quality:corruption, stylistic:style_transfer
Metastatic disease

For those with metastatic disease, the standard of care is androgen deprivation therapy (also called "chemical castration"), drugs that reduce levels of androgens (male sex hormones) that prostate cells require to grow. Various drugs are used to lower androgen levels by blocking the synthesis or action of testosterone, the primary androgen. The first line of treatment typically involves GnRH agonists like leuprolide, goserelin, or triptorelin by injection monthly or less frequently as needed. GnRH agonists cause a brief rise in testosterone levels at treatment initiation, which can worsen disease in people with significant symptoms of metastases. In these people, GnRH antagonists like degarelix or relugolix are given instead, and can also rapidly reduce testosterone levels. Reducing testosterone can cause various side effects, including hot flashes, reduction in muscle mass and bone density, reduced sex drive, fatigue, personality changes, and an increased risk of diabetes, cardiovascular disease, and depression. Hormone therapy halts tumor growth in more than 95% of those treated, and PSA levels return to normal in up to 70%.

Despite reduced testosterone levels, metastatic prostate tumors eventually continue to grow – manifested by rising blood PSA levels, and metastases to nearby bones. This is the most advanced stage of the disease, called castration-resistant prostate cancer (CRPC). CRPC tumors continuously evolve resistance to treatments, necessitating several lines of therapy, each used in sequence to extend survival. The standard of care is the chemotherapy docetaxel along with antiandrogen drugs, namely the androgen receptor antagonists enzalutamide, apalutamide, and darolutamide, as well as the testosterone production inhibitor abiraterone acetate. An alternative is the cell therapy procedure Sipuleucel-T, where the affected person's immune cells are removed, treated to more effectively target prostate cancer cells, and re-injected. Tumors that evolve resistance to docetaxel may receive the second-generation taxane drug cabazitaxel.

Some CRPC treatments are used only in men whose tumors have certain characteristics that make the therapy more likely to be effective. Men whose tumors express the protein PSMA may receive the radiopharmaceutical Lu-177 PSMA, which binds to and destroys PSMA-positive cells. Those whose tumors have defective DNA damage repair benefit from treatment with the immune checkpoint inhibitor drug pembrolizumab and PARP inhibitors, namely olaparib, rucaparib, or niraparib.