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.

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.

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.

Travel health seeking behaviours, masks, vaccines and outbreak awareness of Australian Chinese travellers visiting friends and relatives - Implications for control of COVID-19.

BACKGROUND: The COVID-19 pandemic has highlighted the role of international travel in spreading infections. Travellers visiting friends and relatives (VFR) are at higher risk of acquiring infections than other travellers, therefore improving the travel health behaviour of these travellers is important. Ethnic Chinese are one of the largest migrant groups in many countries, yet there have been no published studies regarding this population as VFR travellers. We present findings of a study of Australian Chinese VFR travellers relevant to the pandemic response. METHODS: In 2013, five focus groups were conducted with Australian Chinese VFR travellers, exploring topics such as vaccines, face masks, outbreaks and travel health seeking behaviour. Participants were aged 18 years or older and had travelled to China for VFR purposes in the preceding 18 months. Sessions were recorded and transcribed, and thematic analysis was undertaken. RESULTS: Participants viewed VFR travel as low risk, and underestimated the risks associated with travelling during an outbreak. However, they were generally willing to receive pre-travel vaccination specifically for an outbreak, but not otherwise. Attitudes towards face masks and other infection control measures were mixed. Multiple factors influenced their travel health behaviour, including low risk awareness, misconceptions, and cultural barriers to seeking health care. CONCLUSION: Our research found that Chinese VFR travellers undertake suboptimal precautions related to VFR travel, associated with an underestimation of risks. While they share many characteristics with other VFR travellers, unique cultural health beliefs should be taken into account when developing risk communication and educational interventions as part of a pandemic response.

Travel health risk perceptions of Chinese international students in Australia - Implications for COVID-19.

BACKGROUND: International students frequently return to their country of origin to visit friends and relatives (VFR), and are at increased risk of travel-associated infections. Little is known of their travel health seeking behaviours. China is the biggest source of international students studying in Australia and the unprecedented epidemic of COVID-19 in China makes this an important area of research. METHODS: Focus groups of Chinese international students were conducted to explore travel health-related knowledge, attitudes and practices. Eligible participants were studying in Sydney, and had travelled to China and Hong Kong to visit friends and relatives in the preceding 18 months. A variety of topics were explored, using a focus group guide. Thematic analysis was undertaken on the transcripts using nVivo software. The list of codes and themes were not pre-determined but developed through content analysis. RESULTS: Two focus groups were held with a total of 28 participants. Risk perception about VFR travel was generally low among Chinese international students. Pre-travel healthcare was not sought. Students strongly relied on the Internet, social media, parents and friends in China for travel health advice. CONCLUSION: This research provides insights into Chinese international students as VFR travellers. It confirms students could be a risk population for importations of infections such as COVID-19 because of low risk perception and lack of seeking travel health advice. This can inform health promotion strategies for students.

Chinese travellers visiting friends and relatives--A review of infectious risks.

BACKGROUND: Travellers are potential vectors in the transmission of infectious diseases across international borders. Travellers visiting friends and relatives (VFR) have a particularly high risk of acquiring certain infections during travel. Chinese VFR travellers account for a substantial proportion of all travel in Western countries with high migrant populations. METHODS: A literature review was undertaken regarding major infectious disease risks for VFR travellers visiting China. This included an examination of the previous pandemics arising in China, the likelihood of future outbreaks in China from H5N1 and H7N9 avian influenza viruses, the potential role of travellers in disease transmission, and the special risks for VFR travellers. RESULTS: China has been the origin of several influenza pandemics in past few decades, and the origin of several emerging infectious diseases with pandemic potential, including SARS. Travel to and from China has the potential for global spread of emergent infectious diseases, as seen in the SARS outbreak in 2003. For VFR travellers, the risk of other infectious diseases may also be greater in China compared to their countries of migration, including hepatitis A and B, dengue fever, typhoid, and other diseases. CONCLUSIONS: VFR travel to China may be associated with increased risk of acquiring a range of infectious diseases, and also poses a potential risk for importation of future pandemics to other countries. Chinese VFR travellers need to be cognisant of these risks and health professionals should consider educational interventions to minimise these risks.