Androgen Receptor Inhibition in CRPC

Part 1: Guidelines and Recommendations for Treating nmCRPC

During a live virtual event, Eleni Efstathiou, MD, PhD, discussed the recommended approach to front-line treatment of castration-resistant prostate cancer.

During a live virtual event, Eleni Efstathiou, MD, PhD, section chief of Genitourinary Medical Oncology Houston Methodist Oncology Partners, discussed the recommended approach to front-line treatment of castration-resistant prostate cancer.

Targeted OncologyTM: What is the recommended approach for a patient with nonmetastatic castration-resistant prostate cancer (nmCRPC)?

EFSTATHIOU: It is important to follow the NCCN [National Comprehensive Cancer Network] guidelines to get [insurance] reimbursement for our patients.1

The NCCN guidelines maintain that conventional imaging [should be used to determine whether there are metastases present, making] the definition of nmCRPC an administrative one. If we could get very detailed imaging, we would probably find [metastases]. A trial from Germany found that 75% of patients had visible metastases on a PSMA [prostate-specific membrane antigen] PET scan.2

Testosterone levels should be assessed to confirm castration.1 If the PSA [prostate-specific antigen] doubling time is over 10 months, the preference is observation. Alternatively, especially if the patient is extremely anxious, a secondary hormone therapy, such as bicalutamide [Casodex], can be added. In fact, there’s a very old practice where they would use a very low dose of dexamethasone or prednisone [for these cases]. When the PSA doubling time is less than 10 months, the preferred regimens, based on category 1 level evidence, are apalutamide [Erleada], darolutamide [Nubeqa], and enzalutamide [Xtandi].1 Other recommended regimens are secondary hormone therapies.

For a PSA doubling time of more than 10 months, when would you use secondary hormone therapy, and which agents would you use?

In those cases, the concern is reimbursement [as the labels for the drugs mentioned above say that they are indicated for] rapidly increasing [PSA levels]. However, the labels don’t list the PSA doubling time, so this might result in a back-and-forth with the insurance company. My concern is that the moment you start these agents, the clock starts counting for a lengthy exposure to enhanced androgen signaling inhibition, which might lead to more osteoporosis and cardiovascular AEs [adverse events]. I try to explain this to my patients to convince them to delay starting treatment.

When do you decide to image?

If the PSA doubling time is less than 10 months, I image regardless of the PSA level. If the doubling time is more than 10 months but the PSA level is above 2, I image as well. This gives me a baseline. Then can we debate with the patient whether we are going to look at things every year or not. [I do this because there are rare cases] where there is progression of disease without the PSA going up. These are the highly aggressive prostate cancers, so it is important to monitor them. These patients, who might have DDR [DNA damage repair] mutations, such as a BRCA2 mutation, might fall under that category.

REFERENCES

1. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 2.2021. Accessed March 30, 2021. https://bit.ly/34xiIXZ

2. Hoffmann MA, Buchholz HG, Wieler HJ, et al. PSA and PSA kinetics thresholds for the presence of 68Ga-PSMA-11 PET/CT-detectable lesions in patients with biochemical recurrent prostate cancer. Cancers (Basel). 2020;12(2):398. doi:10.3390/cancers12020398