Novel Hormonal Therapy Approaches in Prostate Cancer

In part two of this roundtable series on prostate cancer, the panelists share their perspectives on using androgen deprivation therapy in combination with novel hormonal therapies, doublets, and triplets, and when to consider docetaxel for high-risk patients. The conversation highlights practical considerations like patient age, disease volume, and quality of life, offering insights for clinicians navigating the complexities of managing mHSPC in real-world settings.

Watch part three of this series: How Genomic Biomarkers Aid in Risk Stratification of Prostate Cancer

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Dr. Riaz:
So there’s still data that suggests that patients who have metastatic hormone-sensitive prostate cancer, they’re up to 50% of patients are still getting under treatment with just single-agent ADT. What is your practice of adding NHTA agents? Docetaxel. Do you use doublets? Do you use triplets? How do you think about approaching patient with initial metastatic hormone-sensitive disease?

Dr. Cherington:
I can take that. So for any individual with a hormone-sensitive metastatic prostate cancer, I’m always thinking of doublet therapy first. Unless I think they do have higher risk disease than I have a bias towards adding docetaxel, the docetaxel darolutamide with the androgen deprivation therapy or if I think they have adequate performance status. So I’ll look at age performance status. Do I think they have a higher aggressive disease, visceral metastasis, greater than four, bone metastasis and the majority of patients will, I’m going to recommend a doublet or a triplet therapy unless their performance status is very poor and then I may only use androgen deprivation therapy, single agent.

Dr. Kantala:
Yeah, I was thinking through that. I agree. One was, probably one of those in those 50% because that’s a big number and it’s not like we can sit here and discuss as long as we can always say, “I use triplet or doublet too as well.” But I have used single agent as well. I agree with Dr. Cherington that there are other factors, especially where I’m in, in East Mesa where the population is much, much older. Really they don’t want to deal with a lot of side effects and they really prefer quality of life and especially low volume disease, eighty-some year old. I do have a discussion saying adding a second agent really doesn’t add a lot more toxicity, but they’re still very apprehensive, if want to start with single agent. And so I probably would be in those cusp of, but where possible young and perform better performance status, I typically tend to start doublet. And if it’s a very high volume disease with liver disease, I do also consider systemic chemotherapy.

Dr. Ewing:
Mine’s predominantly a doublet or triplet therapy for the majority of patients, if they’re of good performance status and kind of what their expected survival is from other comorbidities. I think the era of single agent ADT is passed. And also thinking about kind of, triple therapy versus quad therapy. Are we including bone strengthening medications and those sorts of things, which can really reduce some of the risks of metastatic prostate cancer.

Dr. Riaz:
I think you raised some very interesting points in relation to real world practice. I think in that context, the ARANOTE data is really interesting. It shows that when darolutamide was added to ADT, there was no real increase in side effects. There was very little increase in fatigue, and patients in the darolutamide arm had fewer side effects.

So I think as we move forward into this doublet and triplets era, I think for most patients, we agree that they should be getting at least doublet treatment with ADT plus NHT, and then thinking about where we should add docetaxel chemotherapy. The way I thought about these patients is, and I would like to hear your thoughts, is if somebody presents with high volume disease and conventional scan and synchronous presentation, I think about triplet therapy.

If the patient has a metachronous presentation where the patient had localized disease before, and got definite treatment now recurring with low volume disease, I think, you know, ADT plus NHT doublet is a standard of care. In between patients, it could be the doublets or triplets. You know, I really don’t use much of the docetaxel doublet ADT plus docetaxel in the CSPC setting or single agent unless there is a very compelling reason for a single agent ADT.

Dr. Kantala:
I agree. That’s what I think we all concurred, right? Docetaxel is an addition to the doublet.