Editing Prostate cancer (section)

=== Metastatic disease ===
[[File:Verlauf Prostatakrebs 2011-01 Posttherapie-Szintigramm cropped.jpg|thumb|Bone scintigraphy scan of a man with metastatic prostate cancer. Dark spots indicate metastases along the pelvis, ribs, and shoulder. |alt=Medical image showing a man's skeleton with several dark spots along the bones.]]
For those with metastatic disease, the standard of care is [[androgen deprivation therapy]] (also called "chemical castration"), drugs that reduce levels of [[androgen]]s (male sex hormones) that prostate cells require to grow.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic hormone-sensitive prostate cancer"}} 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 [[Gonadotropin-releasing hormone agonist|GnRH agonist]]s like [[leuprolide]], [[goserelin]], or [[triptorelin]] by injection monthly or less frequently as needed.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html |access-date=15 May 2023 |title=Hormone Therapy for Prostate Cancer |date=9 August 2022 |publisher=American Cancer Society |archive-date=15 May 2023 |archive-url=https://web.archive.org/web/20230515212541/https://www.cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html |url-status=live }}</ref>{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic hormone-sensitive prostate cancer"}} GnRH agonists cause a brief rise in testosterone levels at treatment initiation, which can worsen disease in people with significant symptoms of metastases.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} In these people, [[Gonadotropin-releasing hormone antagonist|GnRH antagonists]] like [[degarelix]] or [[relugolix]] are given instead, and can also rapidly reduce testosterone levels.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} Reducing testosterone can cause various side effects, including [[hot flash]]es, reduction in muscle mass and bone density, reduced sex drive, fatigue, personality changes, and an increased risk of diabetes, cardiovascular disease, and depression.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} Hormone therapy halts tumor growth in more than 95% of those treated,{{sfn|Achard|Putora|Omlin|Zilli|2022|loc="Introduction"}} and PSA levels return to normal in up to 70%.{{sfn|Scher|Eastham|2022|loc="Outcomes of androgen deprivation"}}

Despite reduced testosterone levels, metastatic prostate tumors eventually continue to grow – manifested by rising blood PSA levels, and metastases to nearby bones.{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic castration-resistant prostate cancer"}} 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]].{{sfn|Teo|Rathkopf|Kantoff|2019|loc="Management of metastatic castration-resistant prostate cancer"}}{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}{{sfn|Teo|Rathkopf|Kantoff|2019|loc="Abiraterone acetate"}} An alternative is the [[Cancer immunotherapy#Cellular immunotherapy|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.{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}} Tumors that evolve resistance to docetaxel may receive the second-generation [[taxane]] drug [[cabazitaxel]].{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}

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 [[prostate-specific membrane antigen|PSMA]] may receive the radiopharmaceutical [[Lutetium (177Lu) vipivotide tetraxetan|Lu-177 PSMA]], which binds to and destroys PSMA-positive cells.<ref>{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer |accessdate=9 January 2024 |title=FDA Approves Pluvicto for Metastatic Castration-Resistant Prostate Cancer |publisher=U.S. Food & Drug Administration |date=23 March 2022 |archive-date=24 March 2022 |archive-url=https://web.archive.org/web/20220324031828/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer |url-status=live }}</ref>{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}} Those whose tumors have defective [[DNA damage repair]] benefit from treatment with the [[immune checkpoint inhibitor]] drug [[pembrolizumab]] and [[Poly (ADP-ribose) polymerase|PARP]] inhibitors, namely [[olaparib]], [[rucaparib]], or [[niraparib]].{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}