The Evolving Role of Prostate-Specific Membrane Antigen–Based Diagnostics and Therapeutics in Prostate Cancer

2019 ◽  
pp. 321-330 ◽  
Author(s):  
Tanya B. Dorff ◽  
Stefano Fanti ◽  
Andrea Farolfi ◽  
Robert E. Reiter ◽  
Taylor Y. Sadun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Standardized Uptake Value ◽  
Response Assessment ◽  
Cancer Staging ◽  
Bone Lesions ◽  
Prostate Specific Membrane Antigen ◽  
Longitudinal Assessment ◽  
Resistant Disease ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA)–based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, 68Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from 177Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.

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.

scholarly journals Prostate-specific Membrane Antigen PET: Therapy Response Assessment in Metastatic Prostate Cancer

Radiographics ◽  
2020 ◽  
Vol 40 (5) ◽  
pp. 1412-1430 ◽  
Author(s):  
Felipe G. Barbosa ◽  
Marcelo A. Queiroz ◽  
Daniela A. Ferraro ◽  
Rafael F. Nunes ◽  
Priscilla R. Dreyer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Therapy Response ◽  
Response Assessment ◽  
Pet Therapy ◽  
Prostate Specific Membrane Antigen ◽  
Therapy Response Assessment ◽  
Specific Membrane

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.

Phase I Trial of Yttrium-90—Labeled Anti—Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Androgen-Independent Prostate Cancer

2004 ◽  
Vol 22 (13) ◽  
pp. 2522-2531 ◽  
Author(s):  
Matthew I. Milowsky ◽  
David M. Nanus ◽  
Lale Kostakoglu ◽  
Shankar Vallabhajosula ◽  
Stanley J. Goldsmith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monoclonal Antibody ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Prostate Specific Membrane Antigen ◽  
Life Threatening ◽  
Indium 111 ◽  
Specific Membrane ◽  
Yttrium 90 ◽  
Androgen Independent

Purpose To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90–labeled anti–prostate-specific membrane antigen monoclonal antibody J591 (90Y-J591) in patients with androgen-independent prostate cancer (PC). Patients and Methods Patients with androgen-independent PC and evidence of disease progression received indium-111–J591 for pharmacokinetic and biodistribution determinations followed 1 week later by 90Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m2. Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Results Twenty-nine patients with androgen-independent PC received 90Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m2, with two patients experiencing thrombocytopenia with non–life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m2 dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. Conclusion The recommended dose for 90Y-J591 is 17.5 mCi/m2. Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of 90Y-J591 in the treatment of patients with PC.

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