Detection efficacy of 18F-rhPSMA-7.3 PET/CT and impact on patient management in patients with biochemical recurrence of prostate cancer after radical prostatectomy and prior to potential salvage treatment.

Purpose: Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are a new class of 18F-labeled PSMA-targeting agents. 18F-rhPSMA-7.3 is a lead compound which is currently under investigation in two multicenter phase III trials for PET-imaging. Here, we report the first retrospective data on its detection efficacy and potential impact on clinical management in a homogeneous cohort of patients with biochemical recurrence after radical prostatectomy, and prior to any salvage therapy. Methods: 242 patients (median [range] PSA, 0.60 [0.2-60.8] ng/mL) who underwent 18F-rhPSMA-7.3 PET/CT were retrospectively selected from the institutions' database. Images were re-read by an experienced nuclear medicine physician. Lesion detection rates were stratified by PSA. Further, potential management before and after PET was assessed by an interdisciplinary simulated tumor board and categorized (major vs. minor vs. no therapeutic change). The distribution of management change identified in each PSA subgroup was determined. Results: In total, 176/242 (72.7%) patients showed PSMA-ligand positive findings. 18F-rhPSMA-7.3 detection rates were 61.8% (63/102), 67.9% (38/56), 81.1% (30/37) and 95.7% (45/47) for PSA-levels of 0.2-<0.5 ng/mL, 0.5-<1 ng/mL, 1-<2 ng/mL and ≥2 ng/mL, respectively. 18F-rhPSMA-7.3 PET/CT revealed local recurrence, pelvic lymph node metastases, retroperitoneal lymph nodes metastases, supradiaphragmatic lymph nodes, bone metastases, and visceral metastases in 48.8% (n = 118), 28.9% (n = 70), 6.6% (n = 16), 1.2% (n = 3), 13.2% (n = 32) and 1.2% (n = 3) of patients, respectively. Notably, bone lesions were identified in 8.8% of patients (9/102) with PSA <0.5 ng/mL. Results from the interdisciplinary simulated tumor board indicated change of therapeutic management in 153/242 patients (63.2%) with 54/242 (22.3%) considered major and 99/242 (40.9%) minor, respectively. 18F-rhPSMA-7.3 PET/CT did not prompt any therapeutic changes in 64/242 patients (26.4%). Conclusion: 18F-rhPSMA-7.3 PET offers high detection efficacy in patients with biochemical recurrence after radical prostatectomy, and prior to potential salvage therapy, and results in a potential change in treatment plans in nearly 2/3 of patients. Keywords: Biochemical recurrence; hybrid imaging; positron emission tomography; prostate cancer; prostate-specific membrane antigen.

Early Prostate-Specific Antigen Changes and Clinical Outcome After 177Lu-PSMA Radionuclide Treatment in Patients with Metastatic Castration-Resistant Prostate Cancer.

Prostate-specific antigen (PSA) is widely used to monitor treatment response in patients with metastatic castration-resistant prostate cancer. However, PSA measurements are considered only after 12 wk of treatment. We aimed to evaluate the prognostic value of early PSA changes after 177Lu-labeled prostate-specific membrane antigen (177Lu-PSMA) radionuclide treatment in metastatic castration-resistant prostate cancer patients. Methods: Men who were treated with 177Lu-PSMA under a compassionate-access program at our institution and had available PSA values at baseline and at 6 wk after treatment initiation were included in this retrospective analysis. Patients were assigned to 3 groups on the basis of PSA changes: response (≥30% decline), progression (≥25% increase), and stable (<30% decline and <25% increase). The coprimary endpoints were overall survival and imaging-based progression-free survival. The secondary endpoints were PSA changes at 12 wk and PSA flare-up. Results: We identified 124 eligible patients with PSA values at 6 wk. A greater than or equal to 30% decline in PSA at 6 wk was associated with longer overall survival (median, 16.7 mo; 95% CI, 14.4-19.0) than stable PSA (median, 11.8 mo; 95% CI, 8.6-15.1) (P = 0.007) or PSA progression (median, 6.5 mo; 95% CI, 5.2-7.8) (P < 0.001). Patients with a greater than or equal to 30% decline in PSA at 6 wk also had a lower risk of imaging-based progression than patients with stable PSA (hazard ratio, 0.60; 95% CI, 0.38-0.94) (P = 0.02), whereas patients with PSA progression had a higher risk of imaging-based progression than patients with stable PSA (hazard ratio, 3.18; 95% CI, 1.95-5.21) (P < 0.001). The percentage changes in PSA at 6 and 12 wk were highly associated (r = 0.90; P < 0.001). Of 31 patients who experienced early PSA progression at 6 wk, 29 (94%) showed biochemical progression at 12 wk. Overall, only 1 (3%) of 36 patients with PSA progression at 6 wk achieved any PSA decline at 12 wk (1% of the entire cohort). The limitations of the study included its retrospective nature and the single-center experience. Conclusion: PSA changes at 6 wk after 177Lu-PSMA initiation are an early indicator of long-term clinical outcome. Patients with PSA progression after 6 wk of treatment could benefit from a very early decision to switch treatment. PSA flare-up during 177Lu-PSMA treatment is very uncommon. Prospective studies are now warranted to validate our findings and potentially inform clinicians earlier on the effectiveness of 177Lu-PSMA.

Evaluation of SUV normalized by lean body mass (SUL) in 68Ga-PSMA11 PET/CT: a bi-centric analysis.

INTRODUCTION: The aim of this analysis was to investigate whether the standardized uptake value (SUV) normalized by lean body mass (SUL) is a more appropriate quantitative parameter compared to the commonly used SUV normalized by patient's weight in 68Ga-PSMA11 PET/CT. MATERIAL AND METHODS: 68Ga-PSMA11 PET/CT scans of 121 patients with prostate cancer from two institutions were evaluated. Liver SUV was measured within a 3-cm volume-of-interest (VOI) in the right hepatic lobe and corrected for lean body mass using the Janmahasatian formula. SUV and SUL repeatability between baseline and follow-up scans of the same patients were assessed. RESULTS: SUV was significantly positively correlated with body weight (r = 0.35, p = 0.02). In contrast, SUL was not correlated with body weight (r = 0.23, p = 0.07). No significant differences were found between baseline and follow-up scan (p = 0.52). CONCLUSION: The Janmahasatian formula annuls the positive correlations between SUV and body weight, suggesting that SUL is preferable to SUV for quantitative analyses of 68Ga-PSMA11 PET/CT scans.