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. 2021 Feb 18:11:630589.
doi: 10.3389/fonc.2021.630589. eCollection 2021.

Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

Panagiotis J Vlachostergios  1 , Muhammad Junaid Niaz  2 , Michael Sun  1 , Seyed Ali Mosallaie  3 , Charlene Thomas  4 , Paul J Christos  4 , Joseph R Osborne  3   5 , Ana M Molina  1   5 , David M Nanus  1   2   5 , Neil H Bander  2   5 , Scott T Tagawa  1   2   5
Affiliations

Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

Panagiotis J Vlachostergios et al. Front Oncol. .

Abstract

Background: Prostate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Patients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0-4 in order to determine an imaging score (IS). The IS (high: 2-4 versus low: 0-1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox's proportional hazards models.

Results: High PSMA expression (IS 2-4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9-19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0-18.1) months compared to those with low expression [22.7 (95%CI: 17.7-30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p<0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2-2.2); p = 0.003].

Conclusion: Presence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes.

Keywords: metastatic castration resistant prostate cancer; nuclear imaging; overall survival; positron emission tomography; prostate specific membrane antigen; single photon emission computed tomography.

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Conflict of interest statement

ST certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: NB is an inventor of patents assigned to the Cornell Center for Technology Licensing for the J591 antibody described in this article. He is also a paid consultant for and holds equity in BZL Biologics, LLC, the company to which these patents were licensed for further research and development and is a SAB member and holds equity in Telix Pharmaceuticals, Ltd, sub-licensed to develop J591-Lu177. ST has served as a paid consultant to Endocyte/AAA/Novartis and Blue Earth, as an unpaid consultant to Atlab and Telix, and Weill Cornell Medicine has received research funding from Endocyte/AAA/Novartis, Progenics, and Atlab/Telix. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Kaplan Meier curve of overall survival (OS) of the entire cohort.
Figure 2
Figure 2
Kaplan Meier curve of overall survival (OS) between patients with high vs. low imaging score (IS).
Figure 3
Figure 3
Kaplan Meier curve of overall survival (OS) across all imaging score (IS) subgroups (0,1,2,3,4).
Figure 4
Figure 4
Kaplan Meier curve of overall survival (OS) between patients with PSMA SPECT vs. PET/CT scan.
See this image and copyright information in PMC

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