H. Gilbert Welch

Effect of three decades of screening mammography on breast-cancer incidence.

BACKGROUND To reduce mortality, screening must detect life-threatening disease at an earlier, more curable stage. Effective cancer-screening programs therefore both increase the incidence of cancer detected at an early stage and decrease the incidence of cancer presenting at a late stage. METHODS We used Surveillance, Epidemiology, and End Results data to examine trends from 1976 through 2008 in the incidence of early-stage breast cancer (ductal carcinoma in situ and localized disease) and late-stage breast cancer (regional and distant disease) among women 40 years of age or older. RESULTS The introduction of screening mammography in the United States has been associated with a doubling in the number of cases of early-stage breast cancer that are detected each year, from 112 to 234 cases per 100,000 women--an absolute increase of 122 cases per 100,000 women. Concomitantly, the rate at which women present with late-stage cancer has decreased by 8%, from 102 to 94 cases per 100,000 women--an absolute decrease of 8 cases per 100,000 women. With the assumption of a constant underlying disease burden, only 8 of the 122 additional early-stage cancers diagnosed were expected to progress to advanced disease. After excluding the transient excess incidence associated with hormone-replacement therapy and adjusting for trends in the incidence of breast cancer among women younger than 40 years of age, we estimated that breast cancer was overdiagnosed (i.e., tumors were detected on screening that would never have led to clinical symptoms) in 1.3 million U.S. women in the past 30 years. We estimated that in 2008, breast cancer was overdiagnosed in more than 70,000 women; this accounted for 31% of all breast cancers diagnosed. CONCLUSIONS Despite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer. Although it is not certain which women have been affected, the imbalance suggests that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.

Current Thyroid Cancer Trends in the United States

IMPORTANCE We have previously reported on a doubling of thyroid cancer incidence-largely due to the detection of small papillary cancers. Because they are commonly found in people who have died of other causes, and because thyroid cancer mortality had been stable, we argued that the increased incidence represented overdiagnosis. OBJECTIVE To determine whether thyroid cancer incidence has stabilized. DESIGN Analysis of secular trends in patients diagnosed with thyroid cancer, 1975 to 2009, using the Surveillance, Epidemiology, and End Results (SEER) program and thyroid cancer mortality from the National Vital Statistics System. SETTING Nine SEER areas (SEER 9): Atlanta, Georgia; Connecticut; Detroit, Michigan; Hawaii; Iowa; New Mexico; San Francisco-Oakland, California; Seattle-Puget Sound, Washington; and Utah. PARTICIPANTS Men and women older than 18 years diagnosed as having a thyroid cancer between 1975 and 2009 who lived in the SEER 9 areas. INTERVENTIONS None. MAIN OUTCOMES AND MEASURES Thyroid cancer incidence, histologic type, tumor size, and patient mortality. RESULTS Since 1975, the incidence of thyroid cancer has now nearly tripled, from 4.9 to 14.3 per 100,000 individuals (absolute increase, 9.4 per 100,000; relative rate [RR], 2.9; 95% CI, 2.7-3.1). Virtually the entire increase was attributable to papillary thyroid cancer: from 3.4 to 12.5 per 100,000 (absolute increase, 9.1 per 100,000; RR, 3.7; 95% CI, 3.4-4.0). The absolute increase in thyroid cancer in women (from 6.5 to 21.4 = 14.9 per 100,000 women) was almost 4 times greater than that of men (from 3.1 to 6.9 = 3.8 per 100,000 men). The mortality rate from thyroid cancer was stable between 1975 and 2009 (approximately 0.5 deaths per 100,000). CONCLUSIONS AND RELEVANCE There is an ongoing epidemic of thyroid cancer in the United States. The epidemiology of the increased incidence, however, suggests that it is not an epidemic of disease but rather an epidemic of diagnosis. The problem is particularly acute for women, who have lower autopsy prevalence of thyroid cancer than men but higher cancer detection rates by a 3:1 ratio.

Prostate Cancer Diagnosis and Treatment After the Introduction of Prostate-Specific Antigen Screening: 1986–2005

BACKGROUND Although there is uncertainty about the effect of prostate-specific antigen (PSA) screening on the rate of prostate cancer death, there is little uncertainty about its effect on the rate of prostate cancer diagnosis. Systematic estimates of the number of men affected, however, to our knowledge, do not exist. METHODS We obtained data on age-specific incidence and initial course of therapy from the National Cancer Institutes Surveillance, Epidemiology, and End Results program. We then used age-specific male population estimates from the US Census to determine the excess (or deficit) in the number of men diagnosed and treated in each year after 1986-the year before PSA screening was introduced. RESULTS Overall incidence of prostate cancer rose rapidly after 1986, peaked in 1992, and then declined, albeit to levels considerably higher than those in 1986. Overall incidence, however, obscured distinct age-specific patterns: The relative incidence rate (2005 relative to 1986) was 0.56 in men aged 80 years and older, 1.09 in men aged 70-79 years, 1.91 in men aged 60-69 years, 3.64 in men aged 50-59 years, and 7.23 in men younger than 50 years. Since 1986, an estimated additional 1 305 600 men were diagnosed with prostate cancer, 1 004 800 of whom were definitively treated for the disease. Using the most optimistic assumption about the benefit of screening-that the entire decline in prostate cancer mortality observed during this period is attributable to this additional diagnosis-we estimated that, for each man who experienced the presumed benefit, more than 20 had to be diagnosed with prostate cancer. CONCLUSIONS The introduction of PSA screening has resulted in more than 1 million additional men being diagnosed and treated for prostate cancer in the United States. The growth is particularly dramatic for younger men. Given the considerable time that has passed since PSA screening began, most of this excess incidence must represent overdiagnosis.

National trends in lower extremity bypass surgery, endovascular interventions, and major amputations

INTRODUCTION Advances in endovascular interventions have expanded the options available for the invasive treatment of lower extremity peripheral arterial disease (PAD). Whether endovascular interventions substitute for conventional bypass surgery or are simply additive has not been investigated, and their effect on amputation rates is unknown. METHODS We sought to analyze trends in lower extremity endovascular interventions (angioplasty and atherectomy), lower extremity bypass surgery, and major amputation (above and below-knee) in Medicare beneficiaries between 1996 and 2006. We used 100% samples of Medicare Part B claims to calculate annual procedure rates of lower extremity bypass surgery, endovascular interventions (angioplasty and atherectomy), and major amputation between 1996 and 2006. Using physician specialty identifiers, we also examined trends in the specialty performing the primary procedure. RESULTS Between 1996 and 2006, the rate of major lower extremity amputation declined significantly (263 to 188 per 100,000; risk ratio [RR] 0.71, 95% confidence interval [CI] 0.6-0.8). Endovascular interventions increased more than threefold (from 138 to 455 per 100,000; RR = 3.30; 95% CI: 2.9-3.7) while bypass surgery decreased by 42% (219 to 126 per 100,000; RR = 0.58; 95% CI: 0.5-0.7). The increase in endovascular interventions consisted both of a growth in peripheral angioplasty (from 135 to 337 procedures per 100,000; RR = 2.49; 95% CI: 2.2-2.8) and the advent of percutaneous atherectomy (from 3 to 118 per 100,000; RR = 43.12; 95% CI: 34.8-52.0). While radiologists performed the majority of endovascular interventions in 1996, more than 80% were performed by cardiologists and vascular surgeons by 2006. Overall, the total number of all lower extremity vascular procedures almost doubled over the decade (from 357 to 581 per 100,000; RR = 1.63; 95% CI: 1.5-1.8). CONCLUSION Endovascular interventions are now performed much more commonly than bypass surgery in the treatment of lower extremity PAD. These changes far exceed simple substitution, as more than three additional endovascular interventions were performed for every one procedure declined in lower extremity bypass surgery. During this same time period, major lower extremity amputation rates have fallen by more than 25%. However, further study is needed before any causal link can be established between lower extremity vascular procedures and improved rates of limb salvage in patients with PAD.

Korea's thyroid-cancer "epidemic"--screening and overdiagnosis.

In 2011, the rate of thyroid-cancer diagnoses in the Republic of Korea was 15 times that observed in 1993, yet thyroid-cancer mortality remains stable — a combination that suggests that the problem is overdiagnosis attributable to widespread thyroid-cancer screening.

Prudent Strategies for Elective Red Blood Cell Transfusion

OBJECTIVE To review the literature on the appropriateness of red blood cell transfusion and current physician practice, with emphasis on the physiologic and symptomatic implications of elective transfusion in the treatment of anemia. DATA SOURCES Studies on the therapeutic use of red blood cell transfusion were identified through a search of MEDLINE (1966 to the present) and through a manual review of bibliographies of identified articles. In addition, evidence was solicited from selected experts in the field and recent consensus panels that have developed transfusion guidelines. DATA SYNTHESIS No controlled trials of blood transfusion were identified, but data were available on four issues relevant to transfusion practice: current physician practice and evidence for excessive use of red blood cell transfusion; physiologic adaptation to anemia; human tolerance of low hemoglobin levels; and strategies for reducing homologous transfusion requirements. CONCLUSIONS Despite the recent decline in red blood cell use because of concerns about infection, current transfusion practice remains variable because physicians have disparate views about its appropriateness. The remarkable human tolerance of anemia suggests that clinicians can accept hemoglobin levels above 70 g/L (7 g/dL) in most patients with self-limited anemia. In patients with impaired cardiovascular status or with anemias that will not resolve spontaneously, however, the data are insufficient to determine minimum acceptable hemoglobin levels, and therapy must be guided by the clinical situation. Several therapeutic strategies and pharmacologic interventions are available in the perioperative and non-operative settings to further reduce red blood cell use.

Esophageal Adenocarcinoma Incidence: Are We Reaching the Peak?

Background: A steep increase in the incidence of esophageal adenocarcinoma has been observed between 1973 and 2001, but recent trends have not been reported. Our aim was to examine recent trends in esophageal adenocarcinoma incidence. Methods: We used the Surveillance Epidemiology and End Results database of the National Cancer Institute to identify all patients who were diagnosed with esophageal adenocarcinoma between 1973 and 2006. Incidence trends were analyzed for esophageal adenocarcinoma overall and by stage using joinpoint regression. Results: Overall esophageal adenocarcinoma incidence increased from 3.6 per million in 1973 to 25.6 per million in 2006. Incidence trend analysis, however, suggests that the increase has slowed, from an 8.2% annual increase prior to 1996 to 1.3% increase in subsequent years (P = 0.03). Stage-specific trend analyses suggest that the change in overall esophageal adenocarcinoma incidence largely reflects a plateau in the incidence of early stage disease. Its slope has changed direction, from a 10% annual increase prior to 1999 to a 1.6% decline in subsequent years (P = 0.01). Conclusions: The incidence of early stage esophageal adenocarcinoma seems to have plateaued. Impact: Although definitive conclusions will require additional years of data, the plateau in early stage disease might portend stabilization in the overall incidence of esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 19(6); 1468–70. ©2010 AACR.

Estimating treatment benefits for the elderly: the effect of competing risks.

The current practice of encouraging patients to participate in treatment decisions requires that clinicians be facile in communicating the risks and benefits of therapy. Sharing numeric data can foster the process. However, because the format in which data are presented influences their interpretation [1-3], clinicians need to consider which format best describes the outcomes their patients face. Consider the tension between relative and absolute risk reduction. The interpretation of even a large relative risk reduction is highly dependent on the baseline risk for the specific disease. A 50% reduction in mortality with early intervention, for example, appears different when the risk for death from disease is changed from 2 per 1000 to 200 per 1000. When the mortality risk is low, the absolute survival benefit is small0.1% (2/1000 to 1/1000); when the risk is high, the absolute benefit is great10% (200/1000 to 100/1000). In the former scenario, patients might reasonably choose to forego a noxious intervention. In the latter, however, patients might be more likely to accept the morbidity of treatment. Because this distinction between relative and absolute risk reduction is concealed when benefit is expressed in only relative terms, many have argued that relative risk reductions should be anchored by baseline risk so that the absolute benefit of treatment is clear [2, 4, 5] However, an absolute measure of disease risk (or risk reduction from therapy) is not the ultimate outcome of interest to patients. Overall risk is more important. The difference is the risks patients face from other conditionsthat is, competing risks. When competing risks are great, they matter. The importance of even a 10% absolute survival benefit from treatment is markedly diminished for a patient who is at greater risk for death from other causes, regardless of the proposed therapy. Such great competing risks are most prevalent among the elderly. Although physicians intuitively understand the relevance of competing risks, they may be less sure about how to quantify the effect. We provide a framework to help physicians gauge the effect of competing risks in their elderly patients. Methods Overview To quantify the effect of competing risks, we used age-specific mortality data from U.S. vital statistics and the declining exponential approximation for life expectancy (DEALE) to model age-specific expectations for persons faced with a particular disease-related mortality. We sought to determine, for example, how a new disease with a 5-year mortality rate of 25% would affect the life expectancy of an average 70-year-old man. We then considered two refinements: the first, to better adjust for the individual patient (using self-reported health status), and the second, to describe more thoroughly the outcome (by including disabling events). Modeling the Effect of a New Disease on Life Expectancy Life expectancy and mortality are fundamentally related to probability estimates. In the general population, life expectancy decreases with increasing age, and annual mortality increases. Gompertz was the first to describe this complex mathematic relation using an exponential function that now bears his name. As life expectancy decreases, mortality rates become almost constant over time. When this occurs, the relation between survival and mortality rates can be approximated with a much simpler mathematic relation: a declining exponential function (the DEALE). This approximation was first validated and popularized by Beck and colleagues [6, 7] and is particularly suited to calculating the effect that a new risk has in older patients. The fundamental assumption behind this technique is that life expectancy equals the inverse of the annual mortality rate: Equation 1 Because mortality rates are essentially constant probability estimates when assessed over relatively short time horizons, patient-specific mortality rates can be expressed as the sum of the disease-independent mortality rate (also known as age-specific mortality rate) and a disease-related mortality rate (also known as case-fatality or excess mortality rate): Equation 2 Note that when disease-related mortality is zero (that is, when the patient does not have the disease or when the disease has no effect on survival), the patient-specific mortality rate (and thus life expectancy) is determined solely by the patients age. Calculation of the life expectancy estimates used in Figure 1 and Figure 2 is relatively simple. Because Figure 1 is the central portion of our paper, we now describe it in detail. Normal life expectancy (the top curves) was determined from the most recent data (1991) from the National Center for Health Statistics, U.S. Department of Health and Human Services [8]. On the basis of remaining life expectancy and the DEALE [6, 7], we calculated the age-specific mortality rate for each age cohort from 65 to 85 years of age. Combining the age-specific mortality with the hypothetical disease-related mortality allowed us to calculate the other four curves. The disease-related annual mortality rate can be calculated from 5-year disease-specific survival using the following equation: Equation 3 Figure 1. The effect of selected disease-related mortality rates on the remaining life expectancy of women (left) and men (right) at the time of diagnosis. Figure 2. The effect of age on the distribution of health states in the future. Thus, if the disease-related 5-year mortality rate is 25% (and the 5-year survival rate is 75%), then the disease-related annual mortality rate is 0.06. Equation 4 A 70-year-old man, for example, has a life expectancy of 12.2 years or an annual age-specific mortality rate of 0.08. Equation 5 Given the foregoing disease, the mans all-cause annual mortality rate is 0.14 (= 0.06 + 0.08), and his life expectancy is 7.2 years. Equation 6 Thus, the sum of the age-specific and disease-related mortality rates gives the patient-specific mortality rate, the inverse of which is life expectancy. Normal life expectancy serves as our proxy for disease-independent data. The mortality reflected in this measure is, of course, itself the result of several diseases in the elderlyprimarily cardiovascular disease and cancer. The method we describe produces a valid approximation whenever the disease in question is not a major contributor to the age-specific mortality rate. For example, if the disease in question was all cardiovascular disease or all cancer, then much of the age-specific mortality rate would already account for the mortality from the disease. Completely successful therapy for such a broad category of disease would move a patient well above his or her normal life expectancy by removing the common causes of death. Thus, the method we describe should be applied only when the physician is considering more discrete diagnoses (for example, aortic aneurysm or breast cancer), which make a relatively small contribution to overall mortality. To provide some quantitative data on how great a contributor to all-cause mortality a given disease can be without affecting our method, we did a sensitivity analysis that removed the contribution of a particular disease from normal life expectancy and accordingly revised the estimate of perfect treatment on life expectancy. For example, for a disease that accounts for 40% of all-cause mortality (such as all cardiovascular diagnoses), revised treatment benefit (in years) was three times the benefit estimated by our method. For a disease that accounts for 30% of all-cause mortality (for example, all cancers considered together), the revised benefit was twice as high as the benefit estimated by our method. However, for a disease that constitutes less than 10% of all-cause mortality (this is the case for any individual cancer), the revised benefit is small (for example, less than 20% higher than that estimated by our method). Adjustments for Health Status The adjustments for health status shown in Table 1 are based on data from the East Boston Senior Health Project. All participants were asked the following question: Compared with others your age, would you rate your overall health as excellent, good, fair, or poor? Analyzing the 1437 men and 2332 women separately, we used 5-year follow-up data to calculate, for each health status self-rating, the proportion of patients who died. The ratio of this health status-specific survival to overall survival served as our health status weight. A more precise analysis for men and women, using five age cohorts (ages 65 to 69 years, 70 to 74 years, 75 to 79 years, 80 to 84 years, and 85 years and older) produced essentially the same weights. Table 1. Estimated Physiologic Age of Elderly Patients Adjusted for Their Self-Reported Health Status* Overall, men who described themselves as in excellent health had a lower mortality rate than average (health status weight, 0.52). Men who reported themselves as in good, fair, and poor health had health status weights of 0.89, 1.26, and 1.88, respectively. The analysis for women showed health status weights of 0.64, 0.88, 1.08, and 1.82 for self-reported health status of excellent, good, fair, and poor, respectively. To approximate a physiologic age to reflect health status, we applied the health status weights to four chronologic ages: 65, 70, 75, and 80 years. Using the age-specific annual mortality from U.S. Vital Statistics data [8] and the health status weight, we calculated a health status-adjusted mortality rate as the following: Equation 7 We then returned to the Vital Statistics data to determine the age at which an average person would have this annual mortality rate. These data do not provide annual mortality rates for persons older than 85 years, forcing us to report 85 years and older for the highest mortality rates. The process was done separately for men and women. Future Disabling Events The expectation of future disabling events (Figure 3) is based on cros

Is Language a Barrier to the Use of Preventive Services

To isolate the effect of spoken language from financial barriers to care, we examined the relation of language to use of preventive services in a system with universal access. Cross-sectional survey. Household population of women living in Ontario, Canada, in 1990. Subjects were 22,448 women completing the 1990 Ontario Health Survey, a population-based random sample of households. We defined language as the language spoken in the home and assessed self-reported receipt of breast examination, mammogram and Pap testing. We used logistic regression to calculate odds ratios for each service adjusting for potential sources of confounding: socioeconomic characteristics, contact with the health care system, and measures reflecting culture. Ten percent of the women spoke a non-English language at home (4% French. 6% other). After adjustment, compared with English speakers, French-speaking women were significantly less likely to receive breast exams or mammography, and other language speakers were less likely to receive Pap testing. Women whose main spoken language was not English were less likely to receive important preventive services. Improving communication with patients with limited English may enhance participation in screening programs.

Addressing overdiagnosis and overtreatment in cancer: a prescription for change

A vast range of disorders--from indolent to fast-growing lesions--are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.