Diagnostic Performance of 18F-rhPSMA-7.3 PET in Men with Newly Diagnosed High-Risk Prostate Cancer and Negative Conventional Imaging.

Abstract

The LIGHTHOUSE study (NCT04186819) evaluated high affinity radio hybrid (rh) prostate-specific membrane antigen (PSMA)-targeted PET radiopharmaceutical, 18F-rhPSMA-7.3, in patients across a range of prostate cancer (PCa) risk groups. Here, we report findings from a subgroup with high/very high-risk PCa who had no evidence of nodal or metastatic disease on conventional imaging. Treatment-naïve patients scheduled for radical prostatectomy (RP) plus pelvic lymph node (PLN) dissection underwent PET 50-70 min after IV administration of 296 MBq 18F-rhPSMA-7.3. Local readers interpreted the scans prior to RP (performed ≤60 d post-PET) and ahead of a blinded read by 3 central readers. If the local read indicated M1 disease, verification (biopsy, surgery, or confirmatory follow-up imaging) of PET-positive M1 lesions was attempted before treatment. The present analysis evaluates the 18F-rhPSMA-7.3 sensitivity and specificity for detection of PLN metastases in all high/very high-risk patients with negative conventional imaging at baseline who underwent 18F-rhPSMA-7.3 PET and subsequent surgery. Histopathology was used as the standard of truth (SoT). Additionally, the M1 verified detection rate (VDR; % of patients with true positive (TP) M1 lesions using histopathology or follow-up imaging as SoT out of all patients scanned) was assessed in an extended population of all patients who had 18F-rhPSMA-7.3 PET regardless of surgery. The sensitivity and specificity for PLN detection among 174 men with very/high-risk PCa and negative conventional imaging ranged from 24-33% and 92-96%, respectively, across readers (Table 1a). Across readers, M1 lesions were identified in 28-51 of the 197 patients in the extended population, giving an overall M1 detection rate of 14-26%. Of the identified lesions, 16-25 were successfully verified (predominantly using follow-up imaging as SoT) as TP, providing a M1 VDR of 8.1-13% (Table 1). 18F-rhPSMA-7.3 PET provides clinically useful information on the presence of both N1 and M1 disease prior to surgery in high/very high-risk PCa patients who were staged N0 M0 on conventional imaging. Specifically, up to 13% of such patients had verified TP M1 lesions. 18F-rhPSMA-7.3 may guide treatment, potentially helping such patients avoid ultimately futile surgery.