True-Positive 18F-Flotufolastat Lesions in Patients with Prostate Cancer Recurrence with Baseline-Negative Conventional Imaging: Results from the Prospective, Phase 3, Multicenter SPOTLIGHT Study

Abstract

¹⁸F-rhPSMA-7.3 (¹⁸F-flotufolastat) is a high-affinity prostate-specific membrane antigen-targeted diagnostic radiopharmaceutical for PET imaging in patients with prostate cancer. Here, we report findings from the SPOTLIGHT study (NCT04186845), assessing the performance of ¹⁸F-flotufolastat PET/CT for identifying prostate-specific membrane antigen-positive lesions confirmed by standard of truth (SoT) in men with biochemical recurrence of prostate cancer and negative conventional imaging at baseline. Methods: Men with biochemical recurrence received 296 MBq of ¹⁸F-flotufolastat intravenously and then underwent PET/CT 50-70 min later. ¹⁸F-flotufolastat PET/CT findings were evaluated by 3 masked central readers and verified using histopathology or follow-up confirmatory imaging (CT, MRI, bone scan, or ¹⁸F-fluciclovine PET/CT) as the SoT. The present analysis evaluated all patients who had negative conventional imaging at baseline, underwent ¹⁸F-flotufolastat PET/CT, and had SoT verification by histopathology or follow-up confirmatory imaging to report detection rate (DR), which is the number of patients with at least 1 PET-positive lesion, divided by the number of evaluable patients, and verified DR (VDR), which is the proportion of patients with at least 1 true-positive lesion as verified by SoT, of all patients scanned (PET-positive and PET-negative scans). DR and VDR were calculated and stratified according to prior therapy. Majority read data (agreement between ≥2 readers) are reported. Results: In total, 171 patients with negative baseline conventional imaging and SoT by histopathology or post-PET confirmatory imaging were evaluated. By majority read, the overall ¹⁸F-flotufolastat DR among these patients was 95% (163/171; 95% CI, 91.0%-98.0%), and 110 of 171 of these patients had at least 1 true-positive lesion identified (VDR, 64%; 95% CI, 56.7%-71.5%). In the postprostatectomy group (133/171), 8.3% of patients had at least 1 true-positive lesion in the prostate bed, 28% in pelvic lymph nodes, and 35% in other sites. Among those who had received radiotherapy (36/171), 50% of patients had true-positive detections in the prostate, 8.3% in pelvic lymph nodes, and 36% in other sites. Conclusion: ¹⁸F-flotufolastat frequently identified true-positive prostate cancer lesions in patients with negative conventional imaging. ¹⁸F-flotufolastat may help to better define sites of disease recurrence and inform salvage therapy decisions than does conventional imaging, potentially leading to improved outcomes.

Keywords: 18F-flotufolastat; PSMA; biochemical recurrence; prostate cancer; rhPSMA.

Graphical abstract

FIGURE 1.

Standards for Reporting of Diagnostic Accuracy flow diagram of study participants. EAP = efficacy analysis population.

FIGURE 2.

Patient- and region-level overall DRs and VDRs (majority read) for ¹⁸F-flotufolastat PET/CT in patients with negative conventional imaging and post-PET SoT (n = 171).

FIGURE 3.

Patient- and region-level overall DRs and VDRs for ¹⁸F-flotufolastat PET/CT (majority read) in patients with negative baseline conventional imaging and histopathology SoT (n = 46) (A) or post-PET imaging SoT (n = 125) (B).

FIGURE 4.

Patient- and region-level overall DRs and VDRs for ¹⁸F-flotufolastat PET/CT (majority read) by baseline PSA category in patients with negative baseline conventional imaging and post-PET SoT.

FIGURE 5.

Patient- and region-level overall DRs and VDRs for ¹⁸F-flotufolastat PET/CT (majority read) in patients with negative baseline conventional imaging and post-PET SoT treated with prior prostatectomy (n = 133) (A) or prior radiotherapy only (n = 36) (B).

FIGURE 6.

CT (left), fused ¹⁸F-flotufolastat PET/CT (middle), and ¹⁸F-flotufolastat PET (right) transverse images of 76-y-old patient initially presenting with high-risk prostate cancer (Gleason score, 4 + 5 = 9) and subsequently with BCR after radical prostatectomy (PSA, 1.0 ng/mL). ¹⁸F-flotufolastat–avid focus was detected within mildly sclerotic right thoracic 5 transverse process (A) and was subsequently verified as true-positive by histopathology. In addition, ¹⁸F-flotufolastat–avid lesion was detected in left seventh rib (B) and was also verified with ¹⁸F-fluciclovine PET/CT (C).