Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [177Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome

Philipp E Hartrampf; Constantin Lapa; Sebastian E Serfling; Andreas K Buck; Anna Katharina Seitz; Philipp T Meyer; Juri Ruf; Kerstin Michalski

doi:10.3390/cancers13174270

Development of Discordant Hypermetabolic Prostate Cancer Lesions in the Course of [¹⁷⁷Lu]PSMA Radioligand Therapy and Their Possible Influence on Patient Outcome

Cancers (Basel). 2021 Aug 25;13(17):4270. doi: 10.3390/cancers13174270.

Authors

Philipp E Hartrampf¹, Constantin Lapa², Sebastian E Serfling¹, Andreas K Buck¹, Anna Katharina Seitz³, Philipp T Meyer⁴, Juri Ruf⁴, Kerstin Michalski⁴

Affiliations

¹ Department of Nuclear Medicine, University Hospital Wuerzburg, Oberdürrbacherstraße 6, 97080 Würzburg, Germany.
² Nuclear Medicine, Medical Faculty, University of Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany.
³ Department of Urology and Paediatric Urology, University Hospital Wuerzburg, Oberdürrbacherstraße 6, 97080 Würzburg, Germany.
⁴ Department of Nuclear Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.

Abstract

Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate-specific membrane antigen (PSMA) is crucial for the assessment of adequate PSMA expression in patients with metastatic castration-resistant prostate cancer (mCRPC) prior to PSMA radioligand therapy (PSMA RLT). Moreover, initial dual tracer staging using combined PSMA and [¹⁸F]fluorodeoxyglucose (FDG) PET/CT provides relevant information, since discordant FDG-positive but PSMA-negative (FDG+/PSMA-) lesions constitute a negative prognostic marker of overall survival (OS) after PSMA RLT. However, little is known about the prognostic implications of dual tracer imaging for restaging at follow-up. The aim of this analysis was to investigate the prognostic implications of new FDG+/PSMA- lesions during or after PSMA RLT.

Methods: This bicentric analysis included 32 patients with mCRPC who underwent both FDG and PSMA PET/CT imaging after two or four cycles of PSMA RLT. Patients with FDG+/PSMA- lesions prior to PSMA RLT were not considered. The presence of FDG+/PSMA- lesions was assessed with follow-up dual tracer imaging of patients after two or four cycles of PSMA RLT. Patients with at least one new FDG+/PSMA- lesion were compared to patients without any FDG+/PSMA- lesions at the respective time points. A log-rank analysis was used to assess the difference in OS between subgroups.

Results: After two cycles of PSMA RLT, four of 32 patients (13%) had FDG+/PSMA- metastases. No significant difference in OS was observed (p = 0.807), as compared to patients without FDG+/PSMA- lesions. Follow-up dual tracer imaging after the 4th cycle of PSMA RLT was available in 18 patients. Of these, four patients presented with FDG+/PSMA- findings (n = 2 already after two cycles). After the fourth cycle of PSMA RLT, no significant difference in OS was observed between patients with and without FDG+/PSMA- lesions (p = 0.442).

Conclusion: This study shows that FDG+/PSMA- lesions develop in a limited number of patients undergoing PSMA RLT. Further studies are needed to establish the clinical relevance of such lesions.

Keywords: FDG; PET/CT; PSMA; prostate cancer; radioligand therapy.