(UroToday.com) The 2022 SUO annual meeting featured a session on prostate cancer, including a presentation by Dr. Brian Chapin discussing results from the phase 3 LIGHTHOUSE trial assessing the diagnostic performance and safety of 18F-rhPSMA-7.3 PET in patients with newly diagnosed prostate cancer. Prostate-specific membrane antigen (PSMA) PET has become the mainstay for prostate cancer imaging. Radiohybrid (rh) PET radiopharmaceutical, 18F-rhPSMA-7.3, is a novel high affinity PSMA ligand. At the 2022 SUO winter meeting, Dr. Chapin and colleagues reported 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.
The LIGHTHOUSE coprimary endpoints, patient-level sensitivity, and specificity of 18F-rhPSMA-7.3-PET for detection of pelvic lymph node metastases using histopathology as the standard of truth, were evaluated for the efficacy analysis population which comprised all patients who underwent 18F-rhPSMA-7.3-PET and had a subsequent radical prostatectomy and pelvic lymph node dissection. Prespecified statistical thresholds for the lower bounds of the 95% confidence intervals 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 radical prostatectomy with regional pelvic lymph node dissection underwent PET/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 radical prostatectomy, before submission for blinded independent evaluation by 3 central readers.
The efficacy analysis population comprised 296 patients (T1 = 121 [41%], T2 = 112 [38%], T3 = 45 [15%]; median last PSA, 8.45 [range: 1.15-120] ng/mL), 197 (67%) of whom had very/high-risk disease. The baseline characteristics are as follows:
Among the efficacy analysis population, between 23 and 37 (7.8-13%) patients had 18F-rhPSMA-7.3-positive pelvic lymph node 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, between 56 and 98 (16-28%) patients had extrapelvic lesions. Sensitivity for pelvic lymph node detection (efficacy analysis population) 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:
Treatment-emergent adverse events were evaluated among the 356 patients in the safety population. Overall, 28/356 (7.9%) of patients experienced a total of 33 adverse events, none of which were serious. Nine (2.5%) patients experienced a total of 10 treatment-emergent adverse events considered possibly related to 18F-rhPSMA-7.3. Injection site pain was experienced by 3 (0.8%) of patients, whereas peripheral swelling, diarrhea, nausea, hyperkalemia, arthralgia, dysgeusia, and hypertension were reported for 1 (0.3%) patient.
Dr. Chapin concluded his presentation by discussing results from the phase 3 LIGHTHOUSE trial assessing the diagnostic performance and safety of 18F-rhPSMA-7.3 PET in patients with newly diagnosed prostate cancer with the following take home messages:
- 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
- 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 radical prostatectomy and pelvic lymph node dissection
Presented by: Brian Chapin, MD, MD Anderson Cancer Center, Houston, TX on behalf of the LIGHTHOUSE group
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 23rd Annual Meeting of the Society of Urologic Oncology (SUO), Nov 30 – Dec 2, 2022. San Diego, CA