scholarly journals Explorative analysis of a predictive score for patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with [177Lu]Lu-labeled prostate-specific membrane antigen

2020 ◽  
Author(s):  
Kai Huang ◽  
Imke Schatka ◽  
Julian M.M. Rogasch ◽  
Randall L. Lindquist ◽  
Maria De Santis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Specific Antigen ◽  
Significant Risk ◽  
Predictive Score ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Specific Membrane

Abstract Background: Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieve partial biochemical response with a decrease of >50% in prostate-specific antigen (PSA) levels. The remaining fraction of patients, however, do not respond to RLT. The aim of this explorative analysis was to identify pretherapeutic factors for the prediction of response. Methods: 46 patients (age = 68 years [53-87]) with mCRPC who consecutively underwent RLT with [177Lu]Lu-PSMA (median applied activity = 6 GBq [2.9-6.2]) were included and analysed retrospectively. Association of different clinical and laboratory factors and parameters from pretherapeutic 68Gallium-PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher’s test). Outcome was defined as PSA changes 8 weeks after the second RLT (partial response [PR], PSA decrease >50%; progressive disease [PD], PSA increase ≥25%; stable disease [SD], others). Significant risk factors were combined in a predictive score.Results: Median pretherapeutic PSA was 79 ng/ml. Thirty percent of the patients showed a post-treatment PR (median: 73% PSA decrease), 35% SD (median: 17% PSA decrease) and 35% PD (median: 42% PSA increase). Significant predictors for PD were alkaline phosphatase (ALP) >135 U/l (p=0.030), PSA >200 ng/ml (p=0.036), and maximum standardized uptake value (SUVmax) of the “hottest lesion” in pretherapeutic PET <45 (p=0.005). The predictive score including PSA, ALP, and SUVmax could separate 2 distinct groups of patients: ≤2 risk factors (81% PR or SD, 19% PD) and 3 risk factors (10% PR or SD, 90% PD). Conclusion: The presented predictive score allowed a pretherapeutic estimate of the expected response to RLT. This is hypothesis generating. Prospective trials are needed to test these predictive risk factors

scholarly journals Explorative analysis of a score predicting the therapy response of patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with 177Lu-labeled prostate-specific membrane antigen

2020 ◽  
Author(s):  
Kai Huang ◽  
Imke Schatka ◽  
Julian M. M. Rogasch ◽  
Randall L. Lindquist ◽  
Maria De Santis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Predictive Factors ◽  
Specific Antigen ◽  
Standardized Uptake Value ◽  
Predictive Score ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Specific Membrane

Abstract Objective Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with 177Lu prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieves a partial biochemical response with a decrease of > 50% in prostate-specific antigen (PSA) levels. The remaining fractions, however, do not respond to RLT. The aim of this explorative analysis was to identify pre-therapeutic factors for the prediction of response. Methods 46 patients [age = 68 years (50–87)] with mCRPC who consecutively underwent RLT with 177Lu PSMA [median applied activity = 6 GBq (2.9–6.2)] were included and analysed retrospectively. The association of different clinical and laboratory factors and parameters from pre-therapeutic 68Ga PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher’s test). Outcome was defined as PSA changes 8 weeks after second RLT [partial response (PR), PSA decrease > 50%; progressive disease (PD), PSA increase ≥ 25%; stable disease (SD), others]. Significant predictive factors were combined in a predictive score. Results 30% showed a post-treatment PR (median 73% PSA decrease), 35% SD (median 17% PSA decrease) and 35% PD (median 42% PSA increase). Significant predictors for PD were alkaline phosphatase (ALP) > 135 U/l (p = 0.002), PSA > 200 ng/ml (p = 0.036), and maximum standardized uptake value (SUVmax) of the “hottest lesion” in pre-therapeutic PET < 45 (p = 0.005). The predictive score including PSA, ALP and SUVmax could separate 2 distinct groups of patients: ≤ 2 predictive factors (19% PD) and 3 predictive factors (90% PD). Conclusion The presented predictive score allowed a pre-therapeutic estimate of the expected response to 2 cycles of RLT. As our study was retrospective, prospective trials are needed for validation.

Heterogeneity of prostate-specific membrane antigen (PSMA) expression in classic and apoptotic circulating tumor cells (CTC) in metastatic castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 198-198 ◽  
Author(s):  
Karen A. Autio ◽  
Aseem Anand ◽  
Rachel Krupa ◽  
Jessica Louw ◽  
Zaina Arslan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Specific Antigen ◽  
Cytotoxic Agents ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Specific Membrane ◽  
Psma Expression

198 Background: Prostate-specific membrane antigen (PSMA) is a folate hydrolase expressed on the surface of PC cells that has been used as a target to detect disease and selectively deliver cytotoxic agents and radionuclides. The ability to detect PSMA levels on circulating tumor cells (CTCs) may identify patients likely to benefit from such targeted therapy. Technology developed by Epic Sciences utilizes high definition imaging of plated nucleated cells. Methods: Blood samples were obtained from patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cells were stained for CK, CD45, PSMA and categorized as classic CTC (CK+, CD45-, intact/morphologically distinct nuclei) or apoptotic CTC (CK+, CD45-, morphology suggesting apoptosis). Clinical data including treatment, metastatic sites, Veridex CellSearch CTC enumeration, prostate-specific antigen, and alkaline phosphatase was collected. Results: Fourteen pts with mCRPC, including eight with serial samples were analyzed (33 samples in total). At the first draw (t1), classic CTC were detected in 13 pts (93%), (median two cells/ml, range 0 to 40 cells/ml) and apoptotic CTC in 14 pts (100%) (median four cells/ml, range 1 to 18 cells/ml), including six pts (42%) with no CTC by Veridex CellSearch. PSMA expression was detected in five pts (36%) with classic CTC of which a median of 32% of cells (range 5 to 100%) expressed the antigen. Similar intra-patient heterogeneity was seen for the 10 pts (71.4%) with PSMA+ apoptotic CTCs (median 33.5%, range 11 to 75% cells). During treatment, often with more complete androgen suppression, PSMA was detected in 3 of the 8 (38%) pts with no PSMA+ classic CTCs at t1. The presence of PSMA expression in apoptotic CTCs did not appear to change while on therapy. Conclusions: A larger percentage of PSMA expression was seen in mCRPC pts in apoptotic CTC (10 out of 14) than classic CTC (5 out of 14) at t1, with intra-patient cell heterogeneity of PSMA expression in both CTC populations. Serial measures suggest dynamic changes in PSMA expression over time. The threshold of detectable cells and proportion and degree of PSMA expression that associates with drug sensitivity is unknown. Larger samples of pts at discrete time points on therapy are underway to further elucidate the potential clinical relevance.

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