Clinical Cases in Advanced Prostate Cancer - Episode 3

Case 1: Approach to Radiation for Nonmetastatic CRPC

Ganesh V Raj, MD, PhD, shares his approach to radiation therapy in patients with nonmetastatic castration-resistant prostate cancer.

Jorge A. Garcia, MD, FACP: Three months later, in February, this gentleman elects to undergo a local definitive therapy with a robotic-assisted radical prostatectomy, and bilateral extended lymph node dissection.

His final pathology is a pT3bN0, 1 positive margin and no evidence of metastatic disease—so basically a seminal vesicle invasion. His Gleason Group was 4 (4 + 4). As I said earlier, he did have 1 surgical margin to the apex. Six weeks later, his post-operative PSA [prostate-specific antigen] is 0.15 [ng/mL], and his baseline serum testosterone level is 420 [ng/mL]. The recommendation at the time by his urologist was to receive “adjuvant or early salvage radiation therapy for the prostate bed due to the positive margin and possibly also due to a seminal vesicle invasion.”

The patient at the time refused radiation therapy and elected to undergo PSA surveillance. His 2 subsequent PSA values are 0.9 and 1.7 [ng/mL], 3 months apart. At the time, his local team decided to take the patient again for restaging imaging. He underwent a bone scan with technetium-99 and a CT scan of the chest, abdomen, and pelvic region. Those scans read as negative.

The decision at the time was made for him to initiate androgen deprivation therapy [ADT], and the patient received LHRH [luteinizing hormone-releasing hormone]-based agonist therapy with leuprolide at 45 mg subcutaneous, with a plan of continuous therapy. Within the first 3 months, his nadir PSA after initiation of ADT was undetectable.

This is his serial PSA follow-up after initiation of ADT. You can see the dates in this table. From July 2017 through May 2018, the patient remained asymptomatic clinically. However, he did have evidence of serologic progression with a PSA that was at nadir before, 3 months after initiation of ADT, all the way to 4.2 [ng/mL] in May 2018.

His PSA value from August 2018 through October 2019 went from 1.2 all the way to 3.81 [ng/mL]. Using PSA doubling time calculators, his PSA doubling time was calculated to be 8.6 months.

Let me stop here. I don’t want to get into the controversies of the timing of initiation of ADT in the rising PSA syndrome. But Dr Raj, is this a patient who right after surgery you thought perhaps to refer him to radiation oncology early on?

Ganesh V Raj, MD, PhD: As we think about this, this is not uncommon. If you have a patient with high-risk prostate cancer undergoing surgery, and after that you have a positive margin, even if it’s focal, the chance of recurrence is much higher. And so, we often offer patients radiation after surgery. But typically, you have to wait 4 to 6 weeks after surgery for them to recover, to get them to the radiation oncologist and get them done. We usually use that opportunity to get to that initial PSA. So it’s often early salvage, rather than truly adjuvant radiation.

This patient had a PSA of 0.9 [ng/mL], the first one that they tested. Six weeks after, he had a PSA of 0.15 [ng/mL]. He clearly has elevated PSA. Typically, if you have somebody who has a residual PSA at that point, it’s clearly not adjuvant anymore—it’s salvage. At that point, the chance of radiation alone working is low.

With the PSA after that subsequently going to 0.9 [ng/mL], that especially tells you that this patient was one of the patients highly doomed to failure of local radiation therapy alone. He probably had micrometastatic disease based on the pathology. Knowing that, we still give him the option in the sense of trying to do something in terms of a curative approach, if this truly represents a last chance for a curative approach rather than a palliative approach.

Transcript edited for clarity.