Authors’ reply: PSMA-PET: is the time to say goodbye to metabolic radiopharmaceuticals in prostate cancer?

Abstract

Dear Sir, We thank Evangelista and Alongi for their interest in our article and their recent letter [1]. The question of which radiotracer is best suited for the detection of prostate cancer is a hotly contested issue in contemporary nuclear medicine, and we must thank Evangelista and Alongi for raising a number of interesting points and observations in relation to our study and for their contribution to this topic of lively debate. They make a cogent argument for a continued role for metabolic tracers such as choline in the detection of recurrent prostate cancer. While we broadly agree with the spirit of the points raised by our colleagues, in response, we must refute the injudicious interpretation that the aim of our study was to “delete” the evidence for metabolic tracers such as choline. On the contrary, by performing a networked meta-analysis, we aimed to include all available data! One would hope that the careful discussion of the data presented in our manuscript would not lead anyone to conclude otherwise. Rather, our aim was to perform a systematic review of available data and to use a networked analytical approach to synthesise these data as coherently and with asmuch statistical stringency as is possible when working with real-life data and all of its inherent limitations [2], particularly where large or robust comparative imaging trials with radiopharmaceuticals are difficult to perform and limited in number. Despite nearly a decade of routine use of PSMA PET/CT since its first clinical description in 2013 [3], a mere 12 studies with 1356 patients represents the sum total of comparative imaging data in this field. Pooling these limited data through networkanalysis can complement traditional meta-analytic methodologies for the reasons outlined in our manuscript. Careful scrutiny of our paper will demonstrate that all of the enumerated points 1–5 listed by Evangelista and Alongi were indeed amply addressed in our discussion. As a matter of fact, wemade explicit mention of the effect of PSA on detection rate, and the likely limited added benefit of PSMA-radiotracers in advanced disease. What is more, we then go on to discuss the utility of additional choline PET/CT in PSMA-negative disease [4]. Although highly vulnerable to bias, and as such not within scope for meta-analysis, this is one area where the traditional case-report or anecdotal study can make a significant contribution to the overall literature. For example, Iravani et al. compare Ga-DOTATATE, Ga-PSMA-11, and F-FDG PET/CT in a series of patients with neuroendocrine differentiated prostate cancer [5]. Furthermore, F-FDG is of value in advanced disease [6], and novel tracers such as Ga-FAPI-04 show promise [7]. Therefore, there are a number of alternatives to both choline and PSMA-based radiotracers and we must remain agnostic as to which tracer might be superior or more cost-effective in the rare case of PSMA-negative disease until further comparative imaging studies are available. Here, we agree that, until such evidence is available, a personalised approach may be of utility. Regrettably, amongst other reporting inconsistencies, not all publications make the details regarding scanner system available. Although our group recognises well the advantages which modern digital PET/CT systems have in the detection of prostate cancer [8, 9], we cannot agree with Evangelista and Alongi’s claim that improvements in scanner technology might act to bias the published data in favour of PSMAtracers. Our study restricted itself to head-to-head data, i.e. an intra-individual comparison where scanner type is largely constant and prima facie unlikely to be a confounder. Moreover, when scrutinising the supplementary materials This article is part of the Topical Collection on Letter to the Editor