Repeatability of 68Ga-PSMA-HBED-CC PET/CT-derived total molecular tumor volume.

Background: Molecular tumor volume (MTV) is a parameter of interest in advanced prostate cancer for assessing total disease burden on prostate specific membrane antigen (PSMA) PET. Although software segmentation tools can delineate whole-body MTV, a necessary step towards meaningful monitoring of total tumor burden and treatment response through PET is establishing the repeatability of these metrics. The present study assesses the repeatability of total MTV and related metrics for 68Ga-PSMA-HBED-CC in advanced prostate cancer. Methods: Eighteen patients from a prior repeatability study who underwent two test-retest PSMA PET/CT scans within a mean interval of 5 days were reanalyzed. Within subject coefficient of variation and repeatability coefficients (RC) were analyzed on a per lesion and per patient basis. For the per lesion analysis, individual lesions were segmented for analysis by a single reader. For per patient analysis, subgroups of up to 10 lesions (single reader) and the total tumor volume per patient were segmented (independently by two readers). Image parameters were: MTV; maximum, peak, and mean standardized uptake value; total lesion PSMA and the related metric PSMA quotient (which is integrating lesion volume and PSMA avidity). Results: In total, 192 segmentations were analyzed for the per lesion analysis and 1662 segmentations for the total tumor volume per patient analysis (combining the 2 readers and 2 scans). The RC of the MTV of single lesions was 77% (95%CI:63-96%). The RC improved after aggregation of up to 10 manually selected lesions into subgroups assessed per patient, 33% (95%CI:25-46%). The RC of the semi-automatic MTVtotal was 35% (95%CI:25-50. Alternating readers between scans led to a comparable RC of 37% (95%CI:28-49%) for MTVtotal meaning that the metric is robust between scanning sessions and between readers. Conclusion: 68Ga-PSMA-HBED-CC PET-derived semi-automatic MTVtotal is repeatable and reader independent with a change of ±35% representing a true change in tumor volume. Volumetry of single manually selected lesions has considerably lower repeatability, and volumetry based on subgroups of these lesions, while showing acceptable repeatability, is less systematic. The semi-automatic analysis of MTVtotal employed in this study offers an efficient and robust means of assessing response to therapy.