Benefits and harms of prostate specific antigen testing according to Australian guidelines.

Guidelines for prostate specific antigen (PSA) testing in Australia recommend that men at average risk of prostate cancer who have been informed of the benefits and harms, and who decide to undergo regular testing, should be offered testing every 2 years from 50 to 69 years. This study aimed to estimate the benefits and harms of regular testing in this context. We constructed Policy1-Prostate, a discrete event microsimulation platform of the natural history of prostate cancer and prostate cancer survival, and PSA testing patterns and subsequent management in Australia. The model was calibrated to pre-PSA (before 1985) prostate cancer incidence and mortality and validated against incidence and mortality trends from 1985 to 2011 and international trials. The model predictions were concordant with trials and Australian observed incidence and mortality data from 1985 to 2011. Out of 1000 men who choose to test according to the guidelines, 36 [21-41] men will die from prostate cancer and 126 [119-133] men will be diagnosed with prostate cancer, compared with 50 [47-54] and 94 [90-98] men who do not test, respectively. During the 20 years of active PSA testing, 32.3% [25.6%-38.8%] of all PSA-test detected cancers are overdiagnosed cases that is, 30 [21-42] out of 94 [83-107] PSA-test detected cancers. Australian men choosing to test with PSA every two years from 50 to 69 will reduce their risk of ever dying from prostate cancer and incur a risk of overdiagnosis: for every man who avoids dying from prostate cancer, two will be overdiagnosed with prostate cancer between 50 and 69 years of age. Australian men, with health professionals, can use these results to inform decision-making about PSA testing.

Health benefits and harms of mammography screening in older women (75+ years)-a systematic review.

BACKGROUND: There is little evidence on the balance between potential benefits and harms of mammography screening in women 75 years and older. The aim of this systematic review was to synthesise the evidence on the outcomes of mammography screening in women aged 75 years and older. METHODS: A systematic review of mammography screening studies in women aged 75 years and over. RESULTS: Thirty-six studies were included in this review: 27 observational studies and 9 modelling studies. Many of the included studies used no or uninformative comparison groups resulting in a potential bias towards the benefits of screening. Despite this, there was mixed evidence about the benefits and harms of continuing mammography screening beyond the age of 75 years. Some studies showed a beneficial effect on breast cancer mortality, and other studies showed no effect on mortality. Some studies showed some harms (false positive tests and recalls) being comparable to those in younger age-groups, with other studies showing increase in false positive screens and biopsies in older age-group. Although reported in fewer studies, there was consistent evidence of increased overdiagnosis in older age-groups. CONCLUSION: There is limited evidence available to make a recommendation for/against continuing breast screening beyond the age of 75 years. Future studies should use more informative comparisons and should estimate overdiagnosis given potentially substantial harm in this age-group due to competing causes of death. This review was prospectively registered with PROSPERO (CRD42020203131).

Low-risk prostate lesions: An evidence review to inform discussion on losing the "cancer" label.

BACKGROUND: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation. METHODS: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. RESULTS: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995). CONCLUSIONS: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.

Should low-risk DCIS lose the cancer label? An evidence review.

BACKGROUND: Population mammographic screening for breast cancer has led to large increases in the diagnosis and treatment of ductal carcinoma in situ (DCIS). Active surveillance has been proposed as a management strategy for low-risk DCIS to mitigate against potential overdiagnosis and overtreatment. However, clinicians and patients remain reluctant to choose active surveillance, even within a trial setting. Re-calibration of the diagnostic threshold for low-risk DCIS and/or use of a label that does not include the word 'cancer' might encourage the uptake of active surveillance and other conservative treatment options. We aimed to identify and collate relevant epidemiological evidence to inform further discussion on these ideas. METHODS: We searched PubMed and EMBASE databases for low-risk DCIS studies in four categories: (1) natural history; (2) subclinical cancer found at autopsy; (3) diagnostic reproducibility (two or more pathologist interpretations at a single time point); and (4) diagnostic drift (two or more pathologist interpretations at different time points). Where we identified a pre-existing systematic review, the search was restricted to studies published after the inclusion period of the review. Two authors screened records, extracted data, and performed risk of bias assessment. We undertook a narrative synthesis of the included evidence within each category. RESULTS: Natural History (n = 11): one systematic review and nine primary studies were included, but only five provided evidence on the prognosis of women with low-risk DCIS. These studies reported that women with low-risk DCIS had comparable outcomes whether or not they had surgery. The risk of invasive breast cancer in patients with low-risk DCIS ranged from 6.5% (7.5 years) to 10.8% (10 years). The risk of dying from breast cancer in patients with low-risk DCIS ranged from 1.2 to 2.2% (10 years). Subclinical cancer at autopsy (n = 1): one systematic review of 13 studies estimated the mean prevalence of subclinical in situ breast cancer to be 8.9%. Diagnostic reproducibility (n = 13): two systematic reviews and 11 primary studies found at most moderate agreement in differentiating low-grade DCIS from other diagnoses. Diagnostic drift: no studies found. CONCLUSION: Epidemiological evidence supports consideration of relabelling and/or recalibrating diagnostic thresholds for low-risk DCIS. Such diagnostic changes would need agreement on the definition of low-risk DCIS and improved diagnostic reproducibility.

Increased diagnosis of attention-deficit hyperactivity disorder despite stable hyperactive/inattentive behaviours: evidence from two birth cohorts of Australian children.

BACKGROUND: Globally, ADHD diagnoses have increased substantially and there is concern that this trend does not necessarily reflect improved detection of cases but that overdiagnosis may be occurring. We directly compared ADHD diagnoses with ADHD-related behaviours and looked for changes across time among Australian children in a large, population-based prospective cohort study. METHODS: We conducted a secondary analysis of the Longitudinal Study of Australian Children, including 4,699 children born 1999/2000 (cohort 1) and 4,425 children born 2003/2004 (cohort 2), followed from 4 to 13 years of age. We compared pre-diagnosis parent-reported hyperactive/inattentive behaviour scores between newly diagnosed (incident cases) and undiagnosed children and fitted Cox's proportional hazards regression models to examine the relationship between birth cohorts 1 and 2 and the risk of incident ADHD diagnosis. RESULTS: Cumulative incident ADHD diagnoses increased from 4.6% in cohort 1 (born in 1999/2000) to 5.6% in cohort 2 (born in 2003/2004), while hyperactive/inattentive behaviour scores remained steady. Among ADHD diagnosed children, 26.5% (88/334) recorded pre-diagnosis behaviours in the normal range, 27.6% (n = 92) had borderline scores and 45.8% (n = 153) scored within the clinical range. Children born in 2003/2004 were more likely to be diagnosed with ADHD compared with those born in 1999/2000 (aHR = 1.33, 95% CI = 1.06-1.67, p = .012), regardless of their ADHD behaviour score (p = .972). CONCLUSIONS: Diagnostic increases were not driven by rises in hyperactive/inattentive behaviours. A quarter of all children with an ADHD diagnosis recorded pre-diagnosis behaviours within the normal range. The increased likelihood of being diagnosed with ADHD for children from the later birth cohort was observed for children across the full range of ADHD-related behaviours.

Behavioural change interventions encouraging clinicians to reduce carbon emissions in clinical activity: a systematic review.

BACKGROUND: Clinical activity accounts for 70-80% of the carbon footprint of healthcare. A critical component of reducing emissions is shifting clinical behaviour towards reducing, avoiding, or replacing carbon-intensive healthcare. The objective of this systematic review was to find, map and assess behaviour change interventions that have been implemented in healthcare settings to encourage clinicians to reduce greenhouse gas emissions from their clinical activity. METHODS: Studies eligible for inclusion were those reporting on a behaviour change intervention to reduce carbon emissions via changes in healthcare workplace behaviour. Six databases were searched in November 2021 (updated February 2022). A pre-determined template was used to extract data from the studies, and risk of bias was assessed. The behaviour change techniques (BCTs) used in the interventions were coded using the BCT Taxonomy. RESULTS: Six full-text studies were included in this review, and 14 conference abstracts. All studies used a before-after intervention design. The majority were UK studies (n = 15), followed by US (n = 3) and Australia (n = 2). Of the full-text studies, four focused on reducing the emissions associated with anaesthesia, and two aimed at reducing unnecessary test ordering. Of the conference abstracts, 13 focused on anaesthetic gas usage, and one on respiratory inhalers. The most common BCTs used were social support, salience of consequences, restructuring the physical environment, prompts and cues, feedback on outcome of behaviour, and information about environmental consequences. All studies reported success of their interventions in reducing carbon emissions, prescribing, ordering, and financial costs; however, only two studies reported the magnitude and significance of their intervention's success. All studies scored at least one item as unclear or at risk of bias. CONCLUSION: Most interventions to date have targeted anaesthesia or pathology test ordering in hospital settings. Due to the diverse study outcomes and consequent inability to pool the results, this review is descriptive only, limiting our ability to conclude the effectiveness of interventions. Multiple BCTs were used in each study but these were not compared, evaluated, or used systematically. All studies lacked rigour in study design and measurement of outcomes. REVIEW REGISTRATION: The study was registered on Prospero (ID number CRD42021272526) (Breth-Petersen et al., Prospero 2021: CRD42021272526).

A systematic review and meta-analysis of the prevalence of left ventricular non-compaction in adults.

AIMS: To assess the reported prevalence of left ventricular non-compaction (LVNC) in different adult cohorts, taking in to consideration the role of diagnostic criteria and imaging modalities used. METHODS AND RESULTS: A systematic review and meta-analysis of studies reporting LVNC prevalence in adults. Studies were sourced from Pre-Medline, Medline, and Embase and assessed for eligibility according to inclusion criteria. Eligible studies provided a prevalence of LVNC in adult populations (≥12 years). Studies were assessed, and data extracted by two independent reviewers. Fifty-nine eligible studies documenting LVNC in 67 unique cohorts were included. The majority of studies were assessed as moderate or high risk of bias. The pooled prevalence estimates for LVNC were consistently higher amongst cohorts diagnosed on cardiac magnetic resonance (CMR) imaging (14.79%, n = 26; I2 = 99.45%) compared with echocardiogram (1.28%, n = 36; I2 = 98.17%). This finding was unchanged when analysis was restricted to studies at low or moderate risk of bias. The prevalence of LVNC varied between disease and population representative cohorts. Athletic cohorts demonstrated high pooled prevalence estimates on echocardiogram (3.16%, n = 5; I2 = 97.37%) and CMR imaging (27.29%, n = 2). CONCLUSION: Left ventricular non-compaction in adult populations is a poorly defined entity which likely encompasses both physiological adaptation and pathological disease. There is a higher prevalence with the introduction of newer imaging technologies, specifically CMR imaging, which identify LVNC changes more readily. The clinical significance of these findings remains unclear; however, there is significant potential for overdiagnosis, overtreatment, and unnecessary follow-up.

The carbon footprint of pathology testing.

OBJECTIVES: To estimate the carbon footprint of five common hospital pathology tests: full blood examination; urea and electrolyte levels; coagulation profile; C-reactive protein concentration; and arterial blood gases. DESIGN, SETTING: Prospective life cycle assessment of five pathology tests in two university-affiliated health services in Melbourne. We included all consumables and associated waste for venepuncture and laboratory analyses, and electricity and water use for laboratory analyses. MAIN OUTCOME MEASURE: Greenhouse gas footprint, measured in carbon dioxide equivalent (CO2 e) emissions. RESULTS: CO2 e emissions for haematology tests were 82 g/test (95% CI, 73-91 g/test) for coagulation profile and 116 g/test (95% CI, 101-135 g/test) for full blood examination. CO2 e emissions for biochemical tests were 0.5 g/test CO2 e (95% CI, 0.4-0.6 g/test) for C-reactive protein (low because typically ordered with urea and electrolyte assessment), 49 g/test (95% CI, 45-53 g/test) for arterial blood gas assessment, and 99 g/test (95% CI, 84-113 g/test) for urea and electrolyte assessment. Most CO2 e emissions were associated with sample collection (range, 60% for full blood examination to 95% for coagulation profile); emissions attributable to laboratory reagents and power use were much smaller. CONCLUSION: The carbon footprint of common pathology tests was dominated by those of sample collection and phlebotomy. Although the carbon footprints were small, millions of tests are performed each year in Australia, and reducing unnecessary testing will be the most effective approach to reducing the carbon footprint of pathology. Together with the detrimental health and economic effects of unnecessary testing, our environmental findings should further motivate clinicians to test wisely.

Estimating the magnitude of cancer overdiagnosis in Australia.

OBJECTIVES: To estimate the proportion of cancer diagnoses in Australia that might reasonably be attributed to overdiagnosis by comparing current and past lifetime risks of cancer. DESIGN, SETTING, AND PARTICIPANTS: Routinely collected Australian Institute of Health and Welfare national data were analysed to estimate recent (2012) and historical (1982) lifetime risks (adjusted for competing risk of death and changes in risk factors) of diagnoses with five cancers: prostate, breast, renal, thyroid cancers, and melanoma. MAIN OUTCOME MEASURE: Difference in lifetime risks of cancer diagnosis between 1982 and 2012, interpreted as probable overdiagnosis. RESULTS: For women, absolute lifetime risk increased by 3.4 percentage points for breast cancer (invasive cancers, 1.7 percentage points), 0.6 percentage point for renal cancer, 1.0 percentage point for thyroid cancer, and 5.1 percentage points for melanoma (invasive melanoma, 0.7 percentage point). An estimated 22% of breast cancers (invasive cancers, 13%), 58% of renal cancers, 73% of thyroid cancers, and 54% of melanomas (invasive melanoma, 15%) were overdiagnosed, or 18% of all cancer diagnoses (8% of invasive cancer diagnoses). For men, absolute lifetime risk increased by 8.2 percentage points for prostate cancer, 0.8 percentage point for renal cancer, 0.4 percentage point for thyroid cancer, and 8.0 percentage points for melanoma (invasive melanoma, 1.5 percentage points). An estimated 42% of prostate cancers, 42% of renal cancers, 73% of thyroid cancers, and 58% of melanomas (invasive melanomas, 22%) were overdiagnosed, or 24% of all cancer diagnoses (16% of invasive cancer diagnoses). Alternative assumptions slightly modified the estimates for overdiagnosis of breast cancer and melanoma. CONCLUSIONS: About 11 000 cancers in women and 18 000 in men may be overdiagnosed each year. Rates of overdiagnosis need to be reduced and health services should monitor emerging areas of overdiagnosis.

Is the risk of cancer in Australia overstated? The importance of competing mortality for estimating lifetime risk.

OBJECTIVES: To calculate lifetime risks of cancer diagnosis and cancer-specific death, adjusted for competing mortality, and to compare these estimates with the corresponding risks published by the Australian Institute of Health and Welfare (AIHW). DESIGN, SETTING: Analysis of publicly available annual AIHW data on age-specific cancer incidence and mortality - for breast cancer, colorectal cancer, prostate cancer, melanoma of the skin, and lung cancer - and all-cause mortality in Australia, 1982-2013. OUTCOME MEASURES: Lifetime risks of cancer diagnosis and mortality (to age 85), adjusted for competing mortality. RESULTS: During 1982-2013, AIHW estimates were consistently higher than our competing mortality-adjusted estimates of lifetime risks of diagnosis and death for all five cancers. Differences between AIHW and adjusted estimates declined with time for breast cancer, prostate cancer, colorectal cancer, and lung cancer (for men only), but remained steady for lung cancer (women only) and melanoma of the skin. In 2013, the respective estimated lifetime risks of diagnosis (AIHW and adjusted) were 12.7% and 12.1% for breast cancer, 18.7% and 16.2% for prostate cancer, 9.0% and 7.0% (men) and 6.4% and 5.5% (women) for colorectal cancer, 7.5% and 6.0% (men) and 4.4% and 4.0% (women) for melanoma of the skin, and 7.6% and 5.8% (men) and 4.5% and 3.9% (women) for lung cancer. CONCLUSION: The method employed in Australia to calculate the lifetime risks of cancer diagnosis and mortality overestimates these risks, especially for men.

The association between induction of labour at 38 to 39 weeks pregnancy and indication for caesarean delivery: An observational study.

BACKGROUND: Induction of labour is associated with a reduction in caesarean delivery, but the mechanism of action and which groups of women might benefit remain unknown. AIMS: To assess the association between induction of labour at 38-39 weeks pregnancy, and caesarean delivery: (i) overall; (ii) for slow progress in labour; and (iii) for suspected fetal compromise. MATERIAL AND METHODS: Retrospective observational study in two Sydney hospitals from 2009 to 2016, among nulliparous women with induction of labour at 38 or 39 completed weeks pregnancy and a singleton, cephalic presenting fetus. The comparator was all planned vaginal births beyond 39(+1/7) weeks, whether or not labour was induced. Binary and multinomial multiple logistic regressions adjusting for multiple confounders were performed. RESULTS: There were 2388 and 15 259 women in the study and comparison groups respectively. Induction of labour was associated with caesarean delivery overall only for women <25 years of age (adjusted odds ratio 1.63; 95% CI 1.17-2.27) and was not associated with caesarean delivery for slow progress. Induction of labour was positively associated with increased caesarean delivery for suspected fetal compromise among young women (<30 years), with the association weakening as maternal age increased. The association between induction of labour and caesarean delivery was different for slow progress compared with suspected compromise (P = 0.005). CONCLUSIONS: Induction of labour has different effects on the likelihood of caesarean delivery for slow progress and for suspected fetal compromise. Women <30 years of age are at higher risk of caesarean delivery for suspected fetal compromise, potentially due to uterine hyperstimulation.

Outcomes of induction of labour in nulliparous women at 38 to 39 weeks pregnancy by clinical indication: An observational study.

BACKGROUND: Knowledge of the outcomes of induction of labour for different indications is sparse. AIMS: To describe the mode of birth and other outcomes for nulliparous women induced at 38-39 weeks gestational age by indication for induction of labour. MATERIAL AND METHODS: This was a retrospective observational study in a tertiary referral hospital, and a metropolitan teaching hospital in Sydney. The study population was nulliparous women with induction of labour at 38 or 39 completed weeks of pregnancy and a singleton, cephalic presenting baby planning a vaginal birth, from 2009 to 2016. The indication for induction of labour was classified into 12 groups. Mode of birth and other maternal and perinatal outcomes were described in each group, for women who spontaneously laboured at 38 or 39 weeks, and for women who gave birth from 40 completed weeks onward. The main outcome measure was mode of birth. RESULTS: There were 3330 women with induction of labour at 38 or 39 weeks gestation. Rates of vaginal birth varied widely, ranging from 54% when the indication for induction was suspected large fetus, to 82% when the indication was suspected fetal compromise, and was 74% overall. Indications for caesarean delivery also varied by indication for induction. Among women giving birth ≥40 weeks gestational age, 75% had a vaginal birth. CONCLUSIONS: In nulliparous women, rates of vaginal birth following induction of labour at 38 or 39 weeks gestation vary widely according to the indication for induction. These data are useful for antenatal counselling.

Patients' experiences of diagnosis and management of papillary thyroid microcarcinoma: a qualitative study.

BACKGROUND: In recent years management practices in relation to low-risk papillary microcarcinoma (PMC) have been evolving with increased awareness of the potential overdiagnosis and overtreatment of PMCs, and guidelines recommendations for non-surgical management options such as active surveillance. This study aimed to develop an in-depth understanding of patients' experiences of the communication of their PMC diagnosis, their treatment preferences and decision making. METHODS: Semi-structured qualitative interviews with 25 patients diagnosed pre-operatively with PMC < 1 year since their diagnosis and treatment. Interviews were conducted between September 2015 and July 2016 and were audio-recorded and transcribed verbatim. Framework analysis method was used to analyse the data. RESULTS: The diagnosis and treatment experience of PMC patients varied widely. The majority of patients were asymptomatic, and their PMC was initially detected via an imaging test requested for a reason unrelated to a thyroid disorder or symptom. Clinicians generally described PMC to patients as being a "small" or "slow-growing" cancer, and there was little evidence that clinicians had discussions about the possibility of overdiagnosis or overtreatment. Overall, surgery was the only option discussed and offered to patients. Patients preference for treatment was largely based on eliminating the possibility of the cancer spreading (thyroidectomy) or not wanting to be on thyroid replacement medication for the rest of their life (hemi-thyroidectomy). Many patients reported emotional and physical side-effects associated with their diagnosis and treatment, however patients generally indicated that active surveillance is not something they would have been interested in if it was offered to them. CONCLUSIONS: Evidence continues to emerge that many patients with PMCs may be overdiagnosed, and management guidelines are recommending more conservative management options for these patients. As a result, shared decision making around treatment options is vital so that patients are fully aware of the meaning of their diagnosis and their management options including active surveillance. Importantly, interventions to reduce unnecessary diagnoses of PMC are critically needed.

Population attributable fractions of perinatal outcomes for nulliparous women associated with overweight and obesity, 1990-2014.

OBJECTIVE: To examine the prevalence across 25 years of overweight and obesity among nulliparous Australian women during early pregnancy; to estimate the proportions of adverse perinatal outcomes attributable to overweight and obesity in this population. DESIGN: Cohort study; retrospective analysis of electronic maternity data. Setting, participants: 42 582 nulliparous women with singleton pregnancies giving birth at the Royal Prince Alfred Hospital, an urban teaching hospital in Sydney, January 1990 - December 2014. MAIN OUTCOME MEASURES: Maternal body mass index (BMI), socio-demographic characteristics, and selected maternal, birth and neonatal outcomes; the proportion of adverse perinatal outcomes that could be averted by reducing the prevalence of overweight and obesity in women prior to first pregnancies (population attributable fraction, PAF). RESULTS: The prevalence of overweight among nulliparous pregnant women increased from 12.7% (1990-1994) to 16.4% (2010-2014); the prevalence of obesity rose from 4.8% to 7.3% in the same period, while the proportion with normal range BMIs fell from 73.5% to 68.2%. The PAFs for key adverse maternal and neonatal outcomes increased across the study period; during 2010-2014, 23.8% of pre-eclampsia, 23.4% of fetal macrosomia, and 17.0% of gestational diabetes were attributable to overweight and obesity. Were overweight and obese women to have moved down one BMI category during 2010-2014, 19% of pre-eclampsia, 15.9% of macrosomia, 14.2% of gestational diabetes, 8.5% of caesarean deliveries, 7.1% of low for gestational age birthweight, 6.8% of post partum haemorrhage, 6.5% of admissions to special care nursery, 5.8% of prematurity, and 3.8% of fetal abnormality could have been averted. CONCLUSIONS: Over the past 25 years, the proportions of adverse perinatal outcomes attributable to overweight and obesity have risen with the increasing prevalence of maternal overweight and obesity. A substantial proportion of these outcomes might be averted with obesity prevention strategies that reduce pre-pregnancy maternal weight.

Impact of extending screening mammography to older women: Information to support informed choices.

From 2013 through 2017, the Australian national breast cancer screening programme is gradually inviting women aged 70-74 years to attend screening, following a policy decision to extend invitations to older women. We estimate the benefits and harms of the new package of biennial screening from age 50-74 compared with the previous programme of screening from age 50-69. Using a Markov model, we applied estimates of the relative risk reduction for breast cancer mortality and the risk of overdiagnosis from the Independent UK Panel on Breast Cancer Screening review to Australian breast cancer incidence and mortality data. We estimated screening specific outcomes (recalls for further imaging, biopsies, false positives, and interval cancer rates) from data published by BreastScreen Australia. When compared with stopping at age 69, screening 1,000 women to age 74 is likely to avert one more breast cancer death, with an additional 78 women receiving a false positive result and another 28 women diagnosed with breast cancer, of whom eight will be overdiagnosed and overtreated. The extra 5 years of screening results in approximately 7 more overdiagnosed cancers to avert one more breast cancer death. Thus extending screening mammography in Australia to older women results in a less favourable harm to benefit ratio than stopping at age 69. Supporting informed decision making for this age group should be a public health priority.

Trends in stage-specific breast cancer incidence in New South Wales, Australia: insights into the effects of 25 years of screening mammography.

PURPOSE: Screening mammography aims to improve breast cancer (BC) prognosis by increasing the incidence of early-stage tumours in order to decrease the incidence of late-stage cancer, but no reports have investigated these potential effects in an Australian population. Therefore we aimed to identify temporal trends in stage-specific BC in New South Wales (NSW), Australia, between 1972 and 2012. METHODS: An observational study of women who received a diagnosis of BC from 1972-2012 as recorded in the NSW Cancer Registry, a population-based registry with almost complete coverage and high rates of histological verification. We analysed trends in stage-specific incidence before screening and compared them to periods after screening began. Our primary group of interest was women in the target age range of 50-69 years, though trends in women outside the target age were also assessed. RESULTS: Screening was not associated with lower incidence of late-stage BC at diagnosis. Incidence for all stages remained higher than prescreening levels. In women aged 50-69 years, the incidence of carcinoma in situ (CIS), localised and regional BC has more than doubled compared to the prescreening era, with incidence rate ratios ranging from 2.0 for regional (95% CI 1.95-2.13) to 121.8 for CIS (95% CI 82.58-179.72). Before the introduction of screening, there was a downward trend in distant metastatic BC incidence, and after the introduction of screening there was an increase (IRR 1.8; 95% CI 1.62-2.00). In women too young to screen the incidence of late-stage BC at diagnosis also increased, whereas localised disease was stable. CONCLUSIONS: The incidence of all stages of BC has increased over the past 40 years, with the greatest rise seen during the established screening period for women aged 50-69 years. Our findings suggest that some of the expected benefits of screening may not have been realised and are consistent with overdiagnosis.

Prevalence of incidental breast cancer and precursor lesions in autopsy studies: a systematic review and meta-analysis.

BACKGROUND: Autopsy studies demonstrate the prevalence pool of incidental breast cancer in the population, but estimates are uncertain due to small numbers in any primary study. We aimed to conduct a systematic review of autopsy studies to estimate the prevalence of incidental breast cancer and precursors. METHODS: Relevant articles were identified through searching PubMed and Embase from inception up to April 2016, and backward and forward citations. We included autopsy studies of women with no history of breast pathology, which included systematic histological examination of at least one breast, and which allowed calculation of the prevalence of incidental breast cancer or precursor lesions. Data were pooled using logistic regression models with random intercepts (non-linear mixed models). RESULTS: We included 13 studies from 1948 to 2010, contributing 2363 autopsies with 99 cases of incidental cancer or precursor lesions. More thorough histological examination (≥20 histological sections) was a strong predictor of incidental in-situ cancer and atypical hyperplasia (OR = 126·8 and 21·3 respectively, p < 0·001), but not invasive cancer (OR = 1·1, p = 0·75). The estimated mean prevalence of incidental cancer or precursor lesion was 19·5% (0·85% invasive cancer + 8·9% in-situ cancer + 9·8% atypical hyperplasia). CONCLUSION: Our systematic review in ten countries over six decades found that incidental detection of cancer in situ and breast cancer precursors is common in women not known to have breast disease during life. The large prevalence pool of undetected cancer in-situ and atypical hyperplasia in these autopsy studies suggests screening programs should be cautious about introducing more sensitive tests that may increase detection of these lesions.

"Standard Care" in Cancer Clinical Trials: An Analysis of Care Provided to Women in the Control Arms of Breast Cancer Clinical Trials.

Background: For trials to validly evaluate new treatments, comparison against the best existing alternative treatment is essential. We reviewed the care provided to women in control arms of breast cancer clinical trials to estimate the proportion consistent with the standard of care as defined in clinical guidelines. Methods: We analyzed phase III randomized controlled breast cancer trials comparing drug treatments with "standard care," enrolling between 2004 and 2014, and registered on ClinicalTrials.gov Our primary outcome was the proportion of trials in which treatment in the control arm was consistent with concurrent NCCN Guidelines. A secondary analysis assessed trials recruiting outside the United States that provided control group therapy not consistent with NCCN Guidelines, comparing them with the German Gynecological Oncology Group (AGO) guidelines. We assessed associations between the primary outcome and a priori selected trial characteristics. Results: This study included 210 trials that recruited 229,182 women worldwide; 29% of trials (60/210) did not provide control group treatment that was consistent with NCCN Guidelines. For trials not recruiting in the United States, results were similar; in 21% of trials, control arm treatment was inconsistent with both AGO and NCCN Guidelines. Factors significantly associated with offering control arm treatment that were inconsistent with guidelines were time period (later trials were less likely to be consistent), breast cancer stage and type (trials in early-stage breast cancer and estrogen receptor-negative disease were less likely consistent), and recruitment in ≥4 countries and recruitment outside the United States. Conclusions: To ensure that clinical trials achieve their goal of obtaining the best information to guide patient treatment, the question of how investigators chose and describe "standard care" for control arm participants warrants further investigation.