Editing Castrate-Resistant Prostate Cancer (section)

=== General principles ===

* '''<span style="color:#ff0000">Clinical trials should remain the first choice in patients with CRPC, whenever possible'''
**Because any treatment for advanced disease remains non-curative, patients with advanced prostate cancer should be encouraged to participate in clinical trials.[https://pubmed.ncbi.nlm.nih.gov/33556313/ §]
* '''<span style="color:#ff0000">Androgen-deprivation therapy (ADT) should be continued for the remainder of a patient’s life, even during the course of subsequent therapies including chemotherapy'''
** Rationale (2):
**#Androgen receptor remains active in most patients who have developed castration-resistant disease
**# Almost all clinical trials that test novel therapies for men with CRPC mandate continued suppression of serum testosterone levels, either with chronic ADT or with surgical castration
** In patients who develop CRPC, the addition or change of first-generation androgen receptor antagonists (flutamide, bicalutamide, or nilutamide) may be considered.[https://pubmed.ncbi.nlm.nih.gov/33556313/ §]
*** Changing the anti-androgen or using corticosteroids with or without ketoconazole have been noted to cause transient PSA reductions in ≈30% of patients but have not been shown to improve any of the clinically meaningful outcome measures
*** In patients treated with luteinizing hormone-releasing hormone (LHRH) analogue monotherapy or those who have had an orchidectomy, the addition of androgen receptor antagonists, such as bicalutamide, can offer modest PSA responses that are short-lived in 30–35% of patients.
** For patients who have undergone total androgen blockade (combination of an AR-antagonist and an LHRH agonist), the androgen receptor antagonist should be discontinued to test for an anti-androgen withdrawal response.[https://pubmed.ncbi.nlm.nih.gov/33556313/ §]
*** Anti-androgen withdrawal phenomenon
**** Patients treated with a combination of an AR-antagonist and an LHRH agonist can experience a decline in PSA and even in objective responses with the withdrawal of the anti-androgen from the combination.
***** Based on this response, it appears that the AR-antagonist is actually exerting agonistic activity on prostate cancer cells
***** 15-30% of patients may have PSA declines of > 50% after antiandrogen withdrawal, and the declines have a median duration of 3.5 to 5 months.
***** Objective, measurable tumor responses are observed less commonly
***** Overall survival is not improved in those patients demonstrating the antiandrogen withdrawal phenomenon compared to those who have not.