Androgen Receptor Inhibition in CRPC
Tanya Dorff, MD, asks the participants of a roundtable discussion if they would order germline testing and molecular imaging in a patient with nonmetastatic 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 (ADT) was initiated. After more than a year the patient re-presented with a PSA doubling time of 8.6 months and was still nonmetastatic.
TANYA DORFF, MD: Is this patient someone you would consider for germline testing?
SANDY LIU, MD: [I would], given his strong family history.
DORFF: Yes, he did have a strong family history. Do you refer to a genetic counselor or do you order it yourself and then only refer if it’s positive?
LIU: I usually refer them to telegenetics.
VEENA CHARU, MD: I usually order it myself, but if the insurance gives me a hard time I send the patient to a genetic counselor.
XINTING FU, MD: We can order our own test. Let’s say the patient has no family history—would you still order the test or refer to a genetic counselor?
DORFF: The NCCN [National Comprehensive Cancer Network] guidelines suggest germline testing for anyone with high-risk [or recurrent] prostate cancer.1
FU: To be honest, I’ve been ordering a lot of tests and have not seen a single positive one.
DORFF: That can be frustrating. But I suppose it provides some reassurance. I always tell [patients] why I want it; [it will potentially impact their] siblings or children and their screening, but when it’s negative then maybe that’s a relief. [The incidence of getting a positive test] should be 10% or 15% according to Pritchard et al in the New England Journal of Medicine, but it feels like a lower rate.2
SAM YEH, MD: Let’s say a patient does not have a strong family history. You’re just checking [for germline mutations] because the patient has prostate cancer. Will you also check for BRCA and homologous recombination repair [deficiency]?
DORFF: Yes, I think that makes a lot of sense, especially in the absence of a family history where you want to know in the future whether you could have a treatment option for them.
How about imaging? Are you using fluciclovine PET scans? Are you referring out for PSMA PET scans or choline PET scans?
ALBERT DEKKER, MD: I’m using fluciclovine and just started to refer for PSMA.
DORFF: Do you order the CT/bone scan first and then go to a PET scan, or do you just go right to the PET scan? Do you feel like it adequately shows you bone?
DEKKER: I will go straight to PET scan.
CHARU: I also order a PET scan.
DORFF: There is a lot of discussion before they’re castration resistant about whether we should change our salvage radiation plan based on the PSMA PET. It’s surprisingly still pretty controversial. To me, if we see something we should react to it because PSMA PET is validated as being accurate. But there’s still controversy and there are some prospective trials trying to validate [PSMA PET further]. They’ve shown that [physicians] do change management, but now they’re trying to go back and prove whether that’s the right thing to do—whether it impacts patient outcomes.
DEKKER: If you find metastatic disease or highly suspected metastatic disease in a borderline patient, you may forgo surgery or move directly to radiation or even basically treat as metastatic up front.
DORFF: Yes, I think [PET scan makes sense for staging high-risk, localized disease]. PET scans are much more useful when the PSA is low, like 0.2, 0.4, or 0.5 ng/mL. [In that case] it makes no sense to get a CT scan.
How often do you image your patients [with rising PSA]?
DEKKER: It depends on what I am planning to do. If I am watching a patient with no therapy, probably every 3 or 4 months.
LIU: I do the same. About 3 months or when the PSA doubles.
1. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 2.2021. Accessed March 30, 2021. https://bit.ly/34xiIXZ
2. Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N Engl J Med. 2016;375(5):443-453. doi:10.1056/NEJMoa1603144