Flotufolastat F 18 scans show high degree of inter- and intra-reader agreement in prostate cancer

Image interpretation with flotufolastat F 18 (formerly ¹⁸F-rhPSMA-7.3, Posluma) scans show a high level of inter- and intra-reader reproducibility in patients with newly diagnosed prostate cancer, according to findings from the phase 3 LIGHTHOUSE trial (NC04186819) presented at the 2023 Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting in Chicago, Illinois.¹

The study included 352 men with unfavorable intermediate to very high-risk prostate cancer.

“Up to 25% of patients with primary prostate cancer may have detectable regional pelvic lymph node metastases, which are correlated with a risk for recurrence and associated overall survival. Effective staging in primary disease—determining its presence and whether it may have metastasized—is critical to establishing optimal clinical management strategies for patients,” said Phillip H. Kuo, MD, PhD, in a news release on the findings.² Kuo is a professor of medical imaging, medicine, and biomedical engineering at the University of Arizona in Tucson.

For the study, flotufolastat F 18 scans from 352 men with unfavorable intermediate to very high-risk prostate cancer were evaluated by 3 independent, blinded readers.

Inter-reader agreement was 95% or greater across pair-wise comparisons across all 3 readers (Fleiss’ κ = .26). Agreement was 81% or greater across pair-wise inter-reader comparisons in all regions, with the highest being in pelvic lymph nodes and other extra-pelvic regions (Cohen’s κ ≥ .45). For the prostate, comparison was not estimable between readers 1 or 2, nor between readers 1 and 3. Cohen’s κ was .50 between readers 2 and 3.

For each reader, the overall intra-reader agreement was 96% or greater. Agreement was 87% or higher across intra-reader agreement in all regions, with Cohen’s κ shown to be higher for pelvic lymph nodes and other extra-pelvic regions compared with that for the prostate.

Kuo concluded, “These findings from the LIGHTHOUSE study showed high reader agreement in interpreting Posluma PET/CT scans among a patient population of men with unfavorable intermediate- to very high-risk prostate cancer prior to initial therapy. The high reproducibility of reader results across all regions is clinically valuable, with the potential to influence patient management prior to surgery for patients with newly diagnosed disease.”

Additional data on flotufolastat F 18, LIGHTHOUSE

The FDA recently approved flotufolastat F 18 for PET imaging of PSMA-positive lesions in men with prostate cancer with suspected metastasis who are candidates for initial definitive therapy or with suspected recurrence based on elevated serum PSA level.

Data on flotufolastat F 18 based on initial findings from phase 3 LIGHTHOUSE trial were presented at the 2022 Society of Urologic Oncology Annual Meeting.³ Findings showed that use of flotufolastat F 18 prior to prostatectomy was associated with positive disease detection and provided clinically meaningful information.

The co-primary end points in the trial were sensitivity and specificity in detecting pelvic lymph node metastases. The prespecified threshold was 22.5% for sensitivity and 82.5% for specificity.

Flotufolastat F 18 did not meet the prespecified statistical threshold for sensitivity, with detection ranging between 23% to 30% between the 3 readers. Investigators noted that sensitivity was higher for those with high-risk or very high–risk disease vs unfavorable intermediate-risk disease.

However, specificity for pelvic lymph node detection exceeded the threshold across all readers, ranging between 93% to 97%. Specificity was high across all readers for both disease risk stratifications, measuring 93% or higher.

References

1. Kuo P, Ravizzini G, Ulaner G, et al. Inter- and intra-reader reproducibility of 18F-rhPSMA-7.3 PET interpretation in patients with newly diagnoses prostate cancer: Results from a phase 3, prospective, multicenter study (LIGHTHOUSE). Presented at the 2023 Society of Nuclear Medicine and Molecular Imaging Annual Meeting, June 24-27, 2023, Chicago, Illinois. Abstract P589

2. Blue Earth Diagnostics announces reader reproducibility results from phase 3 LIGHTHOUSE trial of POSLUMA (Flotufolastat F 18) injection in newly diagnosed prostate cancer. News release. Blue Earth Diagnostics. June 27, 2023. Accessed June 30, 2023. https://www.businesswire.com/news/home/20230627793407/en/Blue-Earth-Diagnostics-Announces-Reader-Reproducibility-Results-from-Phase-3-LIGHTHOUSE-Trial-of-POSLUMA%C2%AE-Flotufolastat-F-18-Injection-in-Newly-Diagnosed-Prostate-Cancer

3. Chapin BF. Diagnostic performance and safety of 18F-rhPSMA-7.3 PET in patients with newly diagnosed prostate cancer: results from a phase 3, prospective, multicenter study (LIGHTHOUSE). Poster presented at Society for Urologic Oncology (SUO) 23rd Annual Meeting; November 30-December 2, 2022; San Diego, CA. Poster 134