Prostate cancer is considered a disease of older men (aged >65 years), but today over 10% of new diagnoses in the USA occur in young men aged ≤55 years. Early-onset prostate cancer, that is prostate cancer diagnosed at age ≤55 years, differs from prostate cancer diagnosed at an older age in several ways. Firstly, among men with high-grade and advanced-stage prostate cancer, those diagnosed at a young age have a higher cause-specific mortality than men diagnosed at an older age, except those over age 80 years. This finding suggests that important biological differences exist between early-onset prostate cancer and late-onset disease. Secondly, early-onset prostate cancer has a strong genetic component, which indicates that young men with prostate cancer could benefit from evaluation of genetic risk. Furthermore, although the majority of men with early-onset prostate cancer are diagnosed with low-risk disease, the extended life expectancy of these patients exposes them to long-term effects of treatment-related morbidities and to long-term risk of disease progression leading to death from prostate cancer. For these reasons, patients with early-onset prostate cancer pose unique challenges, as well as opportunities, for both research and clinical communities. Current data suggest that early-onset prostate cancer is a distinct phenotype-from both an aetiological and clinical perspective-that deserves further attention.
"So far, little is known about early detection or management of prostate cancer in young patients (aged <55 years), due to the severe lack of randomized controlled trials regarding this matter. Most authors believe these cancers represent a distinct phenotype in prostate cancer, etiologically, and clinically, and therefore clear guidelines are needed for appropriate management and consistency of care  . These case reports present different confounding factors responsible for error or delay in diagnosing a prostate cancer with cervical lymphadenopathies. "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer is the most common cancer in men, often presenting with regional lymph node or bone metastasis and rarely with supradiaphragmatic lymph node involvement. Most metastatic cancers involving the cervical lymph nodes are from cancers of the upper aerodigestive tract. In this report, we describe two cases with cervical lymph node enlargement due to metastatic prostate cancer as the initial clinical presentation: a 43-year-old male, initially misdiagnosed with a tumor of the upper aerodigestive tract and an 87-year-old male with right lobe pneumonia and cervical lymph node enlargement, initially attributed to be an acute inflammatory lymph node reaction. To the best of our knowledge, there are less than 50 cases reported in the literature of adenocarcinoma of prostate metastatic to the cervical lymph nodes and only one case presenting in men younger than 45 years. The authors intend to highlight the importance of digital rectal exam and PSA test in case of persistent left cervical lymph node enlargement, including men younger than 45 years of age.
[Show abstract][Hide abstract] ABSTRACT: Although prostate cancer (PCa) is hypothesized to differ in nature between younger versus older patients, the underlying molecular distinctions are poorly understood. We hypothesized that high-throughput transcriptomic analysis would elucidate biological differences in PCas arising in younger versus older men, and would nominate potential age-specific biomarkers and therapeutic targets.
The high-density Affymetrix GeneChip platform, encompassing >1 million genomic loci, was utilized to assess gene expression in 1090 radical prostatectomy samples from patients with long-term follow-up. We identified genes associated with metastatic progression by 10 years post-treatment in younger (age<65) versus older (age⩾65) patients, and ranked these genes by their prognostic value. We performed Gene Set Enrichment Analysis (GSEA) to nominate biological concepts that demonstrated age-specific effects, and validated a target by treating with a clinically available drug in three PCa cell lines derived from younger men.
Over 80% of the top 1000 prognostic genes in younger and older men were specific to that age group. GSEA nominated the proteasome pathway as the most differentially prognostic in younger versus older patients. High expression of proteasomal genes conferred worse prognosis in younger but not older men on univariate and multivariate analysis. Bortezomib, a Food and Drug Administration approved proteasome inhibitor, decreased proliferation in three PCa cell lines derived from younger patients.
Our data show significant global differences in prognostic genes between older versus younger men. We nominate proteasomeal gene expression as an age-specific biomarker and potential therapeutic target specifically in younger men. Limitations of our study include clinical differences between cohorts, and increased comorbidities and lower survival in older patients. These intriguing findings suggest that current models of PCa biology do not adequately represent genetic heterogeneity of PCa related to age, and future clinical trials would benefit from stratification based on age.Prostate Cancer and Prostatic Disease advance online publication, 19 May 2015; doi:10.1038/pcan.2015.22.
Prostate cancer and prostatic diseases 05/2015; 18(3). DOI:10.1038/pcan.2015.22 · 3.43 Impact Factor
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