Androgen Receptor Inhibition in CRPC
Tanya Dorff, MD, asks the participants of a roundtable discussion about their opinion survival data of androgen receptor–targeted therapy and treating patients with PET scan-only metastatic castration-resistant prostate cancer.
A 57-year-old Black man presented with an elevated prostate-specific antigen (PSA) level. He had a history of seizures managed on medication and a family history of cancer (mother and sister had breast cancer and brother had pancreatic cancer). Bone scan was negative for metastases. He underwent a radical prostatectomy and extended lymph node dissection. Adjuvant radiotherapy was recommended but refused. Androgen deprivation therapy was initiated. After more than a year the patient re-presented with a PSA doubling time of 8.6 months and was still nonmetastatic. After shared decision-making, darolutamide was initiated.
What are the practical implications of having both overall survival (OS) and metastasis-free survival (MFS) data for androgen receptor–targeted therapy in nmCRPC?
Does this influence your use of these agents?
How will novel imaging impact your approach?
Do patients with PSMA (prostate-specific membrane antigen)-only metastases fit into this group or do they have low-volume metastatic disease?
TANYA DORFF, MD: Have the survival data for enzalutamide [Xtandi], apalutamide [Erleada], or darolutamide [Nubeqa] changed your enthusiasm? When they were first approved, did MFS feel like a strong enough reason, or is it really the survival that would impact your use of these drugs?
SARMEN SARKISSIAN, MD: I think for me it was always MFS.
VEENA CHARU, MD: I agree with that. I also feel that MFS is important.
ARATI CHAND, MD: Yes, but knowing that it also translates into better OS if you start early is even better because then you feel more strongly about starting earlier.
SANDY LIU, MD: I agree. The data are compelling enough for the MFS and now, with the OS data, it confirms our conclusions that these are good data to start patients early on.
ALBERT DEKKER, MD: [The data show] really long MFS, so you assume that it probably would translate into OS. [If the MFS] had been 4 or 6 months less, it could very well have gone either way.
DORFF: A lot of you said you do go straight to PET scans. I’m not sure whether that’s only in the first biochemical recurrence or even in patients with castration-resistant biochemical recurrence. If so, if they do have a PET-detected metastasis, how do you categorize them? Are you treating them as metastatic, or do you treat them as nonmetastatic?
DEKKER: I treat as metastatic.
DORFF: So are you doing some focal radiation if you find oligometastases on the PET scan?
DORFF: I have had a couple of patients where the PET scan finds inguinal nodes. A lot of us say you don’t get inguinal nodes with prostate cancer. Would you believe that? Would you biopsy it? Would you radiate it if it were the only site of disease?
DEKKER: I would biopsy it.
CHARU: I would…do a core needle biopsy.
XINTING FU, MD: Remember, this is PET scan positive, not CT positive.
CHARU: There is a false positive rate in PET scan, as you know.
FU: There is no PET scan–guided biopsy.
DORFF: I think it’s challenging. I’ve had some PET scans that show something that we cannot biopsy and yet we have some doubts about it. It sounds like a lot of you really trust the PET scan and so then you look at metastatic therapies rather than the nonmetastatic group.
DEKKER: Yes. I believe that the majority of patients diagnosed with nonmetastatic disease actually have metastatic disease.
SAM YEH, MD: Let’s say you do find a focal spot and you radiate the focal spot; what if the patient is totally asymptomatic? What’s the role of that?
DEKKER: We make the same assumption that we do with melanoma, with renal cell, isolated lung, isolated colorectal. Isolated disease could be isolated disease.
CHARU: I think for oligometastases, you can’t radiate them. [If] the patient has an inguinal lymph node, I wouldn’t just consider that as a metastatic disease unless I biopsy it, even though it’s PET positive, because the PET could be a false positive.
DORFF: I think [regarding] oligometastatic radiation we have the SABR-COMET trial [NCT01446744],which wasn’t prostate specific but showed adding stereotactic body radiotherapy to oligometastases on top of standard therapy improved survival.1 You could talk to your radiation oncologist about that. Then the prostate-specific trials are STOMP [NCT01558427], POPSTAR [U1111-1140-7563], [and] ORIOLE [NCT02680587]. I think there’s a growing body of evidence. I agree we don’t know for sure it’s the right way to do things but I guess one of the reasons individuals are using PET scans is the hope to find it before it’s widely metastatic. But we have a lot to learn there.
I thought the quality-of-life data for these trials were interesting: there was a delay in deterioration in quality of life. So, delaying metastasis has that added benefit.
1. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058. doi:10.1016/S0140-6736(18)32487-5