Treatment Options for Metastatic Prostate Cancer


Dr. Oliver Sartor illustrates the systemic treatment options for metastatic castration-resistant prostate cancer and what to consider when choosing therapies.

Matthew Fowler: I want to transition and focus in on metastatic castration-resistant prostate cancer [CRPC]. Can you talk a little about some of the available systemic treatment options for this disease?

Oliver Sartor, MD: We have a lot, so I’m going to run through some of the frontline studies and then move in sequence. The granddaddy was docetaxel chemotherapy back in 2004. Then we transitioned into having sipuleucel-T and cabazitaxel, which was indicated for patients with progressive castration-resistant disease after docetaxel administration. Very importantly, we then had abiraterone, initially starting in the postdocetaxel space and then coming predocetaxel. Enzalutamide was postdocetaxel initially, then predocetaxel. Then we had radium, which was important because it was bifurcated into postdocetaxel or predocetaxel, and the FDA approval came in for both. I’m sticking with metastatic castration-resistant disease. If I went to nonmetastatic, I’d bring in a couple more. But I’m still concentrating on metastatic castration-resistant disease.

Then we have the precision medicines that came in. Pembrolizumab was a tumor-agnostic approval, which a lot of people forget about. Then we had the 2 PARP inhibitors, rucaparib and olaparib. Their indication is for the homologous recombination repair deficiency for those who have olaparib, and BRCA1 and BRCA2 for rucaparib. We’re going to have a new 1 coming, the Lutetium-177–PSMA-617. The NDA [new drug application] has been submitted to the FDA. The FDA is yet to give any wording on it, but I anticipate that sometime in 2022, we’ll have an additional FDA approval for PSMA-617. That’s a little complex. I didn’t go into all the sequencing issues. I’ll simply say that for the olaparib, you should be post abiraterone, enzalutamide, or another novel hormone. For rucaparib, it’s an accelerated approval. It should have a novel hormone and a taxane. For the PSMA [prostate-specific membrane antigen], which is coming, you have to be post a novel hormone and a taxane.

For each of these, there’s a curative sequence in particular ways. Cabazitaxel can come after docetaxel, but not before docetaxel. There’s a little complexity, but you get the idea. I’ve gone through it a bit historically, and then brought in the precursors to where we stand today.

Matthew Fowler: How do you go about selecting the most appropriate treatment option for a patient? What factors do you weigh when considering options?

Oliver Sartor: Great question. It’s a bit of a complex answer. First, we look at simple things like the age and comorbidity of the patient; the 49-year-old marathon runner is a little different from the 99-year-old nursing patient. We must look at the basic parameters of the bloodstream. Some people come in with a baseline thrombocytopenia, and some from chemotherapy may be particularly problematic. On the other hand, we must look at the genomic constitution of the patient: if they’ve got a BRCA1, BRCA2, that brings to the front possibilities that would not otherwise be feasible.

We also must consider clinical trials, because we often run a whole variety of clinical trials, and some of them are targeted toward a very specific alteration. For instance, we have an ATM mutation clinical trial. Then we look at the prior therapies and response to prior therapies and how they tolerated it. If you take somebody who might have had docetaxel as a prior therapy and did very poorly on docetaxel, then coming in with an additional chemotherapy, such as cabazitaxel, may not be the option we want to pursue. On the other hand, if the patient had a great response to their initial hormone therapy, we’re probably thinking more about a secondary hormonal manipulation. But again, the sequence matters because so many patients are getting abiraterone, enzalutamide, darolutamide, apalutamide prior to getting castration-resistant disease.

We didn’t go into the metastatic castration-sensitive space, but we have all sorts of approvals. We didn’t go into the nonmetastatic CRPC space, which has 3 approvals. I might as well mention them: enzalutamide, apalutamide, and darolutamide. Patients, when they’re coming into the metastatic CRPC space, are often different today from how they used to be in the past because their prior therapies are different today from how they were in the past. That’s probably a long, complex answer, but that’s the way it is. It’s not simple. You must look at a variety of parameters: the cost of what you’re dealing with, affordability, the patient’s insurance, and their ability to pay. There are a lot of factors included in decision-making.

Matthew Fowler: How do you monitor these patients once they do start the therapy that you select?

Oliver Sartor, MD: I explain it to patients this way: I need to know how you’re feeling. That’s important. What’s your quality of life? Are you having pain, or are there issues that need to be addressed from a clinical perspective? I just saw a patient who’s having a lot of trouble with urinary bleeding, and I’ve got to be cautious with him about anything that might induce thrombocytopenia because he bleeds at the drop of a hat. Then I think about my laboratory parameters, the simple ones are started out. Things that I look at are, of course, the CBC [complete blood count]. Thrombocytopenia and neutropenia can be very limiting for patients in some therapies; anemia can be very limiting.

Then we look at basic parameters within the comprehensive metabolic panel: the liver functions, the AST, and ALT. They can be problematic, for instance, when you’re treating with abiraterone. Potassium can be problematic, and we need to follow all the glucoses along. I follow the testosterone as well because every now and then, we have these escapees on the testosterone front. Of course, for the scans and the PSA, we monitor the PSAs routinely. I’ve tried to tell patients that PSA is a good marker but not a perfect marker.

Certainly, there are people who secrete a lot of PSA, and then there are people who don’t make much PSA. I just saw a patient who got very significant metastatic disease, and his PSA is only 2.2 ng/mL. That’s a problematic issue. The type of scanning I do is going to be somewhat tailored to the individual patient. The bone scan and CT scan are my basics, but then also the new molecular imaging: I’m beginning to incorporate the PSMA–PET [positron emission tomography]. By looking at these factors taken in total, we’re monitoring the disease of the patient and the toxicities of therapy. Then we’re putting it together in the context of good patient care and seeing the patient on a relatively frequent basis, particularly when we’re introducing new therapies.

Transcript edited for clarity.

Related Videos
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Findings from recent studies support the use of artificial intelligence-based tools in the context of radiation therapy for patients with localized prostate cancer, according to Neeraj Agarwal, MD.
Germline testing may elucidate important mutations in patients with metastatic prostate cancer who may be eligible to receive treatment with PARP inhibitors, according to Neeraj Agarwal, MD.
In this September edition of Snap Recap, we share our highlights from Prostate Cancer Awareness Month, news in the breast cancer space, and the latest FDA updates.
Artificial intelligence programs may help introduce new care strategies that minimize the risk of adverse effects in patients with prostate cancer, according to Wayne G. Brisbane, MD.
An artificial intelligence algorithm appears to create accurate focal treatment margins in patients with prostate cancer, according to Wayne G. Brisbane, MD.
Related Content