PSMA-PET follow-up to assess response in patients not receiving PSMA therapy: Is there value beyond localization of disease?

Introduction: Prostate Specific Membrane Antigen Positron Emission Tomography (PSMA-PET) is routinely used for the staging of patients with prostate cancer, but data on response assessment are sparse and primarily stem from metastatic castration-resistant prostate cancer (mCRPC) patients treated with PSMA radioligand therapy. Still, follow-up PSMA-PET is employed in earlier disease stages in case of clinical suspicion of disease persistence, recurrence or progression to decide if localized or systemic treatment is indicated. Therefore, the prognostic value of PSMA-PET derived tumor volumes in earlier disease stages (i.e., hormone-sensitive prostate cancer (HSPC) and non-[ ¹⁷⁷ Lu]Lu-PSMA-617 (LuPSMA) therapy castration resistant prostate cancer (CRPC)) are evaluated in this manuscript. Methods: A total number of 73 patients (6 primary staging, 42 HSPC, 25 CRPC) underwent two (i.e., baseline and follow-up, median interval: 379 days) whole-body [ ⁶⁸ Ga]Ga-PSMA-11 PET/CT scans between Nov 2014 and Dec 2018. Analysis was restricted to non-LuPSMA therapy patients. PSMA-PETs were retrospectively analyzed and primary tumor, lymph node-, visceral-, and bone metastases were segmented. Body weight-adjusted organ-specific and total tumor volumes (PSMAvol: sum of PET volumes of all lesions) were measured for baseline and follow-up. PSMAvol response was calculated as the absolute difference of whole-body tumor volumes. High metastatic burden (>5 metastases), RECIP 1.0 and PSMA-PET Progression Criteria (PPP) were determined. Survival data were sourced from the cancer registry. Results: The average number of tumor lesions per patient on the initial PET examination was 10.3 (SD 28.4). At baseline, PSMAvol was strongly associated with OS (HR 3.92, p <0.001; n = 73). Likewise, response in PSMAvol was significantly associated with OS (HR 10.48, p < 0.005; n = 73). PPP achieved significance as well (HR 2.19, p <0.05, n = 73). Patients with hormone sensitive disease and poor PSMAvol response (upper quartile of PSMAvol change) in follow-up had shorter outcome (p < 0.05; n = 42). PSMAvol in bones was the most relevant parameter for OS prognostication at baseline and for response assessment (HR 31.11 p < 0.001; HR 32.27, p < 0.001; n = 73). Conclusion: PPP and response in PSMAvol were significantly associated with OS in the present heterogeneous cohort. Bone tumor volume was the relevant miTNM region for OS prognostication. Future prospective evaluation of the performance of organ specific PSMAvol in more homogeneous cohorts seems warranted.
Competing Interests: Competing Interests: David Kersting reports fees from Pfizer (research funding, speaker honoraria), Novartis (speaker honoraria), and funding by the German Research Foundation (DFG, KE2933/1-1) outside of the submitted work. Tugce Telli reports speaker fee from Abx not related to current work. Ken Herrmann, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm reports receiving consultant fees from Advanced Accelerator Applications, a Novartis company, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien München, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, and Theragnostics, ymabs, travel fees from Janssen, payment for educational events from PeerVoice, receiving research grants from Novartis and Sofie Biosciences, having stock or stock option interests with AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences, reports serving on advisory boards for Fusion, GE Healthcare. Axel Rominger has received research support and speaker honoraria from Siemens Healthineers. Wolfgang P. Fendler reports fees from SOFIE Bioscience (research funding), Janssen (consultant, speaker), Calyx (consultant, image review), Bayer (consultant, speaker, research funding), Novartis (speaker, consultant), Telix (speaker), GE Healthcare (speaker), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), Urotrials (speaker) outside of the submitted work. Boris Hadaschik reports serving on advisory boards for Janssen, Bayer, ABX, Lightpoint, Amgen, MSD, Pfizer, and Novartis; being an invited speaker for Accord, Astellas, and Janssen; receiving institutional royalties from Uromed; receiving institutional funding from AAA/Novartis, Bristol Myers Squibb, MS, and German Research Foundation; holding an advisory role for German Cancer Aid; and holding a leadership role/speaker for DKG AUO and DGU. Christopher Darr reports personal fees from Janssen-Cilag and Bayer, travel fees from Janssen-Cilag and Ipsen. Lale Umutlu is a Speaker/Advisory Board Member for Bayer Healthcare and Siemens Healthcare and received research grants from Siemens Healthcare outside of the submitted work. Ken Herrmann reports personal fees from Bayer SIRTEX Adacap Curium Endocyte IPSEN Siemens Healthineers GE Healthcare Amgen Novartis and ymabs personal fees and other from Sofie Biosciences non-financial support from ABX grants and personal fees from BTG outside the submitted work. Robert Seifert has received research support from Boehringer Ingelheim Fonds and Else Kröner-Fresenius-Stiftung. All other authors have no conflicts of interest to declare.
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