Combined androgen blockade therapy can convert RT-PCR detection of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) transcripts from positive to negative in the peripheral blood of patients with clinically localized prostate cancer and increase biochemical failure-free survival after curative therapy

PURPOSE: We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy.PATIENTS AND METHODS: One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure.RESULTS: Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P = .026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P = .009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P = .004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P = .009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results.CONCLUSION: Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.

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

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.198 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 198-198 ◽

Cited By ~ 1

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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Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: A multicenter randomized phase II trial (OCUU-CRPC study).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.168 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 168-168

Author(s):

Taro Iguchi ◽

Satoshi Tamada ◽

Minoru Kato ◽

Sayaka Yasuda ◽

Yuichi Machida ◽

...

Keyword(s):

Prostate Cancer ◽

Response Rate ◽

Specific Antigen ◽

Distant Metastases ◽

Phase Iii ◽

Progression Rate ◽

Castration Resistant Prostate Cancer ◽

Combined Androgen Blockade ◽

Psa Progression ◽

Androgen Blockade

168 Background: In Asia, including Japan, combined androgen blockade (CAB) therapy with bicalutamide is widely administered for metastatic prostate cancer. Alternative anti-androgen therapy (AAT) with flutamide after CAB therapy with bicalutamide was common before the androgen receptor-targeted therapy era. The objective of the OCUU-CRPC study was to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative AAT after CAB therapy that included bicalutamide in patients with CRPC. Methods: A total of 104 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day) and flutamide (375 mg/day) groups. The primary endpoint for the drug efficacy was the response rate of prostate-specific antigen (PSA; i.e., declined by ≥50%) at 3 months. Results: Between January 2015 and February 2018, 103 patients were randomly assigned, 52 to enzalutamide and 51 to flutamide. 25 (48%) and 38 (75%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 13.4 months (IQR 9.6–23.8) in the enzalutamide group and 17.0 months (9.7–24.4) in the flutamide group. Enzalutamide resulted in significant improvements in the response rate of PSA at 3 months (84.6% vs 31.4%; p< 0.001). Enzalutamide significantly improved in all secondary endpoints: the PSA progression rate at 3 months (HR, 0.17; 95% CI, 0.05 to 0.47; p< 0.01) and at 6 months (HR, 0.22; 95% CI, 0.09 to 0.50; p< 0.01); and PSA response rate at 6 months (75.0% vs 29.4%; p< 0.01); and time to PSA progression (median: not reached vs 6.6 months; HR, 0.29; 95% CI, 0.15 to 0.54; p< 0.01). The observed adverse event profile was consistent with that from phase III enzalutamide trials. Conclusions: Enzalutamide significantly reduced risk of progression compared with flutamide in patients with CRPC after CAB therapy with bicalutamide. This trial is registered with ClinicalTrials.gov, number. Clinical trial information: NCT02346578.

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Duplex RT-PCR and chemiluminometric hybridization assay for combined screening of the mRNAs of prostate-specific antigen and prostate-specific membrane antigen in peripheral blood

Analytica Chimica Acta ◽

10.1016/j.aca.2004.10.024 ◽

2005 ◽

Vol 531 (2) ◽

pp. 193-198 ◽

Cited By ~ 1

Author(s):

Evaggelia Emmanouilidou ◽

Bakhos Tannous ◽

Penelope C. Ioannou ◽

Theodore K. Christopoulos

Keyword(s):

Prostate Specific Antigen ◽

Peripheral Blood ◽

Specific Antigen ◽

Hybridization Assay ◽

Prostate Specific Membrane Antigen ◽

Rt Pcr ◽

Specific Membrane

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Prognostic Value of the LATITUDE and CHAARTED Risk Criteria for Predicting the Survival of Men with Bone Metastatic Hormone-Naïve Prostate Cancer Treated with Combined Androgen Blockade Therapy: Real-World Data from a Japanese Multi-Institutional Study

BioMed Research International ◽

10.1155/2020/7804932 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Takashi Kawahara ◽

Shuko Yoneyama ◽

Yoshio Ohno ◽

Junpei Iizuka ◽

Yasunobu Hashimoto ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

High Volume ◽

Low Risk ◽

Free Survival ◽

Combined Androgen Blockade ◽

Number Of Patients ◽

High Risk Disease ◽

Low Volume ◽

Androgen Blockade

Background. The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). Methods. A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. Results. The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. Conclusions. The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients.

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Enhanced detection of hematogenous circulating prostatic cells in patients with prostate adenocarcinoma by using nested reverse transcription polymerase chain reaction assay based on prostate-specific membrane antigen

Clinical Chemistry ◽

10.1093/clinchem/41.12.1698 ◽

1995 ◽

Vol 41 (12) ◽

pp. 1698-1704 ◽

Cited By ~ 53

Author(s):

S Loric ◽

F Dumas ◽

P Eschwege ◽

P Blanchet ◽

G Benoit ◽

...

Keyword(s):

Prostate Cancer ◽

Polymerase Chain Reaction ◽

Prostate Adenocarcinoma ◽

Prostate Specific Membrane Antigen ◽

Rt Pcr ◽

Hematogenous Spread ◽

Chain Reaction ◽

Prostate Cells ◽

Polymerase Chain ◽

Specific Membrane

Abstract We report the development of a new sensitive nested reverse transcription-polymerase chain reaction (RT-PCR) assay, using primers derived from the prostate-specific membrane antigen (PSM) cDNA sequence, to detect an hematogenous spread of prostate adenocarcinoma cells. In 60 patients with a biopsy-proven prostate cancer, PSM and PSA RT-PCR detected circulating prostate cells in 40 and 20 patients, respectively. In pT4 M+ and pT3 M+ disease patients, nested PSM primers detected cells in 28 of 33 patients (85%), whereas nested PSA primers detected cells in 17 of 33 (51%). In patients with organ-confined cancer spread (pT2a and pT2b patients) before radical prostatectomy, nested PSM RT-PCR detected circulating prostatic epithelial cells in 6 of 17 patients (35%), which suggests that an hematogenous spread of prostate cells may occur early in prostate cancer history. Altogether, these results suggest that the detection of PSM-expressing cells in blood may predict the development of cancer in patients without clinically apparent prostate cancer. Nevertheless, the potential application and the clinical significance of detection of hematogenous prostate cells through the use of nested PSM primers need an extensive longitudinal study.

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68Gallium-prostate-specific membrane antigen ligand positron-emission tomography or computed tomography in biochemical failure after radical prostatectomy: A case report

South African Journal of Oncology ◽

10.4102/sajo.v1i0.16 ◽

2017 ◽

Vol 1 ◽

pp. 3

Author(s):

Irene A. Chidothe ◽

David B. Anderson

Keyword(s):

Prostate Cancer ◽

Computed Tomography ◽

Positron Emission Tomography ◽

Case Report ◽

Radical Prostatectomy ◽

Biochemical Failure ◽

Emission Tomography ◽

Prostate Specific Membrane Antigen ◽

Positron Emission ◽

Specific Membrane

Biochemical failure after radical treatment for prostate cancer occurs in up to 30% – 50% of cases. Localisation of clinical disease is challenging because clinical symptoms often manifest long after the initial rise in prostate-specific antigen. The detection rates of imaging modalities such as contrasted computed tomography (CT), bone scan, magnetic resonance imaging and choline positron-emission tomography (PET) or CT, are limited. Prostate-specific membrane antigen (PSMA) ligand PET or CT is a novel imaging modality under investigation for various diagnostic and therapeutic indications in the management of prostate cancer. We present a case report illustrating how <sup><span style="font-size: small;">68</span></sup>Gallium-PSMA ligand PET or CT was used to guide management in a patient presenting with biochemical failure after radical prostatectomy.

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