Combined forced diuresis and late acquisition on [${}^{68}$Ga]Ga-PSMA-11 PET/CT for biochemical recurrent prostate cancer: a clinical practice-oriented study

Increased detection of prostate cancer (PCa) recurrences using [${}^{68}$Ga]Ga-PSMA-11 PET/CT has been reported by adding forced diuresis or late-phase imaging to the standard protocol. However, the combination of these procedures in the clinical setting is still not standardized. One hundred prospectively recruited biochemical recurrent PCa patients were restaged with dual-phase [${}^{68}$Ga]Ga-PSMA-11 PET/CT from September 2020 to October 2021. All patients received a standard scan (60 min), followed by diuretics (140 min) and a late-phase abdominopelvic scan (180 min). PET readers with low (n = 2), intermediate (n = 2), or high (n = 2) experience rated (i) standard and (ii) standard + forced diuresis late-phase images in a stepwise fashion according to E-PSMA guidelines, scoring their level of confidence. Study endpoints were (i) accuracy against a composite reference standard, (ii) reader's confidence level, and (iii) interobserver agreement. Forced diuresis late-phase imaging increased the reader's confidence category for local and nodal restaging (both p < 0.0001), and the interobserver agreement in identifying nodal recurrences (from moderate to substantial, p < 0.01). However, it significantly increased diagnostic accuracy exclusively for local uptakes rated by low-experienced readers (from 76.5 to 84%, p = 0.05) and for nodal uptakes rated as uncertain at standard imaging (from 68.1 to 78.5%, p < 0.05). In this framework, SUVmax kinetics resulted in an independent predictor of PCa recurrence compared to standard metrics, potentially guiding the dual-phase PET/CT interpretation. The present results do not support the systematic combination of forced diuresis and late-phase imaging in the clinical setting, but allow the identification of patients-, lesions-, and reader-based scenarios that might benefit from it. Increased detection of prostate cancer recurrences has been reported by adding diuretics administration or an additional late abdominopelvic scan to the standard [${}^{68}$Ga]Ga-PSMA-11 PET/CT procedure. We verified the added value of combined forced diuresis and delayed imaging, showing that this protocol only slightly increases the diagnostic accuracy of [${}^{68}$Ga]Ga-PSMA-11 PET/CT, thus not justifying its systematic use in clinics. However, it can be helpful in specific clinical scenarios, e.g., when PET/CT is reported by low-experienced readers. Moreover, it increased the reader's confidence and the agreement among observers.