RECIP 1.0 + PSA for response assessment in mCRPC patients treated with 225Ac / 177Lu PSMA combination therapy

Sheikh, Gabriel T.; Delker, Astrid; Zacherl, Mathias J.; Holzgreve, Adrien; Takayama Fouladgar, Sarah L.; Unterrainer, Marcus; Rübenthaler, Johannes; Casuscelli, Jozefina; Gafita, Andrei; Unterrainer, Lena M. (2025): RECIP 1.0 + PSA for response assessment in mCRPC patients treated with 225Ac / 177Lu PSMA combination therapy. EJNMMI Research, 15: 19. ISSN 2191-219X

Abstract

Background

Targeted alpha therapy (TAT) with 225 Ac has shown promising results in metastatic castration-resistant prostate cancer (mCRPC) patients pre-treated with [ 177 Lu]Lu-PSMA radioligand therapy (RLT). A combination treatment regimen adding 177 Lu to decreased 225 Ac activities may improve toxicity profile while maintaining sufficient anti-tumor effect. We therefore evaluated clinical and image-based response parameters in patients treated with 225 Ac-/ 177 Lu-PSMA combination therapies (ALCT).

Results

Complete response (RECIP-CR), partial response (RECIP-PR), stable disease (RECIP-SD), progressive disease (RECIP-PD) according to RECIP 1.0 was observed in 0/25 (0%), 12/25 (48%), 9/25 (36%) and 4/25 (16%) patients, respectively. Response by RECIP + PSA was observed in 14/25 (56%) patients and progression by RECIP + PSA in 8/25 (32%) patients. Interrater reliability for visual RECIP was substantial (κ = 0.757, p < 0.001), while agreement between visual and quantitative RECIP was almost fully congruent (κ = 0.879, p < 0.001). OS did not significantly vary among the four different therapy regimens ( p > 0.05). When grouping patients with declining / stable PSA as responders, these patients showed no significant difference in overall survival compared to patients with progressive PSA after ALCT ( p = 0.312). Similarly, there was no significant difference in median overall survival between patients without RECIP-progression (RECIP-PR + RECIP-SD) and patients with RECIP-progression (RECIP-PD) ( p > 0.05), but when applying the composite classification, RECIP + PSA responders survived significantly longer compared to patients with RECIP + PSA progression ( p = 0.049).

Conclusions

ALCT is a promising therapeutic regimen that may prolong survival in patients who progress during [ 177 Lu]Lu-PSMA RLT. Our results motivate to further investigate the use of RECIP + PSA as tool for response assessment and for overall survival prediction in mCRPC under ALCT.

• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Klinik und Poliklinik für Nuklearmedizin
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892