Diagnostic performance of ¹⁸ F-flotufolastat PET/CT compared with conventional imaging in men with biochemical recurrence of prostate cancer: Descriptive post-hoc analysis from the phase 3 SPOTLIGHT study.

30 Background: SPOTLIGHT (NCT04186845) assessed the diagnostic performance of prostate-specific membrane antigen (PSMA)-targeting PET radiopharmaceutical 18 F-flotufolastat in men with suspected biochemical recurrence (BCR) of prostate cancer. This descriptive post-hoc analysis compared the diagnostic performance of 18 F-flotufolastat with baseline conventional imaging (BCI). Methods: Men with suspected BCR of prostate cancer underwent PET/CT 50–70 min after 18 F-flotufolastat (296 MBq ± 20%) administration. Patients enrolled in SPOTLIGHT underwent BCI with either, CT, MRI, 99m Tc bone scan, 18 F-NaF PET/CT or 18 F-fluciclovine PET/CT based on institute guidelines and read by a study site reader. 18 F-Flotufolastat PET images were interpreted by three blinded independent central readers. This analysis included a subset of patients who had histopathology data from biopsies conducted ≤ 60 days post-PET available as a standard of truth (SoT). Patient-level positive predictive values (PPV), detection rates (DR) and verified detection rates (VDR; equivalent to DR x PPV) were compared between BCI and 18 F-flotufolastat PET. A scan was considered true positive (TP) if it had ≤ 1 scan-positive region confirmed by histopathology, or false positive (FP) if not proven TP. Results: From the 69 patients with histopathology as SoT in SPOTLIGHT, one patient had indeterminate histopathology and one had indeterminate BCI, therefore the 18 F-flotufolastat and BCI groups contain 68 and 67 patients, respectively. Median PSA for patients in the 18 F-flotufolastat and BCI groups was 2.22 and 2.10 ng/mL, respectively. Compared with 18 F-flotufolastat, BCI had a lower DR (94–100% vs 33%, respectively) and accordingly detected fewer TP cases (24%) than 18 F-flotufolastat (63%). This conferred a higher VDR for 18 F-flotufolastat (63%) than BCI (24%) and an anticipatedly comparable PPV given disease on BCI are more overt and amenable to verification (Table). Of note, 18 F-fluciclovine PET was the highest performing BCI modality. Conclusions: This descriptive post-hoc analysis shows that 18 F-flotufolastat PET has superior diagnostic efficacy, including DR and VDR compared with BCI for patients with BCR of prostate cancer. Clinical trial information: NCT04186845 . DR, n (%) VDR, n (%) PPV,TP/TP+FP (%) 18 F-Flotufolastat PET reader 1N=68 68/68 (100) 43/68 (63) 43/68 (63) 18 F-Flotufolastat PET reader 2N=68 64/68 (94) 43/68 (63) 43/64 (67) 18 F-Flotufolastat PET reader 3N=68 66/68 (97) 43/68 (63) 43/66 (65) BCI*N=67 22/67 (33) 16/67 (24) 16/22 (73) Baseline CT † N=31 3/31 (10) 2/31 (7) 2/3 (67) Baseline MRI † N=18 8/18 (44) 5/18 (28) 5/8 (63) Baseline 99m Tc bone scan † N=35 2/35 (6) 2/35 (6) 2/2 (100) Baseline 18 F-fluciclovine † PETN=22 13/22 (59) 10/22 (46) 10/13 (77) *Includes CT, MRI, 99m Tc bone scan, 18 F-fluciclovine PET/CT.