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Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

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Take a look through several of the notable phase 3 trials in progress that will be spotlighted at AUA 2025. 

10 urology trials in progress to be highlighted at AUA 2025

"The AACU has been discussing the evolution of state policy to ensure that biomarker testing, including PSA screening, is covered by payers," writes Ron Lanton, Esq.

Biomarkers in urology: Policy and legislative advances

Pearls & Perspectives, hosted by Amy Pearlman, MD, is the latest multimedia program from Urology Times.

Introducing Pearls & Perspectives, with Amy Pearlman, MD!

Treatment with nadofaragene led to a complete response rate of 75% at 3 months. 

Nadofaragene firadenovec elicits high CR rate in phase 3 trial in Japan 

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In these videos, expert surgeons demonstrate robot-assisted penile inversion vaginoplasty, single-stage metoidioplasty, and simple orchiectomy for transgender patients.

Transgender surgery: Videos demonstrate cutting-edge techniques

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

Men receiving collagenase clostridium histolyticum (CCH, Xiaflex) for Peyronie’s disease appeared to have incremental benefits from each of 4 treatment cycles.

The finding was presented at the 2021 Sexual Medicine Society of North American Fall Scientific Meeting by Matthew J. Ziegelmann, MD, of Mayo Clinic, Rochester, Minnesota.

As explained by the investigators, the safety and efficacy of CCH had previously been demonstrated in two phase 3, randomized, double-blind, placebo-controlled trials in which CCH injections were administered in up to 4 treatment cycles at 6 week intervals. Each cycle comprised 2 injections administered 1 to 3 days apart. For the current study, the authors sought to evaluate incremental changes in penile curvature during the course of CCH treatment.

The investigators utilized pooled data from the 2 placebo-controlled trials to conduct a posthoc analysis. They calculated the change from baseline and from previous penile curvature measurement after each treatment cycle (weeks 6, 12, 18, and 24). A 2-sample t-test was used to compare mean percentage change in penile curvature. The percentage of patients who were classified as treatment responders (curvature reduction of at least 20%) was compared using Fisher’s exact test.

For the study, 832 men were evaluated, 551 of whom received CCH treatment and 281 of whom received placebo. At baseline, the mean ± standard deviation (SD) penile curvature was 50.6±14.7° in the CCH group and 50.4±14.1° in the placebo group. Compared with baseline, the mean ± SD percentage change in penile curvature was as follows:

• -12.8±20.3% for CCH vs -6.2±18.8% for placebo after the first treatment cycle

• -22.6±23.5% vs -10.6±23.1% after the second treatment cycle

• -29.9±25.0% vs -14.6±24.0% after the third treatment cycle

• -33.1±28.0% vs -16.6±25.5% after the fourth treatment cycle.

When comparing change from the previous measurement, ie, between first and second treatment cycle, between second and third treatment cycle, etc, mean ± SD percentage change in penile curvature was as follows:

• 11.1±21.8% vs 5.0±16.4% after the second treatment cycle (

• 9.6±21.8% vs 3.9±17.0% after the third treatment cycle (

• 6.3±23.0% vs 2.0±17.2% after the fourth (

In addition, the percentage of patients with at least a 20% reduction in penile curvature since the previous measurement was as follows:

• 29.9% for patients receiving CCH vs 18.3% in the placebo group after the first treatment cycle (

• 29.1% vs 16.9%, respectively, after the second treatment cycle (

• 25.2% vs 12.8%, respectively, after the third treatment cycle (

• 20.2% vs 10.9%, respectively, after the fourth treatment cycle (

The investigators also reported that in patients with a response after 2 treatment cycles, 40.2% of patients treated with CCH had an additional reduction in curvature of at least 20% after completing 4 treatment cycles vs 19.5% of patients receiving placebo (

= .001). In addition, in patients with less than a 20% reduction after 2 treatment cycles, 29.8% of patients receiving CCH were classified as treatment responders after completing the fourth treatment cycle compared with 20.8% of patients receiving placebo (

“Results would suggest benefits with performing a full series of 4 CCH injections, even among men who are initial non-responders,” the authors concluded.

1. Ziegelmann M, Liu G, McLane M, Hu Y, Trost L. Collagenase clostridium histolyticum treatment for Peyronie’s disease: analysis of outcomes and cumulative benefits after each injection cycle. Paper presented at 2021 Sexual Medicine Society of North American Fall Scientific Meeting; October 21-24; Scottsdale, Arizona. Abstract 059.

Collagenase clostridium histolyticum (CCH) treatment for Peyronie’s disease shows incremental benefits across four treatment cycles. A study presented by Dr. Matthew J. Ziegelmann at the 2021 Sexual Medicine Society of North America meeting analyzed pooled data from two phase 3 trials. The analysis revealed significant reductions in penile curvature with each CCH cycle compared to placebo. The percentage of patients achieving at least a 20% curvature reduction increased with each cycle. The findings suggest that completing all four CCH treatment cycles is beneficial, even for initial non-responders.

Collagenase clostridium histolyticum delivers incremental benefits across treatment cycles for Peyronie’s disease

The National Comprehensive Cancer Network (NCCN)’s recent decision to remove the word “preferred” from its prostate cancer guidelines in reference to active surveillance as an approach for low-risk disease—and subsequent revision “preferred for most patients”—caused a stir within the urology world. The preferred approach for low-risk prostate cancer was the subject of a debate held at 2021 Society of Urologic Oncology Annual Meeting. In this interview, 

 a participant in the debate, explains the rationale for active surveillance in low-risk prostate cancer and offers advice for patients recommended surveillance but who want to undergo treatment. Eggener is the Bruce and Beth White Family Professor of Surgery and Radiology, vice chair of urology, and director of the High Risk and Advanced Prostate Cancer Clinic at the University of Chicago.

You are participating in a debate at the SUO annual meeting regarding the preferred approach for low-risk prostate cancer. Could you summarize the sides of this debate?

For men who are diagnosed with prostate cancer, roughly half are diagnosed with early-stage and what we term low-risk prostate cancer. The debate is over the NCCN guidelines on what the recommendations are for those men and what the options are. Historically, active surveillance was "preferred." Recently, that word was taken out [of the guidelines] and as of about 24 hours ago, the panel inserted it back in, but it's an important topic to debate. What are the things that go into the decision of surveillance vs treatment?

What points are you making in this debate?

First, and most important, there are a lot of data available from many different series showing superb long-term outcomes with active surveillance for men with low-risk prostate cancer, so it's a data-based recommendation that it should be the preferred option. Additionally, all the other international guidelines—our contemporaries from Europe, Australia, Canada—all also recommend surveillance as the preferred or primary consideration for management. However —and I think there'll be some agreement amongst the debaters—there are certain men with low-risk prostate cancer that do have features where treatment should be discussed as an option, side by side with surveillance.

How has your approach to low-risk prostate cancer evolved since you began your clinical practice?

I started practicing about 14-15 years ago, and I was one of the first urologists in the Chicagoland area to routinely offer surveillance. There was a lot of blowback from my colleagues and even some patients. But thankfully, there's been an evolution in the maturation of the data that are available, where they continue to show excellent long-term outcomes. Now, almost all men that I see with low-risk prostate cancer do surveillance. There are rare exceptions. But it's changed quite dramatically over the last 15 years both in my practice/our region and certainly across the United States. But we do have a long way to go across the United States to more appropriately have men do surveillance because there are still way too men in my opinion who get treated unnecessarily for early-stage prostate cancer.

What new and forthcoming advances in prostate cancer diagnosis and treatment, if any, do you think may alter your approach to low-risk disease?

In many men with low-risk disease, I don't know whether it's a service or disservice that they've been diagnosed with it. When we screen men, we're primarily looking for higher grade disease—Grade Group 2 or Gleason 7 or higher. Once a man is diagnosed with low-risk prostate cancer, we have a lot of tools available with MRI, genomic biomarkers, biopsy, PSA, and we need to do a better job of figuring out how to integrate those and minimize the number of biopsies a man has to have, but still maintain the excellent long-term outcomes.

What advice would you have for a patient who is recommended for active surveillance but wants to undergo treatment anyway out of fear of the cancer getting worse?

There certainly are men that hear the word "cancer," and their gut instinct, very appropriately, is to do treatment. My advice would be to make sure that they meet with someone who spends a considerable amount of time with them and thoughtfully reviews the rationale of surveillance —most importantly, the excellent outcomes—and they also have an honest overview of what treatment might entail because there are some risks associated with it that can be life altering.

What are the issues with "overtreatment" in lieu of surveillance?

Overtreatment has been a decades-long problem, and we've made headway in the United States to minimize it, but we still have a long way to go. If treatment had no side effects, or an extremely low likelihood of side effects, there would really be no controversy whatsoever. But even in expert hands, if a man undergoes surgery or radiation, there's unfortunately a risk to their quality of life. There is some potential baggage that can come with it. The great news is most guys do really well. But they need to understand what they're getting involved with.

The recent revision of the NCCN guidelines on prostate cancer, specifically the removal and reintroduction of "preferred" for active surveillance in low-risk cases, has sparked debate. Active surveillance is supported by extensive data showing excellent long-term outcomes and is recommended by international guidelines. Despite this, some patients still opt for treatment due to fear, highlighting the need for informed discussions about the risks and benefits. Advances in diagnostic tools like MRI and genomic biomarkers may further refine management strategies, aiming to reduce unnecessary treatments and maintain quality of life.

Eggener addresses the NCCN’s reversal on its controversial decision to remove the word “preferred” from its guideline on active surveillance for low-risk prostate cancer.

Dr. Eggener on why active surveillance should be “preferred” for low-risk prostate cancer

At the 2021 Society of Urologic Oncology Annual Meeting in Orlando, Florida, Pavlos Msaouel, MD, PhD, gave a presentation titled, “The future of adjuvant therapy for high-risk nonmetastatic RCC.” In this interview, Msaouel discusses some key points from this talk and provides an overview of current challenges in the high-risk non-metastatic renal cell carcinoma space. Msaouel is an assistant professor in the departments of genitourinary medical oncology and translational molecular pathology at the University of Texas MD Anderson Cancer Center, Houston.

You gave a presentation called, "The future of adjuvant therapy for high-risk nonmetastatic RCC" at the SUO annual meeting. Could you provide a brief overview of your presentation and discuss some of the highlights?

With the exciting results of the KEYNOTE-564 trial [NCT03142334], which led to the FDA approval of adjuvant pembrolizumab [Keytruda] for high-risk nonmetastatic renal cell carcinoma, the question now becomes, how do we choose whether or not to offer adjuvant therapy to our patients based on patient-level characteristics? In many cases, we do have enough knowledge to make such precise inferences, but in others we do not, and my talk will focus on identifying these unmet research needs that need to be addressed to further improve the adjuvant treatment landscape for our patients.

What are some current challenges in the treatment of high-risk non-metastatic RCC and what is being done to overcome them?

One challenge that is not discussed as often as it should be is the issue of end points. [One point that] I highlight in my talk is that the overall survival end point, which is a clinically meaningful critical end point, is at higher risk of being estimated in a biased way compared with other outcomes like disease-free survival, using our current methodology. It is an open challenge for us to develop methodology that can properly de-bias our overall survival estimates. Other challenges include unmet needs with regards to observational research. In some cases, we need interventional experimental types of research, but in other cases, we need observational research with representative real-world data. For example, we lack and need to develop contemporary risk nomograms for what the KEYNOTE-564 trial called M1 NED cancer. We need to develop more accurate risk nomograms for rare kidney cancer histologies. We need to improve our recurrence risk estimations by incorporating knowledge from genomics and other types of "omics" such as radiomics. In addition, we need interventional experimental-type research in order to accurately estimate the adjuvant treatment effects for rare kidney cancer histologies because trials like KEYNOTE-564 only included patients with the most common kidney cancer histology, clear cell renal cell carcinoma, and so we need to have accurate estimates for the more rare histologies. In addition, given these exciting results, other new regimens should now start to be explored—both single-agent drugs as well as combination therapies.

What have been some of the notable highlights in the kidney cancer space in 2021? What advances are you anticipating in 2022?

One key highlight is the introduction of adjuvant immunotherapy for the first time as an FDA-approved drug for patients with high-risk localized kidney cancer. That is certainly practice changing. The other exciting thing is that we're focusing more and more on the more rare histologies, which is very helpful to our patients. In 2022 and beyond, we'll see trials dedicated to rare histologies. At the same time, I anticipate that in the coming months and years, we will have trials reading out that test triplet therapies. We currently have doublet therapies for metastatic kidney cancer approved. The question is, can combining the current doublets or other doublets with a third drug meaningfully improve outcomes for patients with metastatic kidney cancer?

What is the current status of adjuvant treatment for RCC and what unanswered questions or unmet needs remain?

The current status has changed. It is very exciting to say that we now have, for the first time, an immunotherapy drug that is FDA approved as an adjuvant therapy for patients with kidney cancer. This will likely change the natural course of the disease and improve outcomes for our patients. But at the same time, more work is certainly necessary. We need to generate the kind of data that will allow us to make patient-specific decisions. How can we say, based on each specific patient, whether an adjuvant therapy is preferable or not, because in some patients, the side effects or other costs, including the financial and other logistical costs of adjuvant therapy may not be worth the benefit that they're getting. Figuring out how to balance that trade-off between risks and benefits for each individual patient is something that we need to work on more.

The introduction of adjuvant immunotherapy, specifically pembrolizumab, marks a significant advancement in treating high-risk nonmetastatic renal cell carcinoma (RCC). However, challenges remain, such as developing unbiased methodologies for overall survival estimates and creating accurate risk nomograms for rare kidney cancer histologies. The need for both interventional and observational research is emphasized to improve treatment strategies. Future directions include exploring new regimens, including triplet therapies, and addressing patient-specific decision-making to balance the benefits and risks of adjuvant therapies.

Pavlos Msaouel, MD, PhD, discusses the latest developments with adjuvant therapy in nonmetastatic renal cell carcinoma.

Adjuvant therapy for high-risk nonmetastatic RCC: Improving the treatment landscape

shares takeaways from the 2022 LUGPA Annual Meeting discussion, “Appreciating Diversity in Urology Care.”Bowen is an assistant professor of Urology at Northwestern University Feinberg School of Medicine.

You were part of the LUGPA discussion “Appreciating Diversity in Urology Care.” Could you share some takeaways from that session?

My talk was really focused on tips and tricks for welcoming any gender-diverse patient into your practice and how to make them have a great health care experience, both in the general clinic sense and for any urologic complaint they come in with outside of the bottom surgery aspect that we talk about so frequently. The takeaways are: don't make assumptions about any patients, ask them about their history, ask them their pronouns, train your staff to address patients in an affirming way—there are many resources for that—and understand that our gender-diverse patients have a history of having many unique barriers to health care, so it's even more important to provide an equitable experience.

Could you talk about some of the biggest unmet needs in urologic care for LGBTQ patients?

Specifically for our transgender and gender-diverse patients, there are still insurance issues and access issues in general. There's also a fear of the health care system; 30% of patients have had a negative health care experience. We are coming into a time where there are lots of positive changes with insurance and access. There's increasing acceptance culturally, and that's going to translate into more patients coming to see us. The more we can take down those barriers to entry—whether they be insurance, or being comfortable with using pronouns, preferred names, and correct terminology—the better.

Could you discuss your own research interests and what you're working on currently?

We have a comprehensive program at Northwestern where we are involved in multiple different research projects, even outside of the urologic space. Specifically, right now, we're embarking on a prostate cancer screening project to better understand in our institution, which is all 11 hospitals in our system, what our rates of prostate cancer screening are in trans women or any non-binary patient assigned male at birth. That'll be important, because there's very little literature on that, so there's no guidelines. I have also just done a survey of the entire pediatric urology network as to how many providers are providing care for transgender patients and what the unmet needs are for adolescents as they emerge into adulthood.

Diana K. Bowen, MD, emphasizes the importance of creating an inclusive healthcare environment for gender-diverse patients, highlighting the need for staff training and understanding unique barriers faced by these patients. She identifies insurance and access issues as significant unmet needs in urologic care for LGBTQ patients, noting the fear many have of the healthcare system. Bowen's research at Northwestern University includes a prostate cancer screening project for trans women and non-binary patients assigned male at birth, addressing the lack of existing guidelines and understanding unmet needs in pediatric urology.

"Specifically for our transgender and gender-diverse patients, there are still insurance issues and access issues in general," said Diana K. Bowen, MD.

Thomas J. Walsh, MD

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