Advanced Prostate Cancer Treatment Benefits From Updated Guidelines and Adaptive Sequencing Strategies

Treatment developments in advanced prostate cancer are hinging on the benefits of triplet therapy and individualized care, the results of which are also informing treatment sequencing, according to Jason M. Hafron, MD.

In an interview during the 2022 LUGPA Annual Meeting, Hafron shared advice on optimizing advanced prostate cancer clinics, recapped the biggest advances in urologic cancer treatment in 2022, and discussed how his use of mitomycin-containing reverse thermal gel (Jelmyto) has evolved over time. Hafron is a partner at the Michigan Institute of Urology, PC; an associate professor of urology at the William Beaumont School of Medicine, Oakland University; and the director of Robotic Surgery at Beaumont Hospital Royal Oak in Michigan.

At the LUGPA Annual Meeting, you participated in a discussion titled, "APCC Optimization.” What are your thoughts on best practices for APCCs?

Hafron: It's really exciting, because in 2011, here at LUGPA, we launched mCRPC management and this APCC concept. So it's been over 10 years that we've been having these CME events revolving around advanced prostate cancer clinics and how to manage these patients appropriately. As things evolve, and as we've gained a lot of experience, I think [we've learned] that there's no one-size-fits-all method to this. There are some key components that every advanced prostate cancer clinic should have. One is a nurse navigator. Having your own pharmacy in house is very helpful. And I think what's really critical as we are seeing more patients and patients are becoming more complex, is the utilization of data analytics to identify these patients and to make sure they are being followed appropriately, according to guidelines.

What have been the biggest advances in urologic cancer treatment in 2022? What advances are you anticipating in 2023?

One of the things that drives me to be a part of advanced prostate cancer care is that literally every 6 months, we are having major trials read out guideline-based changes in care. 2022 was a phenomenal year. We saw lutetium read out in the early part of the year, which raises a whole new disease therapeutic: theranostics. We're just at the tip of the iceberg with that, from the results of the VISION trial [NCT03511664]. I think the biggest thing this year is triplet therapy. The ARASENS trial [NCT02799602] read out, which is a combination of [androgen deprivation therapy], darolutamide [Nubeqa], as well as docetaxel. Then there was the PEACE-1 trial [NCT01957436], which was led in Europe [and looked at] the combination of ADT, docetaxel, and abiraterone [Zytiga]. Those are really significant trials; they led to changes in the National Comprehensive Cancer Network guidelines. I think the most inspiring thing about the results of these trials is these are the first trials we've seen in advanced prostate cancer that have extended survival beyond 5 years. We're making a difference; the combination of therapies are really extending men's lives, and hopefully—maybe I'm being a little presumptuous—getting us closer to a potential cure in this space.

What key research has had a hand in revolutionizing sequencing strategies?

Sequencing is always a challenge. It's hard to do sequencing trials, and it's hard to identify best practices. Where I focused a lot of my work recently is in real-world evidence, looking at claims data, and just looking at how patients are being treated in large volumes across the United States. I think that, really, when you tie that to overall survival, and which combinations in which sequencing, I think it gives you a really good clue. I don't know if it's the best way to look at it, but I think it gives you a good idea, or at least some direction on what's ultimately best practice and best sequencing.

How do you hope to see the field progress in the future in terms of sequencing strategies?

We have to keep doing trials and asking questions. As we keep accumulating new therapies every 6 to 12 months, we need to find out their role and what position they should be in. As we have seen over this 10-year journey of advanced prostate cancer, we always start with the sickest patients. We keep seeing these trials move earlier in the disease spectrum, and when you're doing that, it changes the sequencing of when to use these and how to use these. It's a challenge that we're going to face for many years, but it's an exciting challenge because the therapies are very manageable. That's why, as a urologist, I'm very comfortable using these therapies. Ultimately, they lead to improved progression-free survival. Patients just do better, and that's what keeps me going.

Jelmyto was approved in April 2020 for the treatment of low-grade upper tract urothelial carcinoma. How has your use of this treatment evolved since its approval?

That's a great question. If you look at the original trial, the OLYMPUS trial [NCT02793128], most of the treatments were retrograde through a ureteral catheter. In our practice in Michigan, we've evolved to an antegrade percutaneous approach. We've taken this therapy, and we placed percutaneous nephrostomy tubes in these patients, and we delivered Jelmyto in the office. We're seeing that it's beneficial to the patient—it's easier, they don't require a general anesthetic, and we don't have to bring them to the hospital. Also, we don't have the data yet, but I think we're going to have a lower ureteral stenosis rate because we are going antegrade. That has been a significant change, and a change for the better. It's better for the patient, better for our practice, and hopefully will minimize that ureteral stenosis rate.