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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Metastatic castration-resistant prostate cancer is disease that grows despite castrate testosterone. Sequenced treatments now include androgen receptor inhibitors, docetaxel and cabazitaxel, PARP inhibitors for men with BRCA-type mutations, the radioligand 177Lu-PSMA-617 and radium-223 for bone-predominant disease.
Metastatic castration-resistant prostate cancer is defined by progression on scans or PSA, or new metastases, with castrate testosterone. Nearly every man reaches it from hormone-sensitive disease, and the treatment chosen depends on what he has already had. Men who have not had an androgen receptor pathway inhibitor receive abiraterone or enzalutamide; PROpel, TALAPRO-2 and MAGNITUDE showed that adding olaparib, talazoparib or niraparib helps men with BRCA and other homologous recombination repair mutations, and PROfound showed olaparib alone beats a second hormonal agent in these men. Docetaxel and then cabazitaxel remain the chemotherapies. VISION established 177Lu-PSMA-617 after chemotherapy and PSMAfore moved it before, for PSMA PET-positive disease; 177Lu-PSMA-I&T (SPLASH, ECLIPSE) follows the same path. Radium-223 lengthens life in symptomatic bone-predominant disease without visceral metastases (ALSYMPCA), sipuleucel-T is still approved for minimally symptomatic disease, and pembrolizumab is used for the rare mismatch repair-deficient tumour. Tumour and germline testing for HRR genes and mismatch repair is standard. Actinium-225 PSMA agents, the STEAP1 T-cell engager xaluritamig and the EZH2 inhibitor mevrometostat are in phase 3.
| Setting | Approach | Guideline |
|---|---|---|
| First line, androgen receptor pathway inhibitor-naive | Abiraterone or enzalutamide; add olaparib, talazoparib or niraparib for HRR-mutant, above all BRCA-mutant, disease (PROpel, TALAPRO-2, MAGNITUDE). | not mapped |
| After an androgen receptor pathway inhibitor | Docetaxel; olaparib or rucaparib for BRCA-mutant disease (PROfound); 177Lu-PSMA-617 for PSMA-positive disease before chemotherapy (PSMAfore); pembrolizumab for mismatch repair-deficient tumours. | not mapped |
| After docetaxel | 177Lu-PSMA-617 (VISION), cabazitaxel, radium-223 for symptomatic bone-only disease (ALSYMPCA), or a PARP inhibitor if not yet used. | not mapped |
| Bone health | Denosumab or zoledronic acid to prevent skeletal events, with calcium and vitamin D; palliative radiotherapy to painful metastases. | not mapped |
| Phase 3 options | Actinium-225 PSMA radioligands, the STEAP1 T-cell engager xaluritamig, the EZH2 inhibitor mevrometostat and 177Lu-PSMA-I&T within trials. | not mapped |