Editing AUA: Advanced Prostate Cancer (2023) (section)

=== Non-metastatic castration-resistant prostate cancer (nmCRPC) ===

* '''Novel PET-CT scans have allowed for the discovery of small volume metastases that were previously undetected with conventional imaging. Nevertheless, there remains a subset of patients whose disease remains defined by biochemical PSA rise only.'''

==== Management ====
* '''<span style="color:#ff0000">PSADT >10 months: observation with continuous ADT</span>'''
* '''<span style="color:#ff0000">High risk for developing metastatic disease (PSADT ≤10 months): continuous ADT with either (3):</span>'''
*# '''<span style="color:#ff0000">Apalutamide</span>'''
*# '''<span style="color:#ff0000">Enzalutamide</span>'''
*#'''<span style="color:#ff0000">Darolutamide</span>'''
** Bicalutamide is no longer a viable strategy for treatment of this patient population.
* PSADT is useful in determining which men are at highest risk of developing metastatic lesions or dying from prostate cancer.
** '''Calculate a PSADT starting at the time of development of castration-resistance''' by obtaining serial PSA measurements at 3-6-month intervals
** PSADT <10 months
*** Used to identify the highest risk population for inclusion in the 3 trials that led to approval of the AR antagonists for men with nmCRPC
**** '''FDA approval based on superiority in terms of prolonging MFS by nearly 2 years.'''
***** The use of MFS rather than OS as a regulatory endpoint is novel in solid tumors, and was partially based on the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) meta-analysis of 19 clinical trials demonstrating that MFS is a surrogate for OS for men with localized prostate cancer.
*** Recommended to consider when adding one of the medications to ADT in men with nmCRPC. However, FDA approval of these agents does not specify a doubling time.
* Systemic chemotherapy or immunotherapy should not be used in nmCRPC patients outside the context of a clinical trial.
*'''Follow-up'''
**'''Conventional or PSMA PET imaging q6-12 months to assess for development of metastatic disease'''
***In patients with mCRPC treated with enzalutamide prior to chemotherapy in the PREVAIL trial, radiographic progression occurred in 24.5% of patients without PSA progression, suggesting that routine imaging can identify a significant portion of patients with radiographic progression who would otherwise not be identified. This principle is extrapolated to the nmCRPC population, particularly for men on additional AR antagonist treatment.