Case Presentation: A 64-Year-Old Man with Metastatic Prostate Cancer

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EP: 1.Case Presentation: A 64-Year-Old Man with Metastatic Prostate Cancer

EP: 2.Typical Presentations of Metastatic Prostate Cancer and Risk of Disease Progression

EP: 3.The Utility of Genetic Testing in Patients with Prostate Cancer

EP: 4.Mutations in HRR-Related Genes in Prostate Cancer

EP: 5.Available Treatment Options for Chemotherapy-Naïve mCRPC

EP: 6.Olaparib Safety and Efficacy Data from the PROfound Trial

EP: 7.A Urologist’s Treatment Selection for Metastatic Prostate Cancer

EP: 8.Potential Use of PARP Inhibitors for First-Line Treatment of mCRPC

EP: 9.Current Challenges and Future Directions in Metastatic Prostate Cancer

Case Overview:

Initial Presentation (Jan 2017)

A 64-year-old man is found to have a firm bilateral prostate nodule of 1.8 mm on his routine physical exam

Clinical workup

PSA 109.1 ng/mL

Family history of prostate cancer (father, uncle)

Transrectal ultrasound (TRUS)-guided biopsy of the prostate confirms advanced adenocarcinoma of the prostate and Gleason score of 8 (4 + 4)/Grade Group 4

MRI is negative for pelvic LN involvement but positive for one 1.1-cm mediastinal supraclavicular LN (T2bN0M1a)

His ECOG PS is 1

Germline multigene testing of biopsy specimen revealed a BRCA2 mutation

Initial Treatment (starting Feb 2017)

Patient was started on leuprolide and abiraterone; scheduled for physical exam, PSA assessment, and imaging every 3 months.

By the second follow-up visit (6 months after initiating treatment; August 2017), PSA levels declined to 2.1 ng/mL and prostate nodule size was 1.4 mm.

Patient’s disease remained stable through August 2018 (18 months of treatment).

21- and 24-month Follow-up Notes (November 2018, February 2019)

Patient’s PSA levels increased to 46.9 ng/mL in 11/2018 and 73.7 ng/mL in 2/2019.

MRI revealed that the size of the existing positive LN increased to 1.3 cm, and revealed a new, faintly positive 0.9-cm para-aortic LN.

Given the recent findings and the patient’s known BRCA2 mutation status, the patient and clinician decide to initiate olaparib 300 mg BID.

Neal Shore, MD, FACS: Hi, everyone. I’m Neal Shore. I’m the chief medical officer for urology and surgical oncology at GenesisCare, and I’m the medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina. It’s a pleasure to review with you today this Case-Based Peer Perspectives.

Let’s start right off with a 64-year-old man with metastatic prostate cancer. We’re seeing more patients with metastatic prostate cancer disease, I think globally, certainly in the United States, especially given the decrease in the amount of prostate cancer screening that we’re doing. So, it’s January 2017, and this 64-year-old man presents with a firm, bilateral induration and nodularity. It’s felt to be 1.8 mm on a routine exam. And lo and behold, with a suspicious DRE [digital rectal exam], he also then gets a PSA [prostate-specific antigen test] and he’s found to have a PSA of 109.1 [ng/mL]. Family history is important, and it turns out he has both a father and an uncle with prostate cancer. It’s always important to not just ask about prostate cancer, but all cancers in the family, mother’s side, maternal and paternal grandparents, aunts, uncles, siblings.

The patient undergoes a transrectal ultrasound-guided biopsy, and he’s found to have positive adenocarcinoma. It’s a grade group 4, meaning a Gleason 8 [score]. On the grade group scoring of 1, 2, 3, 4, and 5, he’s a 4. An MRI is obtained, and it’s negative for any pelvic lymph node involvement, but positive for a 1.1-cm mediastinal and supraclavicular node. I don’t typically or always get an MRI for full body evaluation. I’ve been historically getting a CT of the chest, abdomen, pelvis, and a technetium bone scan. Certainly, today with the advent of PSMA PET [prostate-specific membrane antigen positron emission tomography] scanning, this can be potentially a replacement for those 2 conventional modalities. I’ve found MRI to be particularly helpful if I’m dealing with a localized high-risk disease in contemplation of either surgical extirpation or radiation. He’s not an ECOG [performance status] 0. He’s got some comorbidities, so this patient is performance status 1. Germline, or hereditary risk for cancer, testing is done. It’s multi-gene. There are panels, they vary depending upon the assay that you’re using, anywhere from just a few to 50 to 80. And lo and behold, this patient is found to have breast cancer gene 2 mutation, or BRCA2, which is the most common of the homologous recombinant repair gene alterations.

It’s February 2017, and for his initial treatment he’s started on an androgen deprivation therapy [ADT] in the form of leuprolide and abiraterone acetate, presumably also with prednisone. This would largely be based on the data that came forward from the LATITUDE and STAMPEDE trials. He has physical exam follow-up, PSA assessments, I’m sure other laboratory work as well, and imaging every 3 months. And at that time, it certainly would be conventional imaging with CT scan and technetium bone scan. On his second follow-up visit 6 months into initiating treatment, combination therapy, we’re not yet to the point to know that he has any problems, but it looks like he’s tolerating the therapy well. He has low-volume disease based upon that MRI, with that 1 particular lymph node. And he’s high risk based on LATITUDE, a PSA greater than 20 [ng/mL], a Gleason score of 8, and 1 lymph node. Interestingly, he would be clearly low-volume disease based upon the charted definition of 4 or less, or 3 or less bone lesions, no visceral metastases. He sees a PSA decline from 109 to 2.1 [ng/mL], a decrease in the size of the prostate nodule. He seems to be doing well, remaining stable for about 18 months.

Now around the 2-year follow-up, his PSA is found to be going up rather significantly. It’s up to 46 [ng/mL] literally a few months later, then up to 73 [ng/mL]. I don’t think one needs to necessarily calculate a doubling time, but it’s pretty clear that it’s a very rapid doubling time. Sometimes if it’s more subtle, using a calculator algorithm is a good thing to do. The MRI is repeated, and the nodule is decreased. Again, I think this is physician preference. But there is now a new paraaortic lymph node. It is slightly less than 1 cm, and the patient therefore has a rising PSA, castration resistant, failing now abiraterone and ADT, and has new lesions. He is known to have a BRCA2 mutation.

The decision is made to start the patient on olaparib. The starting dose is 300 mg. It’s typically 2 pills, 150 mg each, given twice a day. This has been based upon the data that came forward in the PROfound trial, which ultimately demonstrated the efficacy for patients with mCRPC [metastatic castration-resistant prostate cancer] who had progressed with first-line treatment of either abiraterone or enzalutamide. About two-thirds had also received a taxane. But in cohort A, which included BRCA1/2, and ATM, there was not only a marked rPFS [radiographic progression-free survival] benefit but subsequently a marked overall survival benefit for the patients in PROfound who had high tumor burdens and were significantly pretreated with mandatory progression on a novel hormonal agent, being abiraterone or enzalutamide. And about two-thirds had also received taxane therapy. Of those two-thirds, about a third of them had had at least 2 taxanes, typically docetaxel and cabazitaxel.

Transcript edited for clarity.