Diagnostic performance of ¹⁸ F-flotufolastat PET/CT compared with conventional imaging for detection of pelvic lymph node metastases in men with newly diagnosed prostate cancer: Descriptive post-hoc analysis from the phase 3 LIGHTHOUSE study.

311 Background: 18 F-Flotufolastat is a prostate-specific membrane antigen (PSMA)-targeting PET radiopharmaceutical approved in the US for diagnostic use in men with prostate cancer. The Phase 3 LIGHTHOUSE study (NCT04186819) assessed 18 F-flotufolastat in men with newly diagnosed prostate cancer planned for radical prostatectomy (RP) and pelvic lymph node dissection (PLND). This post-hoc descriptive analysis aimed to compare the diagnostic performance of 18 F-flotufolastat with baseline conventional imaging (CT or MRI). Methods: LIGHTHOUSE enrolled patients with newly diagnosed unfavorable intermediate-risk (UIR) to very high-risk prostate cancer. Patients underwent PET/CT 50–70 min after 18 F-flotufolastat (296 MBq ± 20%) administration. 18 F-Flotufolastat scans were evaluated by three blinded independent central readers. Patients had baseline conventional imaging with CT, MRI or bone scan, within 60 days before screening or at least 24 h before 18 F-flotufolastat PET. Baseline conventional imaging was evaluated by local read. Histopathology was used as standard of truth (SoT), with ≥ 1 PET positive lesion and one histopathological confirmed lymph node (LN) classed as true positive (TP). Study endpoints included patient-level sensitivity and specificity for the detection of pelvic LN metastases. This post-hoc descriptive analysis explored the sensitivity and specificity of baseline conventional imaging with CT and/or MRI in LIGHTHOUSE with the sensitivity and specificity reported for 18 F-flotufolastat PET among the efficacy analysis population (EAP). Results: In total, 296 patients (33% with UIR disease) underwent 18 F-flotufolastat PET followed by RP and PLND (EAP). Within the LIGHTHOUSE EAP, the majority read patient-level sensitivity for detecting pelvic LN metastasis with 18 F-flotufolastat was 24% (23–30% across readers) and specificity was 96% (93–97% across readers). Comparatively, among the subset of patients who had baseline CT and/or MRI scans available (N=267), the majority read patient-level sensitivity and specificity for 18 F-flotufolastat were 23% (22–29% across readers) and 96% (93–97% across readers), respectively. Notably lower sensitivity values were observed for baseline conventional imaging – for CT and/or MRI, the patient-level sensitivity was 3% (CT, 4%; MRI, 0%) and specificity was 95% (CT, 95%; MRI, 93%; N=267). Conclusions: This post-hoc analysis demonstrated the superior sensitivity of 18 F-flotufolastat PET compared with baseline conventional CT or MRI for the detection of pelvic LN metastasis. The very low sensitivity of conventional imaging (3%) highlights that detection of pelvic LN metastasis in the population enrolled in the LIGHTHOUSE study is highly challenging. Clinical trial information: NCT04186819 .