Abstract

PurposeMany radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC.MethodsThe PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination.ResultsA majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network.ConclusionDifferences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

Highlights

  • PSMA-radiotracers are increasingly utilized for the investigation of biochemical recurrence of prostate cancer replacing previous generation radiotracers [1]

  • Thirteen PET-radiotracers of interest were chosen for inclusion: 18F-PSMA-1007, 18FDCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18FFluciclovine, 18F-FACBC, 18F-Choline, 11C-Choline, and 68Ga-RM2

  • The estimated ratios of the rate of pathologic PET-scans for each pairwise comparison between radiotracers of the Network metaanalysis (NMA) are presented in Fig. 3, ordered by the SUCRA values

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Summary

Introduction

PSMA-radiotracers are increasingly utilized for the investigation of biochemical recurrence of prostate cancer (rPC) replacing previous generation radiotracers [1]. Despite the fact that PSMA-radiotracers are well established, agreement for their reimbursement, approval for their use or their inclusion in guidelines has hitherto been limited [3]. Association of Urology (EAU) guidelines rate their recommendation for PSMA-PET/CT in the setting of biochemical recurrence post radical prostatectomy as “weak”, and where PSMA-PET/CT is not available, fluciclovine-PET/CT is endorsed. There is a paucity of “gold standard” comparative imaging trials available to verify claims made for the utility of PSMA-PET/CT [4]. Even in locations where PSMA-PET/CT is available, disparities in access are encountered [8, 9], implying that more robust evidence is needed to improve access to PSMA-PET/CT for men with rPC

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