Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Cheryl Guttman Krader, BS, Pharm

Black men are significantly less likely than White men to undergo surgical treatment for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH), according to the findings of a recently published study.

Conducted by investigators from the University of Colorado Anschutz School of Medicine, Aurora, the study probed the hospital network’s database for the period from January 2011 to October 2018 to identify men aged 40 years and older who were on medical therapy for LUTS and had at least 2 provider visits. Patients with bladder or prostate cancer were excluded.

The study included 30,466 patients, of whom 1028 (2.5%) underwent surgery. The vast majority of the study population was White (80%). Hispanic patients accounted for approximately 9% of the total whereas Black/African American men represented approximately 4% and men of other race/ethnicity made up 6.8% of the study population.

A logistic regression analysis controlling for other major comorbidities, patient age, insurance status, and type of medical therapy found that Black patients were almost 40% less likely than White patients to undergo surgery (

= .03). The odds of undergoing surgery were no different comparing Hispanic patients with White men. Patients whose race/ethnicity was categorized as “other” were almost 30% less likely than Whites to receive surgical treatment for their LUTS/BPH (

“BPH causes an enormous burden in both our country and around the world. Patients should receive the best possible treatment for this disease process and often times this should include surgery. Cost effective and durable care grow ever more important as the population of BPH sufferers is rapidly increasing while the workforce shortage worsens,” said lead author Granville L. Lloyd, MD, an associate professor of surgery-urology at the University of Colorado Anschutz School of Medicine/Rocky Mountain Regional VA Hospital.

“Based on the information collected, we cannot determine drivers of the discrepancy in management. However, it is important to realize that many Black men may have far less faith in organized medicine and surgery than other men. Considering that providers may be working against significant, often quiet mistrust, Black men may benefit from additional efforts to develop a relationship with the care team,” Lloyd said.

Having characterized the disparity in care, the investigators sought and received IRB approval to begin a prospective study that will help understand the underlying reasons. In the forthcoming study, new patients being seen for LUTS/BPH and other prostate complaints will be asked as they move through care to complete a survey that will gather data on comorbidities and demographics as well as examine attitudes toward surgery, medical therapy, personal and sexual attitudes about prostate care, and medical mistrust.

As reviewed by the investigators, a number of other studies identified race/ethnicity as a factor impacting urologic care. Of particular relevance to the current investigation, a previous study looking at all men in a California Medicaid population with a diagnosis of BPH showed that Black patients were less likely to be treated both medically and surgically.

“Importantly, the study of the Medicaid population showed racial/ethnic disparities in management for BPH, particularly with regard to medical treatment, but it is not known if the disparity in surgical management was due to underlying differences in medical therapy,” Lloyd said.

“Our study managed that confounding factor by investigating patients already on medical therapy for BPH and determined the odds of their progressing to surgical treatment. In addition, we included patients with both public and private insurance as well as those without insurance. In our study, insurance status was not independently associated with odds of surgery.”

1. Antoine SG, Carmichael H, Lloyd GL. The impact of race, ethnicity and insurance status on surgery rates for benign prostatic hyperplasia. 

. Published online July 22, 2021. doi:10.1016/j.urology.2021.05.092.

2. Gill H. Racial disparities in the treatment of benign prostatic hyperplasia. 

. 2015;04(04). doi:10.4172/2168-9857.1000157

Articles

A logistic regression analysis controlling for other major comorbidities, patient age, insurance status, and type of medical therapy found that Black patients were almost 40% less likely than White patients to undergo surgery for BPH.

Large retrospective study identifies racial disparity in surgical management for BPH

Adding pharmacotherapy to behavioral modification for treating lower urinary tract symptoms (LUTS) in men improves 24-hour voiding frequency compared with behavioral modification alone, but had no significant benefit for improving nocturia, according to the results of a recently published retrospective study.

“Several papers have questioned the efficacy of non-antidiuretic pharmacological treatment for improving nocturia in men with LUTS, but there is a paucity of real-world data on this issue,” said Connelly Miller, MPH, first author of the paper. “Individualized behavioral counseling targeting lifestyle modifications is recommended as first-line therapy for LUTS-related nocturia. Our study finds no evidence to support supplementing that approach with pharmacotherapy.”

Miller is a fourth year medical student at SUNY Downstate Health Sciences University, Brooklyn, New York who has been conducting retrospective analyses to understand features of nocturia using information from a prospectively kept database of men seen for LUTS at the outpatient clinic of the Veteran Affairs New York Harbor Healthcare System, Brooklyn. The database, which includes voiding diaries, quality of life questionnaires, and patient and visit-level data, was started and is overseen by Jeffrey Weiss, MD, PhD, senior author of the published article and professor and chairman of urology at SUNY Downstate Health Sciences University.

The study investigating the efficacy of non-antidiuretic pharmacotherapy for nocturia identified men aged 18 years or older who had at least 1 pair of nocturnal void entries with the second entry recorded between 2 and 365 days after the first (baseline) date. It excluded men who were prescribed an antidiuretic or had surgery in the interval between the baseline and follow-up entries.

Determination of whether the patient’s management involved behavioral modification alone or concomitant pharmacotherapy with a LUTS drug (alpha-1 adrenergic antagonist, antimuscarinic agent, 5-alpha-reductase inhibitor, beta-3 agonist, or phosphodiesterase inhibitor) was done through chart review. Patients who were on the same pharmacotherapy at the time of their baseline and follow-up entries were included in the behavioral modification-only group. Information on demographics, tobacco use, medical comorbidities, vital signs, laboratory results, and uroflowmetry results was also extracted for each patient.

The study included data from 93 patients who were seen at the outpatient clinic between 2008 and 2019. There were a total of 156 diary entry pairs from patients who received behavioral modification alone and 57 diary pairs from patients who started on pharmacotherapy after the baseline entry. Median time between baseline and follow-up diary entries was 107 days. The patients included in the study had a median age of about 70 years.

Comparisons between the behavioral modification alone and adjunctive pharmacotherapy groups showed that they were similar with respect to all clinical and voiding diary characteristics with the exception that peripheral edema was more prevalent in the behavioral modification group and median maximum voided volume (MVV) was significantly lower in the pharmacotherapy group.

Median nocturnal voids was 2 in both study groups at baseline and did not change significantly between the baseline and follow-up entries in either group. Nocturnal frequency improved by at least 1 void in 38% of diary entries for men treated by behavioral modification alone and in 42% of diary entries for those prescribed adjunctive medication. A crude logistic regression analysis showed that adjunctive pharmacotherapy did not significantly change the odds of improving nocturia severity (odds ratio 1.16 [95% confidence interval: 0.63-2.16]; 

= .63). Further analysis adjusting for the baseline difference between groups in MVV also showed no significant benefit of pharmacotherapy for improving nocturia severity nor was any single class of LUTS drug associated with a significant benefit when added to behavioral modification. Analyses of multiple other nocturnal voiding diary parameters also showed no significant changes from baseline to follow-up in either study group.

Median number of 24-hour voids decreased significantly in the adjunctive pharmacotherapy group from 12 at baseline to 10 at follow-up (

< .001) and was unchanged in the behavioral modification group. In the crude logistic regression analysis, men receiving adjunctive pharmacotherapy had a twofold greater likelihood of achieving improvement in 24-hour urinary frequency compared with their counterparts receiving behavioral modification alone (

 = .04). The significant benefit of pharmacotherapy persisted in an analysis adjusting for between group differences in MVV and comparing the pharmacotherapy group of patients prescribed an antimuscarinic agent to the group receiving behavioral modification alone.

1. Miller CD, Monaghan TF, Robins DJ, Weiss JP. Does traditional pharmacotherapy augment behavioral modification in the treatment of nocturia? 

. Published online May 11, 2021. doi:10.1002/nau.24692

A crude logistic regression analysis showed that adjunctive pharmacotherapy did not significantly change the odds of improving nocturia severity.

Nocturia frequency unchanged by pharmacotherapy augmentation of behavioral modification

A recently published review article highlights sex differences in COVID-19 outcomes and the mechanisms by which testosterone might play a role.

Summarizing the key messages from the research, Mohit Khera, MD, MBA, MPH, told 

®, “Testosterone has been shown to play a role in modulating the immune response and may have a protective role in men who are infected with COVID-19. Although it is too early to assess the true relationship between COVID-19 and testosterone, early data suggest that low testosterone levels increase the risk of developing severe disease and that testosterone supplementation may provide benefit for men who are infected by the SARS-CoV-2 virus.”

Khera is a professor of urology, Baylor College of Medicine, Houston, Texas. He said he was prompted to investigate a potential relationship between testosterone and COVID-19 outcomes because of growing evidence that men were disproportionately affected by the infection compared to women and suffered a threefold higher mortality rate. In addition, observations from several studies indicated that men with low testosterone levels who acquired COVID-19 were more likely to be admitted to the intensive care unit and had increased mortality.

Discussing mechanisms by which testosterone can affect COVID-19 risk and outcomes, the article suggests that susceptibility to infection and its severity may involve effects of testosterone on viral entry into host cells and fusion of the virus with the host cell membrane. The underlying mechanisms might be explained by effects of testosterone on angiotensin-converting enzyme type 2 and transmembrane protease serine 2, respectively.

The explanation for why men suffer worse disease severity and higher mortality could relate to the potential for testosterone to affect the host’s immune response. In particular, testosterone can modulate production of pro-inflammatory cytokines, increase expression of anti-inflammatory mediators, and directly modulate activity of CD4+ T lymphocytes.

Understanding of how testosterone influences immune regulation suggests a potential role of testosterone as a therapeutic intervention for COVID-19, and perhaps particularly in men with low testosterone levels. Testosterone supplementation may also provide value considering clinical evidence from studies of patients with chronic obstructive pulmonary disease that investigated associations between testosterone and lung function. As reviewed in the published article by Khera and coauthor Jeremy M. Auerbach, BA, studies of patients with COPD found relationships between testosterone levels and respiratory muscle activity, exercise capacity, and respiratory parameters. In addition, findings from a randomized controlled trial showed that testosterone replacement in patients with COPD was associated with improvement in peak oxygen consumption and respiratory function.

“We believe that further research is needed to accurately assess the efficacy of testosterone replacement therapy in patients with COVID-19. Ideally, these studies should stratify patients by age and be designed to examine the ideal timing and dosage of testosterone supplementation,” Khera said.

Although the available evidence shows an association between low testosterone levels and worse severity of COVID-19, Khera cautioned that causality cannot be assumed.

He said, “There is still much unknown in this field. We also know that obesity and metabolic syndrome that are risk factors for hypogonadism are also risk factors for greater disease severity and increased mortality with COVID-19.”

1. Auerbach JM, Khera M. Testosterone's role in COVID-19. 

. 2021;18(5):843-848. doi:10.1016/j.jsxm.2021.03.004

"Early data suggest that low testosterone levels increase the risk of developing severe disease and that testosterone supplementation may provide benefit for men who are infected by the SARS-CoV-2 virus," says Mohit Khera, MD, MBA, MPH.

Literature review summarizes evidence on testosterone and COVID-19 

Results from the phase 2/3 OSPREY study showed that the prostate specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging agent 18F-DCFPyL (Pylarify, Lantheus) is highly sensitive and specific for localizing prostate cancer in newly diagnosed high-risk patients and among men being monitored for disease recurrence and metastasis.

Based on its diagnostic performance in OSPREY and in CONDOR, a phase 3 study enrolling men with biochemical recurrence of prostate cancer who had uninformative standard imaging, PET/CT imaging with this recently FDA-approved tracer is expected to transform the landscape for evaluation and management of men with prostate cancer, according to Kenneth J. Pienta, MD.

Pienta, professor of urology and oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, is lead author of the recently published article reporting results of OSPREY.

,“18F-DCFPyL-PET/CT will change the diagnostic work-up for high-risk and recurrent prostate cancer, replacing conventional bone scans and standard CT imaging. It will also re-define ‘biochemical recurrence’ and furthermore, identify patients who may benefit from PSMA-based therapeutics.”

The availability of this powerful imaging agent also raises new considerations for how to approach patient care.

“With 18F-DCFPyL-PET/CT, we can find metastatic disease much sooner. Therefore, 1 question that will need to be addressed is: what do we do now?” said Pienta.

“For example, do we treat PSMA-oligometastatic disease with targeted stereotactic body radiation therapy, or is a positive scan showing us systemic disease earlier? And if systemic, do we need to treat?”

The OSPREY study investigated 18F-DCFPyL in 2 patient cohorts. The first comprised men with high-risk prostate cancer who were undergoing radical prostatectomy with extended template pelvic lymph node dissection. The second cohort enrolled previously treated men with evidence of local recurrence outside the confines of prior treated site(s) or new or progressive metastatic disease demonstrated by CT/MRI, ultrasound, or whole-body bone scan.

All patients received a single intravenous dose of 9 mCi 18F-DCFPyL administered 1 to 2 hours before PET/CT. The results of the radiopharmaceutical imaging were evaluated independently by 3 blinded, central readers.

In the high-risk cohort, which included 252 evaluable patients, detection of pelvic nodal disease with 18F-DCFPyL-PET/CT was compared with histopathology findings from examination of nodal packets collected at lymphadenectomy. In this cohort, 18F-DCFPyL–PET/CT showed a specificity of 96 to 99% across the 3 readers, sensitivities of 31% to 42%, positive predictive values (PPVs) of 78% to 91%, and negative predictive values (NPV) of 81% to 84%.

Although OSPREY did not meet its sensitivity end point in the high-risk cohort, the criterion for sensitivity success was met in a post hoc analysis that evaluated its detection of nodal metastases greater than 5 mm in diameter. Done based on the assumption that smaller tumor deposits were below PET detection limits, the post hoc analysis showed 18F-DCFPyL-PET/CT had a sensitivity of 60% and the same specificity (98%) as in the overall group.

In the second cohort of men, the findings from histopathology examination of tissue obtained from image-guided biopsy of at least one amenable lesion identified on conventional imaging was used as the reference standard for evaluating the performance of 18F-DCFPyL-PET/CT. In this cohort, 18F-DCFPyL had sensitivities of 93% to 99% and PPVs of 81% to 88%.

Sensitivity of the radiopharmaceutical imaging exceeded 88% and its PPV was 75% or higher in analyses examining detection of prostate cancer in different anatomic sites. Subgroup analyses done with men stratified by baseline PSA showed that 18F-DCFPyL PET/CT maintained good performance in detecting disease even in men with a baseline PSA lower than 2 ng/mL.

No significant safety issues emerged and 18F-DCFPyL was well-tolerated. A total of 51 (13.2%) men experienced at least 1 adverse event (AE). The only AEs occurring at a rate of 2% or higher were dysgeusia (2.1%) and headache (2.1%). There were no serious AEs considered related to 18F-DCFPyL.

1. Pienta KJ, Gorin MA, Rowe SP, et al. A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY). 

. 2021;206(1):52-61. doi:10.1097/JU.0000000000001698

“With 18F-DCFPyL-PET/CT, we can find metastatic disease much sooner. Therefore, 1 question that will need to be addressed is: what do we do now?” says Kenneth J. Pienta, MD.









Cheryl Guttman Krader, BS, Pharm

Articles

Large retrospective study identifies racial disparity in surgical management for BPH

Nocturia frequency unchanged by pharmacotherapy augmentation of behavioral modification

Literature review summarizes evidence on testosterone and COVID-19

Phase 2/3 study demonstrates value of PSMA imaging agent for prostate cancer staging