| 1. |
- Bul, Meelan, et al.
(författare)
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Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:4, s. 597-603
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Tidskriftsartikel (refereegranskat)abstract
- Background: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. Objective: To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) <= 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score <= 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.
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| 2. |
- van Leeuwen, Pim J, et al.
(författare)
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Impacts of a population based prostate cancer screening programme on excess total mortality rates in men with prostate cancer: a randomized controlled trial.
- 2013
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Ingår i: Journal of medical screening. - 1475-5793. ; 20:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To assess the effect of screening in terms of excess mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). METHODS: A total of 141,578 men aged 55–69 were randomized to systematic screening or usual care in ERSPC sections in Finland, Italy, the Netherlands and Sweden. The excess number of deaths was defined as the difference between the observed number of deaths in the prostate cancer (PC)patients and the expected number of deaths up to 31 December 2006. The expected number was derived from mortality of all study participants before a diagnosis with PC adjusted for study centre,study arm and study attendance. The excess mortality rates were compared between the two study arms. RESULTS: The PC incidence was 9.25 per 1000 person-years in the intervention arm and 5.49 per 1000 person-years in the control arm, relative risk (RR) 1.69 (95% confidence interval [CI]1.62–1.76). The excess mortality among men with PC was 0.29 per 1000 person-years in the intervention arm and 0.37 per 1000 person-years in the control arm; the RR for excess mortality was 0.77 (95% CI 0.55–1.08). The absolute risk reduction in the excess mortality was 0.08 per 1000 person-years. The overall mortality was not significantly different between the intervention and the control arms of the study: RR 0.99 (95% CI 0.96–1.01). CONCLUSIONS: Although the reduction in excess mortality was not statistically significant, the between arm reduction in excess mortality rate was in line with the previously reported 20% reduction in the disease-specific mortality. This finding indicates that the reduction in PC mortality in the ERSPC trial cannot be due to a bias in cause of death adjudication.
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| 3. |
- Barbieri, Christopher E., et al.
(författare)
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The Mutational Landscape of Prostate Cancer
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:4, s. 567-576
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Forskningsöversikt (refereegranskat)abstract
- Context: Prostate cancer (PCa) is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity that may underlie the variable clinical course of the disease. Objective: In this review, we discuss the common genomic alterations that form the molecular basis of PCa, their functional significance, and the potential to translate this knowledge into patient care. Evidence acquisition: We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Evidence synthesis: Advances in sequencing technology have resulted in an explosion of data regarding the mutational events underlying the development and progression of PCa. Heterogeneity is the norm; few abnormalities in specific genes are highly recurrent, but alterations in certain signaling pathways do predominate. These alterations include those in pathways known to affect tumorigenesis in a wide spectrum of tissues, such as the phosphoinositide 3-kinase/phosphatase and tensin homolog/Akt pathway, cell cycle regulation, and chromatin regulation. Alterations more specific to PCa are also observed, particularly gene fusions of ETS transcription factors and alterations in androgen signaling. Mounting data suggest that PCa can be subdivided based on a molecular profile of genetic alterations. Conclusions: Major advances have been made in cataloging the genomic alterations in PCa and understanding the molecular mechanisms underlying the disease. These findings raise the possibility that PCa could soon transition from being a poorly understood, heterogeneous disease with a variable clinical course to being a collection of homogenous subtypes identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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