Urologic Research Institute

While the molecular and genetic bases of Von Hippel-Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management. Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival. To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.

218 Background: Molecular assays are used to improve risk stratification in prostate cancer. This study determined how the 17-gene Genomic Prostate Score (GPS) assay guides treatment decisions in patients with NCCN favorable intermediate-risk prostate cancer. Methods: This retrospective study included 324 patients from 7 urology practices in the United States. All patients had NCCN favorable intermediate-risk prostate cancer, defined as <50% positive biopsy cores and only one of the following risk factors: grade group 2 (Gleason Score 3+4), clinical stage T2b-T2c, or PSA 10-20 ng/mL. All patients also had a GPS assay report dated May 2017 to April 2019. The GPS assay allows risk stratification into post-GPS very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups, with higher GPS scores representing increased risk. Data were collected from patients' charts/electronic health records. The proportion of patients who selected active surveillance (AS) over immediate definitive treatment and AS, monotherapy, or multimodal therapy was calculated with 95% confidence intervals (CI) using the Clopper-Pearson method. Results: Patients comprised 79% with Gleason Score 3+4, 19% with PSA 10-20 ng/mL, and 2% with clinical stage T2b; median GPS result was 26. Post-GPS risk groups were 0%, 16%, 11%, 57%, and 16% very low-, low-, favorable intermediate-, unfavorable intermediate-, and high-risk groups respectively. Overall, 31% (95% CI 26%, 36%) of patients selected active surveillance (AS), with rate declining as post-GPS risk increased: 57% (95% CI 42%, 71%) selected AS in the post-GPS low-risk, 51% (95% CI 34%, 69%) in the post-GPS favorable intermediate-risk, 26% (95% CI 20%, 33%) in the post-GPS unfavorable intermediate-risk, and 6% (95% CI 1%, 16%) in the post-GPS high-risk group. Post-GPS unfavorable intermediate/high risk-patients were more likely to receive monotherapy than low/favorable intermediate-risk patients (high, 72%; unfavorable intermediate, 64%; favorable intermediate, 37%; and low, 37%); high-risk patients were more likely to receive multimodal therapy (high, 23%; unfavorable intermediate, 10%; favorable intermediate, 11%; and low, 6%). Median follow-up time was 18 months, and one prostate cancer-related metastasis and 2 deaths (neither prostate cancer-related) were reported. Complications (erectile dysfunction, urinary/bowel incontinence) were more common in treated than AS patients. AS persistence was 91% (95% CI 82%, 95%) at 12 months; patients discontinued AS due to disease progression (61%) or patient preference/unknown reasons (39%). Conclusions: The GPS result is associated with selection of AS and treatment intensity in this first examination of genomic classifiers in a cohort of prostate cancer patients with NCCN favorable intermediate-risk.

ABSTRACT Introduction: This Perspective reassesses the consensus opinion that statin-associated muscle symptoms (SAMS) occur in <1% of users and associated myopathic proximal muscle weakness is even more rare. Areas covered: Of the over 180,000 participants in clinical trials and large registries of statin users, only a few studies have included a standard manual muscle test (MMT), dynamometry or a focused questionnaire to assess for proximal weakness and related disability in daily and recreational activities. Formal strength testing suggests, however, that weakness can be demonstrated in at least 10% of users. Expert opinion: Reporting inaccuracies about SAMS, confirmation bias among experts and physicians, absence of a standard questionnaire regarding the potential consequences of weakness on physical capacity, and the failure to routinely perform an objective assessment of strength may have led to under-diagnosis of statin-induced myopathy. A brief MMT before cholesterol-lowering agents are started and at follow-up visits, a 12-week withdrawal of the statin in the presence of new paresis without an alternative cause, and the exam finding that strength recovers off the statin are necessary to assess the incidence of drug-induced proximal weakness and inform alternative therapeutic strategies.

ObjectivesTo evaluate the impact of age on overall survival (OS), freedom from distant metastasis (FDM), rates of therapeutic intervention (TI), and quality of life (QOL) in active surveillance (AS) prostate cancer patients.Materials and methodsThree hundred and five consecutive, prospectively evaluated AS patients who underwent a staging transperineal template‐guided mapping biopsy (TTMB) prior to enrollment on AS were evaluated and stratified by age. Evaluated outcomes included OS, FDM, TI, and QOL to include urinary, bowel, sexual function, and depression. Post void residual (PVR) urine measurements were also followed. Repeat biopsy was based on PSA kinetics, abnormal digital rectal examination or patient preference.ResultsOf the 305 patients, 290 (95.1%) were Gleason 3 + 3 and 15 patients (4.9%) were Gleason 3 + 4. The median follow‐up was 5.5 years (range 1‐14 years). At 10 years, TI was 0%, 1.0%, and 11.4% for patients ≤59, 60‐69, and ≥70 years of age (P < .001). No patient has developed distant metastasis. The median time to TI was 4.71 years. No statistical differences in urinary function, bowel function, or depression were noted. Potency preservation was dependent on patient age.ConclusionWithin the confines of the follow‐up of our series, younger patients were less likely to proceed to therapeutic intervention. In addition, patient age did not adversely impact QOL outcomes.

We present clinical, electroencephalographic and low-resolution electromagnetic tomography data that support combined treatment with insulin and a monoamine oxidase inhibitor in a patient with type 1 diabetes. We suggest that brain imaging data can identify a subgroup of patients who are likely to benefit from an insulin regimen and monoamine oxidase inhibition to improve glycaemic control, cardiovascular function, normalize the circadian rhythm and restore perception of glycaemic awareness.