Shifting Paradigm in Treating Metastatic Prostate Cancer: Judd W. Moul, MD, FACS

Judd Moul, MD, FACS.

The management of metastatic prostate cancer has undergone a paradigm shift over the last few years. Landmark trials including CHAARTED and STAMPEDE have provided evidence for using therapies that were previously reserved for castration-resistant prostate cancer for patients with hormone-sensitive prostate cancer. In this excerpt of the transcript from his continuing medical education (CME)-approved activity, Clinical Updates and Expert Guidance in Prostate Cancer, Dr. Judd Moul, a urologist at Duke University Medical Center, presents a case study of one of his patients with metastatic prostate cancer; in doing so, he shares valuable insights and a look into the treatment options supported by three clinical trials.

Judd Moul, MD, FACS: So here’s a case. A 65-year-old gentleman came into our practice recently with newly diagnosed metastatic prostate cancer. The twister was that he had chronic hepatitis, as well as some other medical issues and a family history of prostate cancer. In 2010, his prostate-specific antigen (PSA) level was only 1.4 ng/mL, but when he presented to his primary care physician in the latter part of 2019, it was 26 ng/mL. Several months later, it was up to 65 ng/mL. We saw him in early January 2020, and I recommended a biopsy right away.

However, he was not so compliant, and he wanted to push it off until March. Fortunately, we got the biopsy done before COVID-19 hit; we did his biopsy on March 10th, and it showed eight of 12 cores positive, including a Gleason score of 8. So he had high-risk prostate cancer. We had him see his liver specialist on March 25th, and they ran tests and labs to determine his expected survival based on his hepatitis. They felt that his median survival was greater than 12 years. That certainly put him in play for long survival and needing to take his prostate cancer seriously. Unfortunately, when we did his metastatic workup, he had widespread metastatic disease in his bones. So the key question here is, should we limit this man to traditional approach of androgen deprivation therapy (ADT) alone?

Up until 2014, it would have been a no-brainer. This guy would have been put on hormone therapy, and we wouldn’t have done anything else. But now in 2021, we have four FDA-approved options. In addition to the ADT, we could do docetaxel chemotherapy, we could do abiraterone acetate, or we could do one of the second- or third-generation oral antiandrogens, enzalutamide or apalutamide. Again, the key teaching point is we have four options.

How would you treat this patient? Data from CHAARTED and the follow-up of CHAARTED supports using chemotherapy for men with high-volume metastatic prostate cancer, very similar to our patient here. He would qualify for use of docetaxel, even though he had hepatitis C. In addition to CHAARTED, the STAMPEDE trial also supported the use of docetaxel in metastatic prostate cancer, although STAMPEDE was not really stratified by burden of disease. It was more of a mixed bag, where 61% of patients had metastatic disease, 24% had high-risk localized disease, and 15% had node-positive disease. But in the metastatic patients, there was about a 15-month survival advantage, 45 versus 60 months in favor of docetaxel.

The GETUG trial, which was slightly before CHAARTED, also supported the use of docetaxel in metastatic prostate cancer. However, it did not really show an overall survival benefit in high-volume metastasis. Overall survival benefit in high-volume metastasis was 4.7 months. It was a positive hazard ratio, but the P value was 0.14. But then CHAARTED came along and showed a clear survival benefit in high-volume metastases, and STAMPEDE came along and showed an overall survival benefit, though not stratified by high-volume metastatic disease. So what seems to have come out of this as I talk to other experts in the field is that docetaxel seems to be the most appropriate therapy for higher-volume metastatic prostate cancer.

About Dr. Moul

Judd W. Moul, MD, FACS, is a Professor of Urologic Surgery at Duke School of Medicine. Dr. Moul is a retired colonel and a noted researcher and clinician in the area of prostate cancer. He is a urologic oncologist who has received numerous honors and awards, including the Gold Cystoscope Award from the American Urologic Association as well as Castle Connelly Physician of the Year for Clinical Medicine in 2009. He has performed more than 2,000 radical prostatectomies since joining the Duke faculty and is committed to outcomes research on this series and in other areas of prostate cancer. In addition to having co-authored hundreds of peer-reviewed publications, Dr. Moul currently serves on the editorial board for several journals including Clinical Genitourinary Cancer and Prostate Cancer and Prostatic Diseases.

Edits have been made to this excerpt for the sake of clarity and brevity. Any views expressed above are the speakers’ own and do not necessarily reflect those of i3 Health. Gain additional expert perspectives from Dr. Moul by completing the full complimentary CME activity. 

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