Using the Behaviour Change Wheel to identify barriers and targeted strategies to improve adherence in randomised clinical trials: The example of MEL-SELF trial of patient-led surveillance for melanoma.

BACKGROUND: Adherence to self-management interventions is critical in both clinical settings and trials to ensure maximal effectiveness. This study reports how the Behaviour Change Wheel may be used to assess barriers to self-management behaviours and develop strategies to maximise adherence in a trial setting (the MEL-SELF trial of patient-led melanoma surveillance). METHODS: The Behaviour Change Wheel was applied by (i) using the Capability, Opportunity, Motivation-Behaviour (COMB) model informed by empirical and review data to identify adherence barriers, (ii) mapping identified barriers to corresponding intervention functions, and (iii) identifying appropriate behaviour change techniques and developing potential solutions using the APEASE (Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side-effects and safety, Equity) criteria. RESULTS: The target adherence behaviour was defined as conducting a thorough skin self-examination and submitting images for teledermatology review. Key barriers identified included: non-engaged skin check partners, inadequate planning, time constraints, low self-efficacy, and technological difficulties. Participants' motivation was positively influenced by perceived health benefits and negatively impacted by emotional states such as anxiety and depression. We identified the following feasible interventions to support adherence: education, training, environmental restructuring, enablement, persuasion, and incentivisation. Proposed solutions included action planning, calendar scheduling, alternative dermatoscopes, optimised communication, educational resources in various formats to boost self-efficacy and motivation and optimised reminders (which will be evaluated in a Study Within A Trial (SWAT)). CONCLUSION: The Behaviour Change Wheel may be used to improve adherence in clinical trials by identifying barriers to self-management behaviours and guiding development of targeted strategies.

Breast Cancer Stage and Size Detected with Film versus Digital Mammography in New South Wales, Australia: A Population-Based Study Using Routinely Collected Data.

BACKGROUND: Digital mammography has replaced film mammography in breast-screening programs globally, including Australia. This led to an increase in the rate of detection, but whether there was increased detection of clinically important cancers is uncertain. METHODS: In this population-wide retrospective cohort study in New South Wales, Australia spanning 2004 to 2016 and including 4,631,656 screens, there were 22,965 cancers in women screened with film (n = 11,040) or digital mammography (n = 11,925). We examined the change in tumor characteristics overall and how these rates changed over time, accounting for changes in background rates using an interrupted time-series. Comparisons were made with unscreened women (n = 26,326) during this time. RESULTS: We found increased detection of in situ cancer (3.36 per 10,000 screens), localized invasive, and smaller-sized breast cancers attributable to the change in mammography technology, whereas screen-detected intermediate-sized and metastatic breast cancers decreased. Rates of early-stage and intermediate-sized interval cancers increased, and late-stage (-1.62 per 10,000 screens) and large interval cancers decreased. In unscreened women, there were small increases in the temporal trends of cancers across all stages. CONCLUSIONS: At least some of the increased detection of smaller early-stage cancers may have translated into a reduction in larger and late-stage cancers, indicating beneficial detection of cancers that would have otherwise progressed. However, the increased detection of smaller early-stage and small cancers may also have increased over-diagnosis of lesions that would otherwise have not caused harm. IMPACT: Robust evaluation of potential benefits and harms is needed after changes to screening programs. See related In the Spotlight, p. 638.

Acceptability of a Hypothetical Reduction in Routinely Scheduled Clinic Visits Among Patients With History of a Localized Melanoma (MEL-SELF): Pilot Randomized Clinical Trial.

BACKGROUND: After treatment for a localized melanoma, patients attend routinely scheduled clinics to monitor for new primary or recurrent melanoma. Patient-led surveillance (skin self-examination with patient-performed teledermoscopy) is an alternative model of follow-up that could replace some routinely scheduled visits. OBJECTIVE: This study aims to assess the acceptability of a hypothetical reduction in routinely scheduled visits among participants of the Melanoma Self Surveillance (MEL-SELF) pilot randomized clinical trial of patient-led surveillance (intervention) versus usual care (control). METHODS: Patients previously treated for localized melanoma in New South Wales who were participating in the MEL-SELF pilot randomized clinical trial were asked to respond to a web-based questionnaire at baseline and after 6 months on trial. We used mixed methods to analyze the data. The main outcome of interest was the acceptability of a hypothetical reduction in routinely scheduled visits for melanoma surveillance. RESULTS: Of 100 randomized participants, 87 answered the questionnaire at baseline, 66 answered the questionnaire at 6 months, and 79 provided a free-text explanation at either time point. At 6 months, 33% (17/51) of the control group and 35% (17/49) of the intervention group indicated that a hypothetical reduction in routinely scheduled visits with all melanoma doctors was at least slightly acceptable (difference in proportions -1%, 95% CI -20% to 17%; P=.89). Participants suggested that prerequisites for a reduction in routinely scheduled visits would include that sufficient time had elapsed since the previous diagnosis without a new primary melanoma or recurrence, an unscheduled appointment could be made at short notice if the patient noticed something concerning, their melanoma doctor had suggested reducing their clinic visit frequency, and patients had confidence that patient-led surveillance was a safe and effective alternative. Participants suggested that a reduction in routinely scheduled visits would not be acceptable where they perceived a very high risk of new or recurrent melanoma, low self-efficacy in skin self-examination and in the use of technologies for the patient-led surveillance intervention, and where they had a preference for clinician-led surveillance. Some patients said that a partial reduction to once a year may be acceptable. CONCLUSIONS: Some patients may be receptive to a reduction in routinely scheduled visits if they are assured that patient-led surveillance is safe and effective. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001716459; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371865&isReview=true; ClinicalTrials.gov NCT03581188; https://clinicaltrials.gov/ct2/show/NCT03581188. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1001/jamadermatol.2021.4704.

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.

Strategies to Improve Adherence to Skin Self-examination and Other Self-management Practices in People at High Risk of Melanoma: A Scoping Review of Randomized Clinical Trials.

Importance: Adherence, both in research trials and in clinical practice, is crucial to the success of interventions. There is limited guidance on strategies to increase adherence and the measurement and reporting of adherence in trials of melanoma self-management practices. Objective: This scoping review aimed to describe (1) strategies to improve adherence to self-management practices in randomized clinical trials of people at high risk of melanoma and (2) measurement and reporting of adherence data in these trials. Evidence Review: Four databases, including MEDLINE, Embase, CENTRAL, and CINAHL, were searched from inception to July 2022. Eligible studies were randomized clinical trials of self-monitoring interventions for early detection of melanoma in people at increased risk due to personal history (eg, melanoma, transplant, dysplastic naevus syndrome), family history of melanoma, or as determined by a risk assessment tool or clinical judgment. Findings: From 939 records screened, 18 eligible randomized clinical trials were identified, ranging in size from 40 to 724 participants, using a range of adherence strategies but with sparse evidence on effectiveness of the strategies. Strategies were classified as trial design (n = 15); social and economic support (n = 5); intervention design (n = 18); intervention and condition support (n = 10); and participant support (n = 18). No strategies were reported for supporting underserved groups (eg, people who are socioeconomically disadvantaged, have low health literacy, non-English speakers, or older adults) to adhere to self-monitoring practices, and few trials targeted provider (referring to both clinicians and researchers) adherence (n = 5). Behavioral support tools included reminders (n = 8), priority-setting guidance (n = 5), and clinician feedback (n = 5). Measurement of adherence was usually by participant report of skin self-examination practice with some recent trials of digital interventions also directly measuring adherence to the intervention through website or application analytic data. Reporting of adherence data was limited, and fewer than half of all reports mentioned adherence in their discussion. Conclusions and Relevance: Using an adaptation of the World Health Organization framework for clinical adherence, this scoping review of randomized clinical trials identified key concepts as well as gaps in the way adherence is approached in design, conduct, and reporting of trials for skin self-examination and other self-management practices in people at high risk of melanoma. These findings may usefully guide future trials and clinical practice; evaluation of adherence strategies may be possible using a Study Within A Trial (SWAT) framework within host trials.

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.

Exploring the Integration of Environmental Impacts in the Cost Analysis of the Pilot MEL-SELF Trial of Patient-Led Melanoma Surveillance.

AIMS: Human health is intrinsically linked with planetary health. But planetary resources are currently being degraded and this poses an existential threat to human health and the sustainability of our healthcare systems. The aims of this study were to (1) describe an approach to integrate environmental impacts in a cost analysis; and (2) demonstrate this approach by estimating select environmental impacts alongside traditional health system and other costs using the example of the pilot MEL-SELF randomised controlled trial of patient-led melanoma surveillance. METHODS: Economic costs were calculated alongside a randomised trial using standard cost analysis methodology from a societal perspective. Environmental impacts were calculated using a type of carbon footprinting methodology called process-based life cycle analysis. This method considers three scopes of carbon emissions: Scope 1, which occur directly from the intervention; Scope 2, which occur indirectly from the intervention's energy use; and Scope 3, which occur indirectly because of the value chain of the intervention. In this study we only included emissions from patient transport to attend their melanoma clinic over the study period of 6 months. RESULTS: The environmental impact per participant across allocated groups for patient transport to their melanoma clinic was estimated to be 10 kg carbon dioxide equivalent. Economic costs across the allocated groups indicated substantial health system costs, out-of-pocket costs, and productivity losses associated with melanoma surveillance. The largest cost contributor was health system costs, and the most expensive category of health system cost was hospital admission. CONCLUSION: Calculating environmental impacts is worthwhile and feasible within a cost analysis framework. Further work is needed to address outstanding conceptual and practical issues so that a comprehensive assessment of environmental impacts can be considered alongside economic costs in health technology assessments.

Considerations for Evaluating the Introduction of New Cancer Screening Technology: Use of Interval Cancers to Assess Potential Benefits and Harms.

This framework focuses on the importance of the consideration of the downstream intermediate and long-term health outcomes when a change to a screening program is introduced. The authors present a methodology for utilising the relationship between screen-detected and interval cancer rates to infer the benefits and harms associated with a change to the program. A review of the previous use of these measures in the literature is presented. The framework presents other aspects to consider when utilizing this methodology, and builds upon an existing framework that helps researchers, clinicians, and policy makers to consider the impacts of changes to screening programs on health outcomes. It is hoped that this research will inform future evaluative studies to assess the benefits and harms of changes to screening programs.

Including Information on Overdiagnosis in Shared Decision Making: A Review of Prostate Cancer Screening Decision Aids.

Background. Overdiagnosis is an accepted harm of cancer screening, but studies of prostate cancer screening decision aids have not examined provision of information important in communicating the risk of overdiagnosis, including overdiagnosis frequency, competing mortality risk, and the high prevalence of indolent cancers in the population. Methods. We undertook a comprehensive review of all publicly available decision aids for prostate cancer screening, published in (or translated to) the English language, without date restrictions. We included all decision aids from a recent systematic review and screened excluded studies to identify further relevant decision aids. We used a Google search to identify further decision aids not published in peer reviewed medical literature. Two reviewers independently screened the decision aids and extracted information on communication of overdiagnosis. Disagreements were resolved through discussion or by consulting a third author. Results. Forty-one decision aids were included out of the 80 records identified through the search. Most decision aids (n = 32, 79%) did not use the term overdiagnosis but included a description of it (n = 38, 92%). Few (n = 7, 17%) reported the frequency of overdiagnosis. Little more than half presented the benefits of prostate cancer screening before the harms (n = 22, 54%) and only 16, (39%) presented information on competing risks of mortality. Only 2 (n = 2, 5%) reported the prevalence of undiagnosed prostate cancer in the general population. Conclusion. Most patient decision aids for prostate cancer screening lacked important information on overdiagnosis. Specific guidance is needed on how to communicate the risks of overdiagnosis in decision aids, including appropriate content, terminology and graphical display. Highlights: Most patient decision aids for prostate cancer screening lacks important information on overdiagnosis.Specific guidance is needed on how to communicate the risks of overdiagnosis.

Prevalence of Subclinical Papillary Thyroid Cancer by Age: Meta-analysis of Autopsy Studies.

CONTEXT: It is not known how underlying subclinical papillary thyroid cancer (PTC) differs by age. This meta-analysis of autopsy studies investigates how subclinical PTC prevalence changes over the lifetime. METHODS: We searched PubMed, Embase, and Web of Science databases from inception to May 2021 for studies that reported the prevalence of PTC found at autopsy. Two investigators extracted the number of subclinical PTCs detected in selected age groups and extent of examination. A quality assessment tool was used to assess bias. Logistic regression models with random intercepts were used to pool the age-specific subclinical PTC prevalence estimates. RESULTS: Of 1773 studies screened, 16 studies with age-specific data met the inclusion criteria (n = 6286 autopsies). The pooled subclinical PTC prevalence was 12.9% (95% CI 7.8-16.8) in whole gland and 4.6% (2.5- 6.6) in partial gland examination. Age-specific prevalence estimates were ≤40 years, 11.5% (6.8-16.1); 41-60 years, 12.1% (7.6-16.5); 61-80 years, 12.7% (8-17.5); and 81+ years, 13.4% (7.9-18.9). Sex did not affect age-specific prevalence and there was no difference in prevalence between men and women in any age group. In the regression model, the OR of prevalence increasing by age group was 1.06 (0.92-1.2, P = .37). CONCLUSION: This meta-analysis shows the prevalence of subclinical PTC is stable across the lifespan. There is not a higher subclinical PTC prevalence in middle age, in contrast to higher observed incidence rates in this age group. These findings offer unique insights into the prevalence of subclinical PTC and its relationship to age.

Can patient-led surveillance detect subsequent new primary or recurrent melanomas and reduce the need for routinely scheduled follow up? Statistical analysis plan for the MEL-SELF randomised controlled trial.

BACKGROUND: The MEL-SELF trial is a randomised controlled trial of patient-led surveillance compared to clinician-led surveillance in people treated for localised cutaneous melanoma (stage 0, I, II). The primary trial aim is to determine if patient led-surveillance compared to clinician-led surveillance increases the proportion of participants who are diagnosed with a new primary or recurrent melanoma at a fast-tracked unscheduled clinic visit. The secondary outcomes include time to diagnosis of any skin cancer, psychosocial outcomes, acceptability, and resource use. OBJECTIVE: The objective of this report is to outline and publish the pre-determined statistical analysis plan before the database lock and the start of analysis. METHODS/DESIGN: The statistical analysis plan describes the overall analysis principles, including how participants will be included in each analysis, the presentation of the results, adjustments for covariates, the primary and secondary outcomes, and their respective analyses. In addition, we present the planned sensitivity and subgroup analyses. A separate analysis plan will be published for health economic outcomes. RESULTS: The MEL-SELF statistical analysis plan has been designed to minimize bias in estimating effects of the intervention on primary and secondary outcomes. By pre-specifying analyses, we ensure the study's integrity and believability while enabling the reproducibility of the final analysis. CONCLUSION: This detailed statistical analysis plan will help to ensure transparency of reporting of results from the MEL-SELF trial. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864. Registered 18 February 2021, https://www.anzctr.org.au/ACTRN12621000176864.aspx.

What is the prevalence of fear of cancer recurrence in cancer survivors and patients? A systematic review and individual participant data meta-analysis.

OBJECTIVE: Care for fear of cancer recurrence (FCR) is considered the most common unmet need among cancer survivors. Yet the prevalence of FCR and predisposing factors remain inconclusive. To support targeted care, we provide a comprehensive overview of the prevalence and severity of FCR among cancer survivors and patients, as measured using the short form of the validated Fear of Cancer Recurrence Inventory (FCRI-SF). We also report on associations between FCR and clinical and demographic characteristics. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we included all studies that used the FCRI-SF with adult (≥18 years) cancer survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. RESULTS: IPD were requested from 87 unique studies and provided for 46 studies comprising 11,226 participants from 13 countries. 9311 respondents were included for the main analyses. On the FCRI-SF (range 0-36), 58.8% of respondents scored ≥13, 45.1% scored ≥16 and 19.2% scored ≥22. FCR decreased with age and women reported more FCR than men. FCR was found across cancer types and continents and for all time periods since cancer diagnosis. CONCLUSIONS: FCR affects a considerable number of cancer survivors and patients. It is therefore important that healthcare providers discuss this issue with their patients and provide treatment when needed. Further research is needed to investigate how best to prevent and treat FCR and to identify other factors associated with FCR. The protocol was prospectively registered (PROSPERO CRD42020142185).

Trends in Prostate Specific Antigen (PSA) testing and prostate cancer incidence and mortality in Australia: A critical analysis.

BACKGROUND: Population trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them. METHODS: We calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45-74, 75-84, and 85 + years. RESULTS: PSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45-84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45-84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45-74 years remained low throughout. Mortality in men 75-84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised. CONCLUSION: Age specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing.

Assessing the Potential for Patient-led Surveillance After Treatment of Localized Melanoma (MEL-SELF): A Pilot Randomized Clinical Trial.

IMPORTANCE: Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. OBJECTIVE: To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had been routinely attending scheduled follow-up visits. The study was conducted from November 1, 2018, to January 17, 2020, with analysis performed from September 1, 2020, to November 15, 2020. INTERVENTION: Participants were randomized (1:1) to 6 months of patient-led surveillance (the intervention comprised usual care plus reminders to perform SSE, patient-performed dermoscopy, teledermatologist assessment, and fast-tracked unscheduled clinic visits) or clinician-led surveillance (the control was usual care). MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of eligible and contacted patients who were randomized. Secondary outcomes included patient-reported outcomes (eg, SSE knowledge, attitudes, and practices, psychological outcomes, other health care use) and clinical outcomes (eg, clinic visits, skin surgeries, subsequent new primary or recurrent melanoma). RESULTS: Of 326 patients who were eligible and contacted, 100 (31%) patients (mean [SD] age, 58.7 [12.0] years; 53 [53%] men) were randomized to patient-led (n = 49) or clinician-led (n = 51) surveillance. Data were available on patient-reported outcomes for 66 participants and on clinical outcomes for 100 participants. Compared with clinician-led surveillance, patient-led surveillance was associated with increased SSE frequency (odds ratio [OR], 3.5; 95% CI, 0.9 to 14.0) and thoroughness (OR, 2.2; 95% CI, 0.8 to 5.7), had no detectable adverse effect on psychological outcomes (fear of cancer recurrence subscale score; mean difference, -1.3; 95% CI, -3.1 to 0.5), and increased clinic visits (risk ratio [RR], 1.5; 95% CI, 1.1 to 2.1), skin lesion excisions (RR, 1.1; 95% CI, 0.6 to 2.0), and subsequent melanoma diagnoses and subsequent melanoma diagnoses (risk difference, 10%; 95% CI, -2% to 23%). New primary melanomas and 1 local recurrence were diagnosed in 8 (16%) of the participants in the intervention group, including 5 (10%) ahead of routinely scheduled visits; and in 3 (6%) of the participants in the control group, with none (0%) ahead of routinely scheduled visits (risk difference, 10%; 95% CI, 2% to 19%). CONCLUSIONS AND RELEVANCE: This pilot of a randomized clinical trial found that patient-led surveillance after treatment of localized melanoma appears to be safe, feasible, and acceptable. Experiences from this pilot study have prompted improvements to the trial processes for the larger trial of the same intervention. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12616001716459.

Rethinking Low-Risk Papillary Thyroid Cancers < 1cm (Papillary Microcarcinomas): An Evidence Review for Recalibrating Diagnostic Thresholds and/or Alternative Labels.

Background: Recalibrating diagnostic thresholds or using alternative labels may mitigate overdiagnosis and overtreatment of papillary microcarcinoma (mPTC). We aimed at identifying and collating relevant epidemiological evidence on mPTC, to assess the case for recalibration and/or new labels. Methods: We searched EMBASE and PubMed databases from inception to December 2020 for natural history, autopsy, diagnostic drift, and diagnostic reproducibility studies. Where a relevant systematic review was pre-identified, only new articles were additionally included. Non-English articles were excluded. One author screened titles and abstracts. Two authors screened full text articles, performed quality assessments, and extracted data. We undertook narrative synthesis of included evidence (pooled estimates from systematic reviews and single estimates from primary studies). Results: One systematic review of patients undergoing active surveillance found that after 5 years of follow-up, 5.3% (95% confidence interval [CI 4.4-6.4%]) of the mPTC lesions had increased in size by ≥3 mm, and 1.6% [CI 1.1-2.4%] of patients had lymph node metastases. Among 7 new primary studies (including 3 updates on 2 studies included in the systematic review), 1-5% of patients undergoing active surveillance had lymph node metastases after a median follow-up of 1-10 years. One systematic review found that subclinical thyroid cancer incidentally discovered at autopsy is relatively common, with a pooled prevalence of 11.2% [CI 6.7-16.1%] among studies that examined the whole thyroid. Four diagnostic drift studies evaluated the new classification of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Three studies of cases previously diagnosed as papillary thyroid cancer found 1.3-2.3% were reclassified as NIFTP (reclassifications were from follicular variation of papillary thyroid cancer [FVPTC]). One study of 48 cases previously diagnosed as mPTC found that 23.5% were reclassified as NIFTP. Thirteen reproducibility studies of papillary thyroid lesions found substantial variation in the histopathological diagnosis of thyroid lesions, including FVPTC and NIFTP classifications (no study evaluated mPTC). Conclusions: This review supports consideration of recalibrating diagnostic thresholds and/or alternative labels for low-risk mPTC.

Evaluation of Gender Inequity in Thyroid Cancer Diagnosis: Differences by Sex in US Thyroid Cancer Incidence Compared With a Meta-analysis of Subclinical Thyroid Cancer Rates at Autopsy.

Importance: Thyroid cancer is more common in women than in men, but the associated causes of these differences are not fully understood. Objective: To compare sex-specific thyroid cancer rates in the US to the prevalence of subclinical thyroid cancer at autopsy. Data Sources: Data on thyroid cancer incidence and mortality by sex among US adults (≥18 years) were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) data for 1975 to 2017. Embase, PubMed, and Web of Science databases were searched for studies on the prevalence of subclinical thyroid cancer at autopsy of men and women, from inception to May 31, 2021. Study Selection: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used to perform a systematic search for articles reporting the prevalence of subclinical thyroid cancer in autopsy results of both women and men. Of 101 studies identified, 8 studies containing 12 data sets met inclusion criteria; ie, they examined the whole thyroid gland, stated the number of thyroids examined, and reported results by sex. Excluded studies reported thyroid cancer in Japan after the atomic bombs or Chernobyl after the nuclear disaster; did not examine the whole thyroid gland or had incomplete information on thyroid examination methods; or did not report rates by sex. Data Extraction and Synthesis: Thyroid cancer incidence and mortality data by sex, histologic type, and tumor size were extracted from SEER. The inverse variance heterogeneity model was used to meta-analyze the prevalence and the odds ratio of subclinical thyroid cancer by sex from 8 studies (12 data sets) on thyroid cancer prevalence in autopsy results. Main Outcomes and Measures: Incidence and mortality of thyroid cancer, by histologic type and tumor size; prevalence of thyroid cancer in autopsy results. Results: In 2017, 90% of thyroid cancers diagnosed were papillary thyroid cancer (PTC) and in 2013 to 2017, the women to men incidence ratio for small (≤2 cm) PTC was 4.39:1. The incidence ratio approached 1:1 as cancer type lethality increased. The ratio of thyroid cancer mortality by gender was 1.02:1 and remained stable from 1992 to 2017. Results of the meta-analysis showed that the pooled autopsy prevalence of subclinical PTC was 14% in women (95% CI, 8%-20%) and 11% in men (95% CI, 5%-18%). The pooled odds ratio of subclinical PTC in women compared with men was 1.07 (95% CI, 0.80-1.42). Conclusions and Relevance: This cohort study and meta-analysis found that the belief that women get thyroid cancer more often than men is an oversimplification. The gender disparity is mostly confined to the detection of small subclinical PTCs, which are equally common in both sexes at autopsy but identified during life much more often in women than men. As the lethality of the cancer type increases, the ratio of detection by gender approaches 1:1. This phenomenon may be associated with gender differences in health care utilization and patterns of clinical thinking and can harm both women, who are subject to overdetection, and men, who may be at risk of underdetection.

Can patient-led surveillance detect subsequent new primary or recurrent melanomas and reduce the need for routinely scheduled follow-up? A protocol for the MEL-SELF randomised controlled trial.

BACKGROUND: Most subsequent new primary or recurrent melanomas might be self-detected if patients are trained to systematically self-examine their skin and have access to timely medical review (patient-led surveillance). Routinely scheduled clinic visits (clinician-led surveillance) is resource-intensive and has not been shown to improve health outcomes; fewer visits may be possible if patient-led surveillance is shown to be safe and effective. The MEL-SELF trial is a randomised controlled trial comparing patient-led surveillance with clinician-led surveillance in people who have been previously treated for localised melanoma. METHODS: Stage 0/I/II melanoma patients (n = 600) from dermatology, surgical, or general practice clinics in NSW Australia, will be randomised (1:1) to the intervention (patient-led surveillance, n = 300) or control (usual care, n = 300). Patients in the intervention will undergo a second randomisation 1:1 to polarised (n = 150) or non-polarised (n = 150) dermatoscope. Patient-led surveillance comprises an educational booklet, skin self-examination (SSE) instructional videos; 3-monthly email/SMS reminders to perform SSE; patient-performed dermoscopy with teledermatologist feedback; clinical review of positive teledermoscopy through fast-tracked unscheduled clinic visits; and routinely scheduled clinic visits following each clinician's usual practice. Clinician-led surveillance comprises an educational booklet and routinely scheduled clinic visits following each clinician's usual practice. The primary outcome, measured at 12 months, is the proportion of participants diagnosed with a subsequent new primary or recurrent melanoma at an unscheduled clinic visit. Secondary outcomes include time from randomisation to diagnosis (of a subsequent new primary or recurrent melanoma and of a new keratinocyte cancer), clinicopathological characteristics of subsequent new primary or recurrent melanomas (including AJCC stage), psychological outcomes, and healthcare use. A nested qualitative study will include interviews with patients and clinicians, and a costing study we will compare costs from a societal perspective. We will compare the technical performance of two different models of dermatoscope (polarised vs non-polarised). DISCUSSION: The findings from this study may inform guidance on evidence-based follow-up care, that maximises early detection of subsequent new primary or recurrent melanoma and patient wellbeing, while minimising costs to patients, health systems, and society. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000176864 . Registered on 18 February 2021.