Biomarkers in localized prostate cancer.
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ABSTRACT:
SUBMITTER: Ferro M
PROVIDER: S-EPMC5549774 | biostudies-other | 2016 Feb
REPOSITORIES: biostudies-other
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Project description:In localized prostate cancer clinicopathologic variables have been used to develop prognostic nomograms quantifying the probability of locally advanced disease, of pelvic lymph node and distant metastasis at diagnosis or the probability of recurrence after radical treatment of the primary tumor. These tools although essential in daily clinical practice for the management of such a heterogeneous disease, which can be cured with a wide spectrum of treatment strategies (i.e., active surveillance, RP and radiation therapy), do not allow the precise distinction of an indolent instead of an aggressive disease. In recent years, several prognostic biomarkers have been tested, combined with the currently available clinicopathologic prognostic tools, in order to improve the decision-making process. In the following article, we reviewed the literature of the last 10 years and gave an overview report on commercially available tissue-based biomarkers and more specifically on mRNA-based gene expression classifiers. To date, these genomic tests have been widely investigated, demonstrating rigorous quality criteria including reproducibility, linearity, analytical accuracy, precision, and a positive impact in the clinical decision-making process. Albeit data published in literature, the systematic use of these tests in prostate cancer is currently not recommended due to insufficient evidence.
| S-EPMC8781984 | biostudies-literature
Project description:Risk stratification of men with clinically localized prostate cancer has historically relied on basic clinicopathologic parameters such as prostate specific antigen level, grade group, and clinical stage. However, prostate cancer often behaves in ways that cannot be accurately predicted by these parameters. Thus, recent efforts have focused on developing tissue-based genomic tests that provide greater insights into the risk of a given patient's disease. Multiple tests are now commercially available and provide additional prognostic information at various stages of the care pathway for prostate cancer. Indeed, early evidence suggests that these assays may have a significant impact on patient and physician decision-making. However, the impact of these tests on oncologic outcomes remains less clear. In this review, we highlight recent advances in the use of tissue-based biomarkers in the treatment of prostate cancer and identify the existing evidence supporting their clinical use.
| S-EPMC8193839 | biostudies-literature
Project description:AIM:This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. METHODS:Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. RESULTS:Several large-scale trials on moderate hypofractionation with single doses from 2.4-3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2-3 years. CONCLUSION:Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.
| S-EPMC5203817 | biostudies-other
Project description:Multiregion Sequencing of Localized Prostate Cancer
| PRJNA530801 | ENA
Project description:Multiregion Sequencing of Localized Prostate Cancer
| PRJNA412429 | ENA
Project description:Although prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI)-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations) with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered widespread allele-specific methylation (ASM) for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease.
| S-EPMC3612910 | biostudies-literature
Project description:Prostate cancer is the most commonly diagnosed cancer among men around the world. Radiotherapy is a standard of care treatment option for men with localized prostate cancer. Over the years, radiation delivery modalities have contributed to increased precision of treatment, employing radiobiological insights to shorten the overall treatment time, improving the control of the disease without increasing toxicities. Stereotactic body radiation therapy (SBRT) represents an extreme form of hypofractionated radiotherapy in which treatment is usually delivered in 1-5 fractions. This review assesses the main efficacy and toxicity data of SBRT in non-metastatic prostate cancer and discusses the potential to implement this scheme in routine clinical practice.
| S-EPMC8395496 | biostudies-literature
Project description:BackgroundThe effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.MethodsFrom November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.ResultsDuring the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.ConclusionsAmong men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).
| S-EPMC3429335 | biostudies-literature
Project description:BackgroundTelomeres play important roles in cancer initiation and progression. The aim of this study is to investigate whether leukocyte telomere length (LTL) is associated with aggressive prostate cancer (PCa).MethodsWe measured relative LTL in a cohort of 1,889 white PCa patients who were treated and followed up at the University of Texas MD Anderson Cancer Center and assessed its associations with aggressive disease characteristics at diagnosis and biochemical recurrence (BCR) after active treatments (radical prostatectomy and radiotherapy). We further used a Mendelian randomization (MR) approach to compute a weighted genetic risk score (GRS) predictive of LTL using 10 established LTL-associated genetic variants and determined whether this GRS is associated with aggressive PCa.FindingsLTL was significantly shorter in patients with higher Gleason scores at diagnosis. Dichotomized at the median value of LTL, patients with short LTL exhibited a 2.74-fold (95% confidence interval, 1.79-4.18, P = 3.11 × 10-6) increased risk of presenting with GS≥8 disease than those with long LTL in multivariate logistic regression analysis. Moreover, shorter LTL was significantly associated with an increased risk of BCR (hazard ratio = 1.53, 95% confidence interval, 1.01-2.34) compared to longer LTL in localized patients receiving prostatectomy or radiotherapy with a significant dose-response association (P for trend = 0.017) in multivariate Cox proportional hazards regression analysis. In MR analysis, genetically predicted short LTL was also associated with an increased risk of BCR (HR=1.73, 95% CI, 1.08-2.78).InterpretationOur results showed for the first time that LTL was shorter in PCa patients with high Gleason scores and that short LTL and genetically predicted short LTL are associated with worse prognosis in PCa patients receiving prostatectomy or radiotherapy.FundingCancer Prevention and Research Institute of Texas (CPRIT) grant (RP140556), National Cancer Institute Specialized Program of Research Excellence (SPORE) grant (CA140388), and MD Anderson Cancer Center start-up fund.
| S-EPMC6992931 | biostudies-literature
Project description:Here we used Illumina NGS for high-throughput profiling of the DNA methylome in seven human benign prostate tissues, seven human primary prostate cancer and six human castration resistant prostate cancer patient samples. These data were used to profile the CpG cytosine methylation pattern at single base resolution in each sample and to determine differentially methylated cytosines and regions among samples. Enhanced Reduced Representation Bisulfite Sequencing (ERRBS, MspI,150M-bM-^@M-^S400 bp size fractions) of 20 human prostate tissues (benign prostate tissues, localized and metastatic prostate cancer)
2013-07-03 | E-GEOD-41701 | biostudies-arrayexpress