastic on H&E, whereas 41 represented benign renal tissue. The final sensitivity and specificity of our study were 79.2% and 95.1%, respectively. Conclusion SIM is a promising technology for rapid, near-patient, ex vivo renal biopsy assessment. By improving the ability to rapidly assess sufficiency of biopsy specimens and enabling immediate diagnostic capability, SIM aids in more effective biopsy performance, tissue triage, and patient counseling regarding management options. Additionally, because tissue is preserved, effective utilization of downstream diagnostic tests and molecular assessments are possible.

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.

Hemorrhage after robotic-assisted partial nephrectomy (RAPN) is uncommon but can cause significant morbidity. We present a case of acute hemorrhage isolated to the collecting system that was managed with renal artery embolization (RAE). A 76-year-old male developed sudden onset transfusion-dependent hematuria and hypotension following uncomplicated RAPN. He had no signs of intra-abdominal bleeding and his hypotension was responsive to volume resuscitation. Renal angiography identified a segmental artery with extravasation into the collecting system. RAE eliminated the patient's hematuria, the need for further transfusion, and allowed preservation of renal function. RAE is a viable option for collecting system hemorrhage following RAPN.

Purpose To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC). Methods This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1–7 and 150 mg/m2 TMZ PO daily on days 1–5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03. Results We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months. Conclusion The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. ClinicalTrials.gov Identifier NCT01205828. Electronic supplementary material The online version of this article (doi:10.1007/s00280-015-2852-2) contains supplementary material, which is available to authorized users.

Peyronie's disease (PD) is an inflammatory disorder characterized by an abnormal collagen deposition in the tunica albuginea of the penis, leading to fibrous and non-compliant plaques that can impede normal erection. Although pharmacological treatments are available, only intralesional injection therapy and surgical reconstruction have demonstrated tangible clinical efficacy in the management of this condition. Intralesional injection of collagenase clostridium histolyticum (CCH) has come to the forefront of minimally invasive treatment of PD. In this review, the authors provide an update on the safety, efficacy, and indications for CCH. The efficacy of CCH will be assessed on the basis of improvement in the severity of penile fibrosis, curvature, and pain. Numerous well-designed clinical trials and post-approval studies involving more than 1,500 patients have consistently demonstrated the efficacy and tolerability of CCH in the treatment of PD. CCH significantly decreases penile curvature and plaque consistency, as well as improves quality of life. Post-approval studies continue to demonstrate the efficacy of CCH despite broader inclusion criteria for treatment, such as the case with acute phase disease and atypical plaque deformities (i.e., ventral plaques, hourglass narrowing). CCH continues to be the gold standard for non-surgical management of stable phase PD, in the absence of strong evidence supporting oral therapy agents and ongoing evaluation of extracorporeal shockwave therapy. However, recent studies are beginning to provide precedent for the use of CCH in the management of acute phase and atypical PD.

Purpose We sought to report outcomes and toxicity in patients with hepatocellular carcinoma (HCC) who received resin yttrium-90 selective internal radiation therapy (90Y-SIRT) and to identify factors associated with declining liver function. Methods Patients treated with 90Y-SIRT were retrospectively evaluated. Radiographic response was assessed using RECIST 1.1. Median liver progression-free survival (LPFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Bivariate analysis was used to examine associations between change in Child-Pugh (CP) score/class and patient characteristics and treatment parameters. Results Twenty-seven patients with unresectable HCC underwent SIRT, 52% were CP Class A, 48% were Class B, 11% were BCLC stage B, and 89% were stage C. Forty-four percent of patients had portal vein thrombus at baseline. One-third of patients received bilobar treatment. Median activity was 32.1 mCi (range 9.18–43.25) and median-­absorbed dose to the liver was 39.6 Gy (range 13.54–67.70). Median LPFS and OS were 2.5 and 11.7 months, respectively. Three-month disease control rate was 63 and 52% in the target lesions and whole liver, respectively. New onset or worsened from baseline clinical toxicities were confined to Grade 1–2 events. However, new or worsened Grade 3–4 laboratory toxicities occurred in 38% of patients at 3 months and 43% of patients at 6 months following SIRT (six had lymphocytopenia, three had hypoalbuminemia, and two had transaminasemia). After 3 months, six patients had worsened in CP score and five had worsened in class from baseline. After 6 months, four patients had worsened in CP score and one had worsened in class from baseline. Pretreatment bilirubinemia was associated with a 2+ increase in CP score within 3 months (P = 0.001) and 6 months (P = 0.039) of 90Y-SIRT. Pretreatment transaminasemia and bilirubinemia were associated with increased CP class within 3 months of SIRT (P = 0.021 and 0.009, respectively). Conclusion 90Y-SIRT was well-tolerated in patients with unresectable HCC, with no Grade 3–4 clinical toxicities. However, Grade 3–4 laboratory toxicities and worsened CP scores were more frequent. HCC patients with pretreatment bilirubinemia or transaminasemia may be at higher risk of experiencing a decline in liver function following 90Y-SIRT.