What is the role of microRNA-301A expression as a diagnostic and predictive marker of biochemical recurrence for prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 19-19
Author(s):  
Adnan Dervishi ◽  
Samarpit Rai ◽  
Kristy Doan Nguyen ◽  
Thomas Michael FitzGibbon ◽  
Paul Knoll ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Clinical Decision ◽  
Definitive Treatment ◽  
Serum Samples ◽  
Prostate Hyperplasia

19 Background: Prostate specific antigen (PSA) screening for prostate cancer (PCa) remains controversial, due to its association with an increase in overdiagnosis of clinically insignificant PCa, and overtreatment. Hence, the need for more specific biomarkers to detect PCa and determine its prognosis. MicroRNA expression has previously been demonstrated as a biomarker to detect several malignancies. Studies suggest that microRNA-301a (miR-301a) inhibits the pro-apoptotic function of RUNX3, a transcription factor, and consequently activates ROCK1-mediated survival signaling in PCa. This study establishes the role of miR-301a as a reliable biomarker that can distinguish between patients with benign prostate hyperplasia (BPH) and PCa, and predict biochemical recurrence (BCR) after definitive treatment of PCa. Methods: Serum samples and tissue from prostate biopsies were collected from patients with an elevated PSA prospectively. The expression of miR- 301a was measured via reverse transcriptase-polymerase chain reaction. Additionally, miR-301a expression was retrospectively evaluated in prostatic tissue of 50 patients with PCa, including benign tissue, and correlated with clinico-pathological characteristics to predict BCR. Immunohistochemistry was performed to confirm the molecular target of miR-301a in cancerous tissue. Results: miR-301a demonstrated a significantly higher expression (p = 0.013) in both PCa tissue (Gleason 6 & 7 PCa) and serum samples (p = 0.011) when compared to BPH. Expression of miR-301a in Gleason 6 & 7 prostatectomy specimens positively correlated with patients who developed BCR when compared to patients who did not. When compared to the current nomogram for the prediction of PCa (i.e., PSA, age, race, Gleason score, and family history), incorporation of miR-301a was associated with a superior prediction of BCR at three years post-prostatectomy. Conclusions: miR-301a expression is a valuable tool for diagnosing PCa in patients with an elevated PSA. Combining miR-301a with PSA is associated with better risk stratification of PCa patients, and may help facilitate clinical decision making.

scholarly journals Pattern of failure in prostate cancer previously treated with radical prostatectomy and post-operative radiotherapy: a secondary analysis of two prospective studies using novel molecular imaging techniques

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lindsay S. Rowe ◽  
Stephanie Harmon ◽  
Adam Horn ◽  
Uma Shankavaram ◽  
Soumyajit Roy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Pet Imaging ◽  
Biochemical Recurrence ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Definitive Treatment ◽  
Pattern Of Failure ◽  
Link Type ◽  
Psma Pet

Abstract Background Prostate Membrane Specific Antigen (PSMA) positron emission tomography (PET) and multiparametric MRI (mpMRI) have shown high accuracy in identifying recurrent lesions after definitive treatment in prostate cancer (PCa). In this study, we aimed to outline patterns of failure in a group of post-prostatectomy patients who received adjuvant or salvage radiation therapy (PORT) and subsequently experienced biochemical recurrence, using 18F-PSMA PET/CT and mpMRI. Methods PCa patients with biochemical failure post-prostatectomy, and no evident site of recurrence on conventional imaging, were enrolled on two prospective trials of first and second generation 18F-PSMA PET agents (18F-DCFBC and 18F-DCFPyL) in combination with MRI between October 2014 and December 2018. The primary aim of our study is to characterize these lesions with respect to their location relative to previous PORT field and received dose. Results A total of 34 participants underwent 18F-PSMA PET imaging for biochemical recurrence after radical prostatectomy and PORT, with 32/34 found to have 18F-PSMA avid lesions. On 18F-PSMA, 17/32 patients (53.1%) had metastatic disease, 8/32 (25.0%) patients had locoregional recurrences, and 7/32 (21.9%) had local failure in the prostate fossa. On further exploration, we noted 6/7 (86%) of prostate fossa recurrences were in-field and were encompassed by 100% isodose lines, receiving 64.8–72 Gy. One patient had marginal failure encompassed by the 49 Gy isodose. Conclusions 18F-PSMA PET imaging demonstrates promise in identifying occult PCa recurrence after PORT. Although distant recurrence was the predominant pattern of failure, in-field recurrence was noted in approximately 1/5th of patients. This should be considered in tailoring radiotherapy practice after prostatectomy. Trial registrationwww.clinicaltrials.gov, NCT02190279 and NCT03181867. Registered July 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02190279 and June 8 2017, https://clinicaltrials.gov/ct2/show/NCT03181867.

Clinical interpretation of prostate-specific antigen values: Type of applied cut-off value exceeds methods bias as the major source of variation

2019 ◽  
Vol 56 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Lieke JJ Klinkenberg ◽  
Eef GWM Lentjes ◽  
Arjen-Kars Boer
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Relative Difference ◽  
Clinical Consequence ◽  
External Quality Assessment Scheme ◽  
Data Set ◽  
Annual Distribution

Background Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS). Methods The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually. Results In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86–93% versus 79% range 63–95%, respectively). Conclusions This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.

scholarly journals THE ROLE OF THE CLINICAL AND MOLECULAR ASSAYS IN PROSTATE CANCER DETECTION

2017 ◽  
Vol 10 (6) ◽  
pp. 11 ◽  
Author(s):  
Fatemeh Mansouri
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Cancer Detection ◽  
Clinical Decision Making ◽  
False Positive Rate ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Therapeutic Success ◽  
Prostate Cancer Detection ◽  
Molecular Assays

To assess the correlation between the clinical and molecular assays in identify early and robust prostate cancer detection. Early detection, management of cancer and decision about the disease are important for beneficial treatment of prostate cancer. We used a computerized search of the Medline/ PubMed databases with the key words prostate cancer, biomarker, and early detection. Clinical management of cancer is facilitated by a conventional test such as prostate-specific antigen and digital rectal exam for application in clinical practice. Although these tests have significantly reduced the mortality with prostate cancer, but have some drawbacks and false positive rate. Fortunately, there are strong correlations between the clinical and molecular assays in identifying early and robust cancer detection, because molecular assays are less invasive and reliable. The use of genetic markers has the potential to providing useful prognostic or predictive information into clinically useful diagnostic tests to improve clinical decision-making and enhance therapeutic success. Different clinical and molecular assays are for detecting prostate cancer and use the biomarkers as potential tumor markers could be a useful predictor in the screening and monitoring to avoid over treatment prostate cancer.

scholarly journals Appropriate Use of Nomograms to Guide Prostate Cancer Treatment Selection

2010 ◽  
Vol 8 (2) ◽  
pp. 201-209 ◽  
Author(s):  
Andrew K. Lee ◽  
Christopher L. Amling
Keyword(s):  
Prostate Cancer ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Ease Of Use ◽  
Due Diligence ◽  
Clinical Factors ◽  
Prostate Cancer Treatment ◽  
Large Numbers ◽  
Continuous Scale

For decades physicians have attempted to accurately predict post-treatment outcomes before performing prostate cancer interventions. Use of basic clinical factors, such as clinical T-stage, biopsy Gleason sum, and pretreatment prostate specific antigen, has allowed some level of prediction of pathologic and clinical outcomes. However, these basic tables and risk stratification schema provide a broad range of potential outcomes. The rapid growth of retrospective research in prostate cancer has yielded an abundance of additional potential prognostic factors that may influence outcomes of interest; however, incorporating and understanding the significance of these ever-expanding factors is difficult for even the most experienced physicians. Nomograms incorporate these factors (including treatment-specific) and assign them relative weights to provide a probability of the outcome of interest on a graphical scale. They distill large numbers of data into a manageable format and provide the probability of outcomes on a continuous scale rather than in categoric groups. However, because they require a computation to generate a probability, they are not amenable to memorization, which decreases ease of use. Furthermore, these numbers still have associated confidence intervals and the models are largely derived from retrospective data, which have inherent drawbacks. Clinicians and patients should still exercise due diligence when interpreting the results of these nomograms, and these prediction tools should not serve as a stand-alone substitute for clinical decision-making.

Circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer: Final results.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 179-179 ◽  
Author(s):  
Jeanny B. Aragon-Ching ◽  
Samuel J. Simmens ◽  
Ramez Andrawis ◽  
Frederick Hendricks ◽  
Harold Frazier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Primary Treatment ◽  
Test Results ◽  
Undetectable Level ◽  
Bony Lesions ◽  
Prognostic Implications

179 Background: CTCs have known prognostic implications in metastatic prostate cancer. We presented initial data on the role of CTCs in BR of prostate cancer (Aragon-Ching et. al., ASCO GU 2011). The primary aim of this study was to determine whether there is a correlation between the number of CTCs with prostate specific antigen (PSA) levels and PSA doubling time (PSADT) in men with BR. Methods: BR was defined as patients who have undergone primary treatment with prostatectomy or radiation or both, with a rise to ≥ 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise for post-nadir radiotherapy. 36 patients (pts) were enrolled from May 2010 to May 2012. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 36 pts was 69.5 (range: 51 – 91) with a median PSA of 1.65 ng/mL (range 0.2 – 65.8) and testosterone levels of 315 ng/dL (range: 31 – 727). Gleason scores ranged from 5 to 9 (median=7). Prostatectomy was the primary treatment in 25 pts, radiotherapy in 9 pts, Cyberknife in 1 pt and combined radiohormones in 1 pt. PSADT varied between 0.35 to 55 months, with a median of 7.43 mos. The incidence of positive CTCs was 8.3% (3 out of 36 pts) of whom 2 had biopsy-proven bony lesions upon presenting with equivocal scans. The 3 pts who had measurable CTCs had PSADT of 2.27, 4.99 and 3.08 months, respectively. Conclusions: Obtaining CTCs in unselected patients presenting with biochemical recurrence have low yield. However, obtaining a positive CTC raises the suspicion of presence of metastatic disease and may have utility for longitudinal follow-ups of patients with BR. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute.

Prospective evaluation of 18F-DCFPyL PET/CT in biochemically recurrent prostate cancer: Analysis of lesion localization and distribution.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5556-5556
Author(s):  
Hong Song ◽  
Heying Duan ◽  
Caitlyn Harrison ◽  
Kip Guja ◽  
Negin Hatami ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Definitive Treatment ◽  
Low Grade ◽  
Prostate Bed ◽  
Academic Center ◽  
Pet Ct ◽  
One Stop ◽  
Post Radiation

5556 Background: 18F-DCFPyL, a promising PET agent targeting prostate specific membrane antigen (PSMA), is prospectively evaluated in a single academic center for detecting recurrent lesions in prostate cancer patients with biochemical recurrence (BCR). Methods: We prospectively enrolled 150 men (51-91 years old, mean ± SD: 70.3±7.5) with biochemical recurrence (PSA median 2.38 ng/mL, range 0.12 to 698.4) after primary definitive treatment with prostatectomy (65%), radiotherapy (35%) or both (19%). The 18F-DCFPyL positive lesions compatible with prostate cancer were evaluated by two independent readers. Impact of 18F-DCFPyL PET/CT on patient management was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 83% (125 scans), which increased with higher prostate specific antigen (PSA) levels (ng/mL): 63% (PSA < 0.5), 75% (0.5≤PSA < 1), 91% (1≤PSA < 2), 95% (2≤PSA < 5) and 98% (PSA≥5), respectively. In the cohort who underwent prostatectomy, 18F-DCFPyL PET/CT had higher positivity rate in patients with shorter PSA doubling time (PSAdt) (94% in PSAdt 0-3 months vs. 53% in PSAdt > 12 months, P< 0.01). No difference of 18F-DCFPyL positivity rate was observed in post-radiation patients with different PSAdt, nor were there differences between patients with low grade (Gleason 6) or higher-grade prostate cancer (Gleason 7-10). 20 patients (13%) had lesions in the prostate bed only and 41 patients (27%) had oligometastatic disease (1-3 lesions), making them candidates for locally targeted therapy. We identified a total of 1455 18F-DCFPyL positive lesions, including 51 lesions in the prostate bed, 271 pelvic and 463 extra-pelvic lymph nodes, approximately 585 osseous lesions, including 5 patients with diffuse osseous metastases, and 85 lesions in other organs (most commonly in the lungs). 91 out of 150 patients (61%) had change in treatment after 18F-DCFPyL PET and, most noticeably, 48 of these patients (32% total) had lesions only localized on 18F-DCFPyL PET/CT despite negative conventional imaging. Conclusions: 18F-DCFPyL PET/CT holds great potential to be a “one-stop shop” diagnostic tool in the work-up of BCR prostate cancer, with high (61%) impact on the management of these patients. Clinical trial information: NCT03501940 .

Prostate-Specific Antigen Kinetics in Clinical Decision-Making During Active Surveillance for Early Prostate Cancer—A Review

2008 ◽  
Vol 54 (3) ◽  
pp. 505-516 ◽  
Author(s):  
Roderick C.N. van den Bergh ◽  
Stijn Roemeling ◽  
Monique J. Roobol ◽  
Tineke Wolters ◽  
Fritz H. Schröder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Prostate Specific Antigen ◽  
Active Surveillance ◽  
Clinical Decision Making ◽  
Specific Antigen ◽  
Clinical Decision ◽  
Early Prostate Cancer
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