Early biochemical and radiographic response after one cycle of [177Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

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

doi:10.1007/s00259-023-06326-w

Early biochemical and radiographic response after one cycle of [¹⁷⁷Lu]Lu-PSMA I&T radioligand therapy in metastatic castration-resistant prostate cancer patients

Eur J Nucl Med Mol Imaging. 2023 Oct;50(12):3765-3776. doi: 10.1007/s00259-023-06326-w. Epub 2023 Jul 21.

Authors

Affiliations

¹ Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
² Department of Nuclear Medicine, Medical University of Gdańsk, Gdańsk, Poland.
³ Department of Radiology, University Hospital Würzburg, Würzburg, Germany.
⁴ Department of Oncology and Radiotherapy, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland.
⁵ Nuclear Medicine, Faculty of Medicine, University of Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany.
⁶ Nuclear Medicine, Faculty of Medicine, University of Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany. constantin.lapa@uk-augsburg.de.

Abstract

Purpose: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

Keywords: Early response assessment; Metastatic castration-resistant prostate cancer; Radioligand therapy; [177Lu]Lu-PSMA I&T.

MeSH terms

Dipeptides / therapeutic use
Heterocyclic Compounds, 1-Ring / therapeutic use
Humans
Lutetium / therapeutic use
Male
Prostate-Specific Antigen
Prostatic Neoplasms, Castration-Resistant* / diagnostic imaging
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / radiotherapy
Retrospective Studies
Treatment Outcome

Substances

Prostate-Specific Antigen
PSMA I&T
Dipeptides
Heterocyclic Compounds, 1-Ring
Lutetium

Grants and funding

71-1212/Gdansk University