Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis

Abstract

Purpose: Many 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.

Methods: The 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.

Results: A 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.

Conclusion: Differences 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.

Keywords: Choline; Comparative imaging; Network meta-analysis; PET/CT; PSMA; Positron emission tomography; Radiotracers.

Fig. 1

PRISMA flowchart for literature search and selection

Fig. 2

The network created by the included studies. The area of the node represents the number of patients in each trial; the thickness of the edge represents the number of studies. The distances are only representative

Fig. 3

Detection rate ratios (odds of pathological PET in tracer A compared to B) for pairwise comparisons, ordered by SUCRA (random effects, informative). Ratios > 1 imply that the radiotracer of comparison which is left most has a greater detection rate

Fig. 4

Forest plot comparing different radiotracers, including inferred comparisons from the network (random effects with informative priors)

Fig. 5

Proportion of studies at low, high, or unclear risk of bias and regarding applicability

Fig. 6

Funnel plot showing PET positivity rate (observed outcome) versus the standard error in the detection rate (p = 0.05) where the x-axis represents standard error and the y-axis detection rate, and each dot represents each study. A number of studies fall outside the 95% control limits and are at risk of small study effects

Fig. 7

Forest plot for fixed effects model, pairwise comparison of direct data