Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

2019 ◽  
Vol 2 (6) ◽  
pp. 670-676 ◽  
Author(s):  
Sue Ping Thang ◽  
John Violet ◽  
Shahneen Sandhu ◽  
Amir Iravani ◽  
Tim Akhurst ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Poor Outcomes ◽  
Specific Membrane ◽  
Psma Expression

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.

scholarly journals Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Panagiotis J. Vlachostergios ◽  
Muhammad Junaid Niaz ◽  
Michael Sun ◽  
Seyed Ali Mosallaie ◽  
Charlene Thomas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Emission Computed Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pet Ct ◽  
Specific Membrane ◽  
Psma Expression ◽  
Systemic Therapies

BackgroundProstate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC).MethodsPatients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0–4 in order to determine an imaging score (IS). The IS (high: 2–4 versus low: 0–1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox’s proportional hazards models.ResultsHigh PSMA expression (IS 2–4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9–19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0–18.1) months compared to those with low expression [22.7 (95%CI: 17.7–30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p<0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2–2.2); p = 0.003].ConclusionPresence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes.

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

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