[68Ga]Ga-PSMA Versus [18F]PSMA Positron Emission Tomography/Computed Tomography in the Staging of Primary and Recurrent Prostate Cancer. A Systematic Review of the Literature

Abstract

Context: In the past 10 yr, several agents based on prostate-specific membrane antigen (PSMA) for positron emission tomography imaging have been introduced in clinical practice for the management of patients with prostate cancer (PCa).

Objective: To analyse the available data in the literature to clarify the advantages and disadvantages of [⁶⁸Ga]Ga-PSMA and [¹⁸F]PSMA in different settings of PCa.

Evidence acquisition: A systematic literature search was made by using two main databases. Only studies published in the past 5 yr (2016-2021) in the English language with >20 enrolled patients were selected. Two reviewers independently appraised each article using a standard protocol. All the studies were analysed using a modified version of the Critical Appraisal Skills Programme checklist for diagnostic test studies.

Evidence synthesis: The systematic evaluation was made in 12 papers. Based on the quality assessment, the analysed studies demonstrated different methodologies. Three papers focused on the head-to-head comparison between ¹⁸F- and [⁶⁸Ga]Ga-PSMA (n = 123 patients). A matched-pair comparison between ¹⁸F- and [⁶⁸Ga]Ga-PSMA was reported in three papers, including 715 patients. The remaining papers used indiscriminately either ⁶⁸Ga-PSMA or [¹⁸F]PSMA (n = 1.157 patients). [¹⁸F]PSMA-1007 is superior to [⁶⁸Ga]Ga-PSMA-11 for the identification of local recurrence (less activity close to the bladder for [¹⁸F]PSMA-1007). Nonspecific/equivocal bone lesions are often recognised at [¹⁸F]PSMA-1007. [¹⁸F]DCFPyL is more reproducible for the identification of lymph nodes, and it shows fewer equivocal skeletal lesions and higher inter-reader agreement on skeletal lesions.

Conclusions: Despite a large body of literature on PSMA radiopharmaceutical agents labelled with ⁶⁸Ga or ¹⁸F, there are limited head-to-head or matched-pair comparative data. Certain clinical indications could trigger a preference, whilst caution is needed in interpreting potential false-positive findings, especially with [¹⁸F]PSMA-1007. Given the excellent performance of all accessible radiopharmaceuticals, the availability of specific tracers will likely guide choice.

Patient summary: In this systematic review, we analysed the currently available literature focused on [⁶⁸Ga] and [¹⁸F]-labelled prostate-specific membrane antigen. Our purpose is to identify which tracers would be correctly employed for the management of patients with prostate cancer.

Keywords: Disease management; Matched-pair analysis; Prostate cancer; Prostate-specific membrane antigen positron emission tomography; [(18)F]PSMA; [(68)Ga]Ga-PSMA-11.