Prostate cancer (PCa) is the second most common malignancy in the male population worldwide [
1]. Localized PCa is mainly treated with radical prostatectomy (RP), external beam radiotherapy (EBRT), or brachytherapy. However, between 27 and 53% of all patients undergoing radical prostatectomy or radiation therapy develop a rising PSA, termed as biochemical recurrence [
2‐
4]. In patients with biochemical recurrence (BCR), studies have shown that
68Ga-PSMA-11-PET/CT is superior to F-18 or C-11 Cholin PET/CT in the detection of a correlate for rising PSA levels [
5‐
8]. Even for BCR at low PSA levels (< 0.5 ng/ml), lesion detection for planning a locoregional therapy is possible [
9‐
11]. A study investigating the detection efficacy of PSMA PET/CT in early-stage BCR revealed metastases even at very low PSA values down to 0.2 ng/ml [
12]. The overall positive detection rate was 55% in patients with PSA 0.2–0.5 ng/ml and 74% in patients with PSA 0.5–1 ng/ml. In 80% and 70%, respectively, of these PSMA PET/CT-positive cases, tracer uptake occurred beyond the prostate bed, i.e., in lymph nodes, bones, or visceral organs [
12]. Not surprisingly, it has been shown that PSMA PET/CT leads to 43% changes in staging and 59% in radiotherapy planning and thus is increasingly used for treatment planning of recurrent prostate cancer [
13]. However, with therapeutic decisions based on
68Ga-PSMA-11-PET/CT results, it is of high relevance to understand and analyze the influence of interobserver variability and demonstrate the robustness of this still relatively novel method. This is especially true for low-level PSA values as the changes in management can be substantial and the findings in PET/CT might often be subtle. The impact of reader’s experience was analyzed by Fendler et al.: in a multicenter study, they reported a positive correlation between interobserver agreement and the readers’ experience and recommend further investigations, as pitfalls in image evaluation can occur independently from the level of knowledge [
14]. Such pitfalls and equivocal uptakes could be seen in benign processes like Wegener’s granulomatosis, sarcoidosis, and Paget’s disease [
15,
16] and also in malignancies such as multiple myeloma [
17] and lung cancer [
18]. These issues in PSMA imaging lead to the development of a 5-point scale standardized molecular imaging reporting and data systems (MI-RADS) by Werner et al. [
19]. However, to the best of our knowledge, there are no data on interobserver variability of
68Ga-PSMA-11-PET/CT in the clinically relevant patient population with low-level biochemical recurrence after RP.
Thus, in this study, we evaluated the performance and interreader variability of 68Ga-PSMA-11-PET/CT in a homogeneous patient population of therapy-naive PCa patients with BCR after RP with PSA < 0.6 ng/ml.