Welcome to the first installment of the three- part CARE™ nmCRPC Case Series!
This series aims to provide context and guidance on how to navigate the evolving treatment landscape and some of the challenges that specialists face in routine practice.
The full patient profile and a summary of key discussion points can be found below the video.
A 69-year-old patient is on continuous ADT for a rising PSA post-prostatectomy and adjuvant RT. He was lost to follow-up and represented with a PSA of 12. Imaging studies (CT chest/abdomen/pelvis and bone scans) were negative for metastatic disease. He was started on ADT which controlled his PSA for 3.5 years (PSA nadir 0.7). His PSA and testosterone levels are being monitored every 3-6 months. His most recent testosterone level was < 0.2 nmol/l and PSA was 4.5 ng/mL. His calculated PSADT is 8 months. Recent CT chest/abdomen/pelvis and bone scans were negative for metastatic disease. He is ECOG 0-1, has no symptoms from his cancer, is not working but still active, and has a ≥ 5-year life expectancy. He has high anxiety about his rising PSA.
The decision was made to start him on oral therapy.
Questions and Summary of Discussion
What options are available for this patient?
There are three treatment options that are available in the Canadian market, darolutamide, enzalutamide, and apalutamide.
Benefit was initially shown with metastasis free survival, and eventually a significant improvement in overall survival (see table below).
Table 1. Efficacy outcomes with available androgen receptor-axis-targeted therapies (ARAT)
(Click on Table to Enlarge)
The important thing when introducing treatment in patients who are completely asymptomatic is that there is no detriment to quality of life. See table 2 for select safety data from SPARTAN, PROSPER, and ARAMIS.
Table 2. Safety outcomes with available androgen receptor-axis-targeted therapies (ARAT)
(Click on Table to Enlarge)
All patients that meet the criteria for high-risk disease with a PSA doubling time of less than 10 months and have a life expectancy of at least five years (per the CUA guidelines 2021) should be intensified with one of these three options.
What did you choose and why?
Initially when we started to use these drugs decisions were based on availability, but now that they’re all available in Canada the decision is based on patient characteristics (age, and comorbidities), side effects and drug-to-drug interactions (DDI). This patient did not have any significant comorbidities or a long list of medications, so he’s a candid for any of the three medications.
When we see older patients with comorbidities (such as cardiovascular disease) it is recommended to use darolutamide which has the lowest rate of DDIs.
The CUA tool for DDIs can be very helpful because it allows a way to figure out what agent has the lowest DDIs for a specific patient. You can also take advantage of the knowledge that the hospital/oncology pharmacists have if you have access.
Are there any high-risk nmCRPC patients that you would not treat with an ARAT?
One of the key pieces in the CUA 2021 guideline is they specified that patients should have a life expectancy of greater than five years. There are only a few patients who should not be chosen for treatment (i.e. those who are more likely going to die of a competing risk than their PC).
What does the future of nmCRPC management look like?
The take-home message is really the fact that we now have level one evidence from the SPARTAN, PROSPER, and ARAMIS showing improvement in overall survival, metastases free survival, and maintenance of quality of life for patients with high-risk nmCRPC. It is unlikely we are going to have more significant data from the nmCRPC area with new drugs, indications, or combinations.
The key moving forward is to better identify patients eligible for treatment by checking PSA frequently and calculating their PSA doubling time.
A big question that remains is on the utility of higher sensitivity tests. We’re having more access now to PSMA PET and it is becoming a great tool, but it is still quite new.
¹ MR Smith, F Saad, S Chowdhury, et al. Apalutamide and overall survival in prostate cancer. Eur Urol, 79 (2021), pp. 150-158
² CN Sternberg, K Fizazi, F Saad, et al. Enzalutamide and survival in nonmetastatic, castration-resistant prostate cancer. N Engl J Med, 382 (2020), pp. 2197-2206
³ K Fizazi, N Shore, TL Tammela, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med, 383 (2020), pp. 1040-1049