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🌱 來自: prostate cancer

Castration-resistant prostate cancer

Mechanism of action of antiandrogen therapies.

• Progressive dz clinically, biochemically, or radiographically despite castrate levels of testosterone (<50 ng/dL). Does not mean independent of androgens; therapy should continue to maintain castrate levels of testosterone
• Germline genetic testing & tumor tissue genetic sequencing for all men w/ metastatic prostate CA who have not already had it
• Neuroendocrine differentiation may emerge after ADT. Rare at ↣ initial dx
• Poorer performance status, the presence of visceral mets, use of opioids for pain relief, an ↑ LDH, an ↑ PSA, an ↑ alkaline phosphatase, a ↓ albumin, & a ↓ hemoglobin are a/w shorter OS in men w/ CRPC treated w/ chemo (J Clin Oncol 2014;32(7):671)
• Agents shown to improve OS in phase III trials CRPC in combination w/ ADT
• Choice of therapy depends on prior systemic tx, extent of dz, & presence of sxs. S/e profiles influence choice. Consider clinical trials
• Cabazitaxel: Only used post docetaxel-consider in symptomatic or rapidly progressive dz (Lancet 2010;376:1147). Less neuropathy than docetaxel
• Docetaxel: Consider if symptomatic or rapidly progressive dz (NEJM 2004;351:1502; JCO 2008;26:242)
• Olaparib: PARP inhibition for men w/ germline or somatic DNA mismatch repair mt (NEJM 2020;383(24):2345). Those w/ BRCA2 may benefit most (Eur Urol 2019;76(4):452)
• 77-Lu-PSMA-617: Small molecule delivers β-particle radiation selectively to PSMA positive cells & surrounding microenvironment. Trial required PSMA-positive on PET/CT w/ 68Ga-PSMA-11 (NEJM 2021;385:1091)
• Abiraterone acetate: W/ steroid. Approved for pre- & postdocetaxel (NEJM 2010;364:1995; NEJM 2013;368:138). S/e can include hypertension, hypokalemia, fluid retention
• Enzalutamide: Approved for metastatic & nonmetastatic CRPC, pre- & postdocetaxel (NEJM 2012;367:1187; NEJM 2014;371:424)
• Apalutamide & darolutamide: Both approved for nonmetastatic CRPC (Ann Oncol 2019;30:1813; J Clin Oncol 2020;38(suppl):abstr 5514)
• Radium-223: α-particle-emitting radiopharmaceutical-bone seeking. OS benefit, for symptomatic bone-only dz (NEJM 2013;369:213)
• Sipuleucel-T: OS benefit but no change in PSA or tumor burden, appropriate only if asx, ECOG 0-1, no visceral mets, not on: Steroids, RT, chemo, or immunotherapy, & life expectancy >6 mos (NEJM 2010;363:411)