Repeatability of ⁶⁸Ga-PSMA-HBED-CC PET/CT-Derived Total Molecular Tumor Volume

Molecular tumor volume (MTV) is a parameter of interest in 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 toward meaningful monitoring of total tumor burden and treatment response through PET is establishing the repeatability of these metrics. The present study assessed the repeatability of total MTV and related metrics for ⁶⁸Ga-PSMA-HBED-CC in prostate cancer. Methods: Eighteen patients from a prior repeatability study who underwent 2 test-retest PSMA PET/CT scans within a mean interval of 5 d were reanalyzed. Within-subject coefficient of variation and repeatability coefficients (RCs) 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 the per-patient analysis, subgroups of up to 10 lesions (single reader) and the total tumor volume per patient were segmented (independently by 2 readers). Image parameters were MTV, SUV_max, SUV_peak, SUV_mean, total lesion PSMA, and the related metric PSMA quotient (which integrates lesion volume and PSMA avidity). Results: In total, 192 segmentations were analyzed for the per-lesion analysis and 1,662 segmentations for the 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 to 33% after aggregation of up to 10 manually selected lesions into subgroups assessed per patient (95% CI, 25%-46%). The RC of the semiautomatic MTV_total (the sum of all voxels in the whole-body total tumor segmentation per patient) was 35% (95% CI, 25%-50%), the Bland-Altman bias was -6.70 (95% CI, -14.32-0.93). Alternating readers between scans led to a comparable RC of 37% (95% CI, 28%-49%) for MTV_total, meaning that the metric is robust between scanning sessions and between readers. Conclusion:⁶⁸Ga-PSMA-HBED-CC PET-derived semiautomatic MTV_total 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, although showing acceptable repeatability, is less systematic. The semiautomatic analysis of MTV_total used in this study offers an efficient and robust means of assessing response to therapy.