Recent Updates in Treatment of Non-Metastatic Castration Resistant Prostate Cancer - Episode 1

Treatment Options for Non-Metastatic Castration-Resistant Prostate Cancer

Dr Aaron Berger discusses systemic therapy options, treatment selection and monitoring for patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC).

Audrey Sternberg: Hello and welcome to this CancerNetwork® OncView™ program titled, “Recent Updates in Treatment of Nonmetastatic Castration-Resistant Prostate Cancer.” I’m Audrey Sternberg with CancerNetwork®. We have with us today Dr Aaron Berger from Associated Urological Specialists in Chicago, Illinois. Thank you for joining us today, Dr Berger.

Aaron Berger, MD: Thank you. It’s a pleasure to be here.

Audrey Sternberg: Let’s get started. When you’re treating a patient with nonmetastatic castration-resistant prostate cancer, what systemic therapy options are available?

Aaron Berger, MD: Over the last few years, several new options for nonmetastatic castration-resistant prostate cancer have come to market. The first was enzalutamide, or Xtandi, followed shortly thereafter by Erleada, or apalutamide, and then most recently was Nubeqa, or darolutamide. We’ve used all of them in our advanced prostate cancer clinic. It’s certainly much improved over the previous options that were available as far as first-generation antiandrogen therapies, in which the most recent one was introduced in 1995. There was a long gap in new treatments for this disease state.

Audrey Sternberg: Fantastic. What aspects, including patient and disease factors, do you consider when you’re selecting treatment for these patients?

Aaron Berger, MD: For nonmetastatic castration-resistant prostate cancer, the first question is, do they really need additional treatment? Certainly, some patients may be on androgen deprivation therapy with a rising PSA [prostate-specific antigen] and a testosterone level of less than 50 ng/dL, which would define them as castration-resistant. It depends on age, other comorbidities, how quickly the PSA is rising—or the PSA doubling time—other things in their life, how compliant they are with medications, and if they already take a lot of other medications as far as polypharmacy. Some of those patients have a lot of other issues and aren’t excited about another medication on a daily basis. Or if you don’t think some of those patients are going to be able to be compliant or are worried about adverse effects, we may just observe, especially if they’re rising somewhat slowly.

But there certainly are patients who are progressing a little faster, and the goal of treating them with their nonmetastatic disease is to prevent them from becoming metastatic. Because the data, although they are a little old at this point, indicate that once you have metastatic disease, your 5-year survival decreases. But some of the data that are often quoted in these studies are a little old, from prior to when a lot of these new treatments were available. Those numbers may be a little dated, but preventing the development of metastatic disease certainly is important when we’re deciding on treating patients or just observing them.

Audrey Sternberg: How do you monitor patients with nonmetastatic castration-resistant prostate cancer for disease progression? What would prompt you to change treatment?

Aaron Berger, MD: In our clinic, we typically check PSA and testosterone levels every 3 months. We occasionally see a patient who has been doing well and suddenly has a rising PSA, and they haven’t had a testosterone check for a while, and their testosterone isn’t actually at castrate level. That’s No. 1. Some people often forget to do the testosterone because part of the definition of castrate resistance is to have a testosterone level less than 50 ng/dL. If we’re only focusing on PSA and forget about the testosterone, they might not really have castrate-resistant disease because their testosterone isn’t at a castrate level. Certainly, that’s No. 1.

But assuming their testosterone is less than 50 ng/dL and their PSA is rising on a couple of different occasions, to make sure it wasn’t just a one-time event. Then again, if they’re otherwise doing well and are interested in treatment, and their PSA doubling time is relatively short—in all of the studies for these drugs, 10 months or less [doubling time] was when they were put on the studies. But that’s not in the labeling for all these medications, you can certainly use the medications if their doubling time is 11 or 12 months. But normally 10 months or less is the population we’re really focused on.

We’ll check their PSA and testosterone every 3 months. If they have any significant rises, we typically will follow RADAR [Radiographic Assessments for Detection of Advanced Recurrence] III guidelines as far as imaging, which would indicate if they have a PSA that gets up to 2 ng/mL or higher, we’d certainly consider doing imaging with conventional imaging initially, like CT or bone scan. If it’s negative, then we’d likely just continue observation unless it gets up to 5 ng/mL. And then every doubling thereafter is what the RADAR guidelines would tell us.

I typically won’t wait until PSA is 5, 10, or 20 ng/mL and just keep doing conventional imaging. We’d likely move on to do a next-generation imaging study, such as a PET [positron emission tomography] scan, earlier. But in general, we check them every 3 months with laboratory tests. We’ll do the imaging per the RADAR guidelines or if they have any new change in their symptoms. If they come in and suddenly have new onset of some pain, whether it’s back pain, hip pain, or leg pain, that might indicate a new bone metastasis. Or if there’s any change in their urinary symptoms or any signs of obstruction in the kidneys or anything that might prompt us to do imaging sooner, that’s when we would do an imaging study a little sooner than what the guidelines say.

This transcript has been edited for clarity.