Evaluation of thresholding methods for the quantification of [68Ga]Ga-PSMA-11 PET molecular tumor volume and their effect on survival prediction in patients with advanced prostate cancer undergoing [177Lu]Lu-PSMA-617 radioligand therapy

Abstract

Purpose The aim of this study was to systematically evaluate the effect of thresholding algorithms used in computer vision for the quantification of prostate-specific membrane antigen positron emission tomography (PET) derived tumor volume (PSMA-TV) in patients with advanced prostate cancer. The results were validated with respect to the prognostication of overall survival in patients with advanced-stage prostate cancer. Materials and methods A total of 78 patients who underwent [177Lu]Lu-PSMA-617 radionuclide therapy from January 2018 to December 2020 were retrospectively included in this study. [68Ga]Ga-PSMA-11 PET images, acquired prior to radionuclide therapy, were used for the analysis of thresholding algorithms. All PET images were first analyzed semi-automatically using a pre-evaluated, proprietary software solution as the baseline method. Subsequently, five histogram-based thresholding methods and two local adaptive thresholding methods that are well established in computer vision were applied to quantify molecular tumor volume. The resulting whole-body molecular tumor volumes were validated with respect to the prognostication of overall patient survival as well as their statistical correlation to the baseline methods and their performance on standardized phantom scans. Results The whole-body PSMA-TVs, quantified using different thresholding methods, demonstrate a high positive correlation with the baseline methods. We observed the highest correlation with generalized histogram thresholding (GHT) (Pearson r (r), p value (p): r = 0.977, p < 0.001) and Sauvola thresholding (r = 0.974, p < 0.001) and the lowest correlation with Multiotsu (r = 0.877, p < 0.001) and Yen thresholding methods (r = 0.878, p < 0.001). The median survival time of all patients was 9.87 months (95% CI [9.3 to 10.13]). Stratification by median whole-body PSMA-TV resulted in a median survival time from 11.8 to 13.5 months for the patient group with lower tumor burden and 6.5 to 6.6 months for the patient group with higher tumor burden. The patient group with lower tumor burden had significantly higher probability of survival (p < 0.00625) in eight out of nine thresholding methods (Fig. 2); those methods were SUVmax50 (p = 0.0038), SUV ≥3 (p = 0.0034), Multiotsu (p = 0.0015), Yen (p = 0.0015), Niblack (p = 0.001), Sauvola (p = 0.0001), Otsu (p = 0.0053), and Li thresholding (p = 0.0053). Conclusion Thresholding methods commonly used in computer vision are promising tools for the semiautomatic quantification of whole-body PSMA-TV in [68Ga]Ga-PSMA-11-PET. The proposed algorithm-driven thresholding strategy is less arbitrary and less prone to biases than thresholding with predefined values, potentially improving the application of whole-body PSMA-TV as an imaging biomarker.

The Impact of PSMA PET/CT on Modern Prostate Cancer Management and Decision Making—The Urological Perspective

“…While those thresholds are currently used by some clinical practitioners and urologists, they remain prone to reader bias due to false-positive PSMA uptake and experience. Interestingly, Kim et al [ 20 ] showed that the use of different semiautomatic PET-derived tumor volume (PSMA-TV) models in patients with advanced prostate cancer predicts overall survival when comparing low and high-volume whole-body uptake. Incorporating similar thresholds into clinical data produces a nomogram predicting similar overall survival outcomes in low and high-volume diseases [ 21 ], supporting the future use of such models to further affect clinical practice.…”

Predictors of Metastasis in 68GA-Prostate Specific Membrane Antigen Pet-CT in the Primary Staging of Prostate Cancer

“…Recent studies have underscored the robust prognostic utility of PSMA PET-CT in managing patients in both the primary setting and after BCR, particularly in cases exhibiting a strong PSA response [13]. Moreover, Ga68 PSMA PET-CT has emerged as a predictive imaging modality for patients with advanced prostate cancer who have undergone Lu-PSMA-617 radionuclide therapy, demonstrating its versatility across various stages of the disease [14]. Notably, a prospective observational study highlighted the critical role of PSMA PET-CT in patients undergoing radical treatment without prior biopsy, emphasizing its significance in treatment planning and monitoring [15].…”