Biomarkers to Personalize Treatment with 177Lu-PSMA-617 in Men with Metastatic Castration-resistant Prostate Cancer - a State of the Art Review

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2022 Mar 11

PMID 35273651

Authors

Isabel Heidegger

Claudia Kesch

Alexander Kretschmer

Igor Tsaur

Francesco Ceci

Massimo Valerio

Derya Tilki

Giancarlo Marra

Felix Preisser

Christian D Fankhauser

Fabio Zattoni

Peter Chiu

Ignacio Puche-Sanz

Jonathan Olivier

Roderik C N van den Bergh

Veeru Kasivisvanathan

Andreas Pircher

Irene Virgolini

Giorgio Gandaglia

Affiliations

Soon will be listed here.

Abstract

Radioligand therapy with Lutetium-177 (177Lu)-Prostate-specific membrane antigen (PSMA) has shown to prolong survival in metastatic castration resistant prostate cancer (mCRPC). One of the major challenges for clinicians in the future is to select those patients who would benefit most from this therapy to position it in the treatment landscape of mCRPC. This, in turn, will lead to the delivery of personalized therapies. In this narrative review article we summarize recent studies investigating both predictive and prognostic clinical, imaging-based, and molecular biomarkers to predict treatment response to 177Lu-PSMA-617 radioligand therapy with the aim of identifying men who should be considered for this approach. Of note, the evidence on the role of biomarkers currently relies on small retrospective trials and their validation in larger prospective cohorts is necessary before these results can be translated in the clinical practice.

Citing Articles

A review of 177Lu dosimetry workflows: how to reduce the imaging workloads?.

Vergnaud L, Dewaraja Y, Giraudet A, Badel J, Sarrut D EJNMMI Phys. 2024; 11(1):65.

PMID: 39023648 PMC: 11554969. DOI: 10.1186/s40658-024-00658-8.

Quantification of biochemical PSA dynamics after radioligand therapy with [Lu]Lu-PSMA-I&T using a population pharmacokinetic/pharmacodynamic model.

Siebinga H, de Wit-van der Veen B, de Vries-Huizing D, Vogel W, Hendrikx J, Huitema A EJNMMI Phys. 2024; 11(1):39.

PMID: 38656678 PMC: 11043318. DOI: 10.1186/s40658-024-00642-2.

Current role of PSMA-PET imaging in the clinical management of prostate cancer.

Georgakopoulos A, Bamias A, Chatziioannou S Ther Adv Med Oncol. 2023; 15:17588359231208960.

PMID: 38028141 PMC: 10676057. DOI: 10.1177/17588359231208960.

Improving Overall Survival and Quality of Life in Patients with Prostate Cancer and Neuroendocrine Tumors Using Lu-iPSMA and Lu-DOTATOC: Experience after 905 Treatment Doses.

Luna-Gutierrez M, Hernandez-Ramirez R, Soto-Abundiz A, Garcia-Perez O, Ancira-Cortez A, Lopez-Buenrostro S Pharmaceutics. 2023; 15(7).

PMID: 37514174 PMC: 10386094. DOI: 10.3390/pharmaceutics15071988.

Single-Time-Point Imaging for Dosimetry After [Lu]Lu-DOTATATE: Accuracy of Existing Methods and Novel Data-Driven Models for Reducing Sensitivity to Time-Point Selection.

Wang C, Peterson A, Wong K, Roseland M, Schipper M, Dewaraja Y J Nucl Med. 2023; 64(9):1463-1470.

PMID: 37500260 PMC: 10478823. DOI: 10.2967/jnumed.122.265338.

References

Cornford P, van den Bergh R, Briers E, Van den Broeck T, Cumberbatch M, De Santis M . EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2020; 79(2):263-282. DOI: 10.1016/j.eururo.2020.09.046. View

Ferdinandus J, Eppard E, Gaertner F, Kurpig S, Fimmers R, Yordanova A . Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617. J Nucl Med. 2016; 58(2):312-319. DOI: 10.2967/jnumed.116.178228. View

Ahmadzadehfar H, Schlolaut S, Fimmers R, Yordanova A, Hirzebruch S, Schlenkhoff C . Predictors of overall survival in metastatic castration-resistant prostate cancer patients receiving [Lu]Lu-PSMA-617 radioligand therapy. Oncotarget. 2017; 8(61):103108-103116. PMC: 5732715. DOI: 10.18632/oncotarget.21600. View

Sandhu S, Guo C, Hofman M . Radionuclide Therapy in Prostate Cancer: from standalone to combination PSMA theranostics. J Nucl Med. 2021; . PMC: 8612178. DOI: 10.2967/jnumed.120.243295. View

Gafita A, Calais J, Grogan T, Hadaschik B, Wang H, Weber M . Nomograms to predict outcomes after Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Lancet Oncol. 2021; 22(8):1115-1125. DOI: 10.1016/S1470-2045(21)00274-6. View

Grubmuller B, Rasul S, Baltzer P, Fajkovic H, DAndrea D, Berndl F . Response assessment using [ Ga]Ga-PSMA ligand PET in patients undergoing systemic therapy for metastatic castration-resistant prostate cancer. Prostate. 2019; 80(1):74-82. DOI: 10.1002/pros.23919. View

Suman S, Parghane R, Joshi A, Prabhash K, Bakshi G, Talole S . Therapeutic efficacy, prognostic variables and clinical outcome of Lu-PSMA-617 PRLT in progressive mCRPC following multiple lines of treatment: prognostic implications of high FDG uptake on dual tracer PET-CT vis-à-vis Gleason score in such cohort. Br J Radiol. 2019; 92(1104):20190380. PMC: 6913363. DOI: 10.1259/bjr.20190380. View

Barinka C, Rojas C, Slusher B, Pomper M . Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer. Curr Med Chem. 2012; 19(6):856-70. PMC: 3341092. DOI: 10.2174/092986712799034888. View

Nagaya N, Nagata M, Lu Y, Kanayama M, Hou Q, Hotta Z . Prostate-specific membrane antigen in circulating tumor cells is a new poor prognostic marker for castration-resistant prostate cancer. PLoS One. 2020; 15(1):e0226219. PMC: 6984691. DOI: 10.1371/journal.pone.0226219. View

10.

Khreish F, Ghazal Z, Marlowe R, Rosar F, Sabet A, Maus S . 177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study). Eur J Nucl Med Mol Imaging. 2021; 49(3):1075-1085. PMC: 8803625. DOI: 10.1007/s00259-021-05525-7. View

11.

Yordanova A, Linden P, Hauser S, Feldmann G, Brossart P, Fimmers R . The value of tumor markers in men with metastatic prostate cancer undergoing [ Lu]Lu-PSMA therapy. Prostate. 2019; 80(1):17-27. DOI: 10.1002/pros.23912. View

12.

Seifert R, Kessel K, Schlack K, Weber M, Herrmann K, Spanke M . PSMA PET total tumor volume predicts outcome of patients with advanced prostate cancer receiving [Lu]Lu-PSMA-617 radioligand therapy in a bicentric analysis. Eur J Nucl Med Mol Imaging. 2020; 48(4):1200-1210. PMC: 8041668. DOI: 10.1007/s00259-020-05040-1. View

13.

Pathmanandavel S, Crumbaker M, Yam A, Nguyen A, Rofe C, Hovey E . Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. J Nucl Med. 2021; 63(4):560-566. PMC: 8973290. DOI: 10.2967/jnumed.121.262552. View

14.

Barber T, Singh A, Kulkarni H, Niepsch K, Billah B, Baum R . Clinical Outcomes of Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy. J Nucl Med. 2019; 60(7):955-962. DOI: 10.2967/jnumed.118.216820. View

15.

Rischpler C, Beck T, Okamoto S, Schlitter A, Knorr K, Schwaiger M . Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging. J Nucl Med. 2018; 59(9):1406-1411. DOI: 10.2967/jnumed.117.204677. View

16.

Giacinti S, Poti G, Roberto M, Macrini S, Bassanelli M, Di Pietro F . Molecular Basis of Drug Resistance and Insights for New Treatment Approaches in mCRPC. Anticancer Res. 2018; 38(11):6029-6039. DOI: 10.21873/anticanres.12953. View

17.

Gafita A, Heck M, Rauscher I, Tauber R, Cala L, Franz C . Early Prostate-Specific Antigen Changes and Clinical Outcome After Lu-PSMA Radionuclide Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer. J Nucl Med. 2020; 61(10):1476-1483. DOI: 10.2967/jnumed.119.240242. View

18.

Michalski K, Klein C, Brueggemann T, Meyer P, Jilg C, Ruf J . Assessing Response to [Lu]PSMA Radioligand Therapy using modified PSMA PET Progression Criteria. J Nucl Med. 2021; . PMC: 8612188. DOI: 10.2967/jnumed.120.260836. View

19.

Wade C, Kyprianou N . Profiling Prostate Cancer Therapeutic Resistance. Int J Mol Sci. 2018; 19(3). PMC: 5877765. DOI: 10.3390/ijms19030904. View

20.

Ahmadzadehfar H, Rahbar K, Baum R, Seifert R, Kessel K, Bogemann M . Prior therapies as prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients treated with [Lu]Lu-PSMA-617. A WARMTH multicenter study (the 617 trial). Eur J Nucl Med Mol Imaging. 2020; 48(1):113-122. PMC: 7835179. DOI: 10.1007/s00259-020-04797-9. View