A 76-Year-Old Man With Recurrent Castrate-Sensitive Prostate Cancer - Episode 6
Best practices for monitoring patients’ response to AR-targeted therapy as used to treat castrate-sensitive prostate cancer and considerations for managing patients to help prevent the emergence of castrate-resistant disease.
Nicholas Vogelzang, MD, FASCO, FACP: I monitor patients every 3 months. If their nadir is deep, and their PSA [prostate-specific antigen] becomes undetectable, I will go 3, maybe 4, sometimes 6 months. If their PSA remains above 0.1 ng/mL, I remain vigilant. If, however, their PSA never achieves 0.1 ng/mL or hovers above 4 ng/mL, that was an ominous finding in the SWOG [Southwest Oncology Group] data. If they range in that 2, 3, or 4 ng/mL range, that means that there is some resistance to AR [androgen receptor] inhibitor therapy, and I tend to be more willing to do chemotherapy. That is the point at which castrate-sensitive disease is transitioning to castrate-resistant disease, and therefore those are patients with whom we need to have a discussion about early use of the alternative agents: chemotherapy, radium, sipuleucel-T, PARP inhibitors, etc. These patients need to be educated as you go through their course.
On the other hand, if they get a phenomenal response, and their PSA becomes undetectable, those patients may sometimes go years before they move on to alternative regimens. It all depends upon how low their PSA drops. It reminds us of the old song, “How Low Can You Go?” If their PSA goes very low and stays low, they may be one of those sensitive patients who does not need to move beyond androgen receptor inhibition therapy. It depends upon their sensitivity to hormone therapy. That is all we can say right now.
What is it that triggers the flip from hormone-sensitive disease to become hormone-resistant? We do not know. When does the cancer cell decide that it does not need the testosterone mechanism for growth anymore and becomes autonomous or becomes independent? I have had many discussions about what to call that. Is that androgen-resistant? Is it castrate-independent? Is it hormone-refractory? It is unknown; it is probably a gradual process, and it is probably independent. It is probably cell by cell, but it also may occur quickly, and it may be a harbinger mechanism that occurs as LDH [lactate dehydrogenase] and PSA go up, but it is almost certainly a function of tumor bulk.
The larger volume of cancer is more likely to progress to castrate-resistant, whereas a small volume of tumor is more likely to stay castrate-sensitive. That is why I tend to radiate the tumors because, by radiating the tumor that is metastatic, you may prevent the development of castrate-resistant disease because you eliminate clones of cancer that may evolve to castrate-resistant disease. I for one tend to radiate metastatic disease, hoping perhaps somewhat optimistically that I can prevent the emergence of castrate-resistant disease.
Much of the decision about switching mechanisms or adding a mechanism relates to the PSA values and the clinical picture. When the PSA starts to rise when there are new bone lesions or new nodal lesions, that is when you start saying, “It is time to flip to something else.” I said that before, but that is docetaxel, radium, sipuleucel-T, and PARP inhibitors if the patient has an appropriate target. Those should all be considered earlier, and those are for when you switch to a different mechanism. When you have a rise in PSA, that is the easiest thing to do. You also have to be aware that some cancers do not make more PSA when they progress: 20% of cancers progress without a PSA rise, so pay attention. Symptoms, weight loss, bone pain, etc, can all occur without necessarily having a rise in PSA.
Transcript has been edited for clarity.
Case: A 76-Year-Old Male With Recurrent Castrate-Sensitive Prostate Cancer
Treatment and Follow-Up