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

Abstract

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 perpatient 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, SUVmax, SUVpeak, SUVmean, total lesion PSMA, and the relatedmetric PSMA quotient (which integrates lesion volume and PSMA avidity). Results: In total, 192 segmentations were analyzed for the perlesion 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 MTVtotal (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 26.70 (95% CI, 214.32-0.93). 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 semiautomatic MTVtotal is repeatable and reader-independent, with a change of 635% 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 MTVtotal used in this study offers an efficient and robustmeans of assessing response to therapy.