Clinical Cases in Advanced Prostate Cancer - Episode 4

Case 1: Initiating ADT for Nonmetastatic CRPC

Mary-Ellen Taplin, MD, reviews the criteria used to initiate androgen deprivation therapy in the setting of rising PSA syndrome for patients with nonmetastatic castration-resistant prostate cancer.

Jorge A. Garcia, MD, FACP: Mary-Ellen, let me ask if you can perhaps give us your thoughts. What are the criteria that you use to initiate androgen deprivation therapy [ADT] in the rising PSA [prostate-specific antigen] syndrome after a patient has undergone local definitive therapy where it’s surgery, radiation, or radiation followed by surgery?

Mary-Ellen Taplin, MD: Thanks, Jorge. I use several criteria. I look at the overall level of the PSA and decide to get basically an Axumin PET [positron emission tomography] scan at this point. I try to wait until the PSA is around 1, or at least 0.8 to 1 [ng/mL], to get the scan. I’ll then take stock of what I find on the scan—often they’re negative—and have a conversation with the patient about holding off of hormone therapy.

In the absence of any detectable metastasis on imaging, I do put a lot of stock in the PSA doubling time. I have lived with PSA doubling time as an important marker for approaching 30 years, and I really do believe that it is important.

My patients who have PSA doubling times of over a year, sometimes in the range of 2 years, can go to very high PSAs without having metastasis. I really try to avoid starting hormone therapy. I think the important point here is it’s not one-size-fits-all. I have seen some practitioners who say, “When your PSA gets to 2, or 3, or 5, you’re going to start hormone therapy.” I strongly believe that you need to look at the patient’s initial Gleason score, when the PSA rose from the time of surgery and what they’re doubling time is, and try to keep patients off hormone therapy as long as possible.

Jorge A. Garcia, MD, FACP: Thank you. I think the important point is that we all believe when you look at this case, that unequivocally in the absence of positive objective findings in the scans, this gentleman has met the definition for castration-resistant disease. I don’t think we have his testosterone, but if his testosterone is at castrated level—less than 50 [ng/dL] by guidelines—the rising of his PSA, even in the absence of symptoms and even in the absence of positive findings in the scans defines this patient as castration-resistant, certainly M0 CRPC [nonmetastatic castration-resistant prostate cancer]. I think the importance of that is we believe that we induce that sort of a stage by virtue of the early initiation of ADT in that biochemical recurrence after local definitive therapy.

Patrick, how do you convey that message to patients and our colleagues in the community as to the importance of following that strict definition for castration-resistant disease? Mary-Ellen and I and many others have always reviewed this topic as we go throughout the country, and I’m afraid that it’s a misperception of the definition of castration-resistant disease. Oftentimes, physicians feel that you need to have symptomatic disease or objective progression. And clearly that is not the case.

Patrick G. Pilié, MD: Absolutely. The first discussion with the patients all the time, as Mary-Ellen already pointed out, is that there’s not really an absolute PSA value that points you to start or not to start. It is the trend and the individual characteristics of the patient, both clinically, and what are their comorbidities? What is their age at diagnosis? We all know that prolonged time on androgen deprivation therapy comes with its own bag of morbidity and serious impacts on quality of life for these patients.

So the PSA trend, the doubling time is extremely important. It’s also important that patients and providers in the community have that very objective definition of castrate-resistant in terms of making next treatment decisions with the addition of second-generation antiandrogens, which I know we’ll talk about, on top of androgen deprivation therapy.

Mary-Ellen Taplin, MD: I almost have gotten to the point where I never order a PSA without getting a testosterone level because I always want to know how to interpret the PSA in the context of the testosterone. Even in my own practice, I’ve had a couple of advanced practitioners who find a PSA is rising, don’t know what the testosterone is, and tell the patient, “You need to restart Lupron.” But their [testosterone level] was 10 [ng/dL], and restarting the Lupron isn’t really the point of what’s going to help the patient. I would go as far as saying that unless you know what the patient’s testosterone is, you can’t interpret the PSA.

Ganesh V Raj, MD, PhD: I totally agree. It’s something that I tell all my residents, that it has to be a part of your armamentarium. You’ve got to look at that.

One other thought I was going to tell you, Jorge, was that we talk about using radiation therapy, whether it’s an adjuvant or a salvage, or radiation therapy. But remember if you had a Gleason 8 [score] prostate cancer, the radiation is never given alone. Radiation is always given in conjunction with androgen deprivation therapy. Typically, the patient will go on ADT for at least 3 months prior to them initiating radiation therapy. And so even if a patient, especially with a high Gleason prostate, was being considered for radiation therapy, the first move would be to start them on ADT, which basically negates the whole point of waiting for PSA anyway. For that reason we, more than not, wait for that initial PSA to come back before we intervene.

Jorge A. Garcia, MD, FACP: Yes. I find that lack of testosterone far more relevant when patients have undergone local definitive radiation therapy with 24 months of ADT for high-risk disease instead of surgery. Or for that matter, for that patient, phenotype that has undergone salvage radiotherapy with ADT, which is now the standard of care for most patients. And yet, many of them remain suppressed even after the completion of those 6 months of ADT, yet they develop castration-resistant disease. But we never check the testosterone, at least in a community setting sometimes. Those are great points, thank you.

Transcript edited for clarity.