Lutetium-177 PSMA radioligand therapy in taxan-naive first- and second-line metastatic castration resistant prostate cancer after first-line ARPI therapy

Mike Wenzel; Benedikt Hoeh; Carolin Siech; Florestan Koll; Clara Humke; Daniel Groener; Thomas Steuber; Markus Graefen; Tobias Maurer; Severine Banek; Felix K H Chun; Philipp Mandel

doi:10.1007/s00259-025-07076-7

Lutetium-177 PSMA radioligand therapy in taxan-naive first- and second-line metastatic castration resistant prostate cancer after first-line ARPI therapy

Eur J Nucl Med Mol Imaging. 2025 Jan 13. doi: 10.1007/s00259-025-07076-7. Online ahead of print.

Authors

Affiliations

¹ Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Frankfurt, Germany. Mike.Wenzel@unimedizin-ffm.de.
² Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Frankfurt, Germany.
³ Department of Nuclear Medicine, University Hospital Frankfurt, Goethe University Frankfurt Am Main, Frankfurt, Germany.
⁴ Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

PMID: 39804375
DOI: 10.1007/s00259-025-07076-7

Abstract

Purpose: Lutetium-177 Prostate-specific membrane antigen (Lu-PSMA) radioligand therapy is EMA-approved for metastatic castration resistant prostate cancer (mCRPC) after androgen receptor pathway inhibition (ARPI) and taxan-based chemotherapy. However, its effect in taxan-naïve patients is under current investigation.

Methods: We relied on the FRAMCAP database to elaborate Lu-PSMA therapy outcomes of progression-free (PFS) and overall (OS) in taxan-naïve mCRPC patients after previous ARPI treatment. Comparison was made against current standard of care with ARPI or docetaxel, irrespective of the previous used staging modality.

Results: Of 269 patients, 11% received Lu-PSMA in first/second-line mCRPC vs. 57% ARPI vs. 33% docetaxel. Mostly no significant baseline differences between Lu-PSMA and ARPI patients were observed, while Lu-PSMA patients were significantly older, received less systematic treatments and ECOG1-2 proportions were higher, relative to docetaxel patients. In PFS (13.3 vs. 8.2 months, hazard ratio [HR]: 0.70, p = 0.16) and OS analyses (68.9 vs. 39.1 months, HR: 0.64, p = 0.2), Lu-PSMA was numerically more favorable than ARPI. In additional multivariable Cox regression models, Lu-PSMA was significant better regarding PFS and OS, relative to ARPI (both p < 0.05). Compared to docetaxel, also significant better PFS (13.3 vs. 8.1 months, HR: 0.46) and OS (68.9 vs. 27.3 months, HR: 0.34, both p < 0.01) was observed for Lu-PSMA treatment. The OS advantage was also observed after multivariable adjustment (p < 0.01).

Conclusion: This retrospective single-center study including a substantial proportion of patients with treatment preference for Lu-PSMA suggests that Lu-PSMA therapy provides significantly more favorable PFS and OS outcomes in taxan-naïve mCRPC patients after previous ARPI treatment, relative to ARPI or docetaxel treatment and may be considered as an early mCRPC treatment option.

Keywords: Lu-177; MCRPC; OS; PFS; Survival.