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Prostate-specific membrane antigen (PSMA)-targeting PET imaging is becoming the reference standard for prostate cancer staging, especially in advanced disease. Yet, the implications of PSMA PET-derived whole-body tumor volume for overall survival are poorly elucidated to date. This might be because semiautomated quantification of whole-body tumor volume as a PSMA PET biomarker is an unmet clinical challenge. Therefore, in the present study we propose and evaluate a software that enables the semiautomated quantification of PSMA PET biomarkers such as whole-body tumor volume. Methods: The proposed quantification is implemented as a research prototype. PSMA-accumulating foci were automatically segmented by a percental threshold (50% of local SUV max ). Neural networks were trained to segment organs in PET/CT acquisitions (training CTs: 8,632, validation CTs: 53). Thereby, PSMA foci within organs of physiologic PSMA uptake were semiautomatically excluded from the analysis. Pretherapeutic PSMA PET/CTs of 40 consecutive patients treated with 177 Lu-PSMA-617 were evaluated in this analysis. The whole-body tumor volume (PSMA TV50 ), SUV max , SUV mean , and other whole-body imaging biomarkers were calculated for each patient. Semiautomatically derived results were compared with manual readings in a subcohort (by 1 nuclear medicine physician). Additionally, an interobserver evaluation of the semiautomated approach was performed in a subcohort (by 2 nuclear medicine physicians). Results: Manually and semiautomatically derived PSMA metrics were highly correlated (PSMA TV50 : R  2 = 1.000, P &lt; 0.001; SUV max : R  2 = 0.988, P &lt; 0.001). The interobserver agreement of the semiautomated workflow was also high (PSMA TV50 : R  2 = 1.000, P &lt; 0.001, interclass correlation coefficient = 1.000; SUV max : R  2 = 0.988, P &lt; 0.001, interclass correlation coefficient = 0.997). PSMA TV50 (ml) was a significant predictor of overall survival (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006, P = 0.002) and remained so in a multivariate regression including other biomarkers (hazard ratio: 1.004; 95% confidence interval: 1.001-1.006 P = 0.004). Conclusion: PSMA TV50 is a promising PSMA PET biomarker that is reproducible and easily quantified by the proposed semiautomated software. Moreover, PSMA TV50 is a significant predictor of overall survival in patients with advanced prostate cancer who receive 177 Lu-PSMA-617 therapy.

Semiautomatically Quantified Tumor Volume Using 68Ga-PSMA-11 PET as a Biomarker for Survival in Patients with Advanced Prostate Cancer

Semiautomatically Quantified Tumor Volume Using ⁶⁸Ga-PSMA-11 PET as a Biomarker for Survival in Patients with Advanced Prostate Cancer