Shifting the view of prostate cancer from "androgen-driven" to "androgen receptor-driven" provides a new framework. In curative settings, after the androgen receptor is targeted for a defined period, restoring testosterone is seen as logical to improve patient quality of life once the cancer is destroyed.

When PSA levels rise after initial treatments, patients face the difficult realization that their cancer is likely a chronic condition to be managed, not a disease to be cured. This existential moment requires a fundamental shift in their approach and expectations for the rest of their lives.

The term "hormone resistance" was misleading. Researchers discovered that even in a castrate state, prostate cancer tumors produce their own testosterone locally. This maintained androgen receptor signaling, proving the disease was still "androgen addicted" and opening the door for new targeted therapies.

Intensive treatments like ADT plus an ARPI can suppress a patient's PSA so effectively that it becomes an unreliable marker of disease status. Patients may show radiographic progression on scans even while their PSA remains low and they feel clinically well. This discordance necessitates periodic imaging to avoid missing actual disease progression.

New guidelines from an international working group are replacing patient-insensitive terms like "castration-resistant" with "Androgen Pathway Modulator (APM) resistant/naive." This modernizes language to encompass a broader range of therapies and improve patient communication, while also incorporating sensitive imaging like PSMA PET.

The oral antagonist relugolix allows for rapid testosterone recovery after discontinuation. While useful for planned intermittent therapy, a case study shows this can be a clinical pitfall. In non-adherent patients who self-discontinue, it can lead to an equally rapid rise in PSA and disease progression.

Key resistance biomarkers in prostate cancer, such as AR alterations, are acquired over time. This means that a biomarker test performed at initial diagnosis in the hormone-sensitive stage (MHSPC) is not sufficient for guiding therapy decisions in the castrate-resistant (CRPC) setting.

For high-risk biochemically recurrent prostate cancer, intermittent androgen deprivation therapy (ADT) is the standard of care, not continuous therapy. This approach significantly improves quality of life, bone health, and metabolic health while effectively delaying progression to metastatic disease for years. Continuous therapy is vehemently discouraged in this setting.

The term "castration sensitive or resistant" is being phased out for more patient-centric language. "Androgen pathway modulation" better reflects the biological state, especially as new treatments are used without traditional testosterone-lowering therapy, a shift recommended by the Prostate Cancer Working Group 4.