EP. 3A: Androgen Deprivation Therapy Failure and Second-Line Options in Advanced Prostate Cancer


In the third video of the series, Alicia K. Morgans, MD, MPH, of the Dana-Farber Cancer Institute sheds light on the rapidly developing treatment landscape for advanced prostate cancer.

[Androgen deprivation therapy] (ADT) is really the backbone of systemic therapy for advanced prostate cancer, and it has been for decades. Importantly, we now know that in many situations of advanced prostate cancer, it's ADT intensification or ADT combinations that are really now standard of care.

When ADT or a combination therapy starts to fail the patient, and the [prostate–specific antigen] (PSA) is rising, and the disease looks like it may be spreading or growing on scans, we absolutely need to think about next steps. And, in most cases, I try to think about next steps in our treatment journey before we get to that point, just to make sure I understand what our options are so that I'm ready to move forward, especially if it's an emergent situation. Some of that preplanning, of course, requires that we do additional testing. And particularly for things like PARP inhibitors, where we need to do genetic germline or somatic testing, that is going to need to happen in advance of when we need that treatment.

The more we test, the more we'll find, and the more opportunities we'll have to use these agents. And these agents, particularly pembrolizumab and other [immune] checkpoint inhibitors, as well as PARP inhibitors, are being tested in earlier and earlier stages of prostate cancer. And so we may find that we're using these agents even in localized disease at some point in time and certainly early enough [in the] hormone-sensitive metastatic setting, as well. So the more we test, the more we find.

It's a great thing that the NCCN … continues to meet and update its prostate cancer guidelines continuously, as it does with all of its cancer guidelines. And 1 of the updates that has been made within the last year or 2 has been to really solidly recommend that as soon as a patient has metastatic prostate cancer or high-risk or very high–risk localized prostate cancer, that patient is eligible for—and, in fact, recommended to undergo—germline genetic testing. And the reason that the guidelines suggest this is because the earlier we can get that testing done in a population that is at high-enough risk (where we will see mutations, so that it's worth doing the testing) … the earlier we can have that information … at our disposal should we need it in the future.

I think that the next few years are going to be incredibly rich when it comes to prostate cancer clinical trials, and the advances are going to be coming fast and furious. It's been only 6 months or even less since we learned the results of the VISION trial. I do expect that the ongoing trials investigating lutetium [Lu 177] PSMA[-617] are going to probably move it forward, and we will be able to see its benefits be even more pronounced as we move it earlier in the disease spectrum.

Beyond that, we're going to see combinations of drugs that we already have and new drugs come into play, I think, that are going to further prolong life expectancy and also maintain or improve quality of life because of better disease control and good tolerability of these drugs. The combinations really are pretty endless, but the good thing is that this is all [the] interest [of] trying to find new treatments, new combinations, and new ways to help people live longer and feel better. So I'm really heartened that it's going to be a whirlwind, but it's also going to be a really, really hopeful one, and I look forward to seeing where this journey takes us.

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