Androgen Receptor Inhibition in CRPC

Part 1: The Role and Availability of Germline Testing and PSMA Scans in nmCRPC

During a live virtual event, Alicia Morgans, MD, MPH, discusses the appropriate usage of new genetic testing and PSMA scans in nonmetastatic castration-resistant prostate cancer.

CASE SUMMARY

In October 2016, a 57-year-old black man was referred to the urology department with a PSA (prostate-specific antigen) of 6.8 ng/mL. His medical history included seizures that were controlled with oxcarbazepine. His mother and sister had a history of breast cancer, and his brother had a history of pancreatic cancer. A multiparametric MRI scan showed a 58 cc index lesion to his left prostate zone, and prostate imaging reporting and data system showed it to be 4/5, 1.8 cm. 3 months later, he had a robotically assisted radical prostatectomy and extended lymph node dissection. 6 weeks post operation, the patient had a PSA of 0.15 ng/mL and baseline serum testosterone of 420 ng/mL.

Androgen deprivation therapy (ADT) was initiated with leuprolide depot at 45 mg. The patient returned in August 2019. His PSA doubling time (PSA-DT) was 8.6 months with a PSA of 1.2 ng/mL. In October 2019 he was restaged, and bone scans showed he was negative for metastatic disease with an ECOG performance score of 0. In October 2020, the patient’s PSA was 3.81 ng/mL.

DISCUSSION QUESTIONS

  • Is there a role for hereditary germline testing in this patient?
  • At this point, when do you restage/image this patient?
  • What is the role of molecular imaging (fluciclovine/axumin, PSMA [prostate-specific membrane antigen], choline)?

ALICIA MORGANS, MD, MPH: He has nonmetastatic disease and a rising PSA, so, really, a biochemical recurrence. At this point, he’s still on leuprolide [Lupron]. Because of that, the disease is castration resistant. What do you think about germline genetic testing in this patient?

EDWARD KAPLAN, MD: With that family history, we probably should have been testing right from the beginning.

MORGANS: I would agree with you. It’s interesting that the NCCN [National Comprehensive Cancer Network] guidelines are recommending germline genetic testing, especially in patients who have family history, all the way back in the localized disease state for patients who have the higher-risk disease features.1 I think his pT3b disease would qualify him, as would the grade group 4—especially with that family history [of breast and pancreatic cancer]. I love that you said that [you would test him at the beginning]. As medical oncologists, we don’t always see these patients, so I think it’s not necessarily our domain, but it’s something for us to be aware of.

AJAY KANDRA, MD: His disease is starting to behave like metastatic [cancer]. I don’t know if it’s purely localized or margin-positive. There may be some unknown metastases somewhere. So, it’s reasonable to do the genetic testing, especially if his family history is positive.

Now, I would be really interested in trying the fluciclovine F18 (Axumin) PET scan, to see if any other lesions are found elsewhere. Increasingly, we are coming to know that there are people with micrometastatic, or something like oligometastatic disease, where you’re addressing the primary, but you’re not addressing that isolated lesion elsewhere. Maybe it’s in the bone, or somewhere in the pelvis. I think it gives us an opportunity, if insurance and NCCN endorse doing very advanced scans up front, to leave behind all these [older types of] bone scans and similar tests.

MORGANS: What do you think about using things like PSMA PET-CT, fluciclovine F18 PET, choline C-11 PET, in patients in the biochemical recurrent state, who now have nonmetastatic castrate-resistant prostate cancer?

MOHAMED KHASAWNEH, MD: When I encounter this situation, there is always the insurance issue. I try to send the PSMA PET; outside of a clinical trial, it’s really hard to get the PSMA PET, but hopefully the [scan] will be available in the coming few months. I think it’s just on the cusp of getting regulatory approval, so hopefully we’ll get less pushback from the insurance. At the University of Louisville, there was a clinical study for those patients with biochemical recurrence, to see if you can salvage them, whether with surgery or with salvage radiation on a clinical trial. That was the only venue for me available to get the PSMA PET.

But, definitely, the data are very convincing. This would be a candidate for those kind of specific non-gadolinium PET scans to hopefully see if we can salvage those patients.

MORGANS: Yes, I think that’s definitely what is happening at this time in our clinics, too. Dr Shah, what are your thoughts on this type of imaging modality?

NEEL SHAH, MD: Yes, it’s very expensive. I think one thing is that insurance generally isn’t paying for a lot of this stuff. I’m not sure there’s any role for this right now. In terms of germline testing, I will generally use Ambry Genetics to get bracket testing. I think it’s reasonable. If someone has metastatic disease, I’m now doing liquid biopsies. Typically, I use Guardant [Health].

As far as imaging, I agree with my colleague; I’m generally doing PET scans and finding bone metastases in those patients. Unfortunately, I’m typically seeing them a little bit late, because the urologist will try to hold on to them as long as possible.

Reference:

1. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 1.2022. Accessed November 1, 2021. https://bit.ly/2Y5BmGi