Ron Golan

Age-related testosterone decline is due to waning of both testicular and hypothalamic-pituitary function

Abstract Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males.

Partial Gland Treatment of Prostate Cancer Using High-Intensity Focused Ultrasound in the Primary and Salvage Settings: A Systematic Review

Purpose: Advances in prostate imaging, biopsy and ablative technologies have been accompanied by growing enthusiasm for partial gland ablation, particularly using high‐intensity focused ultrasound, to treat prostate cancer. Preserving noncancerous prostate tissue and minimizing damage to the neurovascular bundles and external urethral sphincter may improve functional outcomes. Materials and Methods: A systematic review was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines using a combination of MeSH® terms, free text search and examination of relevant bibliographies using MEDLINE® and Embase® from the inception of each database through October 10, 2016. We excluded studies describing exclusively whole gland ablation, case reports and series where treatment was followed by immediate resection. Results: A total of 13 studies that enrolled 543 patients were included. Of the studies 11 were performed in the primary setting and 2 in the salvage setting. Median followup ranged from 6 months to 10.6 years. Rates of posttreatment erectile dysfunction and urinary incontinence ranged from 0% to 48% and 0% to 50%, respectively, with definitions varying by study. Overall there were 254 reported complications. Marked heterogeneity between studies limited the ability to pool results regarding functional and oncologic outcomes. A total of 76 patients (14%) subsequently received further oncologic treatment. Conclusions: Early evidence suggests that partial gland ablation is a safe treatment option for men with localized disease. Longer term data are needed to evaluate oncologic efficacy and functional outcomes, and will aid in identifying the optimal candidates for therapy. Standardization of outcomes definitions will allow for better comparison between studies and among treatment modalities.

Vasectomy and Risk of Prostate Cancer in a Screening Trial

Background: Vasectomy has been implicated as a risk factor for prostate cancer in multiple epidemiologic studies over the past 25 years. Whether this relationship is causal remains unclear. This study examines the association between vasectomy and prostate cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which randomized men to usual care or annual prostate cancer screening. Methods: We performed a retrospective analysis of 13-year screening and outcomes data from the PLCO trial. Multivariable Cox proportional hazards regression stratified by study arm and age at vasectomy was performed. Results: There was an increased risk of prostate cancer in men who had undergone a vasectomy and were randomized to the usual care arm of the study (adjusted HR, 1.11; 95% confidence interval, 1.03–1.20; P = 0.008). There was no association between vasectomy and diagnosis of prostate cancer in men randomized to the prostate cancer screening arm. Only men undergoing vasectomy at an older age in the usual care arm of the study, but not the prostate cancer screening arm, were at increased risk of being diagnosed with prostate cancer. Conclusions: Vasectomy was not associated with prostate cancer risk among men who were screened for prostate cancer as part of a clinical trial, but was associated with prostate cancer detection in men receiving usual care. Impact: The positive association between vasectomy and prostate cancer is likely related to increased detection of prostate cancer based on patterns of care rather than a biological effect of vasectomy on prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(11); 1653–9. ©2017 AACR.

Contemporary Incidence and Outcomes of Prostate Cancer Lymph Node Metastases

Purpose: The incidence of localized prostate cancer has decreased with shifts in prostate cancer screening. While recent population based studies demonstrated a stable incidence of locoregional prostate cancer, they categorized organ confined, extraprostatic and lymph node positive disease together. However, to our knowledge the contemporary incidence of prostate cancer with pelvic lymph node metastases remains unknown. Materials and Methods: We used SEER (Surveillance, Epidemiology and End Results) data from 2004 to 2014 to identify men diagnosed with prostate cancer. We analyzed trends in the age standardized prostate cancer incidence by stage. The impact of disease extent on mortality was assessed by adjusted Cox proportional hazard analysis. Results: During the study period the annual incidence of nonmetastatic prostate cancer decreased from 5,119.1 to 2,931.9 per million men (IR 0.57, 95% CI 0.56–0.58, p <0.01) while the incidence of pelvic lymph node metastases increased from 54.1 to 79.5 per million men (IR 1.47, 95% CI 1.33–1.62, p <0.01). The incidence of distant metastases in men 75 years old or older reached a nadir in 2011 compared to 2004 (IR 0.81, 95% CI 0.74–0.90, p <0.01) and it increased in 2012 compared to 2011 (IR 1.13, 95% CI 1.02–1.24, p <0.05). The risk of cancer specific mortality significantly increased in men diagnosed with pelvic lymph node metastases (HR 4.5, 95% CI 4.2–4.9, p <0.01) and distant metastases (HR 21.9, 95% CI 21.2–22.7, p <0.01) compared to men with nonmetastatic disease. Conclusions: The incidence of pelvic lymph node metastases is increasing coincident with a decline in the detection of localized disease. Whether this portends an increase in the burden of advanced disease or simply reflects decreased lead time remains unclear. However, this should be monitored closely as the increase in N1 disease reflects an increase in incurable prostate cancer at diagnosis.

Development of a nationally-representative coordinated registry network for prostate ablation technologies

Purpose: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. Materials and Methods: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. Results: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF‐5 (International Index of Erectile Function‐5), the I‐PSS (International Prostate Symptom Score), the EPIC‐26 (Expanded Prostate Cancer Index Composite‐26) and the MSHQ‐EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. Conclusions: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

The clinical presentation and outcome of urothelial atypia on biopsy of the bladder.

OBJECTIVES To examine the presentation and clinical outcome of patients diagnosed with reactive urothelial atypia (RUA) or urothelial atypia of unknown significance (AUS) on tissue biopsy of the bladder. METHODS AND MATERIALS We performed a retrospective cohort study of all patients who were diagnosed with either RUA or AUS on biopsy of the bladder at our institution from November 2000 to May 2008. Excluded from the analysis were patients with a history of or a concurrent diagnosis of urothelial carcinoma. A total of 66 patients were available for final analysis. RESULTS The mean patient age at diagnosis was 63 years (range: 18-89 years). There were 46 men (70%) and 20 women (30%). The indication for cystoscopic examination included lower urinary tract symptoms in 29 (44%), gross hematuria in 17 (26%), microscopic hematuria in 12 (18%), urolithiasis in 2 (3%), and hydronephrosis in 6 (9%) patients. On biopsy, 54 (82%) had RUA and 12 (18%) had AUS. The mean follow-up was 36 months (range: 0-271 months). During this period, 37 (56%) patients underwent at least 1 additional cystoscopy with negative result. None of the 66 (0%) patients developed biopsy-proven urothelial carcinoma. CONCLUSION Urothelial atypia is common in men older than 60 years and often presents with either hematuria or lower urinary tract symptoms. Both RUA and AUS have a similar benign clinical course. Therefore, after diagnosis, further intervention or surveillance is unnecessary.

A contemporary analysis of dual inflatable penile prosthesis and artificial urinary sphincters outcomes

Purpose: Inflatable penile prostheses and artificial urinary sphincters are used to treat men with erectile dysfunction and stress urinary incontinence, respectively. After prostate cancer treatment men often experience erectile dysfunction and stress urinary incontinence. Dual prosthetic implantation can improve the quality of life of these men. We evaluated reoperation outcomes in men who underwent dual implantation compared to each device implanted individually. Materials and Methods: We queried the SPARCS (New York State Department of Health Statewide Planning and Research Cooperative) database for men who underwent inflatable penile prosthesis and/or artificial urinary sphincter insertion between 2000 and 2014. The primary outcomes were the inflatable penile prosthesis and artificial urinary sphincter reoperation rates (revision, replacement or removal). Multivariable regression analysis was performed to assess the association of dual implantation with reoperation. Adjusted time to event analysis was also performed. Results: Median followup in the inflatable penile prosthesis cohort was 66 months (IQR 25–118) and in the artificial urinary sphincter cohort it was 69 months (IQR 27–121). Compared with men who received a penile prosthesis alone those with a penile prosthesis and an artificial urinary sphincter had a higher likelihood of undergoing inflatable penile prosthesis reoperation at 1 year (OR 2.08, 95% CI 1.32–3.27, p <0.01) and 3 years (OR 2.60, 95% CI 1.69–3.99, p <0.01). Compared with an artificial urinary sphincter alone patients with an inflatable penile prosthesis and an artificial urinary sphincter did not have a higher likelihood of undergoing artificial urinary sphincter reoperation at 1 year (p = 0.76) or 3 years (p = 0.73). Conclusions: Combined inflatable penile prosthesis and artificial urinary sphincter insertion portends a higher likelihood of inflatable penile prosthesis reoperation at 1 and 3 years. However, artificial urinary sphincter outcomes remain comparable. These findings should be used to better counsel patients about the risk of reoperation when undergoing dual implantation.

Fertility Preservation in the Male Adolescent Patient

Over 15,000 children develop cancer in the United States (US) each year (Ward et al., CA Cancer J Clin 64(2):83–103, 2014), with a 5-year survival rate for childhood cancer being roughly 80% (Robison and Hudson, Nat Rev Cancer 14(1):61–70, 2014). This extrapolates to over 385,000 childhood cancer survivors living in the United States (Phillips et al., Cancer Epidemiol Biomark Prev 24(4):653–663, 2015). With a growing number of childhood cancer survivors, oncologic counseling has seen a shift in focus from concentrating solely on short- and long-term survival benefits of treatment regimens to survivorship and long-term effects of treatments. With this shifting paradigm, short- and long-term gonadotoxic effects of cancer treatment have become a major concern for clinicians treating and patients diagnosed with malignancies. Because of this, fertility preservation (FP) among adolescent and young adult (AYA) cancer patients has become a significant area of interest and research.

Surgical approach does not impact margin status following partial nephrectomy for large renal masses

PURPOSE While surgical approach has recently been associated with positive surgical margin (PSM) after partial nephrectomy (PN) for small (<4 cm) renal masses, its impact on margin status for large (>4 cm) masses is unclear. We sought to evaluate the relationship between margin and surgical approach in patients undergoing PN for large renal masses. MATERIALS AND METHODS Using the National Cancer Database (NCDB), we identified patients undergoing PN for pathological T1b and T2a renal-cell carcinoma diagnosed from 2010 to 2013. Conversions to open surgery were also included in our analysis. The primary outcome was surgical margin status. Multivariable regression modeling was performed to identify factors associated with PSM. A propensity score matching analysis was then performed to evaluate the impact of margin status on overall survival (OS). RESULTS Of the 7495 patients undergoing PN for pT1b and pT2a renal masses over the study period, 504 (6.7%) had PSM. On multivariable analysis, surgical approach (laparoscopic or robot assisted vs open) was not significantly associated with surgical margin (p = 0.12 and p = 0.44, respectively). Tumor stage (T2a vs T1b) also showed no significant association (p = 0.18). A subsequent multivariable analysis using clinical staging showed that surgical approach (p = 0.28 and p = 0.54, respectively), tumor stage (p = 0.78), and conversion-to-open surgery (p = 0.98) had no significant association with PSM. Propensity score matched analysis showed that PSM was not significantly associated with OS (hazard ratio 0.95 [95% confidence interval 0.47-1.92] p = 0.88). CONCLUSION In a contemporary nation-wide cohort, surgical approach was not associated with an increased risk of PSM for large, noninvasive renal masses. Furthermore, increased size from T1b to T2a was not associated with an increased risk of PSM. These data suggest that surgical approach should be selected by surgeon comfort level with an individual tumor, rather than the size of the tumor itself.

Increased resource use in men with metastatic prostate cancer does not result in improved survival or quality of care at the end of life: Testing in Metastatic Prostate Cancer

Cancer care and end‐of‐life (EOL) care contribute substantially to health care expenditures. Outside of clinical trials, to our knowledge there exists no standardized protocol to monitor disease progression in men with metastatic prostate cancer (mPCa). The objective of the current study was to evaluate the factors and outcomes associated with increased imaging and serum prostate‐specific antigen use in men with mPCa.