Rationale: [177Lu]Lutetium prostate-specific membrane antigen radioligand therapy ([177Lu]Lu-PSMA) is EMA-approved for certain indications in metastatic castration resistant prostate cancer (mCRPC). However, cancer-control outcomes in specific and trial-underrepresented subgroups are scant. Methods: We relied on the FRAMCAP database to elaborate progression-free (PFS) and overall (OS) survival in elderly (≥75 yrs), frail (ECOG status ≥1) mCRPC patients or those with cardiovascular disease (CVD) treated with [177Lu]Lu-PSMA. Results: Of 312 [177Lu]Lu-PSMA mCRPC patients, 76% were ≤75 vs. 24% >75 years. Patients >75 years received [177Lu]Lu-PSMA more frequently within the first three mCRPC lines (85% vs. 62%) and harbored more frequently ECOG status ≥2 (13% vs. 4.3%, both p < 0.01). In PFS and OS analyses, no significant difference between patients aged ≤75 vs. >75 years was observed (hazard ratios [HR] 0.97 & 0.85, both p≥0.4) with median PFS of 12.7 vs. 11.7 and OS of 15.1 vs. 19.8 months. In ECOG-stratified analyses, no PFS difference was observed, with significantly better OS for ECOG 0 vs. ≥1 (HR 1.69, p < 0.01), but not after further multivariable adjustment. In CVD-stratified analyses, PFS failed to provide significant differences between CVD vs. no CVD (HR: 1.44, p = 0.051). However, in OS analyses, significant worse OS for CVD mCRPC [177Lu]Lu-PSMA patients was observed (HR: 1.93, p < 0.01). After multivariable adjustment, CVD was an independent predictor for worse PFS and OS (both p < 0.01). Conclusions: Real-world evidence suggests equally effective cancer-control outcomes in elderly and frail mCRPC patients treated with [177Lu]Lu-PSMA. However, patients with CVD are of higher risk for shorter PFS and OS.
Theranostics. 2025 Jan 27*** epublish ***
Mike Wenzel, Carolin Siech, Cristina Cano Garcia, Clara Humke, Daniel Groener, Maximilian Kriegmair, Markus Graefen, Tobias Maurer, Georg Salomon, Severine Banek, Felix K H Chun, Philipp Mandel
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany., Department of Nuclear Medicine, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany., Urologische Klinik München Planegg, Planegg, Germany., Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.