American Urological Association - Early Detection of Prostate Cancer. H. Ballentine Carter, Peter C. Albertsen, Michael J. Barry, Ruth Etzioni, Stephen J. Freedland, Kirsten Lynn Greene, Lars Holmberg, Philip Kantoff, Badrinath R. Konety, Mohammad Hassan Murad, David F. Penson and Anthony L. Zietman. Purpose. This guideline addresses prostate cancer early detection for the purpose of reducing prostate cancer mortality with the intended user as the urologist. The Evolution of the Human: The universe is constructed from a multitude of various materials. It is dynamic in form and shape due to a multitude of various. Homo erectus migrated from out of Africa via the Levantine corridor and Horn of Africa to Eurasia during the Early Pleistocene, possibly as a result of the operation. Watch breaking news videos, viral videos and original video clips on CNN.com.
This document does not make a distinction between early detection and screening for prostate cancer. Early detection and screening both imply detection of disease at an early, pre- symptomatic stage when a man would have no reason to seek medical care –an intervention referred to as secondary prevention. In the US, early detection is driven by prostate specific antigen (PSA)- based screening followed by prostate biopsy for diagnostic confirmation. While the benefits of PSA- based prostate cancer screening have been evaluated in randomized- controlled trials, the literature supporting the efficacy of DRE, PSA derivatives and isoforms (e. PCA3) for screening with the goal of reducing prostate cancer mortality provide limited evidence to draw conclusions. While some data suggest use of these secondary screening tools may reduce unnecessary biopsies (i. However, the likelihood of a future population- level screening study using these secondary screening approaches is highly unlikely at least in the near future. Therefore, this document focuses only on the efficacy of PSA screening for the early detection of prostate cancer with the specific intent to reduce prostate cancer mortality and not secondary tests often used after screening to determine the need for a prostate biopsy or a repeat prostate biopsy (e. PSA isoforms, PCA3, imaging). The framework for this guideline follows that of the Institute of Medicine (IOM) recommendations for guideline development, including a systematic review of the evidence by a multidisciplinary panel. While the evidence that guideline panels evaluate may be the same, the weighting of the evidence and the Panel's perspective can be very different (e. Figure 1). It is important to note that the guideline statements listed in this document target men at average risk, defined as a man without risk factors, such as a family history of prostate cancer in multiple generations and/or family history of early onset below age 5. African American race. Because the harm- benefit profile of PSA- based prostate cancer screening is highly age dependent, guideline statements included in this document target four index patients; these age ranges were chosen to correspond to age ranges tested in randomized trials and data from population and simulation studies. Four Index Patients. Men < 4. 0 years of age. Men age 4. 0- 5. 4 years. Men age 5. 5- 6. 9 years. Men age 7. 0+ years. Figure 1: Influence of evidence and interpretation on policy creation. Methodology. Consistent with AUA published guideline methodology,3 the process started by conducting a comprehensive systematic review. The AUA commissioned an independent group to conduct a systematic review and meta- analysis of the published literature on prostate cancer detection and screening. The protocol of the systematic review was developed a priori by the expert panel. The search strategy was developed and executed by reference librarians and methodologists and spanned across multiple databases including Ovid Medline In- Process & Other Non- Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials and Scopus. Controlled vocabulary supplemented with keywords was used to search for the relevant concepts of prostate cancer, screening and detection. The search focused on DRE, serum biomarkers (PSA, PSA Isoforms, PSA kinetics, free PSA, complexed PSA, pro. PSA, prostate health index, PSA velocity, PSA doubling time), urine biomarkers (PCA3, TMPRSS2: ERG fusion), imaging (TRUS, MRI, MRS, MR- TRUS fusion), genetics (SNPs), shared- decision making and prostate biopsy. The expert panel manually identified additional references that met the same search criteria to supplement the electronic search. The outcomes of interest were also a priori determined by the Panel and included prostate cancer incidence, mortality, quality of life, the diagnostic performance of each of the tests and the harms of testing (premature death and complications from testing and biopsy). Modeling studies were included when original studies were limited by follow- up time and screening protocols. The methodology team independently rated the methodological quality of the studies and provided an overall judgment of the whole body of evidence based on their confidence in the available estimates of effect. The framework for rating the quality of evidence is an adaptation and modification. GRADE framework (Grading of Recommendations, Assessment, Development and Evaluation). In this adaptation, the AUA rates the quality of evidence as high, moderate or low (A, B or C). The strength of a statement was rated according to AUA guideline methodology as further described below. The confidence in the estimates of effect (quality of the evidence) was determined based on study quality, imprecision, indirectness, inconsistency and the likelihood of reporting and publication bias. The methodology team summarized the data with an explicit description of study characteristics, methodological quality, main findings and the quality of the evidence (confidence in the estimates). The methodology team attended panel meetings and facilitated incorporation of the evidence into the guideline. AUA Nomenclature: Linking Statement Type to Evidence Strength. The AUA nomenclature system explicitly links statement type to body of evidence strength and the Panel's judgment regarding the balance between benefits and risks/burdens (see Table 1). Standards are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken based on Grade A or Grade B evidence. Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken based on Grade C evidence. Options are non- directive statements that leave the decision to take an action up to the individual clinician and patient because the balance between benefits and risks/burdens appears relatively equal or appears unclear; Options may be supported by Grade A, B or C evidence. For some clinical issues, little or no evidence may exist from which evidence- based statements can be constructed. In such instances, the Panel may provide guidance in the form of Clinical Principles or Expert Opinions with consensus achieved using a modified Delphi technique if differences of opinion exist among Panel members. A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge and judgment and for which there is no evidence. In the case of this guideline, such statement types were not included. The completed evidence report may be requested through the AUA by emailing guidelines@AUAnet. Table 1: AUA Nomenclature. Linking Statement Type to Evidence Strength Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A or B evidence. Recommendation: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade C evidence. Option: Non- directive statement that leaves the decision regarding an action up to the individual clinician and patient because the balance between benefits and risks/burdens appears equal or appears uncertain based on Grade A, B or C evidence. Clinical Principle: a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion: a statement, achieved by consensus of the Panel, that is based on members' clinical training, experience, knowledge, and judgment for which there is no evidence. Quality of Individual Studies and Determination of Evidence Strength. The systematic review included over 3. In brief, six well known randomized trials addressed the question of mortality benefit of prostate cancer screening. Considering various methodological limitations and biases, the estimate for the effect of screening (versus no screening) on prostate cancer- specific mortality was obtained from the European Randomized Study of screening for Prostate Cancer (ERSPC). The quality of the evidence was moderate for benefits and high for harms in men aged 5. RCTs). Follow- up was quite limited, and quality of evidence was low on screening benefits in men outside of this age range, population subgroups with greater than average risk of the disease and screening protocols different from those used in the ERSPC. Modeling studies were considered by the Panel to address these issues. A modeling study considers disease progression as a process of clinical or prognostic states and aims to estimate the rates of progression through these states in the absence of screening. Given the rate estimates, different screening protocols can be superimposed and their tradeoffs projected via computer simulation. To validate the models, specific screening protocols used in published studies can be considered and the model- projected incidence patterns compared with those observed in these studies. The primary model considered by the Panel.
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