A recent study published in Urology described how American Urological Association–accredited urological residency training programs are organized in terms of clinical exposure and teaching of their residents.

First study portrays urology resident clinical experience in the United States

The FDA has granted a priority review to a supplemental New Drug Application (sNDA) for olaparib (Lynparza) for use in combination with abiraterone acetate (Zytiga) and prednisone or prednisolone for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC).

The sNDA is supported by the phase 3 PROpel trial, which showed that adding olaparib (Lynparza) to frontline abiraterone acetate (Zytiga) and prednisone/prednisolone significantly improved radiographic progression-free survival (rPFS) in patients with mCRPC.

The findings, which were presented at the 2022 ASCO Genitourinary Cancers Symposium andpublished in the 

, showed that the median investigator-assessed rPFS was 24.8 months with olaparib/abiraterone vs 16.6 months with placebo/abiraterone translating to a 34% reduction in the risk of radiographic disease progression or death (HR, 0.66; 95% CI, 0.54-0.81; P <.0001).

 The 1- and 2-year rPFS rates were 71.8% and 51.4% in the olaparib/abiraterone arm, respectively; these rates were 63.4% and 33.6% with placebo/abiraterone, respectively.

When evaluated by blinded independent central review, the median rPFS with olaparib/abiraterone was 27.6 months vs 16.4 months with placebo/abiraterone, leading to a 39% reduction in the risk of radiographic disease progression or death (HR, 0.61; 95% CI, 0.49-0.74; P <.0001). The 1- and 2-year rPFS rates with olaparib plus abiraterone were 73.8% and 53.7%, respectively. In the placebo/abiraterone arm, these rates were 60.6% and 34.1%, respectively.

Under the priority designation, the FDA will review the sNDA within 6 months from the acceptance of the filing, compared with the standard 10 months.

“There remains a critical unmet need among patients diagnosed with metastatic castration-resistant prostate cancer, where the prognosis remains poor and treatment options are limited. Today’s news is another step towards bringing forward a new, much-needed treatment option in this setting. If approved, Lynparza with abiraterone will become the first combination of a PARP inhibitor and a new hormonal agent for patients with this disease,” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, the codeveloper of olaparib with MSD (Merck), stated in a press release.

In the international, double-blind, phase 3 PROpel trial (NCT03732820), investigators randomized patients with mCRPC in the first-line setting 1:1 to receive olaparib at 300 mg twice daily plus abiraterone at 1000 mg daily (n = 399) or placebo and abiraterone at 1000 mg daily (n = 397). Patients could have received docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting, but no prior abiraterone was allowed. Other NHAs were permitted if they were stopped at least 12 months prior to study enrollment. Patients also had ongoing androgen deprivation therapy and an ECOG performance status of 0 or 1.

Stratification factors included site of distant metastases (bone-only vs visceral vs other) and prior taxane in the mHSPC setting (yes vs no).

The primary end point was investigator-assessed rPFS, with OS as a secondary end point. Additional outcome measures included time to first subsequent therapy or death (TFST), time to second progression or death (PFS2), objective response rate (ORR), HRR mutation prevalence (retrospective testing), health-related quality of life, and safety and tolerability.

Baseline characteristics were well-balanced between the 2 arms. The median age was 69.5 years (range, 43-91), and most patients had an ECOG performance status of 0 (70.1%). Of note, symptomatic patients (Brief Pain Inventory-Short Form ≥4 and/or opiate use) comprised 25.8% and 20.2% of olaparib- and placebo-treated patients, respectively; 22.5% of patients had received docetaxel at the mHSPC stage.

Additionally, patients either had HRR mutations (27.8% with olaparib vs 29.0% with placebo), non-HRR mutations (69.9% vs 68.8%, respectively), or unknown HRR mutation status (2.3% each). The median PSA was 17.90 ug/L (interquartile range [IQR], 6.09-67.00) with olaparib/abiraterone and 16.81 ug/L (IQR, 6.26-53.30) with placebo/abiraterone. Most metastases occurred in the bone at 87.5% and 85.4% of patients, respectively.

Additional findings showed that the rPFS benefit was observed across all prespecified subgroups, including age (<65 years, HR, 0.51; 95% CI, 0.35-0.75; ≥65 years, HR, 0.78; 95% CI, 0.62-0.98), site of distant metastases (bone-only, HR, 0.73; 95% CI, 0.54-0.98; visceral, HR, 0.62; 95% CI, 0.39-0.99; other, HR, 0.62; 95% CI, 0.44-0.85) prior docetaxel (yes, HR, 0.61; 95% CI, 0.40-0.92; no, HR, 0.71; 95% CI, 0.56-0.89) and HRR mutation status (HRR mutant, HR, 0.50; 95% CI, 0.34-0.73; non–HRR mutant, HR, 0.76; 95% CI, 0.60-0.97).

OS data, which were at 28.6% maturity, showed that the median OS was not reached in either arm but trended toward improved survival with olaparib/abiraterone vs placebo/abiraterone (HR, 0.86; 95% CI, 0.66-1.12; prespecified 2-sided alpha P = .29).

TFST also was favored with the addition of olaparib. The median TFST was 25.0 months in the olaparib/abiraterone arm compared with 19.9 months with placebo/abiraterone (HR, 0.74; 95% CI, 0.61-0.90; P = .004). Furthermore, the median PFS2 was not reached in either arm, but supported longer-term benefit with olaparib/abiraterone (HR, 0.69; 95% CI, 0.51-0.94; P = .0184).

When evaluated for response, the ORR with olaparib plus abiraterone was 58.4% with a 4.3% complete response (CR) rate and a 54.0% partial response (PR) rate. The stable disease (SD) rate was 26.1% and the progressive disease (PD) rate was 13.7%. In the placebo/abiraterone arm, the ORR was 48.1%, which comprised a 6.3% CR rate and a 41.9% PR rate; the SD and PD rates were 28.1% and 19.4%, respectively. The odds ratio in ORR between olaparib/abiraterone and placebo/abiraterone was 1.60 (95% CI, 1.02-2.53; P = .0409).

Overall, 40.3% of the overall study population had measurable disease via RECIST v1.1 criteria at baseline.

Regarding safety, adverse effects (AEs) occurred in 97.2% and 94.9% of olaparib/abiraterone- and placebo/abiraterone-treated patients, respectively; grade 3 or higher AEs occurred in 47.2% and 38.4% of patients, respectively. AE-related deaths occurred in 4.0% (n = 16) of those on the olaparib arm compared with 4.3% (n = 17) of patients on the placebo arm.

Dose interruptions and reductions occurred in 44.7% and 20.1% of patients who received the addition of olaparib; these rates were 25.3% and 5.6% for those on the placebo arm.

Additionally, more patients discontinued olaparib due to an AE (13.8%) compared with 7.8% of patients receiving placebo. A total of 8.5% and 8.8% of patients in each arm, respectively, discontinued abiraterone due to an AE.

There were no cases reported of myelodysplastic syndrome or acute myeloid leukemia, and the incidence of new primary cancers and pneumonitis were balanced between the 2 arms.

The AE profiles were consistent with the known toxicity profiles of the individual agents. The most common all-grade and grade 3 or higher AE with olaparib was anemia (46.0% and 15.1%, respectively). In the placebo arm, this occurred in 16.4% and 3.3% of patients, respectively.

Cardiac failure occurred at similar rates between the 2 arms at 1.5% with olaparib and 1.3% with placebo; arterial thromboembolic events were also similar at 2.0% and 2.5%, respectively. However, numerically higher venous thromboembolic events were reported for olaparib/abiraterone (7.3%) vs placebo/abiraterone (3.3%), with pulmonary embolism being the most reported venous thromboembolic event (6.5% vs 1.8%, respectively). Pulmonary embolism events were mostly incidental findings via CT scans, and this did not lead to treatment discontinuation with either olaparib or abiraterone.

Quality of life was also found to be comparable between the 2 groups.

1. First PARP inhibitor to demonstrate clinical benefit in combination with a new hormonal agent irrespective of homologous recombination repair (HRR) gene mutations. August 16, 2022. August 16, 2022. https://bit.ly/3A0kVtN

2. Saad F, Armstrong AJ, Thiery-Vuillemin A, et al. PROpel: Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). 

 40, no. 6_suppl (February 20, 2022) 11-11. doi: 10.1200/JCO.2022.40.6_suppl.011

3. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer [published online June 21, 2022]. NEJM Evidence. doi: 10.1056/EVIDoa2200043

Articles

The application is supported by the phase 3 PROpel trial, which showed that adding olaparib to frontline abiraterone acetate and prednisone/prednisolone significantly improved radiographic progression-free survival in patients with mCRPC.

FDA grants priority review to olaparib/abiraterone combo for mCRPC

, discusses the potential of adding immune-checkpoint inhibitors, such as the PD-L1 inhibitor atezolizumab (Tecentriq) to bladder-preservation, or “trimodal,” therapy for patients with bladder cancer. Kamran is a radiation oncologist at Massachusetts General Hospital and assistant professor of Radiation Oncology at Harvard Medical School.

Videos

“The NRG SWOG 1806 trial is a phase 3 trial randomizing patients to standard trimodality therapy or trimodality therapy plus atezolizumab,” says Sophia Kamran, MD. 

Dr. Kamran on including immunotherapy in bladder-preservation therapy

, a recent graduate of the Urologic Oncology fellowship at the University of Kansas Health System, provides great insight on his unique journey. He discusses the life of a urologist in the Army and the characteristics that make an optimal physician within the military. Dr. Banti also offers his thoughts on his life overall as a urologic oncologist and how he can best serve the country as an extremely specialized professional.

On this podcast, Lieutenant Colonel Matthew Banti, MD, FACS, a recent graduate of the Urologic Oncology fellowship at the University of Kansas Health System, is interviewed about his career journey as a urologist in the United States Army.

Lt. Col. Matthew Banti, MD, discusses his unique experience as a urologist in the military

 is the president of Dowling Medical Director Services, a private health care consulting firm specializing in quality improvement, clinical informatics, and health care policy affecting specialty care. He is the former medical director of a large, metropolitan, single-specialty urology group in Fort Worth, Texas.

It’s quite possible if you are reading this article and have been in practice for several years that you have received a letter from Centers for Medicare & Medicaid Services (CMS) entitled, “CERT documentation request.” You may have wondered why you were selected to receive this letter, what happens with the information, what happens if you don’t respond, and what purpose the program serves.

In this article, I will break down the basics of the CERT program and what it means for your practice.

The Comprehensive Error Rate Testing (CERT) program was implemented to measure improper payments in the Medicare fee-for-service program. CERT is part of an annual effort based in statute (most recently, the Payment Integrity Information Act of 2019) to identify and reduce improper payments and hold government agencies accountable. Those agencies, in turn, are required to report to Congress and the public. Improper payments can be overpayments or underpayments and can include payments for services not received, payments for an incorrect amount, or other issues deriving from noncompliance with rules and regulations.

How exactly does CMS determine that a particular Medicare payment is “improper”? The answer is: through a sampling methodology. Each year, a statistically valid random sample of approximately 50,000 claims for Part A, Part B, and durable medical equipment services is selected for review. Then medical records are requested from both the billing provider and the ordering/referring provider (those letters you may have received). Once those records are received, a medical review professional (doctor, nurse, or certified coder) reviews the submitted documentation to determine whether the claim was paid or denied properly under Medicare coverage, coding, and billing rules. Any improper payments are assigned an error category (no documentation, insufficient documentation, medical necessity, incorrect coding, other). An improper payment rate based on this sample (improper payments/total payments) is then assigned and used to project the total improper payments in Medicare for the time period. Each improper payment is also reported to the Medicare administrative contractors, who are then responsible for recouping overpayments (another letter you may have received) or even repaying underpayments.

How big a problem are improper payments in the Medicare fee-for-service program? In the fiscal year 2021 report, CMS projected that $25 billion (6.3%) of payments were improper; all but $400 million were overpayments.

 The 2021 improper payment rate of 6.3% is the lowest since 2009 (6.3%-12.7%). Improper payments in 2021 included $14.2 billion for Part A, $8.5 billion for part B, and $2.4 billion for durable medical equipment. Most of these improper payments were based upon insufficient documentation (64%) or medical necessity (13.6%). Claims errors are classified as medical necessity when the records allow the reviewer to determine that services billed were not medically necessary based upon Medicare coverage and payment policies. Incorrect coding only accounted for 10.6% of all improper payments in 2021 but a significant portion of Part B improper payments (see below).

How do urologists compare with other provider types in terms of improper payments determined through this program? Urologists had an improper payment rate of 3.4% and accounted for $70 million (0.8% of Part B improper payments and 0.3% of all improper payments in 2021). The physician provider types with the highest improper Part B payment rates were psychiatry (16.3%), endocrinology (13.6%), infectious disease (13.5%), interventional cardiology (13.1%), and hospitalist (13.1%); those with the lowest rates were ophthalmology, pathology, allergy/immunology, medical oncology, and rheumatology (all under 2%). The overall average improper payment rate for Part B was 8.5%.4

What procedures were most commonly determined to be improperly paid in the Part B program? According to CMS data, the codes most frequently deemed improper among physician provider types were evaluation and management codes. 

 shows the rates at which reviewers disagreed by code for all provider types and for urologists. Level 4 and level 5 new and established patient office visits, level 3 hospital visits, and chronic care management codes topped the list of codes with improper payments. A total of 263 procedures performed by urologists were reviewed in 2021, and 25 (9.5%) were deemed improper. The majority of these were evaluation and management codes, and the most common denial category was incorrect coding (

There are laws that compel government agencies to identify and reduce improper payments to suppliers, and your Medicare claims may be reviewed as part of this initiative. The latest data (fiscal year 2021) published by CMS on the CERT program indicate that approximately 8.5% of Part B payments were improper, including about 3.4% of payments to urologists. Urologists should take note that high-level (4/5) evaluation and management codes and chronic care management codes were most likely to be deemed improper in this sampling and be sure that their claims are supported both by medical necessity and appropriate documentation. Urologists compare favorably with other specialties in this regard according to the latest data from CMS.

1. Comprehensive Error Rate Testing (CERT): background. Centers for Medicare & Medicaid Services. Updated December 1, 2021. Accessed July 8, 2022. 

2. Comprehensive Error Rate Testing (CERT) program. Centers for Medicare & Medicaid Services. Accessed July 8, 2022. 

3. Medicare fee-for-service Comprehensive Error Rate Testing. Centers for Medicare & Medicaid Services. Updated January 13, 2022. Accessed July 8, 2022. 

4. US Department of Health and Human Services. 2021 Medicare fee-for-service supplemental improper payment data. Accessed July 8, 2022. 

Latest data indicate that approximately 8.5% of Part B payments were improper.

What you need to know about Medicare’s CERT program

Bilal Chughtai, MD, an associate professor of Urology at Weill Cornell Medical College, discusses ongoing research with saw palmetto extract for patients with benign prostatic hyperplasia and lower urinary tract symptoms. Chughtai was part of an international panel of leading urologists from North America and Europe who published the 

, “Rethinking the Role of Saw Palmetto Extract for Men with Lower Urinary Tract Symptoms in North America.”

“We’re in the process of following patients who have taken saw palmetto extract and tracking their clinical diagnosis,” says Bilal Chughtai, MD.

Dr. Chughtai on next research steps with saw palmetto extract for BPH/LUTS

 paper, “The burdens of incontinence: Quantifying incontinence product usage and costs in women,” for which she served as a study author. Sebesta is an assistant professor of urology at Vanderbilt University Medical Center in Nashville, Tennessee.

“Health care disparities are very complex issues; it’s not like a linear cause-and-effect relationship,” says Elisabeth M. Sebesta, MD.

Dr. Sebesta discusses disparities in incontinence product usage, costs

 is professor of surgery in the division of urology at Albany Medical College in New York.

The effect of 5-α-reductase inhibitors (5-ARIs) such as finasteride (Proscar) and dutasteride (Avodart) on prostate cancer–related outcomes has been hotly debated for almost 2 decades. The initial cause for debate arose from data from 2 clinical trials of 5-ARIs for chemoprevention of prostate cancer (PCPT and REDUCE [NCT00056407]), which showed a reduction in the risk of a prostate cancer diagnosis, but an increased incidence of high-risk prostate cancer. Further, observational studies have demonstrated conflicting results on the association between 5-ARI use and prostate cancer–specific mortality (PCSM).

In a recent population-based study, Björnebo et al investigated the association of treatment with 5-ARIs with PCSM in a large cohort of men receiving 5-ARIs for lower urinary tract symptoms (LUTS).

 This study from Stockholm, Sweden was conducted between January 1, 2007, and December 31, 2018, and included 429,977 men who had a prostate-specific antigen (PSA) test within the study period. Investigators linked multiple large registries including the Stockholm PSA and Biopsy Register, National Prostate Cancer Register of Sweden, Prescribed Drug Register, Swedish Cause of Death Register, and others. Only men without a previous prostate cancer diagnosis could enter the study. Men with prior transurethral resection of the prostate or treatment with a 5-ARI before their first PSA test were excluded. A minimum of 1.5 years between the start of 5-ARI treatment and first PSA test was required. A PSA level of 3 ng/mL or greater was considered elevated, and the PSA level was doubled if a 5-ARI had been used for at least 3 months.

Of the final cohort of 349,152 men, 26,190 were 5-ARI recipients with at least 2 filled prescriptions during follow-up. Median follow-up time was 8.2 years. The median exposure to 5-ARI was 4.5 years (interquartile range, 2.1-7.4). Men exposed to a 5-ARI during the study period were older, more likely to have had a previous negative biopsy, and had higher PSA levels than men not exposed to a 5-ARI. Prostate cancer was diagnosed in 1377 (0.4%) and 14,804 men (4.2%) with and without 5-ARI exposure, respectively. The exposed group also had a larger prostate volume, higher Gleason score, and higher primary tumor, lymph node, and metastases stage at diagnosis. A total of 35,767 patients (10.2%) died during follow-up, with 852 deaths attributed to prostate cancer.

Multivariable Cox regression demonstrated no difference in all-cause mortality for any duration of 5-ARI exposure (<2 years adjusted HR, 0.99; >8 years adjusted HR, 0.97). However, use of a 5-ARI was associated with a decrease in PCSM with longer exposure (<2.0 years adjusted HR, 0.89 vs >8 years adjusted HR, 0.44 [adjusted HR difference, 0.50]). Men treated with a 5-ARI had more PSA tests per year (median, 0.63 vs 0.33) and more biopsies per year (median, 0.22 vs 0.12) than the unexposed group. The time from elevated PSA levels to prostate biopsy was shorter in men treated with a 5-ARI than the unexposed group (median, 1.17 vs 1.20 years).

The study investigators found a decreased risk of dying of prostate cancer in men treated for LUTS with 5-ARI for more than 2 years compared with men not treated with a 5-ARI. These results suggest the safety of 5-ARI treatment and that the increased grade and stage of prostate cancer at diagnosis for men receiving 5-ARI treatment are not associated with increased PCSM.

Men receiving treatment with a 5-ARI had significantly higher diagnostic activity, with more PSA tests and prostate biopsies per year than nonrecipients of 5-ARI.

Data from previous studies on the use of 5-ARIs have shown a significantly lower diagnostic activity and prolonged time to prostate biopsy in those receiving treatment with a 5-ARI (median, 3.60 vs 1.40 years) in a cohort of men within the Veterans Affairs health care system.

 They also showed an increased PCSM that was associated with 5-ARI (adjusted HR, 1.39; 95% Cl, 1.27-1.52), which was likely related to inappropriate accounting for the effect of 5-ARI on PSA levels, with delays in diagnosis and treatment, resulting in worse PCSM. A possible explanation for the observed differences in the current study population may be that men receiving a 5-ARI had more frequent contact with urologists, with more frequent PSA tests and biopsies. The increased surveillance of men receiving treatment with 5-ARIs could explain the observed decrease in PCSM in this cohort.

It is important to consider the findings from various studies of 5-ARI effect on prostate cancer–related outcomes in light of the range of questions addressed by those studies such as incidence or detection rate, grade of cancer, and effect on PCSM and overall mortality. Similarly, the distinct features of the health care system and study population should be considered when comparing the results of those studies, as differences in clinical management and diagnostic activity may explain the disparate results.

The question remains whether the prostate cancer–related outcomes from the use of 5-ARIs are due to an effect on cancer biology or some other factors related to clinical practice. As the authors point out, it cannot be determined whether this is a causal relationship or a result of detection bias resulting from a more intensified diagnostic activity (more PSA tests, more biopsies, earlier biopsies) in the 5-ARI group. Could a similarly intensive diagnostic activity in the group without 5-ARI result in similar outcomes?

 with a 5-ARI is not the same as taking the drug for 

. Most studies on this subject include men receiving 5-ARI for treatment of LUTS. Whether the results of those studies can be extrapolated to a chemoprevention paradigm, in asymptomatic men who otherwise had no clinical reason to use a 5-ARI, remains unclear. Findings from most, but not all, observational studies suggest that despite the increased incidence of high-grade prostate cancer associated with 5-ARI usage, it is not associated with worse prostate cancer–related mortality. It is evident, however, that the safety of 5-ARIs as it relates to prostate cancer outcomes is contingent upon the clinician understanding its effect on PSA level and making appropriate adjustments to ensure timely deployment of diagnostic imaging and biopsy.

1. Björnebo L, Nordström T, Discacciati A, et al. Association of 5α-reductase inhibitors with prostate cancer mortality. 

2022;8(7):1019-1026. doi:10.1001/jamaoncol.2022.1501

2. Mian BM. What do recent studies tell us about finasteride and PCa? 

®. December 5, 2019. Accessed August 8, 2022. https://bit.ly/3Q8aRpx

"It is evident...that the safety of 5-ARIs as it relates to prostate cancer outcomes is contingent upon the clinician understanding its effect on PSA level and making appropriate adjustments to ensure timely deployment of diagnostic imaging and biopsy," writes Badar M. Mian, MD.

Do 5-ARIs protect against death from prostate cancer?

Matthew T. Campbell, MD, discusses the abstract, “Interim Results From a Phase 1b Clinical Trial Evaluating Tolerability and Activity of FGFR Inhibition in Localized Upper Tract Urothelial Carcinoma (UTUC),” which he presented at the 2022 AUA Annual Meeting (

). The interim study data showed that infigratinib demonstrated strongactivity in patients with localized UTUC harboring

mutations. Campbell is an assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

“Several of these patients were able to undergo surgery that spared them the need to remove their ureter and their kidney,” says Matthew T. Campbell, MD.

Dr. Campbell on promise of infigratinib in FGFR3 mutation–positive UTUC

The prevalence of erectile dysfunction (ED) increases with age, making it common for those affected to have other comorbidities or treatment regimens. Many of the medications used in the treatment of ED have interactions with other medications, so it is crucial to carefully examine patient profiles to optimize therapy and ensure safety.

The most common cause of ED is when blood flow to the penis is reduced. This can be caused by a multitude of reasons, but we most often see this issue arise commonly in patients who suffer from hypertension and atherosclerosis. The antihypertensive drugs designed to lower blood pressure in those patients can also contribute to reducing blood flow to the penis.

ED can also be associated with diabetes, obesity, smoking, and excessive alcohol consumption. Stress, anxiety, and depression can also psychologically affect a man’s ability to get an erection.

Phosphodiesterase type 5 (PDE-5) inhibitors are considered the first line and the mainstay treatment for ED. When sexually stimulated, nitric oxide is released locally, which increases cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation, which permits more blood flow into the penis, allowing for an erection. PDE-5 is a natural enzyme that degrades cGMP and shuts off the erection mechanism when sexual stimulation ends.

By inhibiting PDE-5, drugs such as sildenafil (Viagra; Pfizer), tadalafil (Cialis; Eli Lilly and Co.), vardenafil (Levitra; Bayer Pharmaceuticals), and avanafil (Stendra; Metuchen Pharmaceuticals) work to temporarily maintain an erection.

PDE-5 inhibitors have very important interactions that must be kept in mind at all times. It is contraindicated to use these meds with nitrates [e.g., nitroglycerin (Nitrostat; Pfizer)], isosorbide mononitrate (Imdur; TopRidge Pharma), isosorbide dinitrate (Isordil; Bausch), or riociguat (Adempas; Bayer).

Doing so can result in severe hypotension, potentially leading to fainting, heart attack, or stroke. Patients who take nitrate-containing products for angina or other cardiac-related problems must avoid using PDE-5 inhibitors. If a patient experiences angina and needs nitroglycerin, it cannot be used until 24 hours after sildenafil or vardenafil, 12 hours after avanafil, and 48 hours after tadalafil.

In general, sexual activity can put a strain on the heart, so it ends up being an even more dangerous situation for those with cardiac issues if they take PDE-5 inhibitors. Additionally, PDE-5 inhibitors also need to be used in caution with other drugs that can cause hypotension, such as antihypertensives and alpha blockers, because they potentiate the hypotensive effects when used together.

Other than these interactions, PDE-5 inhibitors should also be avoided with moderate to strong CYP450 3A4 inhibitors, because these drugs can increase the levels of PDE-5 inhibitors in the body. The reverse is also true for the opposite; CYP450 3A4 inducers could decrease drug levels.

Another drug used to treat ED is alprostadil (injection: Edex; Endo Pharmaceuticals) or (pellets: Muse; Mylan), which is Prostaglandin E1. It acts as a vasodilator, allowing increased blood to flow into the penis. The delivery method of this drug is more invasive because it needs to either be injected directly into the penis or inserted as a pellet into the urethra. Though it’s not often used, it is recommended in patients where PDE-5 inhibitor drugs are contraindicated.

Alprostadil, because it has more of a local effect than a systemic one, does not have many drug-drug interactions. You would still exercise caution while taking other drugs with hypotensive effects, including the PDE-5 inhibitors. Use of alprostadil is contraindicated in certain conditions that predispose patients to priapism, such as leukemia, multiple myeloma, and sickle cell anemia.

It should also be kept in mind that patients may sometimes resort to OTC medicines to self-treat their ED rather than going to a medical professional. There are many natural products that have become popularized for their supposed positive effects.

At the time of writing this article, the most common mainstream ones include ashwagandha, yohimbe, and L-arginine. None of these have sufficient evidence at this time proving efficacy toward treating ED, but because patients may still take them, it is important to know about potential interactions.

Studies have shown ashwagandha to have sedative and GABAnergic properties, causing additive effects with anticonvulsants, barbiturates, and benzodiazepines. Yohimbe should be avoided if patients are on any monoamine oxidase inhibitors, such as phenelzine (Nardil; Kyowa Kirin) and tranylcypromine (Parnate; Concordia).

Finally, L-arginine may have potential interactions with anticoagulant and antiplatelet drugs, increasing the risk of bleeding. It can also potentially lower blood pressure and should be used in caution with other drugs with hypotensive effects. Many of these natural products do not have enough safety and efficacy studies to properly and safely recommend their use for ED treatment.

ED is a growing problem in our aging populations. When treating these patients, it is essential to identify and rectify potential drug interactions.

Steven P. Mathew, PharmD, is a pharmacist with Community Care Rx, a full-service, long-term care pharmacy with offices in Hempstead, NY, and Totowa, NJ.

Sooriyamoorthy T, Leslie SW. Erectile Dysfunction. [Updated 2022 Feb 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. Available from https://www.ncbi.nlm.nih.gov/books/NBK562253/

Many of the medications used in the treatment of ED have interactions with other medications, so it is crucial to carefully examine patient profiles to optimize therapy and ensure safety.

Drug interactions to monitor when prescribing erectile dysfunction medications

The journey from prostate cancer surgery to regular three-month visits to the REACH for Survivorship Clinic at Vanderbilt University Medical Center has not been what was expected by Nashville native and Bellevue resident Scott Sullivant, 60, but could have been much different without the resources he had at his disposal.

Sullivant, a musician and commercial property manager, was diagnosed with prostate cancer at age 58 when his internist, William Martinez, MD, at Vanderbilt Health One Hundred Oaks, noticed that his PSA was starting to go up and referred him to David Penson, MD, professor and chair of Urology.

In Sullivant’s case, Penson and his surgical team did a great job of removing the cancer, but the story didn’t end there.

“I thought it was going to be over after the surgery. I did a discovery process with Dr. Penson, and also did my own research, and concluded that surgery was the best route for me because, based on the biopsy, it looked like it wasn’t too aggressive and we would just cut it out, and I would be done,” he said.

“But that’s not what happened. It was a difficult surgery. Most people wear a catheter for maybe a week; I had mine for a month. Dr. Penson always says, ‘You don’t want to be the one that I’ll remember, and I will never forget you.’”

Sullivant’s regular visits to the Survivorship Clinic, now in its third year, helped to make him whole again.

“I like to say the doctors healed me, but the Survivorship Clinic made me whole,” Sullivant said. “It is lifesaving. The Survivorship Clinic has addressed many other issues for me besides the typical long-term effects of incontinence and ED. The post-op pathology and tests confirmed my disease had metastasized to my spine, which added many new elements and treatments to my recovery. The help and advice I received from the Survivorship Clinic was invaluable.”

Prostate cancer is the most prevalent cancer diagnosis in men, with roughly 200,000 cases diagnosed every year. With a 99% survival rate after five years, there are more than 3.5 million prostate cancer survivors alive today.

Surgery to treat prostate cancer is common and also effective, but side effects like urinary incontinence and sexual dysfunction are quality of life issues that in many cases go overlooked.

Niels Johnsen, MD, MPH, assistant professor of Urology, Division of Reconstructive Urology and Pelvic Health, said VUMC is one of the highest volume prostate cancer treatment hospitals in the country in terms of robotic prostatectomies.

The Survivorship Clinic for prostate cancer patients was originally tailored to address urinary incontinence and sexual dysfunction or erectile dysfunction, with around 50% of men experiencing erectile dysfunction after prostatectomy and 15-20% with urinary issues after the surgery. But joining forces with Liz Winkler, MSN, APN-BC, a nurse practitioner with the REACH for Cancer Survivorship Clinic, gave it a much more holistic approach.

“I have worked with cancer patients for 30 years,” Winkler said. “In that time, I have seen cancer take so much from the patients and the families it affects. Cancer Survivorship is about taking it back.”

The first clinic visit with Winkler is a full hour in order to gain a clear understanding of all of the patient’s needs and concerns. Winkler conducts a review of symptoms after prostatectomy: pain, constipation, infectious symptoms, fatigue, urine control, erectile dysfunction. She then discusses the pathology report and significance of non-detectable PSA and continued monitoring of PSA.

“I try to bridge the gap between primary care and oncology. Many of them don’t have primary care,” she said. “I also talk about cardiovascular wellness because cardiovascular disease is one of the highest causes of noncancer deaths in cancer survivors.”

Winkler has made referrals for everything from psychiatric counseling for depression and anxiety, tobacco treatment, alcohol treatment, lung cancer screening, colonoscopy, medical weight loss, hereditary cancer clinic, Dayani Center for lymphedema therapy, pelvic floor therapy and cardio-oncology.

“We also discuss dietary guidelines (Mediterranean diet), exercise guidelines, tobacco use, alcohol consumption, guidelines for other cancer screenings and stress reduction,” Winkler added.

Sullivant said the clinic has primarily helped him manage expectations and hang on to hope that things would get better.

“It was like a human Google; they had the answers. I can’t imagine what the experience would have been like without them,” he said.

“I truly believe that part of the healing process is the mind. It is the mental aspect of it. It would have been very easy to give up on myself without people like that who were in my corner and encouraging me and giving me the resources to keep pushing forward. Dr. Penson, Dr. Johnsen, they cured me medically. Liz and nurse practitioner Michael Radyko made me whole again. They helped me get back to being myself.”

Johnsen said the emphasis of the survivorship clinic is “living with, through and beyond cancer.

“The benefit of the clinic is a holistic approach to the survivorship care that takes into account things that we as urologists don’t usually consider in our everyday patient encounters,” Johnsen said.

“Liz provides a dedication to our patients that I think we weren’t providing before we started this clinic three years ago. We are finding that patients feel their concerns are being addressed, and there is more investment in the care they are getting after treatment.”

“The benefit of the clinic is a holistic approach to the survivorship care that takes into account things that we as urologists don’t usually consider in our everyday patient encounters,” said Niels Johnsen, MD, MPH, assistant professor of Urology, Division of Reconstructive Urology and Pelvic Health, Vanderbilt University Medical Center.

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