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Alan Bryce: Hello, I'm Alan Bryce, medical oncologist at City of Hope Cancer Center in Phoenix, Arizona. I'm here today with Dr. Mary-Ellen Taplin from Dana-Farber Cancer Center in Boston, Massachusetts.

We're here today to speak about some of the recommendations that came out of the US Prostate Cancer Consensus Conference from 2024. This conference was an expert consensus conference, where key opinion leaders were gathered to debate the areas of gray and unanswered questions in the management of patients with advanced prostate cancer. Dr. Taplin, pleasure to be with you today.

Mary-Ellen Taplin: Thank you, Alan. It's a pleasure to be here.

Alan Bryce: So let me ask you about some of the areas of consensus that the committee members came to. And for the listeners, I'll point out, the consensus meant that 75% of the panel agreed that this is what they would do. So we'll speak to areas of consensus and lack thereof. So one clear consensus that came out is the committee felt that PSMA PET scanning is the preferred imaging approach in patients with biochemically recurrent disease. So could you speak to why that is and why we recommend that.

Mary-Ellen Taplin: Yeah. PSMA PET scans have really been integrated into clinical medicine over the last few years, and they're very sensitive at picking up small volumes of disease. So it's in the NCCN guidelines. And PSMA PET scans are approved for staging patients who have a rising PSA after their local prostate cancer therapy. So I would say, Alan, that it's very routine to do PET scans in this setting.

Alan Bryce: Yeah, I know. I mean I absolutely agree. And let me ask you a different issue, this question of, when we have a patient, a man who's had his prostatectomy, he now has biochemical recurrence some years later, the common scenario, low PSA. So we get the PSMA PET as recommended, and it's PET negative.

Now the committee unequivocally recommends that prostate bed radiation therapy with ADT is preferred over ADT alone. What do we need to remind the listeners here? Why is that a firm recommendation?

Mary-Ellen Taplin: It's very important and a firm recommendation because this type of therapy is potentially curative. And we want to give our patients every opportunity to be cured and spare them any potential for morbidity from more hormone therapy down the road. So that's the number one reason. It's potential for cure.

Alan Bryce: Yeah, absolutely. I think we worry that some people will reflex to ADT without radiation therapy. And it's the radiation that's the curative modality.

Mary-Ellen Taplin: Yeah. And there may be certain patients who are not eligible for radiation, such as a patient who might have had a past rectal cancer and has had pelvic radiation before or a patient whose preference, say, is not to have radiation. But in general, for the vast majority of the patients, it would be radiation after prostatectomy for recurrence.

Alan Bryce: What about the recommendation here that patients who have biochemical recurrence with a nadir PSA of less than 0.2 after months of ADT should be offered treatment interruption, take a drug holiday? What are we trying to emphasize with this point?

Mary-Ellen Taplin: Yeah. So, Alan, I believe what you're talking about is the patient who's had local therapy, either prostatectomy and radiation or started with primary radiation and then relapsed, and now they're in this phase where they have PSA recurrence without any potential curative local options. So in those patients, a very key in point here is that we look at the PSA doubling time because this is a very heterogeneous group of prostate cancer patients. And if the PSA doubling time is favorable, say, over the 10- to 12-month range, those patients have a very long natural history and might not need any prostate cancer treatment at the moment.

But in the patients that I believe you're referring to, those that have the PSA doubling time of 10 months or less, those patients are at risk for metastasis in a shorter time period. This is very old data from Johns Hopkins, actually, natural history studies, and especially with PSA doubling times that are very low, like in the three- to six-month range, we generally will start have a discussion with the patient about the pros and cons. But generally, we'll start them on androgen deprivation therapy. And the intent is not that androgen deprivation therapy is indefinite, that it will be a limited time of hormone therapy.

And a lot of even older studies and newer studies used a 9- to 12-month range of androgen deprivation therapy. There's really no one right or wrong in terms of the exact amount, but in that ballpark of 9 to 12 months is what we would consider treating. You achieve an undetectable PSA on that treatment. And then the treatment is stopped, and a treatment holiday ensues.

Alan Bryce: Now this is an old recommendation, but I think it's really meant here to be a reminder. Could you speak to why the committee emphasizes the importance of prophylactic breast radiation being offered for men going on antiandrogen monotherapy?

Mary-Ellen Taplin: Oh, antiandrogen monotherapy, that's become a hot topic these days. So over the years, there's been many trials looking at antiandrogen monotherapy. And to be honest with you, they were less effective than medical castration.

However, there's been a new trial, new data from the EMBARK trial, in which patients with a rising PSA, with a PSA doubling time of less than 10 months, were randomly assigned to three treatment groups. One was androgen deprivation therapy alone, say, with a drug like leuprolide. One was a androgen deprivation therapy with enzalutamide, so an ARPI. And the third group was antiandrogen monotherapy with enzalutamide.

And what the EMBARK study showed was that there was a favorable delay in time to metastasis, time to castration resistance with both of the enzalutamide cohorts compared to the ADT alone cohort. So that study has brought up the option for patients with rising PSA alone after their curative local therapy to consider antiandrogen monotherapy.

Now, when you're making these choices with a patient, it's very important to really look at the fine print of the EMBARK study because there are clear pros and cons of the noncastrating enzalutamide alone. You might say, why wouldn't I want noncastrating therapy? Well, the downsides of the enzalutamide monotherapy included a side effect of breast tenderness, nipple tenderness, and breast enlargement. And I believe that was seen in up to about 40% of the participants, so quite a large number. So as a potential mitigating factor for that, for men who are choosing antiandrogen monotherapy, one can consider prophylactic breast radiation to-- it doesn't eliminate the potential for gynecomastia, but it reduces it significantly.

Alan Bryce: Yeah, absolutely. And maybe I'll follow up on that. As an area of nonconsensus amongst the committee was whether or not enzalutamide monotherapy should be offered in that setting of high-risk BCR. And you've touched on it somewhat. But could you speak to why that remains controversial and with no consensus?

Mary-Ellen Taplin: Yep. It remains controversial, and that's why I said if you're interested in this topic, please read the EMBARK study. For me, the most important thing to talk to my patients about is the amount of time during the off period from hormone therapy in the nonmedical castration versus medical castration cohorts.

So in the EMBARK study, there were target PSAs, which triggered the patients to restart hormone therapy. So there was a fixed duration, if you will, off. And in the patients who had enzalutamide monotherapy, the time off was, I believe, about 11 months compared to something in the range of 25 or 26 months with the ADT involved with enzalutamide.

So it's important, when you're talking to patients, that they understand that the therapies are not equal in terms of time off. And so now you have to understand when you're on a Lupron-like drug, your time off may be 25 months, but only half of that in general is going to be with a normal testosterone. So in the end, the amount of time with a normal testosterone might be similar, but perception-wise to the patient being off for 25 versus 11 months is meaningful.

Alan Bryce: Yeah, absolutely. All right. Let me ask you one more recommendation here. And this one I think becomes interesting because this is something where I think in the United States we have a different practice than we see with some of our colleagues overseas and speaks to why we feel having a US consensus conference is so important.

So on the topic of metastasis-directed therapy for oligometastatic disease, our US expert panel achieved consensus in the recommendation that for men receiving systemic therapy for biochemically recurrent disease who develop oligometastatic disease, MDT should be offered in addition to continued systemic therapy. So the idea that come in, let's radiate the oligometastatic disease, as opposed to making a systemic therapy switch. So can you speak to the logic behind that and why this is the preferred practice amongst our panel?

Mary-Ellen Taplin: Yeah. I can, and that's how I do practice, generally. The way I describe it to my patients is you want to squeeze all the goodness out of that medicine that they're on, say, it's an ARPI, a first ARPI, and they've been on it for 20 months, and their PSA is slowly trending up, and you decide to stage them with, say, a PET scan, and they have two very small mets.

You don't know the next treatment is going to work as well, if at all. So I think the idea behind that focal radiation to the sites of small sites of known diseases, treat those, follow them. Oftentimes, the PSA will go back down. Everybody's happy. And you've avoided switching to a potentially more toxic therapy that would negatively affect their quality of life.

Alan Bryce: Yeah. Well, Dr. Taplin, thank you so much for your insights. It's always a pleasure to learn from you. Thank you for being here.

Mary-Ellen Taplin: Oh, pleasure. Nice to be here.