Randomized, controlled chemoprevention trials in populations at very high risk for prostate cancer: Elevated prostate-specific antigen and high-grade prostatic intraepithelial neoplasia

Urology ◽  
2001 ◽  
Vol 57 (4) ◽  
pp. 185-187 ◽  
Author(s):  
Larry C Clark ◽  
James R Marshall
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
High Grade ◽  
Randomized Controlled ◽  
Very High

Effects of Lycopene Supplementation in Patients with Localized Prostate Cancer

2002 ◽  
Vol 227 (10) ◽  
pp. 881-885 ◽  
Author(s):  
Omer Kucuk ◽  
Fazlul H. Sarkar ◽  
Zora Djuric ◽  
Wael Sakr ◽  
Michael N. Pollak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Dietary Intake ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Intervention Group ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Control Group ◽  
High Grade

Epidemiological studies have shown an inverse association between dietary intake of lycopene and prostate cancer risk. We conducted a clinical trial to investigate the biological and clinical effects of lycopene supplementation in patients with localized prostate cancer. Twenty-six men with newly diagnosed prostate cancer were randomly assigned to receive a tomato oleoresin extract containing 30 mg of lycopene (n = 15) or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous prostate tissues. Oxidative stress was assessed by measuring the Peripheral blood lymphocyte ONA oxidation product 5-hydroxymethyl-deoxyuridine (5-OH-mdU). Usual dietary Intake of nutrients was assessed by a food frequency questionnaire at baseline. Prostatectomy specimens were evaluated for pathologic stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. After intervention, subjects in the intervention group had smaller tumors (80% vs 45%, less than 4 ml), less involvement of surgical margins and/or extra-prostatic tissues with cancer (73% vs 18%, organ-confined disease), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs 0%, focal involvement) compared with subjects in the control group. Mean plasma prostate-specific antigen levels were lower in the intervention group compared with the control group. This pilot study suggests that lycopene may have beneficial effects in prostate cancer. Larger clinical trials are Warranted to investigate the potential preventive and/or therapeutic role of lycopene in prostate cancer.

Clinical and genomic characterization of low-prostate-specific antigen, high-grade prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 59-59
Author(s):  
Brandon Arvin Virgil Mahal ◽  
David Dewei Yang ◽  
Natalie Wang ◽  
Mohammed Alshalalfa ◽  
Elai Davicioni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
High Grade ◽  
Grid Data ◽  
Genomic Features ◽  
Transcriptome Database ◽  
Genomic Characterization ◽  
Very High

59 Background: The consequences of a low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown. We sought to evaluate the clinical implications and genomic features of this entity. Methods: Clinical and transcriptomic data from 626,057 patients with N0M0 prostate cancer were collected from two national cohorts and a large transcriptome database. Multivariable Fine-Gray and Cox regressions analyzed prostate-cancer specific mortality (PCSM) and all-cause mortality, respectively. GRID data were used to analyze transcriptomic features. Results: For Gleason 8-10 disease, the distribution of PCSM was U-shaped by PSA (PSA 4.1-10.0 ng/mL = referent), with adjusted hazard ratio (AHR) 2.70 for PSA ≤2.5 ng/mL (P < 0.001) versus 1.97, 1.36, and 2.56 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively. In contrast, distribution of PCSM by PSA was linear for Gleason ≤7 with AHR 0.41 for PSA ≤2.5 ng/mL (P = 0.127) versus 1.38, 2.28, and 4.61 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL, respectively (PGleason*PSA interaction< 0.001). Gleason 8-10, PSA ≤2.5 ng/mL disease had a significantly higher PCSM than standard high and very high-risk disease with PSA > 2.5 ng/mL (AHR 2.15, P = 0.009; 47-month PCSM 13.8% versus 4.9%). Among Gleason 8-10 patients treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with a survival benefit for PSA > 2.5 ng/mL (AHR 0.87, P < 0.001) but not for ≤2.5ng/mL (AHR 1.36, P = 0.084; PADT*PSA interaction= 0.021). For Gleason 8-10 tumors, PSA ≤2.5 ng/mL was associated with a higher expression of neuroendocrine markers compared to > 2.5 ng/mL (P = 0.046), with no such relationship for Gleason ≤7. Conclusions: Low-PSA, high-grade prostate cancer appears to be a unique entity that has a very high risk for PCSM, potentially responds poorly to ADT, and is associated with neuroendocrine genomic features.

Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5080-5080
Author(s):  
David Dewei Yang ◽  
Brandon Arvin Virgil Mahal ◽  
Christopher Sweeney ◽  
Quoc-Dien Trinh ◽  
Felix Yi-Chung Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Prostate Specific Antigen ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Molecular Classification ◽  
High Grade ◽  
Biological Insight ◽  
Cancer Specific Mortality ◽  
New Treatment

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P < 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.

scholarly journals Increased serum level of early prostate cancer antigen is associated with subsequent cancer risk in men with high-grade prostatic intraepithelial neoplasia

2010 ◽  
Vol 17 (2) ◽  
pp. 505-512 ◽  
Author(s):  
Zhigang Zhao ◽  
Guohua Zeng
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
High Grade ◽  
Cancer Antigen ◽  
Early Prostate Cancer ◽  
Prostate Cancer Antigen ◽  
Subsequent Cancer

Early prostate cancer antigen (EPCA) has been recently suggested as a novel biomarker in malignant and premalignant lesions of the prostate. This study was to examine serum expression of EPCA and to further clarify the relationship between initial serum EPCA levels and the presence of subsequent cancer in the individuals with isolated high-grade prostatic intraepithelial neoplasia (HGPIN). An indirect ELISA was used for initial serum EPCA measurement in 112 men with isolated HGPIN, who were enrolled and completed a follow-up of ≥5 years. All patients had a detectable concentration of EPCA in the initial serum, with a mean of 0.64±0.13 absorbance at 450 nm. Thirty-three patients had an initial serum EPCA level of ≥1.10, in which 31 cases were subsequently identified as having prostate cancer on follow-up. However, in the remaining 79 cases, serum EPCA levels were all <1.10, and none was diagnosed with cancer later. Statistical analysis showed a significantly higher serum ECPA level in isolated HGPIN patients with subsequent cancer than those without cancer (P<0.001). The area under the receiver operating characteristic curves showed that serum EPCA level had better predictive accuracy of cancer onset on follow-up than prostate specific antigen velocity and abnormal digital rectal examination findings. Furthermore, univariate and multivariate Cox regression analyses demonstrated the predictive performance independently by initial serum EPCA≥1.10 absorbance (relative risk, 3.32; 95% confidence intervals, 2.62–5.03, P<0.001). These preliminary findings first show the potential of serum EPCA to serve as a significant predictor for subsequent cancer in isolated HGPIN.

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