PSMAfore: Taxane-naive PSMA-positive mCRPC after one prior ARPI progression

Authored by Neal Shore, published on 2026-05-08 20:56:52.0

  1. Start: progressive mCRPC on exactly one prior ARPI
    Continue ADT/castrate testosterone management. Confirm adenocarcinoma, adult patient, ECOG 0–1, and disease progression after abiraterone, enzalutamide, apalutamide, or darolutamide.
    • Is patient taxane-naive in the metastatic setting and appropriate to delay taxane chemotherapy?
      • No
        This is outside the core PSMAfore population. Use standard mCRPC sequencing: taxane chemotherapy, post-taxane radioligand therapy when indicated, clinical trial, or other guideline-directed care.
      • Yes
        Proceed to PSMA-PET selection and rule out trial-defined exclusions before choosing radioligand therapy versus ARPI change.
        • 68Ga-PSMA-11 PET/CT: ≥1 PSMA+ lesion and no exclusionary PSMA-negative lesion?
          • No / equivocal
            Do not use the PSMAfore-preferred pathway. Consider ARPI change only if clinically appropriate, chemotherapy, targeted therapy if eligible, trial enrollment, or other non-PSMA-directed care.
          • Yes
            Confirm no better standard alternative was identified by genomics or prior therapy history. PSMAfore excluded known candidates for alternative standard therapies based on genomic alterations.
            • Prior disallowed therapy or better biomarker-driven option?
              • Yes
                Not a PSMAfore-like decision. Examples: Prior taxane in metastatic setting Recent systemic/hemibody radiotherapy Prior immunotherapy except sipuleucel-T PARP-inhibitor candidacy Other trial-excluded standard option
              • No
                PSMAfore-like patient: favor 177Lu-PSMA-617 over switching to another ARPI when the practical goal is to delay taxane chemotherapy.
                • Preferred PSMAfore-based treatment choice
                  177Lu-PSMA-617 7.4 GBq (200 mCi) ±10% every 6 weeks for 6 cycles + best supportive care/ADT. Do not administer ARPI concurrently with 177Lu-PSMA-617 in the study-treatment period.
tosprivacyFinal overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer