Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years.
OBJECTIVES:
A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system.
DATA SOURCES:
A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC.
REVIEW METHODS:
A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality.
RESULTS:
The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm.
CONCLUSIONS:
There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality.
BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the United States (U.S.). Aspirin may inhibit CRC development and related mortality.
PURPOSE: We conducted this systematic evidence review on aspirin use for the prevention of CRC to support the U.S. Preventive Services Task Force (USPSTF) in updating its previous recommendation. Our review addressed four key questions in adults without a history of CRC, familial adenomatous polyposis, or Lynch Syndrome: 1) Does regular aspirin use reduce CRC mortality or all-cause mortality? 2) Does regular aspirin use reduce the incidence of CRC? 3) Does regular aspirin use reduce the incidence of colorectal adenoma? 4) What are the harms of regular aspirin use for the prevention of colorectal cancer?
DATA SOURCES: We performed a search of MEDLINE, PubMed, and the Cochrane Collaboration Registry of Controlled Trials for studies published from January 2004 through May 2014. We supplemented searches by examining bibliographies from previous systematic reviews, retrieved articles, and the previous USPSTF review. We searched federal agency trial registries for ongoing and/or unpublished trials.
STUDY SELECTION: We conducted a dual review of 865 abstracts against prespecified inclusion criteria. We retrieved 149 potentially relevant articles, which two reviewers independently evaluated using well-defined inclusion/exclusion criteria and critically appraised for risk of bias. Discrepancies were resolved by discussion with a third reviewer.
DATA EXTRACTION AND ANALYSIS: For all fair-quality and good-quality studies, a single investigator extracted study characteristics and outcomes into structured tables and a second investigator verified accuracy. Elements abstracted for each study included study design, population characteristics, sample sizes, exposures, outcomes, and measures of association. We created summary evidence tables to capture key study characteristics and sources of heterogeneity. In addition to the overall results for each included study, we also presented results by dose, duration, latency, and adenoma history where possible. We used forest plots stratified by potentially important exposure and study characteristics to visually identify patterns in the study results and help determine if pooling across studies was appropriate. We used the Mantel-Haenszel fixed effects model to estimate the combined effect and confidence interval; for very rare events (incidence less than one percent), we calculated the Peto odds ratio.
RESULTS: Daily or alternate-day aspirin at ≥75 mg was associated with a small reduction in all-cause mortality risk in the first 10 years after randomization (summary relative risk, RR, 0.94, [95% confidence interval, CI, 0.89 to 0.99]) in 11 randomized controlled trials (RCTs) among persons in the general population (i.e., selected without considering their adenoma history). Over a 20+ year period, aspirin appeared to reduce the risk of CRC mortality by approximately 33%. However, long-term data on CRC mortality may have limited applicability, particularly from the perspective of a low-dose aspirin benefits in a primary CVD population addressing women as well as men. Two of four trials were in those with pre-existing cardiovascular disease and two involved dosages of 500 mg or greater daily, with no longer-term mortality results available for alternate-day regimens. Data on mortality among persons with a prior colorectal adenoma were also sparse. Six RCTs of aspirin for primary and secondary CVD prevention provided data on the effect of regular aspirin use on invasive CRC incidence in the general population. In this population, aspirin had no effect on CRC incidence in the first 10 years following randomization, but reduced CRC incidence by approximately 40 percent after a latency of 10 years (summary RR, 0.60 [95% CI, 0.47 to 0.76]). Over a 20+ year period, aspirin appeared to reduce the risk of CRC incidence by approximately 20 to 24%. Data on aspirin use and CRC incidence in persons with a prior adenoma were limited and represented only short-term followup (fewer than 5 years) and could not, therefore, provide sufficient information on the effect of aspirin use on CRC incidence. In persons with a prior adenoma, data were conflicting, but there was some suggestion of a decreased risk of adenoma incidence over a 3- to 4- year period. Data on aspirin and adenoma risk in the general population were sparse. Data from RCTs suggested that aspirin increased the risk of serious gastrointestinal bleeding (summary OR, 1.94 [95% CI, 1.44 to 2.62]), intracranial bleeding (summary OR, 1.53 [95% CI, 1.21 to 1.93]), and hemorrhagic stroke (summary OR, 1.47 [95% CI, 1.16 to 1.88]), but not fatal gastrointestinal bleeding (summary OR, 1.00 [95% CI, 0.43 to 2.36]).
LIMITATIONS: Limited data were available to address differences in possible effects of aspirin in subgroups (e.g., age, sex, race) or to compare daily vs. alternate-day aspirin use. Long-term followup data were not identified for persons with a history of adenoma.
CONCLUSIONS: Aspirin appears to reduce the risk of CRC incidence after an induction and latency period of approximately 10 years, with a similar effect on CRC mortality. The applicability of data for long-term effects of low-dose aspirin on CRC mortality, however, is limited, particularly in the context of a population selected for primary CVD prevention. Aspirin does not appear to have a strong effect on all-cause mortality within 10 years of initiating use, and data on long-term cumulative risk of all-cause mortality were sparse.
IMPORTANZA: Il cancro al seno è la seconda causa di decessi per cancro tra le donne degli Stati Uniti. Lo screening mammografico può essere associata ad una ridotta mortalità per tumore al seno, ma può anche causare danni. Le linee guida raccomandano di screening decisioni individuando, in particolare per le donne più giovani.
OBIETTIVI: Abbiamo esaminato le prove sul beneficio mortalità e principali danni dello screening mammografico e ciò che è noto su come individuare le decisioni di screening mammografico, inclusa la comunicazione dei rischi e dei benefici per i pazienti.
PROVE DI ACQUISIZIONE: Abbiamo cercato MEDLINE from 1960-2014 di descrivere (1) i benefici della mammografia, (2) danni di mammografia, e (3) individuando le decisioni di screening e di promuovere il processo decisionale informato. Abbiamo anche cercato manualmente la bibliografia degli articoli chiave recuperati, recensioni selezionate, meta-analisi, e le raccomandazioni di pratica. Abbiamo valutato il livello di prova secondo le linee guida dell'American Heart Association.
RISULTATI: lo screening mammografico è associato ad una riduzione complessiva del 19% di mortalità per cancro al seno (circa il 15% per le donne tra i 40 ei 32% per le donne nel loro 60s). Per una donna a 40 o 50-year-old undergoing 10 anni di mammografie annuali, il rischio cumulativo di un risultato falso-positivo è circa il 61%. Circa il 19% dei tumori diagnosticati nel corso di tale periodo di 10 anni non sarebbe diventato clinicamente evidente senza di screening (sovradiagnosi), anche se vi è incertezza di questa stima. Il beneficio netto dello screening dipende molto dalla linea di base del rischio di cancro al seno, che devono essere introdotte in decisioni di screening. Aiuti decisionali hanno il potenziale per aiutare i pazienti a integrare le informazioni sui rischi e benefici con i propri valori e le priorità, anche se non sono ancora ampiamente disponibili per l'uso nella pratica clinica.
Concludono gli autori: Per massimizzare i benefici dello screening mammografico, le decisioni devono essere personalizzati in base ai profili di rischio e le preferenze dei pazienti. Modelli di rischio e aiuti decisionali sono strumenti utili, ma sono necessarie ulteriori ricerche per ottimizzare questi e quantificare ulteriormente sovradiagnosi. La ricerca dovrebbe anche esplorare altre strategie di screening del cancro al seno.
BACKGROUND: L'efficacia di antigene prostatico specifico (PSA) per lo screening della popolazione ha presentato risultati controversi in grandi prove e recensioni precedenti. Abbiamo studiato l'efficacia dello screening di popolazione PSA in una revisione sistematica.
METODI: Lo studio è stato condotto utilizzando revisioni sistematiche esistenti. Abbiamo cercato Ovid MEDLINE, Embase, Cochrane Library, e le principali banche dati coreani. La qualità delle revisioni sistematiche è stato valutato da due revisori indipendenti che utilizzano AMSTAR. Studi randomizzati controllati sono stati valutati utilizzando il rischio di parzialità strumento nel gruppo Cochrane. Meta-analisi sono state condotte utilizzando Review Manager. Il livello di evidenza di ogni risultato è stato valutato usando GRADO.
RISULTATI: mortalità Prostate-cancro-specifica non è stata ridotta basato su simili recensioni precedenti (rischio relativo [RR] 0,93; 95% intervallo di confidenza [IC], 0,81-1,07, p = 0,31). Il tasso di rilevamento di fase 1 cancro alla prostata non è stato maggiore, con un RR di 1.67 (95% CI, 0,95-2,94) e alta eterogeneità. Il tasso di rilevamento di tutte le fasi di cancro nel gruppo di screening era alta, con un RR di 1,45 (95% CI, 1,13-1,85). Nessuna differenza in tutte le cause di mortalità è stata osservata tra i gruppi di screening e di controllo (RR, 0,99; 95% CI, 0,98-1,01, p = 0,50). Mortalità Prostate--cancro-specifica, per tutte le cause di mortalità, e la diagnosi di cancro alla prostata nelle fasi 3-4 mostravano livelli moderati di prove.
CONCLUSIONI: A differenza di studi precedenti, la nostra recensione inclusi aggiornati dati Norrköping e valutato l'unico effetto di test PSA per lo screening del cancro della prostata. Lo screening PSA da solo non ha aumentato la diagnosi precoce del cancro alla prostata palco e ha fatto la mortalità non inferiori.
OBJECTIVES: Compare the benefits and harms of corticosteroids, oral and biologic disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis.
DATA SOURCES: English-language articles from 1980 to February 2011 identified through PubMed, Embase, Cochrane Library, and International Pharmaceutical Abstracts; unpublished literature including dossiers from pharmaceutical companies.
METHODS: Two people independently selected relevant head-to-head trials of any sample size, prospective cohort studies with at least 100 participants, and relevant good- or fair-quality meta-analyses that compared benefits or harms of 14 drug therapies. Retrospective cohort studies were also included for harms. For biologic DMARDs, placebo-controlled, double-blind RCTs were also included. We required trials and cohort studies to have a study duration of at least 12 weeks. Literature was synthesized qualitatively within and between the two main drug classes (oral and biologic DMARDs). Network meta-analysis also was performed to examine the relative efficacy of biologic DMARDs and comparing withdrawal rates from placebo controlled trials.
RESULTS: Head-to-head trials showed no clinically important differences in efficacy among oral DMARD comparisons (methotrexate, sulfasalazine, leflunomide). The only head-to-head trial comparing biologic DMARDs (abatacept vs. infliximab) found no clinically important differences. Combination therapy of biologic DMARDs plus methotrexate improved clinical response rates and functional capacity more than monotherapy with methotrexate. Network meta-analyses found higher odds of reaching ACR 50 response for etanercept compared with most other biologic DMARDs (abatacept, adalimumab, anakinra, infliximab, rituximab, tocilizumab) for methotrexate-resistant patients with active rheumatoid arthritis. Similar overall tolerability profiles were found among oral and biologic DMARDs, but short-term adverse events were more common with biologic DMARDs. Adjusted indirect comparisons of biologic DMARDs found that certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates due to lack of efficacy than adalimumab, anakinra, and infliximab. Certolizumab and infliximab had more, while etanercept had fewer withdrawals due to adverse events than most other drugs. Evidence was insufficient to assess comparative risk of serious adverse events among biologic DMARDs. Combinations of biologic DMARDs have higher rates of serious adverse events than biologic DMARD monotherapy. Limited data existed for subgroups.
CONCLUSIONS: Limited head-to-head comparative evidence does not support one therapy over another for adults with rheumatoid arthritis. Network meta-analyses from placebo-controlled trials of biologics suggest some differences, including higher odds of reaching ACR 50 response, but strength of evidence was low.
CONTEXT: Breast cancer screening in community practices may be different from that in randomized controlled trials. New screening modalities are becoming available.
OBJECTIVES: To review breast cancer screening, especially in the community and to examine evidence about new screening modalities.
DATA SOURCES AND STUDY SELECTION: English-language articles of randomized controlled trials assessing effectiveness of breast cancer screening were reviewed, as well as meta-analyses, systematic reviews, studies of breast cancer screening in the community, and guidelines. Also, studies of newer screening modalities were assessed.
DATA SYNTHESIS: All major US medical organizations recommend screening mammography for women aged 40 years and older. Screening mammography reduces breast cancer mortality by about 20% to 35% in women aged 50 to 69 years and slightly less in women aged 40 to 49 years at 14 years of follow-up. Approximately 95% of women with abnormalities on screening mammograms do not have breast cancer with variability based on such factors as age of the woman and assessment category assigned by the radiologist. Studies comparing full-field digital mammography to screen film have not shown statistically significant differences in cancer detection while the impact on recall rates (percentage of screening mammograms considered to have positive results) was unclear. One study suggested that computer-aided detection increases cancer detection rates and recall rates while a second larger study did not find any significant differences. Screening clinical breast examination detects some cancers missed by mammography, but the sensitivity reported in the community is lower (28% to 36%) than in randomized trials (about 54%). Breast self-examination has not been shown to be effective in reducing breast cancer mortality, but it does increase the number of breast biopsies performed because of false-positives. Magnetic resonance imaging and ultrasound are being studied for screening women at high risk for breast cancer but are not recommended for screening the general population. Sensitivity of magnetic resonance imaging in high-risk women has been found to be much higher than that of mammography but specificity is generally lower. Effect of the magnetic resonance imaging on breast cancer mortality is not known. A balanced discussion of possible benefits and harms of screening should be undertaken with each woman.
CONCLUSIONS: In the community, mammography remains the main screening tool while the effectiveness of clinical breast examination and self-examination are less. New screening modalities are unlikely to replace mammography in the near future for screening the general population.
Prostate cancer (PC) is the most commonly diagnosed non-cutaneous cancer in men and their second or third leading cause of cancer death. Prostate-specific antigen (PSA) testing for PC has been in common practice for more than 20 years.
OBJECTIVES:
A systematic review of the scientific literature was conducted to determine the effectiveness of PSA-based population screening programs for PC to inform policy decisions in a publicly funded health care system.
DATA SOURCES:
A systematic review of bibliographic databases was performed for systematic reviews or randomized controlled trials (RCT) of PSA-based population screening programs for PC.
REVIEW METHODS:
A broad search strategy was employed to identify studies reporting on key outcomes of PC mortality and all-cause mortality.
RESULTS:
The search identified 5 systematic reviews and 6 RCTs. None of the systematic reviews found a statistically significant reduction in relative risk (RR) of PC mortality or overall mortality with PSA-based screening. PC mortality reductions were found to vary by country, by screening program, and by age of men at study entry. The European Randomized Study of Screening for Prostate Cancer found a statistically significant reduction in RR in PC mortality at 11-year follow-up (0.79; 95% CI, 0.67-0.92), although the absolute risk reduction was small (1.0/10,000 person-years). However, the primary treatment for PCs differed significantly between countries and between trial arms. The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) found a statistically non-significant increase in RR for PC mortality with 13-year follow-up (1.09; 95% CI, 0.87-1.36). The degree of opportunistic screening in the control arm of the PLCO trial, however, was high. None of the RCTs found a reduction in all-cause mortality and all found a statistically significant increase in the detection of mainly low-risk, organ-confined PCs in the screening arm.
CONCLUSIONS:
There was no evidence of a PC mortality reduction in the American PLCO trial, which investigated a screening program in a setting where opportunistic screening was already common practice. Given that opportunistic PSA screening practices in Canada are similar, it is unlikely that the introduction of a formal PSA screening program would reduce PC mortality.
