This protocol addresses the specific management of men with castration-resistant prostate cancer that remains non-metastatic on conventional imaging (M0 CRPC), with castrate testosterone below 50 ng/dL, biochemical progression, and a short PSA doubling time of 10 months or less — a high-risk group for rapid metastatic spread.
Patients in this category have rising PSA despite castrate androgen levels, no detectable distant metastases on standard imaging, and a PSA-DT of ≤10 months. This short doubling time identifies those at greatest near-term risk of developing metastatic disease, making timely, evidence-guided treatment intensification a priority.
The evidence-supported approach in this setting involves adding an oral androgen receptor pathway inhibitor to ongoing androgen deprivation therapy. Specific agent selection and full dosing are provided in the complete protocol.
Full regimen, comparative options, and decision algorithm available via the structured protocol below.
The principal aims are prolonged metastasis-free survival and meaningful PSA decline. Three pivotal phase III trials demonstrated a survival benefit with this treatment strategy after more than 30 months of follow-up.
Three large phase III RCTs, PROSPER, SPARTAN and ARAMIS, evaluated MFS as the primary endpoint in patients with nmCRPC (M0 CRPC) treated with enzalutamide (PROSPER) vs. placebo or apalutamide (SPARTAN) vs. placebo or darolutamide (ARAMIS) versus placebo, respectively.
Only patients at high risk for the development of metastasis with a short PSA-DT of ≤ 10 months were included.
All trials showed a significant MFS benefit. All three trials showed a survival benefit after a follow-up of more than 30 months.
View source ↗