Detection of true positive M1 lesions by 18F-rhPSMA-7.3 PET in newly diagnosed prostate cancer: Results from the phase 3 prospective LIGHTHOUSE study.

Abstract

315 Background: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high affinity prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) radiopharmaceutical. The LIGHTHOUSE study (NCT04186819) evaluated the diagnostic performance of 18F-rhPSMA-7.3 in newly diagnosed prostate cancer. Here we report the 18F-rhPSMA-7.3 verified detection rate (VDR), defined as the proportion of patients with M1 lesions identified by blinded image evaluation (BIE) and subsequently confirmed true positive (TP) by biopsy or confirmatory imaging. Methods: Men with treatment-naïve, unfavorable intermediate to very high-risk prostate cancer who were scheduled to undergo radical prostatectomy underwent PET 50-70 min after IV administration of 296 MBq 18F-rhPSMA-7.3. Onsite readers interpreted the images before submission for BIE by 3 central readers.Ifthe onsite read indicated M1 disease, verification (by biopsy, surgery or additional imaging) of PET-positive M1 lesions was attempted prior to treatment. 18F-rhPSMA-7.3 M1 VDR was evaluated amongall study patients without major protocol deviations. Results: Of the 335 men analyzed (median [range] PSA, 8.89 [1.15-120] ng/mL), 58 (17%) had M1 lesions by majority read. In total, 34 (10%) had verified M1 lesions with individual readers’ M1 VDR ranging from 10-15%. By region, verified M1 lesions were most common in bone, ranging from 6.0-11% across readers (majority read, 6.6%). Similar data were shown among a subgroup who had negative baseline conventional imaging. In these patients, the VDR ranged from 8.9-13% across readers (majority read, 8.6%). Again, bone showed the highest regional VDR, ranging from 4.8-9.2% (majority read, 5.1%). Conclusions: Further to its clinically meaningful sensitivity and specificity for pelvic lymph node metastases (reported separately), here we show 18F-rhPSMA-7.3 PET to be a useful staging tool, as distant metastatic lesions were verified in 10-15% of newly diagnosed patients with unfavorable intermediate to very high-risk prostate cancer. Determining the presence of M1 disease prior to surgery may help guide treatment planning by identifying patients for whom surgery is the optimal approach, or those for whom alternatives such as radiation therapy and/or androgen deprivation may be more suitable. Clinical trial information: NCT04186819 . [Table: see text]