Over time, some tumor cells develop mutations that let them grow despite very low testosterone. This is called castration-resistant prostate cancer (CRPC). The timeline is highly variable—sometimes just a couple of years, sometimes many years.
Impact of combining therapies: Clinical trials (like LATITUDE, STAMPEDE, ARASENS) show that adding a second-generation drug up front delays disease progression and improves survival compared to ADT alone. So while castration resistance can still occur, the time to CRPC is usually significantly prolonged in men who start with combination therapy versus Lupron alone.
But not a guarantee: Some men’s cancers evolve faster than others depending on tumor biology, genetics, disease burden, and other factors. That’s why even with the best modern therapy, doctors monitor PSA, scans, and symptoms closely.

@barblouise
Actually, that isn’t true. They’ve been studies done and one of the people in this forum is in one of those studies taking Apalutamide. The studies have shown that people who take ARSI along with ADT can delay the time to castrate resistance.

You can search it yourself using this search “ can taking an ARSI along with ADT delay the time to castrate resistance”

From AI
Yes, combining an ARSI with Androgen Deprivation Therapy (ADT) can delay time to castration resistance by improving outcomes in metastatic castration-sensitive prostate cancer (mCSPC). Clinical trials have shown that adding an ARSI to ADT leads to significant improvements in radiographic progression-free survival (rPFS) and overall survival (OS), effectively prolonging the period before the cancer progresses to a castration-resistant state. This combination therapy is now a standard-of-care treatment for patients with advanced prostate cancer.

Here is one of a few references
https://link.springer.com/article/10.1007/s10147-024-02670-5