Introduction:

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has become the mainstay for prostate cancer imaging. Radiohybrid (rh) PET radiopharmaceutical, 18F-rhPSMA-7.3, is a novel high affinity PSMA ligand. Here, we report the first data on the diagnostic performance and safety of 18F-rhPSMA-7.3 from the Phase 3 LIGHTHOUSE study (NCT04186819) that evaluated 18F-rhPSMA-7.3 in men with newly diagnosed prostate cancer planned to undergo radical prostatectomy (RP).

Methods:

The LIGHTHOUSE coprimary endpoints, patient-level sensitivity and specificity of 18F-rhPSMA-7.3-PET for detection of pelvic lymph node (PLN) metastases using histopathology as the standard of truth, were evaluated for the efficacy analysis population (EAP) which comprised all patients who underwent 18F-rhPSMA-7.3-PET and had subsequent RP and PLN dissection. Prespecified statistical thresholds for the lower bounds of the 95% confidence intervals [95%CI] were set at 22.5% and 82.5% for sensitivity and specificity, respectively. Further subgroup analyses of the coprimary endpoints were conducted with patients stratified by prostate cancer risk category.

Treatment-naïve patients with unfavorable intermediate-to-very high-risk prostate cancer who had elected to undergo RP with regional PLN dissection underwent PET/Computed Tomography (CT) 50-70 minutes after intravenous administration of 296 MBq (8mCi) 18F-rhPSMA-7.3. Safety follow-up occurred within 5 days and planned surgery within 60 days. Local readers interpreted the images prior to RP, before submission for blinded independent evaluation by 3 central readers.

Results:

The EAP comprised 296 patients (T1=121 [41%], T2=112 [38%], T3 =45 [15%]; median[range] last PSA, 8.45[1.15-120] ng/mL), 197 (67%) of whom had very/high-risk disease. Among the EAP, 23-37 (7.7-13%) patients had 18F-rhPSMA-7.3-positive PLN according to the 3 readers. Extrapelvic lesions were reported for an extended population comprising all patients who underwent 18F-rhPSMA-7.3-PET irrespective of surgery (n=352); across the readers, 56-98 (16-28%) had extrapelvic lesions.

Sensitivity for PLN detection (EAP) was 30% (95%CI, 19.6-42.1), 27% (95%CI, 17.2-39.1) and 23% (95%CI, 13.7-34.4) for Readers 1-3, respectively, not meeting the prespecified statistical threshold. Specificity was 93% (95%CI, 88.8-95.9), 94% (95%CI, 89.8-96.6) and 97% (95%CI, 93.7-98.7) for Readers 1-3, respectively, exceeding the threshold for all 3 readers.

Table 1 presents sensitivity and specificity stratified by risk category. While specificity was high (≥93%) for all readers across both risk stratifications, sensitivity was higher for very/high-risk disease than intermediate-risk disease.

No serious adverse events were observed.

Conclusion:

These data support that 18F-rhPSMA-7.3-PET/CT provides clinically useful information regarding identification of clinical N1 disease prior to surgery, particularly among patients with high- or very high-risk disease. The trend of lower sensitivity observed in this population is consistent with sensitivity reported to date within the class of PSMA-targeted diagnostic radiopharmaceuticals and is balanced by a high specificity.

In summary, 18F-rhPSMA-7.3 is well tolerated by patients and exhibits a favorable benefit to risk ratio in men with newly diagnosed prostate cancer scheduled for RP and PLN dissection.

Funding: Blue Earth Diagnostics