The aim of this study was to investigate very early radiographic PSMA PET response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC) and to assess its role in predicting overall response and survival.
This retrospective study enrolled 40 mCRPC patients who were treated with a median of 3 (2-9) [177Lu]Lu-PSMA I&T RLT cycles. Biochemical response was based on the relative change of serum PSA according to PCWG3 criteria, while radiographic response referred to the relative change of PSMA-derived total viable tumor volumes expressed as total lesion PSMA (TLP).
After one cycle of RLT, biochemical partial response (PR) was seen in 8/40 (20.0%), stable disease (SD) in 22/40 (55.0%), and progressive disease (PD) in 10/40 (25%) patients. In PSMA PET, very early molecular PR was observed in 12 (30.0%), SD in 19 (47.5%), and PD in 9 (22.5%) subjects. The PSA and TLP nadir were achieved after a median of 1 (1-5) and 2 (1-6) cycles, respectively. Nineteen (47.5%) patients showed overall biochemical PR, 11 (27.5%) had SD, and 10 (25%) experienced PD. In PSMA-directed PET, 4 patients experienced molecular complete response (CR), 24 (60.0%) had PR, 4 (10.0%) SD, and 8 (20.0%) PD. Early biochemical or radiographic response was not associated with longer overall survival (OS). Overall biochemical responders had a nearly significantly longer median OS (22.7 months) than non-responders (14.4 months, p = 0.08). Early PSA progression was associated with shorter OS (12.2 months), compared to biochemical SD/PR (18.7 months, p = 0.09).
In this retrospective cohort, there was no association between early PSMA PET radiographic response and overall survival; hence, treatment should not be prematurely discontinued. In contrast, early PSA progression after one cycle of [177Lu]Lu-PSMA I&T RLT was an indicator of overall progression and poor clinical outcome.
European journal of nuclear medicine and molecular imaging. 2023 Jul 21 [Epub ahead of print]
Wojciech Cytawa, Robin Hendel, Bartłomiej Tomasik, Franz-Xaver Weinzierl, Thorsten Bley, Jacek Jassem, Andreas Schirbel, Andreas K Buck, Ralph A Bundschuh, Philipp E Hartrampf, Rudolf A Werner, Constantin Lapa
Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany., Department of Radiology, University Hospital Würzburg, Würzburg, Germany., Department of Oncology and Radiotherapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland., Nuclear Medicine, Faculty of Medicine, University of Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany., Nuclear Medicine, Faculty of Medicine, University of Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany. .