Monitoring Patients With mCRPC

EP: 1.Case Overview: 62-Year-Old Man With Metastatic CRPC

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EP: 2.Monitoring Patients With mCRPC

EP: 3.Frontline Treatment Options for mCRPC

EP: 4.Role of Molecular Testing in mCRPC

EP: 5.ARAMIS and ODENZA Trials in CRPC

EP: 6.Using Darolutamide in Clinical Practice for mCRPC

EP: 7.Approaching Systemic Therapy for mCRPC

EP: 8.Future Directions for the Treatment of mCRPC

Tomasz M. Beer, MD, FACP: What is the typical monitoring? We could think about different points in time in this case to consider that. Early on, the patient had a PSA [prostate-specific antigen] recurrence after surgery. This was 2017, and the care was in line with the standard at the time. But in 2021, we have more sensitive PET [positron emission tomography]–based imaging, in particular PSMA [prostate-specific membrane antigen] PET/CT imaging, increasingly available. Even in 2017, we had Axumin PET/CT, and these high-sensitivity imaging studies might be considered for a rising PSA patient after surgery, especially a rapidly rising PSA early in the course of the disease. Such imaging might have revealed more extensive disease than would have been appreciated with conventional imaging and might have led the treating physicians to go directly to systemic therapy and omit salvage radiation, for example. We don’t know that, but that would be 1 of the goals of more sensitive imaging.

At this point, for patients in response status on a next-generation androgen signaling inhibitor, we see those folks approximately every 3 months. We routinely obtain PSA monitoring, and the frequency of imaging monitoring is more difficult to sort out. The studies that evaluated these agents initially repeated imaging every 12 weeks and did identify some patients who had radiographic progression in the absence of PSA rises. We published on that from the PREVAIL trial, for example. One could make a case for periodic imaging in addition to PSA, but most practitioners wouldn’t recommend imaging at a 12-week interval in somebody whose PSA is controlled and who is asymptomatic. We might consider imaging every 6 to 12 months in a patient who’s responding and doing well on an androgen signaling inhibitor for metastatic disease.

In thinking about different approaches to the treatment of this patient, we could again consider a couple of moments in his prostate cancer history. One areas where I might have considered a different approach is when he was first diagnosed with metastatic disease. This patient, at the time of metastatic diagnosis, had what would be considered low volume. He had a single bone lesion, low-volume recurrent metastatic disease.

Several randomized studies that have shown that in newly diagnosed metastatic disease, combination therapies yield improvements in progression-free and overall survival. We have that evidence for docetaxel chemotherapy, for abiraterone, enzalutamide, and apalutamide, and recently for the combination of docetaxel and abiraterone presented at the ESMO [European Society for Medical Oncology Congress] in September 2021. The benefit in low-volume disease is not completely clear for docetaxel chemotherapy. Typically for low-volume metastatic disease, we will choose an all-hormonal strategy. But the standard of care today for newly diagnosed low-volume metastatic prostate cancer would have been combination therapy and not just leuprolide alone. In his case, he progressed quickly and ended up essentially on combination therapy with a novel androgen signaling inhibitor within about 6 months of that period of time, so we got to the same place fairly quickly. But that’s 1 area where I might have considered a different approach.

At this point, with the patient in response status, we would continue the androgen signaling inhibitor therapy for as long as the disease remains controlled. We’re typically conservative about changing therapy just for a rise in the PSA. All the studies that have been carried out in castration-resistant metastatic disease, and demonstrated an overall survival benefit, treated patients until radiographic progression. We generally maintain therapy until we see some evidence of radiographic progression or worsening of disease. At that point we would have to contemplate what the next line of therapy is. That’s certainly a complex and individualized discussion.

Transcript Edited for Clarity

A 62-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer

Jan. 2017

Initial presentation

• A 62-year-old man is found to have a firm prostate nodule of 1.5 mm on his routine physical exam

Clinical workup

• PSA 15.5 ng/mL
• Family history of prostate cancer
• Hypertension
• Digital rectal exam and transrectal ultrasound (TRUS) of the prostate confirm advanced adenocarcinoma of the prostate and Gleason score of 7 (3 + 4)
• MRI shows lack of metastasis and node involvement (cT2bN0M0)
• His ECOG PS is 1

Treatment

• In Feb. 2017, patient was treated with radical prostatectomy (RP) with nerve sparing surgery and there were no complications.
• PSA levels go down to 0.3 ng/ml post-operatively but rise to 1.5 ng/ml within 3 months.
• Patient receives local salvage radiation therapy and PSA goes down to 0.1 ng/ml.
• PSA levels are checked every 3 months.

Nov. 2017

• PSA doubling time increased between 2 last check-ups and now PSA is 3.5 ng/ml.
• Patient undergoes CT and bone scans and is found to 1 metastatic bone lesion.
• Patient is treated with androgen deprivation therapy (ADT), leuprolide, as continuous treatment and PSA levels go down to 0.2 ng/ml.

May 2018

• PSA levels rise to 5 ng/ml, but patient is asymptomatic and has adequate organ and bone marrow function.
• Patient meets the inclusion criteria for the ODENZA trial and is enrolled in it.
• Patient is treated with darolutamide(1200 mg/day) for 12 weeks, followed by enzalutamide (160 mg/day) for 12 weeks, in addition to continuing on ADT
• Patient is currently in the extension phase of the study and is being treated with darolutamide.