Sequencing by Prior Exposure: How the mCRPC Treatment Map Has Changed

The reorganization of the metastatic CRPC (mCRPC) systemic therapy section by prior treatment exposure—pre-ARPI, post-ARPI, and post-docetaxel—reflects a clinical reality that has been building for several years. Oliver Sartor, MD, director of the Transformational Prostate Cancer Research Center at East Jefferson General Hospital in Metairie, Louisiana, explains that as ARPIs and docetaxel have migrated into the frontline hormone-sensitive setting, the options available to patients in the castration-resistant phase are now defined by what they have already received. The guidelines are catching up with the approvals that transformed the hormone-sensitive space, Sartor explains.
This organizational shift has direct practical implications. Clinicians must now think carefully about whether a patient has had ADT alone, ADT plus docetaxel, ADT plus an ARPI, triple therapy combining all three, or—increasingly—prior PARP inhibitor exposure. Each combination creates a different downstream landscape.
Sartor further elaborates on the nuances within the ARPI class itself. While the amide-based ARPIs (enzalutamide, apalutamide, darolutamide) are generally not used sequentially with one another given limited cross-resistance benefit, patients previously treated with abiraterone—a CYP17 inhibitor rather than an androgen receptor antagonist—may still derive meaningful responses from a subsequent amide-based ARPI. Enzalutamide holds the castration-resistant indication and is typically the agent of choice in that setting. Understanding these class-level distinctions is essential for navigating the increasingly complex mCRPC treatment landscape.