This study showed that after implementation of mammography screening, the increase in the incidence of small lesions exceeded the decline in the incidence of large lesions, which implied that many of ...the small tumors were unlikely to become large lesions had they not been detected.
Although it may be possible to show the efficacy of screening mammography in reducing cancer-specific mortality in the relatively controlled setting of randomized trials, those trials may not accurately reflect the actual effectiveness of screening when it is used in clinical practice. Differences between efficacy and effectiveness with respect to the benefit of screening may be particularly stark when the treatments administered in practice have markedly changed from those administered in the trials that led to the implementation of widespread screening. Furthermore, although trial data may provide an assessment of some negative consequences of screening, such as false positive results . . .
Controversy continues to roil around the role of PSA screening in prostate cancer. The authors review the available data and its quality and conclude that the evidence does not indicate that the ...benefits outweigh the harms.
After a quarter century of extensive screening for prostate cancer with prostate-specific antigen (PSA) in the United States, and after the completion of two major trials examining the effects of such screening, the medical community is still divided with regard to its effectiveness and its benefits-to-harms ratio. Here, we review the current status of PSA screening and examine emerging trends.
In 2012, after publication of the findings from the major randomized trials of PSA-based screening for prostate cancer — the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) . . .
BACKGROUND
The National Lung Screening Trial (NLST), which compared lung cancer screening with low‐dose computed tomography (LDCT) versus chest radiography (CXR), demonstrated a statistically ...significant mortality benefit of LDCT screening. In the current study, the authors performed a post hoc analysis to examine whether the benefit was affected by various baseline factors, including age, sex, and smoking status, and whether it differed by tumor histology.
METHODS
Lung cancer death rates were computed as events over person‐years of observation; the mortality risk ratio (RR) was defined as the lung cancer death rate in the LDCT versus CXR trial arms. Poisson regression was used to test for interactions of sex, age (< 65 years vs ≥ 65 years), and smoking status (current vs former) with trial arm. Mortality RRs were also computed for specific lung cancer histologies.
RESULTS
The overall mortality RR was 0.92 in men and 0.73 in women, with a P value for interaction of .08. RRs were similar for individuals aged < 65 years versus those aged ≥ 65 years (0.82 vs 0.87), and for current versus former smokers (0.81 vs 0.91). By tumor histology, mortality RRs were 0.75 for adenocarcinoma, 0.71 for all non‐small cell lung cancers except squamous, 1.23 for squamous cell carcinoma, and 0.90 for small cell carcinoma. RRs were similar for men and women for nonsquamous non‐small cell lung cancers (0.71 and 0.70, respectively); women were found to have lower RRs for small cell and squamous cell carcinoma.
CONCLUSIONS
A benefit of LDCT did not appear to vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist. Cancer 2013;119:3976–3983. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
The benefit of computed tomography screening in the National Lung Screening Trial did not vary substantially by age or smoking status; there was weak evidence of a differential benefit by sex. A differential benefit across lung cancer histologies may exist.
Epidemiologic Signatures in Cancer Welch, H. Gilbert; Kramer, Barnett S; Black, William C
The New England journal of medicine,
10/2019, Letnik:
381, Številka:
14
Journal Article
Recenzirano
Odprti dostop
The authors use 40 years of data on cancer incidence and mortality to produce curves that show changes in cancer incidence (decreasing, increasing, or staying stable) and the effect of early ...detection efforts on cancer incidence and that help to distinguish treatment advances from overdiagnosis.
Summary Background Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This ...study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. Methods We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55–74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov , number NCT00047385. Findings Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 95% CI 337·97–408·26 per 100 000 person-years vs 661·23 622·07–702·21) and had lower lung cancer-related mortality (185·82 95% CI 162·17–211·93 per 100 000 person-years vs 277·20 252·28–303·90). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 95% CI 162·17–211·93 per 100 000 person-years to 212·14 186·80–239·96) over the course of the trial. Interpretation Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. Funding None.
Based on current recommendations, 30+ pack-years of smoking are required for eligibility for low-dose CT (LDCT) lung cancer screening; former smokers must have quit within 15 years. We investigated ...whether current smokers with 20 to 29 pack-years have similar lung cancer risks as eligible former smokers and also whether they have a different demographic profile.
The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was a randomly assigned screening trial of subjects age 55 to 74 years with chest radiographs (CXR) used for lung cancer. Subjects completed a baseline questionnaire containing smoking history questions. Cox proportional hazards models, adjusted for age and sex, were utilized to estimate hazard ratios (HRs) for various smoking history groups. Next, we utilized the National Health Interview Survey (NHIS), which inquired about smoking history and race/ethnicity, to analyze the demographic profiles of various high-risk smoking history categories. All statistical tests were two-sided.
The PLCO cohort included 18 114 former and 12 243 current LDCT-eligible smokers, plus 2283 20- to 29-pack-year current smokers. The hazard ratio for 20- to 29-pack-year current smokers compared with eligible (30+ pack-year) former smokers was 1.07 (95% confidence interval CI = 0.75 to 1.5). Based on the NHIS, 10 million persons in the United States are currently LDCT eligible; an additional 1.6 million (16%, 95% CI = 13.6% to 19.0%) are 20- to 29-pack-year current smokers. The percentage increase in eligibles if 20- to 29-pack-year current smokers were included was substantially greater for women than men (22.2%, 95% CI = 17.9% to 26.7%; vs 12.2%, 95% CI = 9.3% to 15.3%, P < .001) and for minorities than non-Hispanic whites (30.0%, 95% CI = 24.2% to 36.0%; vs 14.1%, 95% CI = 11.1% to 17.0%, P < .001).
The potential benefits and harms of recommending LDCT screening for 20 to 29-pack-year current smokers should be assessed.
Several important lessons have been learnt from our experiences in screening for various cancers. Screening programmes for cervical and colorectal cancers have had the greatest success, probably ...because these cancers are relatively homogenous, slow-growing, and have identifiable precursors that can be detected and removed; however, identifying the true obligate precursors of invasive disease remains a challenge. With regard to screening for breast cancer and for prostate cancer, which focus on early detection of invasive cancer, preferential detection of slower-growing, localized cancers has occurred, which has led to concerns about overdiagnosis and overtreatment; programmes for early detection of invasive lung cancers are emerging, and have faced similar challenges. A crucial consideration in screening for breast, prostate, and lung cancers is their remarkable phenotypic heterogeneity, ranging from indolent to highly aggressive. Efforts have been made to address the limitations of cancer-screening programmes, providing an opportunity for cross-disciplinary learning and further advancement of the science. Current innovations are aimed at identifying the individuals who are most likely to benefit from screening, increasing the yield of consequential cancers on screening and biopsy, and using molecular tests to improve our understanding of disease biology and to tailor treatment. We discuss each of these concepts and outline a dynamic framework for continuous improvements in the field of cancer screening.
For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening ...programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods of progression and death. Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours. In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms). More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers. In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.
The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an ...urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child–Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost–benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.
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