Detection of bone metastases in men with low PSA biochemical recurrence of prostate cancer with ¹⁸ F-flotufolastat PET/CT: A post-hoc analysis from the phase 3 SPOTLIGHT study.

31 Background: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has become the mainstay of prostate cancer imaging. The SPOTLIGHT study (NCT04186845) assessed the diagnostic performance of PSMA-targeted PET radiopharmaceutical, 18 F-flotufolastat, in men with suspected biochemical recurrence (BCR) of prostate cancer and showed it to have high detection rates even among patients with low prostate-specific antigen (PSA) values. Here, we present the results of a post-hoc analysis of SPOTLIGHT that aimed to determine the 18 F-flotufolastat verified detection rate for bone metastases in patients with a PSA level <0.5 ng/mL. Methods: Men with suspected BCR of prostate cancer underwent PET/CT 50–70 min after IV administration of 18 F-flotufolastat (296 MBq ± 20%). Three blinded central readers interpreted the 18 F-flotufolastat scans, with results presented as a majority read. Standard of truth (SoT) was established for each patient using histopathology or confirmatory conventional imaging (including CT, MRI, 99m Tc bone scan, 18 F-NaF PET/CT or 18 F-fluciclovine PET/CT). For the present analysis, all patients who had an evaluable scan were included if they had a baseline PSA level <0.5 ng/mL. Results: In total, data from 121 patients with an evaluable scan and PSA level <0.5 ng/mL were evaluated. Of these, 105 patients had sufficient data to determine a SoT (median PSA, 0.30 ng/mL). The patient-level 18 F-flotufolastat DR for this cohort of patients with low PSA was 64% (77/121) by majority read, with a DR of 21% (25/121) in extrapelvic lesions. Bone lesions were detected in 15% (18/121) of the patients. SoT verification of these bone lesions was predominantly by conventional imaging, with histopathology available for just 2/18 (11%) bone lesions. In total, 10/18 bone lesions were confirmed as true positive, yielding a verified detection rate in bone of 9.5% (10/105). Conclusions: This post-hoc analysis of a prospective Phase 3 clinical study demonstrates that 18 F-flotufolastat has a clinically meaningful detection rate for bone metastases in this low PSA population, identifying a true positive bone metastasis in at least one in ten patients (as bone biopsy is not often clinically indicated to allow for histopathology as SoT) with a PSA level <0.5 ng/mL. Clinical trial information: NCT04186845 .