PCA3 detected in the post-digital rectal examination urine of patients with prostate cancer correlated with pathological findings. Therefore, it could provide prognostic information. To our knowledge this is the first report of a molecular urine assay that predicts extracapsular extension.
Our findings indicate that as men age, parameters consistent with more aggressive disease become more prevalent. The etiology of this trend is unknown. However, these data may have implications for current screening and treatment recommendations.
OBJECTIVE
To describe metastasis-free survival (MFS) and overall survival (OS) among men with prostate-specific antigen (PSA)-recurrent prostate cancer after radical prostatectomy who did not receive additional therapy until metastasis, using a multicentre database capturing a wide ethnic mix.
PATIENTS AND METHODS
A retrospective analysis of the Center for Prostate Disease Research National Database (comprised of five US military hospitals and one civilian centre) was performed for patients with PSA relapse (≥0.2 ng/mL) after radical prostatectomy who had no additional therapy until the time of radiographic metastatic disease.
We investigated factors influencing metastasis and all-cause mortality using univariate and multivariate Cox regression analysis.
RESULTS
There were a total of 346 men who underwent radical prostatectomy between May 1983 and November 2008 and fulfilled the entry criteria. All patients had information on survival and 190 men had information on metastasis. Among patients with survival data (n = 346), 10-year OS was 79% after a median follow-up of 8.6 years from biochemical recurrence.
Among men with metastasis data (n = 190), 10-year MFS was 46% after a median follow-up of 7.5 years.
In Cox regressions, four clinical factors (Gleason score, pathological stage, time to PSA relapse and PSA doubling time), as well as age, were predictive of OS and/or MFS in univariate analysis, although only PSA doubling time (≥9 vs 3–8.9 vs <3 months) remained independently predictive of these outcomes in multivariate analysis (P < 0.001).
CONCLUSIONS
This multicentre multi-ethnic dataset shows that OS and MFS can be extensive for men with PSA-recurrent prostate cancer, even in the absence of further therapy before metastasis.
This unique patient cohort, the second largest of its type after the Johns Hopkins cohort, confirms that PSA doubling time is the strongest determinant of OS and MFS in men with PSA-recurrent disease.
Longer follow-up and more events will be required to determine whether other variables may also contribute to these outcomes.
Oncogenic activation of ERG resulting from gene fusion is present in over half of all patients with prostate cancer in Western countries. Although the underlying genetic mechanisms have been extensively studied, evaluation of the ERG oncoprotein--the translational product of ERG gene fusions--has just begun. The robust correlation between ERG oncoprotein detection and gene fusion status enables rapid characterization of this protein in large patient cohorts. Recent studies have focused on characterizing the ERG oncoprotein and determining its potential role in the diagnosis and biological stratification of prostate cancer.
Background:Germline mutations in BRCA2 have been linked to a higher risk of prostate cancer (PCa), and high frequency of BRCA1 and BRCA2 (BRCA1/2) gene alterations was recently reported in metastatic castration-resistant PCa specimens. Mutations in BRCA2 vary in racial and ethnic groups including African-American (AA) and Caucasian-American (CA) populations.Methods:BRCA1 and BRCA2 genes were sequenced (Ion AmpliSeq targeted sequencing) in archived blood DNA specimens in 1240 PCa patients, including 30% AA patients, in three different cohorts: localized early stage (T2) PCa (N = 935); advanced PCa (50% T3–4) (N = 189); and metastatic PCa (N = 116). The sequences were analyzed for known and novel mutations in BRCA1/2. Statistical analyses were performed to determine associations of the mutations with clinico-pathological parameters.Results:BRCA2 mutations with known pathogenic annotation were significantly more prevalent in men with advanced and metastatic PCa (3.1%) compared to patients with an organ-confined disease (0.7%). AA patients carried more frequently BRCA1/2 variants of unknown significance (VUS) when compared to Caucasian Americans (4.6 vs. 1.6%, respectively). Significantly, pathogenic BRCA2 mutations in men with localized early stage PCa increased the risk of distant metastasis.Conclusions:Germline variants of unknown significance in BRCA1/2 are more frequent in AA than CA PCa patients; however, the prevalence of pathogenic mutations were similar across the races. Patients carrying BRCA2 pathogenic mutations are more likely to progress to metastasis.
Despite the potential for adverse pathological features in anterior-based disease, there appears to be no demographic predilection, notable delay in diagnosis or significant difference in survival outcomes.
Introduction:In this review, the International Agency for Research on Cancer's cancer epidemiology databases were used to examine prostate cancer (PCa) age-standardized incidence rates (ASIR) in selected Asian nations, including Cancer Incidence in Five Continents (CI5) and GLOBOCAN databases, in an effort to determine whether ASIRs are rising in regions of the world with historically low risk of PCa development.Materials and Methods:Asian nations with adequate data quality were considered for this review. PCa ASIR estimates from CI5 and GLOBOCAN 2008 public use databases were examined in the four eligible countries: China, Japan, Korea and Singapore. Time trends in PCa ASIRs were examined using CI5 Volumes I-IX.Results:While PCa ASIRs remain much lower in the Asian nations examined than in North America, there is a clear trend of increasing PCa ASIRs in the four countries examined.Conclusion:Efforts to systematically collect cancer incidence data in Asian nations must be expanded. Current CI5 data indicate a rise in PCa ASIR in several populous Asian countries. If these rates continue to rise, it is uncertain whether there will be sufficient resources in place, in terms of trained personnel and infrastructure for medical treatment and continuum of care, to handle the increase in PCa patient volume. The recommendation by some experts to initiate PSA screening in Asian nations could compound a resource shortfall. Obtaining accurate estimates of PCa incidence in these countries is critically important for preparing for a potential shift in the public health burden posed by this disease.
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