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“We are witnessing the dawn of teletreatment,” says Jihad Kaouk, MD, FACS. 

Urologists perform first remote robot-assisted HIFU for prostate cancer

Two recent Clinical Forum discussions sought to examine how emerging therapeutic options and evolving treatment standards in non–muscle invasive bladder cancer affect clinical practices and patient outcomes.

NMIBC Clinical Forums highlight novel therapies and treatment strategies

Three recent expert-led Clinical Forums explored current challenges and advancements in the management of non–muscle invasive bladder cancer.

Exploring new avenues in non–muscle invasive bladder cancer treatment

Data showed a significant association between the C allele of the SNP-765G>C of the PTGS2 gene and BPH.

Gene variant associated with increased risk of BPH 

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The inclusion of PAE in the American Urological Association BPH Guidelines offers a non-surgical alternative that can provide long-term relief with minimal downtime and fewer complications, according to the United Urology Group.

United Urology Group and its affiliate practices and Prostate Centers USA® are collaborating to revolutionize men's health care with minimally invasive solutions

Dr. De La Cerda provides an overview of a patient case involving a 68 year-old male presenting with severe back pain, with an analysis of the clinical presentation, workup, and medical history.

Bone Predominant mCRPC Patient Case

Video content above is prompted by the following:

What are your initial impressions of the case?

Video Series

The FDA has accepted a Biologics License Application (BLA) seeking approval of nivolumab (Opdivo) co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20), or subcutaneous nivolumab, for the treatment of patients with all previously approved solid tumor indications for nivolumab as a monotherapy, monotherapy maintenance following completion of combination therapy with nivolumab plus ipilimumab (Yervoy), or in combination with chemotherapy or cabozantinib (Cabometyx).

Nivolumab is currently approved under several indications, including in combination with ipilimumab for the first-line treatment of patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), in combination with cabozantinib for the first-line treatment of patients with advanced RCC, for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy, and in combination with cisplatin and gemcitabine for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma.

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024.

 According to a news release from Bristol Myers Squibb,

 approval of the formulation would make it the first and only subcutaneously administered PD-1 inhibitor.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application,” said Gina Fusaro, PhD, vice president, global program lead, Bristol Myers Squibb, in the news release.

 “Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in 3 to 5 minutes rather than a 30-to-60-minute infusion.”

The BLA submission is supported by findings from the phase 3 CheckMate-67T trial (NCT04810078), in which subcutaneous nivolumab met the study’s co-primary end points by demonstrating noninferiority to intravenous (IV) nivolumab regarding time average nivolumab serum concentration over 28 days (C

; geometric mean ratio [GMR}, 2.098; 90% CI, 2.001-2.200) and minimum serum concentration at a steady state (C

Data from the study, which were presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California,

 also showed that subcutaneous nivolumab demonstrated noninferiority to IV nivolumab in the key powered secondary end point of objective response rate (ORR). Specifically, the subcutaneous arm demonstrated an ORR of 24.2% (95% CI, 19.0-30.0) per blinded independent central review (BICR), compared with 18.2% (95% CI, 13.6-23.6) in the IV arm.

The safety profile for subcutaneous nivolumab was consistent with that of the IV formulation. Among patients who received the subcutaneous formulation, 8.1% experienced injection-site reactions, with all being low-grade and transient. Deaths due to study drug toxicity occurred in 3 patients in the subcutaneous arm and 1 patient in the IV arm. Most deaths that occurred during the study were due to disease progression.

In total, the phase 3, open-label CheckMate-67T trial enrolled 495 patients with advanced or metastatic ccRCC who had received prior systemic therapy. Patients were randomly assigned 1:1 to receive 1200 mg subcutaneous nivolumab plus rHuPH20 every 4 weeks (n = 248) or to 3 mg/kg IV nivolumab every 2 weeks (n = 247) for up to 2 years of treatment or until disease progression, unacceptable toxicity, withdrawal, or death.

The co-primary pharmacokinetic end points for noninferiority testing were C

 of subcutaneous nivolumab vs IV nivolumab. The key secondary end point was ORR per BICR.

Final completion of the CheckMate-67T study is expected in January 2026.

1. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 7, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

2. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Published online and accessed May 21, 2024. https://investors.bms.com/iframes/press-releases/press-release-details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx

3. George S, Bourlon TB, Chacon MR, et al. Subcutaneous nivolumab (NIVO SC) vs intravenous nivolumab (NIVO IV) in patients with previously treated advanced or metastatic clear cell renal cell carcinoma (ccRCC): Pharmacokinetics (PK), efficacy, and safety results from CheckMate 67T. 

4. A study of subcutaneous nivolumab versus intravenous nivolumab in participants with previously treated clear cell renal cell carcinoma that is advanced or has spread (CheckMate-67T). ClinicalTrials.gov. Last updated March 1, 2024. Accessed May 7, 2024. https://clinicaltrials.gov/study/NCT04810078

The FDA is set to have a decision regarding the subcutaneous nivolumab formulation on or by December 29, 2024. 

News

FDA accepts BLA for subcutaneous nivolumab in solid tumors

ImmunityBio announced that it has submitted a supplemental biologics license application (sBLA) to the FDA seeking an expanded approval for nogapendekin alfa inbakicept-pmln (Anktiva) in combination with BCG for BCG-unresponsive non–muscle invasive 

 in April 2024 for use in combination with BCG for patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary disease.

According to the company, “This combination immunotherapy wherein ANKTIVA rescues BCG efficacy, currently approved in the BCG-unresponsive CIS indication, may provide an effective therapeutic option for papillary patients who did not respond to BCG alone and face the prospect of a radical cystectomy.”

The sBLA is supported by data from cohort B of the pivotal QUILT-3.032 trial (NCT03022825), which assessed Anktiva in combination with BCG in patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC.

The median age of patients in this cohort was 72 years (range, 46 to 93 years). The primary end point was disease-free survival (DFS). 

Overall, the study found a DFS of 55.4% (95% CI, 42.0% to 66.8%) at 12 months, 51.1% (95% CI, 37.6% to 63.1%) at 18 months, and 48.3% (95% CI, 34.5% to 60.7%) at 24 months, per Kaplan-Meier estimates. The median DFS was 19.3 months (95% CI, 7.4 to NR).

Progression-free survival (PFS) was 97.1% (95% CI, 88.8% to 99.3%) at 12 months, 94.8% (95% CI, 84.3% to 98.3%) at 18 months, and 88.8% (95% CI, 74.1% to 95.4%) at 24 months. Overall survival was 98.6% (95% CI, 90.2% to 99.8%) at 12 months, 94.3% (95% CI, 82.9% to 98.1%) at 18 months, and 91.7% (95% CI, 79.0% to 96.9%) at 24 months. Disease-specific survival was 100% (95% CI, 100% to 100%) and 97.7% (95% CI, 84.6% to 99.7%) at 12 and 24 months, respectively.

At a median follow-up of 20.7 months (range, 2.9 to 37.1), the cystectomy rate was 7% (5 of 72).

According to ImmunityBio, “In 88% and 82% of subjects, the probability of avoiding surgical removal of the bladder was achieved for as long as 2 and 3 years, respectively, following treatment with ANKTIVA plus BCG.”

The majority (86%) of treatment-emergent adverse events (TEAEs) were grade 1 to 2. According to the authors, “The most frequently reported TEAEs for patients who received BCG plus NAI (cohorts A and B, n=161) were those expected for intravesical instillation of BCG and included dysuria, pollakiuria, and hematuria.”

The most common grade 3 TEAEs included hematuria (2%) and urinary tract infection (2%).

Overall, the QUILT-3.032 trial enrolled patients across 3 study cohorts. Cohorts A and C in the trial included patients with BCG-unresponsive bladder CIS with or without Ta/T1 papillary tumors who received Anktiva plus BCG (cohort A) or Anktiva alone (cohort C). The trial also enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received Anktiva plus BCG (cohort B).

The QUILT-3.032 trial is ongoing, with final completion expected in March 2029.


1. ImmunityBio announces FDA submissions of supplemental BLA for NMIBC papillary disease and for expanded access of ANKTIVA to treat lymphopenia. News release. ImmunityBio. April 15, 2025. Accessed April 15, 2025. https://immunitybio.com/immunitybio-announces-fda-submissions-of-supplemental-bla-for-nmibc-papillary-disease-and-for-expanded-access-of-anktiva-to-treat-lymphopenia/

2. Chamie K, Chang SS, Kramolowky E, et al. IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer. 

. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167

3. QUILT-3.032: A multicenter clinical trial of intravesical Bacillus Calmette-Guerin (BCG) in combination with ALT-803 (N-803) in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Last updated April 13, 2025. Accessed April 15, 2025. https://clinicaltrials.gov/study/NCT03022825

ImmunityBio has submitted a supplemental biologics license application to the FDA for expanded approval of Anktiva in combination with BCG for BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) in the papillary indication. The application is supported by data from the QUILT-3.032 trial, which demonstrated promising disease-free survival rates and a low cystectomy rate. The trial also reported manageable treatment-emergent adverse events. Anktiva, previously approved for BCG-unresponsive NMIBC with carcinoma in situ, may offer an effective therapeutic option for papillary patients.

The sBLA is supported by data from cohort B of the pivotal QUILT-3.032 trial.

FDA approval sought for Anktiva in papillary NMIBC

investigated the impact of conservative management, specifically an app-based therapeutic, on lower urinary tract symptoms (LUTS) in men.

 The 12-week randomized controlled trial involved more than 200 men with LUTS, who were randomly assigned to an intervention group using the app in addition to their usual medication, or a control group maintaining their regular medication.

The app incorporates various modules focusing on physiotherapy, lifestyle adjustments, and other resources aimed at enhancing patient motivation and adherence. It also includes a game that can be played to defer the urge to void. The primary outcome, the International Prostate Symptom Score (IPSS), showed a significant 8-point reduction in the intervention group, whereas no change was observed in the control group. The study also reported significant improvements in overactive bladder symptoms and overall quality of life in the group using the app. Although the individual contribution of each app 

component wasn't specifically measured, study author 

said he believes physiotherapy to be a particularly strong element. “We concluded that by using this app, in addition to the patient's usual medication, it is possible to improve [LUTS] by only looking at conservative measurements,” Gratzke said. In the following interview, Gratzke discusses the study and highlights the app’s utility. Gratzke is professor and chair of urology at the Albert-Ludwigs-University in Freiburg, Germany.

Please provide an overview of this study and its notable findings.

The idea was to look at the improvement of conservative measurements that we do in men with [LUTS]. As you know, we have conservative options, we have medical options, and invasive options. In this trial, we were particularly interested in doing the less invasive treatment options that are all recommended by all the guidelines—by the AUA [American Urological Association], by the EAU [European Association of Urology]. We constructed a randomized controlled trial for 12 weeks where we looked at the improvement of [LUTS] as measured by the IPSS and also overactive bladder as measured by the OAB-q. We did this by using an app. We had more than 200 patients [who were randomly assigned into] 2 groups: an intervention group and a control group. Patients [in the intervention group] were asked to follow the instructions of the app, in addition to the treatment they were already given, and [those in] the control group were just kept on their usual medication.

The app is made up of various modules, which consist of physiotherapy, lifestyle modification, and other modules that reinforced the patient’s motivation to carry on with the app, so it adapted to the individual needs of those patients. We showed in the trial that in the intervention group, the improvement of LUTS was significant as measured by the IPSS. There was a reduction of 8 points, whereas there was no change in the control group, which was an important validation of this study. There was also a significant improvement in overactive bladder symptoms and quality of life. We concluded that by using this app, in addition to the patient's usual medication, it is possible to improve [LUTS] by only looking at conservative measurements.

The study demonstrated a statistically significant improvement in IPSS with app-based therapeutics. Could you elaborate on the specific components of the app-based therapy that you believe contributed most to this improvement? What specific exercises or educational components were included?

We don't know which module was the most important one, because we didn't measure that. We just looked at the whole program, but we will do step analysis and look at individual modules and how much each of them contributed to the improvement of the symptoms. I personally believe that the physiotherapy component is a very strong [part], because, as we know, female patients use physiotherapy all the time, and it improves the pelvic floor, whereas in male patients, we neglect this. I think this study might be a good basis to recommend more physiotherapy. It is a conservative measurement. You have very few [adverse events], if any, and this is a very strong component that contributes to the improvement of LUTS. There's also a knowledge section that provides information on reducing fluid intake at night. It elucidates what [LUTS] actually are. It looks at the anatomy of the prostate. It explains what incontinence actually is, and you get pieces of information every day and every week for those 12 weeks. There is also a 

 button, which, if you experience a significant urge, you press this button, and then you play a little game, which should defer the desire to void.

The minimal clinically important difference for IPSS is 3 points. The intervention group demonstrated a LSM of -7.0 points. How does this translate to clinically meaningful improvement in your opinion, and how does this compare to other standard LUTS treatments?

For anyone working in the BPH [benign prostatic hyperplasia]/LUTS space, you would expect for anything to work to be in the 3-, 4-point difference when you look at the IPSS. If you have less than that, it's usually not clinically meaningful. By having a 7- or 8-point improvement, that would actually show a clinically substantial improvement in LUTS. If you compare this to gold standard medication—tamsulosin [Flomax], alpha blockers—if you look at what you get by doing a minimally invasive treatment option such as UroLift or iTind, by using this app for 12 weeks, you do achieve a significant improvement. So, compared to what you usually use as a first step, we believe that it is really worthwhile performing that intervention, because it's only the first step, and we don't do it in the very severely obstructed patients. This is really important. This is in mild and moderately [obstructed] patients where this is the first step. If this works, this is great. It’s also good because the patient really thinks about how to behave. It explores the body. Usually, the patient has very little knowledge about what the prostate is and what those symptoms are, and it might help to actually inform the patient better.

You mentioned that physiotherapeutic approaches are often neglected in LUTS management. How does this app-based therapy aim to bridge the gap between traditional medical care and these conservative treatments, and what are the barriers you see to wider adoption?

Physiotherapy might not be used by a patient simply because it’s not reinforced by the doctor or the nurse. Nurses play a major role here. If physiotherapy is instructed by somebody who's really knowledgeable, then that might work by itself, without using the app. But the app, of course, uses various components. It gives you haptic feedback. It's adaptive to the individual patient's needs, and you can do it wherever you are and wherever you work. Many patients, as you know, travel a lot. [You can use this] app no matter where you are. It's very easy to use, so I think the barriers to using any of those conservative measurements might be overcome by [it]. It highlights why you should be actually using the individual components, because physiotherapy is also divided into various components, [such as] the strength component and the endurance component. It highlights why each of those components is important.

Given the app-based nature of the intervention, what are your recommendations for health care professionals in terms of integrating this type of therapy into their clinical practice, and what are the training requirements for patients to use it effectively?

I believe that if you look at a certain algorithm that a urologist would hand out to a patient, this might provide the first step in this algorithm. So, before going into any interventions, whether they are medical or surgical interventions, you might be able to use this app in a meaningful fashion. The training requirements are really minimal. It is very easy to use. It is self-explanatory, so I would give it a go. If I were the urologist, there's nothing to lose. Worst-case scenario, it doesn't help, but the threshold to use it is very low.

1. Gratzke C, Schönburg S, Eger S, et al. A randomized trial of an app-based therapeutic for lower urinary tract symptoms. 

2025;4(4):EVIDoa2400290. doi:10.1056/EVIDoa2400290

A recent study explored the efficacy of an app-based therapeutic in managing lower urinary tract symptoms (LUTS) in men. Conducted over 12 weeks with more than 200 participants, the trial revealed a significant 8-point reduction in the International Prostate Symptom Score (IPSS) for the intervention group using the app, compared to no change in the control group. The app, which includes physiotherapy and lifestyle modules, also improved overactive bladder symptoms and quality of life. The study suggests that conservative management can effectively enhance LUTS outcomes.

Christian Gratzke, MD, explains why an app shows promise for patients with lower urinary tract symptoms.

App shows promise in managing lower urinary tract symptoms

The use of a polygenic risk score to select patients to undergo prostate cancer (PCa) screening may identify more patients with clinically significant disease than the use of prostate-specific antigen (PSA) or MRI, according to data from the BARCODE1 trial (NCT03857477) published in the 

“With this test, it could be possible to turn the tide on prostate cancer,” said professor Ros Eeles, of The Institute of Cancer Research, London, England, in a news release on the findings.

 “We have shown that a relatively simple, inexpensive spit test to identify men of European heritage at higher risk due to their genetic makeup is an effective tool to catch prostate cancer early. Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice—we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments.”

The polygenic risk score was developed using 130 variants known to be associated with an increased risk of prostate cancer. According to the authors, “Participants with a polygenic risk score in the 90th percentile or higher were invited to undergo prostate cancer screening with multiparametric [MRI] and transperineal biopsy, irrespective of PSA level.”

To be included in the study, patients had to be aged 55 to 69 years, of European ancestry, and have a World Health Organization performance status of 0 to 2. Additionally, participants could not have any psychological, familial, sociological, or geographical situation that would impede study participation.

In total, 6393 patients had their polygenic risk score calculated. Of those, 745 (11.7%) had a risk score in the 90% percentile and were invited to undergo screening. MRI and prostate biopsy were completed in 468 (62.8%) of invited participants. The most common reason for patients choosing to withdraw from the study before and after MRI was reluctance to undergo prostate biopsy, reported by 40.7% of nonparticipants.

Of those who did participate, prostate cancer was detected in 187 patients (40%). The median age at diagnosis was 64 years (range, 57 to 73 years), and the median PSA level was 2.1 μg/L (range, 0.3 to 274).

The detected cancer was classified as intermediate- or high-risk disease (Gleason score of 7 or higher) per National Comprehensive Cancer Network (NCCN) criteria in 103 patients (55.1%). Additionally, the detected cancer was classified as unfavorable intermediate-, high-, or very high-risk per NCCN criteria in 40 patients (21.4%).

The current prostate cancer diagnostic pathway in the UK is based on high PSA levels and positive MRI results. If this pathway was used, prostate cancer would have been missed in 74 of the patients (71.8%) determined to have intermediate- or high-risk disease. Prostate cancer would have also been missed in 17 patients (42.5%) determined to have unfavorable intermediate-, high-, or very high-risk disease.

Of the 187 patients with cancer detected, 100 patients (53.5%) had either a high PSA level (defined as greater than 3.0 μg/L) or a lesion with a Prostate Imaging–Reporting and Data System (PI-RADS) score of 3 or higher.

The authors also noted, “Only 30 (16.0%) had both a high PSA level and a lesion with a PI-RADS score of 3 or higher and therefore met the standard criterion for progression to prostate biopsy in accordance with the traditional management pathway in the United Kingdom.”

The investigators also estimate that disease was overdiagnosed in 39 participants with a risk score in at least the 90% percentile. They defined overdiagnosis as patients’ screen-detected prostate cancer taking longer than their remaining lifetime to progress to clinical disease.

Based on these findings, the authors concluded, “In a population-based prostate cancer screening program involving participants in the top decile of risk as determined by a polygenic risk score, the percentage found to have clinically significant prostate cancer (Gleason score 7 or higher) warranting treatment in accordance with national guidelines was higher than the percentage that would have been identified with the use of PSA or MRI.”

However, they acknowledge that future research is still warranted.

“To evaluate fully the implementation of polygenic risk score alongside established risk factors in a national screening program, further research is required, including research into the recommended age at which to obtain a polygenic risk score, tests of replication in persons of non-European ancestry, and an evaluation of economic effects.”

The BARCODE1 study remains ongoing, with final completion planned for December 2028.

“We’re now excited to be rolling out our updated test, PRODICT, to diverse populations—as Black men are twice as likely to develop prostate cancer—and younger groups, as those with a genetic predisposition are more likely to be diagnosed at younger ages,” Eeles added in the news release.

 “We are also currently comparing the saliva test to other potential screening options, as part of the TRANSFORM trial, to assess the most cost-effective and accurate way to screen men for prostate cancer.”

1. McHugh JK, Bancroft EK, Saunders E, et al. Assessment of a polygenic risk score in screening for prostate cancer. 

. 2025;392(14):1406-1417. doi:10.1056/NEJMoa2407934

2. Simple spit test could finally turn the tide on prostate cancer. News release. The Institute of Cancer Research. April 9, 2025. Accessed April 10, 2025. https://www.icr.ac.uk/about-us/icr-news/detail/simple-spit-test-could-finally-turn-the-tide-on-prostate-cancer

3. The BARCODE 1 study (full study): the use of genetic profiling to guide prostate cancer targeted screening. (BARCODE1). ClinicalTrials.gov. Last updated August 13, 2024. Accessed April 10, 2025. https://clinicaltrials.gov/study/NCT03857477

A polygenic risk score (PRS) may enhance prostate cancer screening by identifying more patients with clinically significant disease compared to PSA or MRI. The BARCODE1 trial demonstrated that a PRS, developed using 130 genetic variants, effectively identified men at higher risk, leading to early detection of aggressive cancers. The study involved 6393 participants, with 745 invited for screening based on their PRS. Results showed that 40% of screened participants had prostate cancer, with 55.1% having intermediate- or high-risk disease. Further research is needed to optimize PRS implementation in diverse populations.

"Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice—we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments," says professor Ros Eeles. 

Polygenic risk score may identify more clinically significant PCa than PSA, MRI

In February 2025, the labeling requirements for testosterone caught up with what urologists and other prescribers have known for years: testosterone does not increase the risk of adverse cardiovascular outcomes.

The journey to this conclusion began in 2014, when the FDA first convened a Joint Meeting of the Bone, Reproductive and Urologic Drugs and the Drug Safety and Risk Management Advisory Committee to discuss increased reports of stroke, heart attack, and death in men who were taking testosterone. The result of these discussions was to initiate a trial to assess the safety of testosterone in men with hypogonadism—a trial we now know as the TRAVERSE trial (NCT03518034).

The results from TRAVERSE were reassuring. Published in 2023 in the 

, the data showed that the incidence of major adverse cardiac events (MACE) for men on testosterone was non-inferior to that of those on placebo. Specifically, a MACE event occurred in 7.0% of patients taking testosterone vs 7.3% of patients taking placebo (HR, 0.96; 95% CI, 0.78 to 1.17; 

It's important to take into consideration the design of the TRAVERSE trial. TRAVERSE was a randomized controlled study that enrolled 5246 men aged 45 to 80 years who had a preexisting or a high risk of cardiovascular disease at study entry. Patients received either transdermal 1.62% testosterone gel (with the dose adjusted to maintain testosterone levels between 350 and 750 ng/dL) or placebo gel.

Although these results confirmed what many urologists already knew, the data may alleviate concerns for other prescribers of testosterone, such as those in primary care.

“There was a lot of fear and caution on a provider standpoint, even if you knew the data and knew that the risks were not significant or not dramatic,” said Landon Trost, MD, founder and director of the Male Fertility and Peyronie’s Clinic in Orem, Utah, in an interview with 

More importantly, these findings may alleviate concerns for patients.

“Men have been deprived of testosterone therapy because of fears of MACE, and it now opens up testosterone therapy to very large groups of men who will benefit from it,” John P. Mulhall, MD, a urologic surgeon at Memorial Sloan Kettering Cancer Center in New York, New York, told 

These findings push back against previous studies that raised concerns about the safety of testosterone. The original studies, though, had design flaws that called into question the accuracy of their findings.

According to Trost, “The original studies that reported these risks had numerous major flaws, and those involved in the testosterone side of things even called for retractions of some of these papers.”

This is important to discuss with patients when counseling them on the risks and benefits for testosterone, especially for those who may have concerns based on the original studies.

Helen L. Bernie, DO, MPH, an assistant professor of urology at Indiana University School of Medicine in Indianapolis, Indiana, explained her approach, saying, “When I'm talking to my patients, I explain the studies with them. I explain to them why we had that data. I talk to them about the newer studies and the safety. I specifically mention the TRAVERSE trial, because I think that helps give patients a lot of reassurance, because they recognize that it's a large, randomized controlled trial that showed safety in men who already were at high risk for cardiovascular disease.”

However, testosterone should be used wisely in clinical practice, considering that TRAVERSE assessed MACE risk in a controlled environment, according to Steven E. Nissen, MD, a cardiologist at Cleveland Clinic in Cleveland, Ohio. Patients should be carefully counseled on the risks and benefits, and initiation of therapy should be done with a careful titration of dosage.

He cautioned, “I want to say that while we agree with the FDA taking away the black box warning, this is not a license to give testosterone to every aging man who doesn't feel like they felt when they were 18 years old.”

In 2025, labeling for testosterone was updated to reflect that it does not increase cardiovascular risk, aligning with findings from the TRAVERSE trial. This trial, involving 5,246 men, demonstrated that testosterone therapy's risk of major adverse cardiac events (MACE) is non-inferior to placebo. Despite these findings, caution is advised due to potential venous thromboembolic events. The updated labeling is expected to alleviate prescriber and patient concerns, potentially expanding testosterone therapy access. Experts hope for further guideline updates to reflect these findings.

In February 2025, the FDA recommended a removal of the black box warning related to an increased risk of adverse cardiovascular outcomes for all testosterone products. This recommendation has important implications for urologists and the patients they treat.

United Urology Group

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