Tomasz M. Beer, MD, FACP, presents the case of a 62-year-old man with metastatic castration-resistant prostate cancer (mCRPC) and shares his initial impressions.
Tomasz M. Beer, MD, FACP: I’m pleased to be with you to present a case that I was recently consulted on. This is a case of a 62-year-old man that began in January 2017. At that time this patient was found to have a firm prostate nodule on a routine physical exam. A follow-up PSA [prostate-specific antigen] was elevated at 15.5 ng/mL. The man had a family history of prostate cancer, and his other medical conditions included hypertension. He underwent a transrectal ultrasound-guided biopsy that documented the presence of prostate cancer, adenocarcinoma of the prostate, Gleason grade 3+4. A follow-up MRI revealed no metastasis in the pelvis, no lymph node involvement, and or extraprostatic extension. He was a T2bN0 patient and had a good ECOG performance status of 1.
The next month, he underwent a radical prostatectomy, a nerve-sparing procedure, and there were no unusual complications. His postoperative PSA came down from 15.5 to 0.3 ng/mL, but it did not achieve an undetectable level as 1 would have hoped. Within several months, it began to rise and was as high as 1.5 ng/mL after 3 months. At that point, the patient received local salvage radiation therapy and saw a second PSA response to treatment—his PSA dropped to 0.1 ng/mL—but as you can note, it remained in the detectable range.
Follow-up PSAs continued, and unfortunately, his PSA began to go up. By November 2017, the PSA had reached 3.5 ng/mL, indicating a rapid PSA doubling time. At that point, the patient was staged with a CT scan and a bone scan and was noted to have a single metastatic bone lesion. Treatment was started with conventional androgen deprivation therapy: leuprolide as continuous treatment with initial PSA decline to 0.2 ng/mL.
About 6 months later, in May 2018, the PSA began to rise, and it quickly reached a level of 5 ng/mL. The patient remained asymptomatic and had unremarkable blood test testing and all the usual organ functions, and at that point the patient met inclusion criteria for the ODENZA trial and enrolled. As part of that trial, the patient was treated with darolutamide 1200 mg per day for 12 weeks, then crossed over to enzalutamide 160 mg per day for 12 weeks, in addition to continuing androgen deprivation therapy. The patient remains on the extension phase of the study and is being treated with darolutamide.
What are the general impressions, and how does this case compare with the common presentation of disease? There are a couple of unusual features. This patient appears to have an unusually aggressive prostate cancer. Of course, the disease has a broad range of presentations, and there are patients who present with widespread metastatic disease on day 1. This patient is not quite in that situation. But because he presented with organ-confined prostate cancer, Gleason 3+4, a PSA of 15.5 ng/mL—which marks him as higher risk in the intermediate category—1 would have hoped for a better outcome with initial prostatectomy. One would hope to see at least an undetectable PSA initially, and typically recurrences after surgery take a longer period of time. But this patient clearly had aggressive disease. That was evidenced with the rapid rise in the PSA immediately after recurrence after surgery and then again after the salvage radiation. The PSA kinetics suggest aggressive disease, it’s not surprising to see metastatic disease develop within a year of diagnosis.
The response to androgen deprivation therapy, leuprolide, was less than optimal. A PSA of 0.2 ng/mL is certainly indicative of hormonal sensitivity, but for a patient whose PSA is only 3.5 ng/mL and who has a single metastatic lesion, I would have hoped to see an undetectable PSA after initiation of hormonal therapy. He’s responsive but not completely responsive to initial hormonal therapy and then has an unusually rapid progression on hormonal therapy. Typically for limited metastatic disease, initial hormonal therapy provides disease control for several years, but this patient saw progression within 6 months.
Interestingly and thankfully, he appears to have been quite responsive to next-generation androgen signaling inhibitors, darolutamide and enzalutamide, and has remained in response status for over 2 years. That’s good news for the patient.
Transcript Edited for Clarity
A 62-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer