Cancer Screening, Incidental Detection, and Overdiagnosis.

BACKGROUND: In the past, patients were only diagnosed with cancer because they had symptoms. Now, because of screening and incidental detection, some patients are diagnosed with cancer when they are asymptomatic. While this shift is typically viewed as desirable, it has produced an unfortunate side-effect: it is now possible to be diagnosed with a cancer not destined to cause symptoms or death-a phenomenon labeled as overdiagnosis. CONTENT: We begin with a brief introduction to the heterogeneity of cancer progression: at one extreme, some cancers are already systemic by the time they are detectable; at the other, some grow extremely slowly or even regress. The ensuing sections describe the evidence that the pursuit of earlier detection has led to overdiagnosis. Although rarely confirmed in an individual, overdiagnosis is readily identifiable in a long-term follow-up of a randomized trial of screening. Furthermore, 2 population signatures for overdiagnosis exist: (a) rising incidence coupled with stable mortality and (b) rising early-stage incidence coupled with stable late-stage incidence. Finally, we review the misleading feedback produced by overdiagnosis-such as rising 5-year survival rates and more cancer survivors. This feedback is erroneously interpreted as reinforcing the value of early detection, encourages more screening/incidental detection and, ironically, promotes more overdiagnosis. SUMMARY: Overdiagnosis is an unintended consequence of the desire to detect cancer early. Given the evolving understanding that tumor biology and host response are more relevant to prognosis than early vs late diagnosis, it is time to challenge the assertion that early diagnosis is always the best approach to curing cancer.

Deceptive measures of progress in the NHS long-term plan for cancer: case-based vs. population-based measures.

The NHS Long Term Plan for cancer aims to increase early-stage diagnoses from 50% to 75% and to have 55,000 more people each year survive their cancer for at least 5 years following diagnosis. The targets measures are flawed and could be met without improving outcomes that really matter to patients. The proportion of early-stage diagnoses could increase, while the number of patients presenting at a late-stage remains the same. More patients could survive their cancer for longer, but lead time and overdiagnosis bias make it impossible to know whether anyone had their life prolonged. The target measures should switch from biased case-based measures to unbiased population-based measures that reflect the key objectives in cancer care: reducing late-stage incidence and mortality.

Variation in Ultrasound Diagnostic Thresholds for Carotid Stenosis in the United States.

BACKGROUND: Individuals with carotid stenosis enter surveillance or are considered for surgery on the basis of disease severity assessed by ultrasound. However, there is variation in the ultrasound diagnostic thresholds used to determine disease severity. Our objective was to describe this variation and its potential impact on patients. METHODS: To describe the variation in carotid ultrasound diagnostic thresholds, we examined testing protocols from 338 accredited vascular testing centers in the United States. To determine the potential impact of this variation, we applied the range of thresholds to carotid ultrasound parameters from 2 groups: a population-based sample ≥65 years of age in the Cardiovascular Health Study (n=4791), and a cohort of patients who underwent surgery for asymptomatic carotid stenosis in the Vascular Quality Initiative registry (n=28 483). RESULTS: Internal carotid artery peak systolic velocity was used by all centers to assess disease severity, with 60 distinct thresholds in use. The peak systolic velocity threshold for moderate (≥50%) stenosis ranged from 110 to 245 cm/s (median, 125; 5th and 95th percentile, 125 and 150), and the threshold for severe (≥70%) stenosis ranged from 175 to 340 cm/s (median, 230; 5th and 95th percentile, 230 and 275). In the population-based sample, the 5th percentile threshold would assign a diagnosis of moderate carotid stenosis to twice as many individuals as the 95th percentile threshold (7.9% versus 3.9%; relative risk, 2.01 [CI, 1.70-2.38]). In the surgical cohort, 1 in 10 (9.8%) patients had peak systolic velocity values that warranted the diagnosis of severe carotid stenosis at centers in the 5th percentile, but not in the 95th. CONCLUSIONS: The diagnostic threshold for carotid stenosis varies considerably. Whether or not a person is said to have moderate stenosis and enters surveillance, and whether or not they have severe stenosis and are candidates for surgery, can depend on which center performs their ultrasound.

Cancer in the Shadow of COVID: Early-Stage Breast and Prostate Cancer Patient Perspectives on Surgical Delays Due to COVID-19.

BACKGROUND: During the height of the coronavirus disease 2019 (COVID-19) pandemic, elective surgeries, including oncologic surgeries, were delayed. Little prospective data existed to guide practice, and professional surgical societies issued recommendations grounded mainly in common sense and expert consensus, such as medical therapy for early-stage breast and prostate cancer patients. To understand the patient experience of delay in cancer surgery during the pandemic, we interviewed breast and prostate cancer patients whose surgeries were delayed due to the pandemic. PATIENTS AND METHODS: Patients with early-stage breast or prostate cancer who suffered surgical postponement at Brigham and Women's Hospital (BWH) were invited to participate. Semi-structured telephone interviews were conducted with 21 breast and prostate cancer patients. Interviews were transcribed, and qualitative analysis using ground-theory approach was performed. RESULTS: Most patients reported significant distress due to cancer and COVID. Key themes that emerged included the lack of surprise and acceptance of the surgical delays but endorsed persistent cancer- and delay-related worries. Satisfaction with patient-physician communication and the availability of a delay strategy were key factors in patients' acceptance of the situation; perceived lack of communication prompted a few patients to seek care elsewhere. DISCUSSION: The clinical effect of delay in cancer surgery will take years to fully understand, but there are immediate steps that can be taken to improve the patient experience of delays in care, including elicitation of individual patient perspectives and ongoing communication. More work is needed to understand the wider experiences of patients, especially minority, socioeconomically disadvantaged, and uninsured patients, who encounter delays in oncologic care.

Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness.

BACKGROUND: The goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms. Effective screening should therefore lead to the detection of a greater number of small tumors, followed by fewer large tumors over time. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) program, 1975 through 2012, to calculate the tumor-size distribution and size-specific incidence of breast cancer among women 40 years of age or older. We then calculated the size-specific cancer case fatality rate for two time periods: a baseline period before the implementation of widespread screening mammography (1975 through 1979) and a period encompassing the most recent years for which 10 years of follow-up data were available (2000 through 2002). RESULTS: After the advent of screening mammography, the proportion of detected breast tumors that were small (invasive tumors measuring <2 cm or in situ carcinomas) increased from 36% to 68%; the proportion of detected tumors that were large (invasive tumors measuring ≥2 cm) decreased from 64% to 32%. However, this trend was less the result of a substantial decrease in the incidence of large tumors (with 30 fewer cases of cancer observed per 100,000 women in the period after the advent of screening than in the period before screening) and more the result of a substantial increase in the detection of small tumors (with 162 more cases of cancer observed per 100,000 women). Assuming that the underlying disease burden was stable, only 30 of the 162 additional small tumors per 100,000 women that were diagnosed were expected to progress to become large, which implied that the remaining 132 cases of cancer per 100,000 women were overdiagnosed (i.e., cases of cancer were detected on screening that never would have led to clinical symptoms). The potential of screening to lower breast cancer mortality is reflected in the declining incidence of larger tumors. However, with respect to only these large tumors, the decline in the size-specific case fatality rate suggests that improved treatment was responsible for at least two thirds of the reduction in breast cancer mortality. CONCLUSIONS: Although the rate of detection of large tumors fell after the introduction of screening mammography, the more favorable size distribution was primarily the result of the additional detection of small tumors. Women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a tumor that was destined to become large. The reduction in breast cancer mortality after the implementation of screening mammography was predominantly the result of improved systemic therapy.

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.

Repeated upper endoscopy in the Medicare population: a retrospective analysis.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is done often for various indications. Little is known about the frequency of repeated EGD and the diagnoses that drive it. OBJECTIVE: To describe the frequency of repeated EGD in the Medicare population and determine diagnoses most often associated with it. DESIGN: Retrospective analysis. SETTING: Medicare database. PATIENTS: Among a 5% random sample of Medicare beneficiaries, Current Procedural Terminology (CPT) codes were used to identify patients who had an index EGD between 2004 and 2006. Diagnoses from the International Classification of Diseases, Ninth Revision, Clinical Modification, reported for the index endoscopy were divided into 3 diagnostic groups on the basis of whether the index diagnosis suggested that repeated EGD was expected, uncertain, or not expected. MEASUREMENTS: Proportion of patients with repeated EGD within 3 years of an index EGD. RESULTS: Approximately 12% of Medicare beneficiaries had an EGD between 2004 and 2006 (n = 108 785). Of these, 33% (n = 36 331) had at least 1 repeated EGD within 3 years. Of all patients with initial EGDs, 10% (n = 11 370) had an associated diagnosis suggesting a need for follow-up examination, whereas 61% (n = 66 307) did not. Of all patients with repeated examinations, 54% (n = 19 687) came from the group in which repeated EGD was not expected. When new clinical events were excluded, 43% of all patients with repeated EGDs (n = 15 706) did not have a diagnosis at index or repeated EGD that justified a repeated examination. LIMITATION: Whether individual procedures were clinically indicated cannot be verified. CONCLUSION: One in 3 Medicare beneficiaries who received an EGD had a repeated EGD within 3 years. Nearly one half of repeated examinations were done in patients with diagnoses at index or repeated EGD that did not suggest the need for a repeated examination. PRIMARY FUNDING SOURCE: None.