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.

Testing Whether Cancer Screening Saves Lives: Implications for Randomized Clinical Trials of Multicancer Screening.

Importance: Cancer screening is often promoted as a means to save lives. The question of whether cancer screening truly saves lives is becoming increasingly relevant given the growing enthusiasm for multicancer detection blood tests (ie, liquid biopsies). It is possible in randomized clinical trials for screening to reduce deaths due to the targeted cancer without reducing deaths due to all causes. To explore the feasibility of powering studies for cancer-specific vs all-cause mortality, a series of sample size calculations was performed for selected cancers (breast, colorectal, liver, pancreas, and prostate) and for all cancers combined. Observations: Randomized clinical trials of screening for an individual cancer typically require 100 000 or more participants to test its effect on cancer-specific mortality. Testing all-cause mortality requires trials of more than a million participants. However, the sample size requirements change markedly when considering a randomized clinical trial of screening for all cancers, as is envisioned when using multicancer detection blood tests. In this setting, the question of whether cancer screening reduces all-cause mortality can be reasonably addressed in a trial of fewer than 100 000 participants. Conclusions and Relevance: It is not feasible to test all-cause mortality when screening for an individual cancer. However, it is feasible to test all-cause mortality for multicancer screening because cancer deaths are such a large component of deaths in general. Observational data on the effects of cancer screening are misleading. Multicancer screening would entail tremendous costs and potentially substantial harms. For these reasons, a randomized clinical trial is mandatory not only to learn if multicancer screening saves lives, but also to learn how frequently it causes harm.

Assessing the Clinical Utility of Liquid Biopsies Across 5 Potential Indications From Therapy Selection to Population Screening: A Review.

Importance: There has been great enthusiasm for the emerging technology of molecular-based tests to detect and quantify tumor DNA circulating in the bloodstream, colloquially known as a liquid biopsy. However, less attention has been given to how their clinical utility depends on the indication for testing, which includes a range of clinical situations, each presenting unique challenges. Observations: Five indications for circulating tumor DNA (ctDNA) blood testing were considered. (1) For therapy selection, ctDNA tests can identify genetic alterations in patients with cancer amenable to targeted therapy, but most patients do not have a targetable alteration. (2) For response to therapy, the absence of residual tumor DNA following cancer surgery could reduce the use of adjuvant chemotherapy, but it is unclear that this will happen in practice. (3) For disease surveillance following cancer treatment, ctDNA tests may well detect cancer recurrence before symptoms appear, yet earlier intervention may have no effect on mortality. (4) For diagnosis of suspected cancer, ctDNA tests are able to identify some symptomatic cancers, but how they add to the conventional diagnostic evaluation is unknown. (5) For screening for cancer, multicancer tests can detect many types of cancer, but their low sensitivity for early-stage tumors raises questions as to whether screening can help patients live longer or live better. Conclusions and Relevance: Circulating tumor DNA tests are being promoted for multiple indications. Numerous studies are ongoing, but randomized clinical trials of their effect on patient-centered outcomes are rare. While these tests have the potential to improve care in selected indications, this must be proven, as they will add cost, complexity, and unintended adverse effects for patients.

Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

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.

Portfolios in practice: Developing advancing practice within a musculoskeletal competency-based model.

INTRODUCTION: The development of professional portfolios and the relevance of this within professional practice, competency and capability is gaining significant credibility in line with professional requirements. Nursing and medicine in terms of historical perspectives have long held the need for clinicians to maintain a portfolio for professional validation, whilst in other professional groups it is a requirement of registration. The allied health professionals, physiotherapy and ultimately musculoskeletal practice within this context are rapidly developing advancing and consultant practice. This professional development further requires appropriate verification and validation of practice, and achieving this can be through formal and non-formal routes. PURPOSE: This paper looks to explore this and give direction to professionals developing portfolios whilst placing the requirements in context to contemporary practice in the U.K. Universities, professional bodies and special interest groups are now aligning in the need to support practice in a multi-format way, that moves away from traditional methods of evaluation into more diverse models of competency-based assessment. IMPLICATIONS: With improvement in technology, the development of national frameworks and standards, portfolios in practice although commonly considered as standard practice will be a requirement not only of registration but as a criteria of maintaining status, career development and expansion of roles. BACKGROUND: Musculoskeletal (MSK) physiotherapy in the U.K. has moved forward significantly in the last 20 years. Sitting within a clinical reasoned framework, the introduction of additional skills such is image requesting, injection therapies, and non-medical prescribing has further underpinned the advanced practice agenda (Langridge et al., 2015). While these advancements in practice are driving the profession forward, challenges remain in providing the workforce with a clear process of career development. Alongside developing professional pathways methods of evidencing advanced knowledge and skills acquired outside formal routes are required to support practitioners' career pathway into advancing practice.

Association of UV Radiation Exposure, Diagnostic Scrutiny, and Melanoma Incidence in US Counties.

Importance: Although UV radiation exposure is the conventionally reported risk factor for cutaneous melanoma, an alternative exposure is diagnostic scrutiny: the more physicians look for and biopsy moles, the more melanoma they find. Objective: To assess the association of proxies for UV radiation exposure and diagnostic scrutiny with geographical patterns of melanoma incidence. Design, Setting, and Participants: This was a cross-sectional ecological analysis of the 727 continental US counties reporting to the Surveillance, Epidemiology, and End Results (SEER) Program (among a total of 3108 counties). Environmental data relevant to UV radiation exposure (from a variety of sources), Health Resources and Services Administration data relevant to diagnostic scrutiny, and SEER data on melanoma incidence among the non-Hispanic White population diagnosed with melanoma from 2012 through 2016 were combined. Data analysis was performed between January 2020 and July 2022. Exposures: Three UV radiation proxies (UV daily dose, cloud variability, and temperature variability) and 3 diagnostic scrutiny proxies (median household income, dermatologists, and primary care physician supply). Main Outcomes and Measures: Melanoma incidence (in situ and invasive cancers). Results: In total, 235 333 melanomas were diagnosed. Proxies for UV radiation exposure changed gradually across geography, while melanoma incidence and proxies for diagnostic scrutiny changed abruptly across contiguous counties. The UV daily dose, a variable the National Cancer Institute specifically developed for melanoma analyses, was uncorrelated with incidence (r = 0.03; P = .42). For context, smoking prevalence was highly correlated with lung cancer incidence in the same counties (r = 0.81; P < .001). Melanoma incidence was correlated with median household income (r = 0.43; P < .001). Counties with no dermatologists and shortages of primary care physicians had the lowest incidence, while counties amply supplied with both had the highest, despite having lower mean UV daily dose. There was little association between melanoma incidence and melanoma mortality (r = 0.09; P = .05), while the analogous association in lung cancer was strong (r = 0.96; P < .001). Conclusions and Relevance: In this cross-sectional ecological study, the current geographical pattern of melanoma incidence across US counties was less associated with proxies for UV radiation exposure and more so with proxies for diagnostic scrutiny. Incidence-the fundamental epidemiologic measure of disease frequency-now had little association with the feared outcome of melanoma: death.

Estimating Overdiagnosis of Melanoma Using Trends Among Black and White Patients in the US.

Importance: The incidence of cutaneous melanoma has been rising rapidly among White patients in the US; however, a commensurate increase in mortality due to melanoma has not been observed. These trends suggest overdiagnosis is occurring. Objective: To quantify melanoma overdiagnosis among White patients compared with Black patients in the US. Design, Setting, and Participants: This cohort study used joinpoint regression of Surveillance, Epidemiology, and End Results data from 1975 to 2014 to determine melanoma incidence and mortality trends among Black and White patients in the US. Using trends in mortality due to melanoma in Black patients as a marker for improvements in medical care, the expected mortality trends in White patients if medical care had not improved were estimated. This served as a marker for the change in true cancer occurrence. Overdiagnosis was calculated as the difference between observed incidence and estimated true cancer occurrence. Analyses were stratified by sex. Data were analyzed from September to December 2017. Main Outcomes and Measures: Proportion of melanoma cases overdiagnosed among White patients in 2014. Results: From 1975 to 2014, melanoma incidence increased approximately 4-fold in White women (incidence rate ratio [IRR], 4.01 [95% CI, 3.65-4.41]) and 6-fold in White men (IRR, 5.97 [95% CI, 5.47-6.52]), whereas it increased less than 25% in Black women (IRR, 1.21 [95% CI, 0.97-1.49]) and men (IRR, 1.17; [95% CI, 0.77-1.78]). Mortality due to melanoma decreased approximately 25% in Black women (morality rate ratio [MRR], 0.76 [95% CI, 0.63-0.90]) and men (MRR, 0.72 [95% CI, 0.62-0.84]), was stable in White women (MRR, 1.02 [95% CI, 0.96-1.09]), and increased almost 50% in White men (MRR, 1.49 [95% CI, 1.25-1.77]). Had medical care not improved, estimated mortality would have increased 60% in White women and more than doubled in White men. Based on these trends, an estimated 59% (95% CI, 45%-70%) of White women and 60% (95% CI, 32%-75%) of White men with melanoma were overdiagnosed in 2014. Conclusions and Relevance: The discrepancies in incidence and mortality trends found in this cohort study suggest considerable overdiagnosis of melanoma occurring among White patients in the US.

Association of Computed Tomographic Screening Promotion With Lung Cancer Overdiagnosis Among Asian Women.

IMPORTANCE: As smoking continues to decline in many developed countries, the proportion of lung cancers in nonsmokers will rise. This shift may create substantial pressure to further expand lung cancer screening to lower-risk groups. OBJECTIVE: To determine the association of lung cancer incidence with the promotion of screening in a largely nonsmoking population. DESIGN, SETTING, AND PARTICIPANTS: This population-based ecological cohort study of stage-specific lung cancer incidence used the Taiwan Cancer Registry to identify women diagnosed with lung cancer from January 1, 2004, to December 31, 2018. Smoking prevalence among Taiwanese women has been less than 5% since 1980. Data were analyzed from February 13, 2020, to November 10, 2021. EXPOSURES: Low-dose computed tomography (LDCT) screening for lung cancer, initiated during the early 2000s. MAIN OUTCOMES AND MEASURES: Change in stage-specific lung cancer incidence. An effective cancer screening program will not only increase the incidence of early-stage cancer but also decrease the incidence of cancer presenting at a late stage. RESULTS: A total of 57 898 women were diagnosed with lung cancer in a population of approximately 12 million Taiwanese women. After the introduction of LDCT screening, the incidence of early-stage (stages 0-I) lung cancer in women increased more than 6-fold, from 2.3 to 14.4 per 100 000 population (absolute difference, 12.1 [95% CI, 11.3-12.8]) from 2004 to 2018. There was no change, however, in the incidence of late-stage (stages II-IV) lung cancer, from 18.7 to 19.3 per 100 000 (absolute difference, 0.6 [95% CI, -0.5 to 1.7]). Because the additional 12.1 per 100 000 early-stage cancers were not accompanied by a concomitant decline in late-stage cancers, virtually all the additional cancers detected represent overdiagnosis. Despite stable mortality, 5-year survival more than doubled from 2004 to 2013, from 18% to 40%, which is arguably the highest lung cancer survival rate in the world. CONCLUSIONS AND RELEVANCE: This population-based ecological cohort study found that low-dose computed tomographic screening of mostly nonsmoking Asian women was associated with considerable lung cancer overdiagnosis. Five-year survival is biased by the increased LDCT detection of indolent early-stage lung cancers. Unless randomized trials can demonstrate some value to low-risk groups, LDCT screening should remain targeted only to heavy smokers.