Analysis of Molecular Imaging and Laboratory Baseline Biomarkers in PSMA-RLT: Whole-Body Total Lesion PSMA (TLP) Predicts Overall Survival.

The aim of this retrospective study was to identify pre-therapeutic predictive laboratory and molecular imaging biomarkers for response and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT). Pre-therapeutic laboratory and [68Ga]Ga-PSMA-11 PET/CT data of n = 102 mCRPC patients receiving [177Lu]Lu-PSMA-617 RLT within a prospective registry (REALITY Study, NCT04833517) were analyzed including laboratory parameters such as alkaline phosphatase (ALP), prostate-specific antigen (PSA), gamma glutamyl transferase (GGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neuron specific enolase (NSE), hemoglobin (Hb), and imaging parameters such as maximum standardized uptake value of the tumor lesions (SUVmax), the mean standardized uptake value of all tumor lesions (SUVmean), the whole-body molecular tumor volume (MTV), and the whole-body total lesion PSMA (TLP). Mann-Whitney U test, univariate and multivariable Cox-regression were performed to test for association of the parameters with response and OS. The SUVmean of all lesions was significantly different between responders and non-responders (SUVmean responders 8.95 ± 2.83 vs. non-responders 7.88 ± 4.46, p = 0.003), whereas all other tested biochemical and imaging parameters did not reveal significant differences. Hb and the molecular imaging parameters MTV and TLP showed a significant association with OS (p = 0.013, p = 0.005; p = 0.009) in univariant Cox regression; however, only TLP remained significant in multivariable analysis (Hazard ratio 1.033, p = 0.009). This study demonstrates a statistically significant association between the quantitative PET/CT imaging parameter SUVmean and PSA response, as well as between the baseline TLP and OS of mCRPC patients undergoing RLT.

Change in total lesion PSMA (TLP) during [177Lu]Lu-PSMA-617 radioligand therapy predicts overall survival in patients with mCRPC: monocentric evaluation of a prospective registry.

PURPOSE: This study investigates imaging response of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) based on the whole-body parameter total lesion PSMA (TLP), derived by PSMA-PET/CT and reflecting the total tumor burden, in patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective registry (NCT04833517). METHODS: A total of n = 102 mCRPC patients received a [68Ga]Ga-PSMA-11 PET/CT at baseline and after two cycles of PSMA-RLT, in which TLP was measured by using a semi-automated tumor segmentation. TLP was defined as the summed products of volume and uptake (∑ Volume × SUVmean) of all tumor lesions. The Kaplan-Meier method was used to determine the most appropriate ∆TLP thresholds for classification into partial remission (PR), stable disease (SD), and progressive disease (PD) regarding overall survival (OS). Furthermore, we analyzed criteria that are also frequently used in established response frameworks, such as the occurrence of new metastases as independent criterion (I) or in combination with change in tumor burden (II), and the change in PSA serum value (III). RESULTS: For the ∆TLP thresholds -30%/+30% (and also for higher thresholds, -40%/+40% or -50%/+50%), significant differences between all three response categories became apparent (PR/PD: p = 0.001; PR/SD: p = 0.001; SD/PD: p = 0.018). Including the development of new metastases as independent criterion of PD, there was no significant difference in OS between SD and PD (p = 0.455), neither when applied in combination with TLP (p = 0.191). Similarly, significant differentiation between SD and PD was not achieved by PSA serum value (p = 0.973). CONCLUSION: In the largest monocentric study to date, TLP is shown to be a qualified prognostic biomarker, applying ∆TLP thresholds of -30%/+30%. It significantly differentiated between PR, SD, and PD, whereas other response criteria did not differentiate SD vs. PD. Using TLP, the development of new metastases is not a required information for predicting OS.

Metabolic Tumour Volume from PSMA PET/CT Scans of Prostate Cancer Patients during Chemotherapy-Do Different Software Solutions Deliver Comparable Results?

(1) Background: Prostate-specific membrane antigen (PSMA)-derived tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) from PSMA PET/CT scans are promising biomarkers for assessing treatment response in prostate cancer (PCa). Currently, it is unclear whether different software tools for assessing PSMA-TV and TL-PSMA produce comparable results. (2) Methods: 68Ga-PSMA PET/CT scans from n = 21 patients with castration-resistant PCa (CRPC) receiving chemotherapy were identified from our single-centre database. PSMA-TV and TL-PSMA were calculated with Syngo.via (Siemens) as well as the freely available Beth Israel plugin for FIJI (Fiji Is Just ImageJ) before and after chemotherapy. While statistical comparability was illustrated and quantified via Bland-Altman diagrams, the clinical agreement was estimated by matching PSMA-TV, TL-PSMA and relative changes of both variables during chemotherapy with changes in serum PSA (ΔPSA) and PERCIST (Positron Emission Response Criteria in Solid Tumors). (3) Results: Comparing absolute PSMA-TV and TL-PSMA as well as Bland-Altman plotting revealed a good statistical comparability of both software algorithms. For clinical agreement, classifying therapy response did not differ between PSMA-TV and TL-PSMA for both software solutions and showed highly positive correlations with BR. (4) Conclusions: due to the high levels of statistical and clinical agreement in our CRPC patient cohort undergoing taxane chemotherapy, comparing PSMA-TV and TL-PSMA determined by Syngo.via and FIJI appears feasible.