Cancer

In Australia, there is a paucity of coordinated strategies for preventing, detecting, and managing NAFLD

Lucy Gracen · Elizabeth E Powell

To the Editor: The broadly accepted definition of a cancer survivor recognises that the survivorship begins at diagnosis.1 However, survivorship care pathways conventionally begin at completion of active treatment, presenting a challenge for addressing survivorship needs at diagnosis and for people living with incurable cancer.2 A revision of the concept of cancer survivorship is needed, placing the survivor at the centre of a dynamic experience of life after a cancer diagnosis and opening up the survivorship experience to persons at any stage of cancer and at any phase of their disease trajectory. Until now, clinical care guidelines and models of survivorship have typically not included consumer input, but rather have been developed principally through health professional expert consensus.3,4 In a novel approach from 2019–2020, a panel of 47 experts and consumers across Australia and New Zealand came together to define six key domains of survivorship care in a Prostate Cancer Survivorship Essentials Framework:5 health promotion and advocacy, shared management, vigilance, personal agency, care coordination, and evidence‐based survivorship interventions. These six domains reached high consensus as being essential, with the 26 elements within domains all rated as high importance. Almost one‐third of the 47‐member panel were cancer survivors working collaboratively with medical, allied health and nursing expert representatives. The degree of consensus in such a broad coalition is remarkable, underscoring the validity of the approach that reflects the lived experience driven by survivors’ preferences. Importantly, the central domain related to personal agency of a survivor as a key element that linked all others (Box) and all domains were framed around outcomes that mattered for the patient (eg, empowerment, information, shared decision making, care coordination, symptom management). While the framework was developed for prostate cancer survivorship, none of the elements were unique to prostate cancer, highlighting the potential relevance of the framework to other cancers. More broadly, this approach aligns with existing models of chronic disease management and frameworks of consumer engagement in care that are fundamental to the delivery of health care in Australia and New Zealand. We believe the essentials framework is applicable to other adult cancer patient cohorts and presents an opportunity to move forward on cancer survivorship in Australia, taking forward a unique consumer–practitioner model where the survivor is not just the passive object of care but an actor in their own health and an empowered and supported agent of change. Box – Prostate Cancer Survivorship Essentials Framework

Jeff Dunn · Bogda Koczwara · Suzanne Chambers

Objectives: To evaluate the implementation and acceptability of the self‐collection cervical screening pathway since commencement of the renewed National Cervical Screening Program (rNCSP), from the perspectives of screening participants and primary care practitioners. Design, setting, participants: Qualitative study; individual semi‐structured interviews with 45 screening participants and 18 primary care practitioners in Victoria who had engaged with the self‐collection pathway during the first 17 months of the rNCSP (1 December 2017 ‒ 30 April 2019). Results: The self‐collection pathway was highly acceptable as an alternative cervical screening pathway for most participating screening participants and practitioners. Some screening participants indicated that they would not have been screened had the pathway not been available. Acceptability was lower among those who had tested positive for HPV types not 16/18, a result that requires additional testing of a clinician‐collected cervical sample. Use of the self‐collection pathway is driven more by practitioners than their patients. Interpretations of the self‐collection guidelines varied between practices. Barriers to expanding promotion of the pathway by practitioners included difficulties with identifying eligible participants. Conclusions: Increasing the accessibility of the self‐collection pathway to under‐ and never screened women could reduce inequities in cervical cancer outcomes for those not participating in the main screening pathway. Practitioners should be provided resources to integrate self‐collection into routine practice and to efficiently implement the entire self‐collection pathway, in order to maximise its use and to optimise the experience for screening participants.

Nicola S Creagh · Claire Zammit · Julia ML Brotherton · Marion Saville · Tracey McDermott · Claire Nightingale · Margaret Kelaher

A new clinical trials network aims to bridge the gap in cancer outcomes between rural and metropolitan cancer patients in Victoria

Arun Muthusamy · Donna Long · Craig R Underhill

A 56-year-old man presented with cough, dyspnoea and urinary symptoms

Michael A Cilento · Christopher M Hocking

To the Editor: In the retrospective study by te Marvelde and colleagues,1 the proportions of men in public and private health services receiving radical prostatectomy and curative external beam radiation therapy were examined in a multivariable logistic regression analysis. However, only age, International Society of Urological Pathology (ISUP) tumour grade, and comorbidity were studied. Prostate‐specific antigen (PSA) level and T stage are two of the strongest determinants of choice of treatment modality in clinical practice and have not been considered or discussed by the authors. We consider this to be a major flaw in this study and a failure of the peer‐review process to highlight this deficiency, which has a significant impact on the results and subsequent conclusions reached by the authors. Furthermore, patient comorbidities have not been adequately accounted for. The authors identify comorbidity as a factor influencing treatment, but they fail to assess and account for this variable in a reliable way. Victorian Admitted Episodes Dataset (VAED) data for the year preceding the prostate cancer diagnosis and up to 30 days after diagnosis were assessed to identify comorbid conditions other than cancer according to the Charlson Comorbidity Index, categorised as 0 or at least 1. This variable provided little discriminatory power (3% v 6%), and yet it was the only surrogate variable that accounted for comorbidity in the study’s key multivariable analyses. Additionally, the odds ratios for this variable in these analyses were not reported. It should be noted that 38% of the study population were men older than 70 years, but only 3.8% scored 1 or more on the VAED‐derived Charlson Comorbidity Index. We believe that the method used in this study to account for comorbidity is not adequately robust to provide an accurate picture of the patients’ general health status. The authors also cite the ProTect trial2 to suggest no major differences between active treatment options exist; however, they did not identify the vast differences in the disease characteristics of men in the ProTect trial compared with those included in their study (77% ISUP 1 and 2% ISUP 4/5 v 35% ISUP 1 and 18% ISUP 4/5). Moreover, te Marvelde and colleagues did not address clinical outcomes and have not presented evidence that the variation in treatment modalities between public and private services has had a negative impact on the final clinical outcome. Outcomes data can be helpful in identifying systematic shortcomings, inequities and barriers to just health care, but the authors missed the opportunity to highlight these issues. They concluded that the treatment of people with cancer should be consistent, safe, of high quality and evidence‐based, but did not provide evidence that the current practice is to the contrary.

Stephen Mark · Prem Rashid · Peter Heathcote · Kamran Zargar Shoshtari

Introduction: The Australian Council on Healthcare Standards (ACHS) sponsored an expert‐led, consensus‐driven, four‐stage process, based on a modified Delphi methodology, to determine a set of clinical indicators as quality measures of cancer service provision in Australia. This was done in response to requests from institutional health care providers seeking accreditation, which were additional and complementary to the existing radiation oncology set. The steering group members comprised multidisciplinary key opinion leaders and a consumer representative. Five additional participants constituted the stakeholder group, who deliberated on the final indicator set. Methods and recommendations: An initial meeting of the steering group scoped the high level nature of the desired set. In stage 2, 65 candidate indicators were identified by a literature review and a search of international metrics. These were ranked by survey, based on ease of data accessibility and collectability and clinical relevance. The top 27 candidates were debated by the stakeholder group and culled to a final set of 16 indicators. A user manual was created with indicators mapped to clinical codes. The indicator set was ratified by the Clinical Oncology Society of Australia and is now available for use by health care organisations participating in the ACHS Clinical Indicator Program. This inaugural cancer clinical indicator set covers high level assessment of various critical processes in cancer service provision in Australia. Regular reviews and updates will ensure usability. Changes in management as a result of this statement: This is the inaugural indicator set for cancer care for use across Australia and internationally under the ACHS Clinical Indicator Program. Multidisciplinary involvement through a modified Delphi process selected indicators representing both generic and specific aspects of care across the cancer journey pathway and will provide a functional tool to compare health care delivery across multiple settings. It is anticipated that this will drive continual improvement in cancer care provision.

Eva Segelov · Christine Carrington · Sanchia Aranda · David Currow · John R Zalcberg · Alexander G Heriot · Linda Mileshkin · John Coutsouvelis · Jeremy L Millar · Brian T Collopy · Jon D Emery · Phoebe Zhang · Simon Cooper · Carmel O’Kane · Janet Wale · Stephen J Hancock · Anthony Sulkowski · John Bashford

Screen‐detected breast cancer overdiagnosis occurs, but each woman has been diagnosed with cancer that cannot be ignored There are an increasing number of publications estimating the extent of cancer overdiagnosis, which for breast cancer is in the context of population cancer screening programs.1 Researchers investigating overdiagnosis point to a range of related harms, but it is important to view these in the context of screening benefits, such as reductions in risk of breast cancer death.2 Care needs to be taken not to conflate formal screening programs with informal or opportunistic approaches to early detection, such as prostate‐specific antigen (PSA) testing in prostate cancer. This article focuses on the risk of overdiagnosis in the context of population‐based breast screening programs, given that overdiagnosis is often at the heart of calls to cease mammographic breast cancer screening.3,4 Despite the emphasis often given to breast cancer screening in discussions of overdiagnosis, the concept should not be regarded as only applying to breast cancer screening, or to cancer screening more generally, but as an outcome that could apply, to varying degrees, to a wider range of screening and diagnostic practices. Defining overdiagnosis Overdiagnosis of a cancer is not a false positive or misdiagnosis; it is a diagnosis with histological verification of a cancer that would otherwise not have gone on to cause morbidity or death — although it cannot be determined at the time of diagnosis whether the cancer would have progressed to cause morbidity or death.5 An overdiagnosed cancer is in part a consequence of our capacity to diagnose cancers at increasingly earlier stages. It depends on competing causes of death; that is, a cancer will not cause morbidity or death in people who die beforehand from other causes, such as respiratory or cardiac diseases or trauma. The reality that a proportion of cancers will therefore be overdiagnosed is inherent in all screening programs, although the issue is not limited to screening. Major international reviews have concluded, after a careful evaluation of the balance between benefits and harms, that there is a net benefit from inviting women to receive breast screening (ie, benefits outweigh harms).2 The problem of overdiagnosis Concerns about overdiagnosis stem from the potential harms that may be experienced by a person receiving the overdiagnosis. Harms can range from the psychological stress of receiving a diagnosis through to the potential for complications and adverse effects of diagnostic procedures or treatments. However, the challenge is that for any individual, it is not possible at diagnosis to determine whether their cancer is overdiagnosed or not. The cancers that are overdiagnosed are indistinguishable from other cancers histologically. As this is a post mortem classification, cancers can only be classified as overdiagnosed when another cause of death supervenes. Estimating overdiagnosis and mortality benefits Estimates of overdiagnosis within breast cancer screening programs vary widely, and this is in part due to methodological as well as programmatic differences. Recent Australian modelling suggested that the rate of overdiagnosis across five cancers (breast, prostate, renal, thyroid and melanoma) was 18% in women and 24% in men.1 However, of these cancers, only breast cancer is part of population screening in Australia. Other studies of breast cancer overdiagnosis specifically point to much lower levels of overdiagnosis. Based on British and European reviews, Cancer Australia has estimated that for every 1000 Australian women screened for breast cancer every 2 years from age 50 to 74 years, around eight breast cancers (range, 2–21) may be found and treated which would not otherwise have been found in a woman’s lifetime.6 In addition, an equivalent number of breast cancer deaths would be avoided in these women.6 The European Screening Network (EUROSCREEN) Working Group calculated a summary estimate of overdiagnosis as about 6.5% of the expected number of diagnosed breast cancers (range, 1–10%) in screened women, based on data from studies in Europe.2 Overall, data from around the world indicate that breast screening confers an estimated reduction in breast cancer mortality of 23% in women invited for screening and 40% or more among those women who are screened.2 Cancer screening programs need to balance benefits and harms Decisions about whether to implement screening at a national level in any country should follow a comprehensive assessment of likely benefits at a population level (mortality reduction, delivery of more conservative therapy to people diagnosed with cancer via screening), harms (unnecessary treatments, psychological impacts) and costs (health service, individual out‐of‐pocket expenses, societal costs). In Australia, this principle is encapsulated in the Australian Population Based Screening Framework.7 It is well understood that some cancers are slower growing while others are more aggressive, but there are significant limits to our capacity to determine at diagnosis these characteristics at both an individual tumour and patient level. The concern, therefore, is that the potential to discourage women from breast screening through concerns of overdiagnosis would result in harms associated with later diagnosis, including deaths from breast cancer. Based on current international evidence, if left untreated, more than 90% of cancers found through routine screening would progress and become symptomatic and be potentially lethal, depending on modelling assumptions.2 Even drawing from the higher estimates of overdiagnosis, data would support that more than 70% of screen‐detected invasive cancers would progress to become symptomatic without treatment.8 These estimates are indicative of the scale of risk of developing a symptomatic breast cancer which could be detected earlier through screen detection. Screen‐detected cancers are found at an earlier stage and tend to be smaller; treatment guidelines advise less extensive surgery and reduced need for adjuvant treatments, as well as being associated with improved survival.9 Reducing the harms of overdiagnosed cancers The most readily recognised harm of overdiagnosis is overtreatment. However, overtreatment is distinct from overdiagnosis and the effects can be mitigated by promotion of evidence‐based clinical management guidelines. Significant advances have been made in tailoring treatment for breast cancer. These include advances in surgery and radiotherapy and using tumour characteristics such as oestrogen receptor, progesterone receptor, and HER2 status to tailor systemic therapies. Research is also being undertaken to investigate using active monitoring rather than surgery for ductal carcinoma in situ, as there is debate regarding the potential for this type of carcinoma, if left untreated, to progress to invasive cancer. Research is underway to determine if genomic or other molecular signals in tumours will provide clearer indications of which ductal carcinoma in situ and invasive cancers need treatment, including chemotherapy, and at what level of aggressiveness, irrespective of whether found through screening or other means.10 Advances from this research will better support women to make informed decisions about treatment. Population screening programs are offered within a policy framework that carefully considers the target population that stands to benefit from screening, including age criteria, and ongoing monitoring and reporting of sensitivity, specificity and interval cancers.7 There are also ongoing research efforts to improve the effectiveness of breast screening, including evaluation of new approaches to tailor screening to the individual woman’s risk profile to maximise benefit and minimise harms. Informed consent about breast screening needs to balance the potential harms with the demonstrated benefits of the current national screening program.

Vivienne Milch · Sanchia Aranda · Karen Canfell · Megan Varlow · David M Roder · David Currow · Cleola Anderiesz · Dorothy Keefe

An 88-year-old white woman presented with a subcutaneous mass on the left lateral brow

Tung T Hoang · Graham A Lee · Timothy J Sullivan

Improving integrated care and systematically targeting major cancer and non- cancer causes of morbidity and mortality could yield major benefits

Emily Banks · Grace Joshy

To the Editor: Hereditary cancer predisposition syndromes (HCPS) account for at least 10% of paediatric cancers.1 Li‐Fraumeni syndrome (LFS) is a dominant HCPS caused by mutations in the TP53 gene and is associated with an 80–90% lifetime risk of cancer, commencing in infancy.2 Children of affected individuals are at 50% risk of inheriting the family mutation. Surveillance programs, involving clinical review and medical imaging, are being used in paediatric populations with HCPS, as significantly higher overall survival is reported with early tumour detection.3 In 2018, the Paediatric Surveillance Clinic was established at Perth Children’s Hospital to provide surveillance for asymptomatic children with, or at 50% risk of developing, LFS and with other HCPS, and to address the needs of their families. Families with at‐risk children can choose to attend the clinic, allowing them to receive information, support and sufficient time to make a decision regarding genetic testing. The quarterly clinic is in a general paediatric setting and offers surveillance for mutation‐positive children in line with eviQ guidelines — a free resource of evidence‐based, consensus‐driven cancer treatment and genetic testing protocols hosted by Cancer Institute NSW.4 Children at 50% risk of LFS, who have not had genetic testing, receive a six‐monthly clinical review and prompt assessment of any concerning symptoms during the interim period. Over an 18‐month period, the Paediatric Surveillance Clinic has seen 11 children from five families, aged from 3 months to 14 years. Most of these children are at risk of or have a TP53 mutation and one child has a VHL (Von‐Hippel‐Lindau) mutation. The Paediatric Surveillance Clinic offers a holistic service with a multidisciplinary team consisting of a general paediatrician, a paediatric nurse, a paediatric oncologist, a genetic counsellor and a clinical geneticist. The clinic has highlighted the specific and unmet needs of families dealing with HCPS and has allowed for essential integration of genetic, paediatric and oncology services for these families.5 As the number of identified HCPS grows, the Paediatric Surveillance Clinic will continue to offer a flexible service that supports families, assisting with decisions around genetic testing and surveillance for malignancy during childhood and adolescence.

Nicholas Leedman · Murray Princehorn · Nicholas Gottardo · Claire Franklin · Rebecca D'Souza · Catherine E Kiraly‐Borri

Prostate cancer specialists working in collegiate, multidisciplinary teams are most likely to provide the best outcomes for patients

Henry H Woo · Amy Teh

Putting the patient at the core of personalised cancer care delivery remains the elusive final frontier Over 20 years ago, the Australian House of Representatives Inquiry into the management of breast cancer recommended that cancer care should be delivered using a multidisciplinary approach.1 Ten years later, an article published in this Journal articulated how to put multidisciplinary care into practice,2 paving the way for the concept to be embedded into clinical cancer practice and policy of today.3 One of the key recommendations made in the article, and since adopted as national policy, was for the patient to be included “as a member of the multidisciplinary team”. But as of today, multidisciplinary care does not routinely include input from patients themselves. Patients do not attend multidisciplinary meetings. Rather, their circumstances are discussed and treatment recommendations are made. They may subsequently make a shared decision with the clinician, but their input tends to occur after the multidisciplinary discussion and it is uncommon for the patients’ perspectives to systematically inform these discussions. Putting the patient at the core of personalised cancer care delivery thus remains the elusive final frontier. The potential benefits of such an approach are well established and include a greater alignment of care with individual patient goals, better understanding of needs, and better patient outcomes and satisfaction.4 Health care providers are poor surrogates for assessment of patients’ symptoms, needs and experiences and patient‐reported outcomes (PROs) collection is a way to systematically integrate patients’ perspectives into assessment, treatment planning, and ongoing monitoring.5 PROs report on patients’ subjective perception of health, functional status, unmet needs, and quality of life and are collected directly from patients either online, via a smartphone, or through paper‐based means. While there are many sets of questions that are relevant to any patient with cancer, specific questions can be tailored to particular cancer types, populations, or different phases of cancer trajectory.6 PROs as a concept are not new and not unique to cancer. However, while they have been used extensively in research, including clinical trials, their adoption in routine clinical care has received much less attention, with only one article on the topic published in this Journal over 10 years ago.7 This article summarises the current evidence supporting the use of PROs in cancer as an example of their potential of relevance to broader health care delivery, and argues for their routine adoption into practice. The evidence for the utility of PROs in cancer care is compelling. A single‐institution randomised controlled study of 766 patients included participants with multiple metastatic cancers and assigned them to a usual care group or a group that reported on their symptoms using an electronic portal.8 The study found that patients reporting PROs had longer survival, with a median prolongation of 5.2 months; comparable in effect size to many effective, novel cancer therapies.8 In Ontario, where PROs have been routinely collected since 2007, administrative data analysis has shown survival improvement irrespective of the phase of cancer treatment, as well as reduced hospitalisation and emergency department presentations.9 Two systematic reviews concluded there was strong evidence that implementation of PROs improves patient–provider communication and patient satisfaction.10,11 PROs are recommended by the Australian Commission on Safety and Quality in Health Care, have been advocated for by the Clinical Oncology Society of Australia, and have been included as a critical element of care in the Australian Digital Health in Cancer Care Roadmap.12 But to date, their adoption into routine clinical practice has been limited. Like multidisciplinary care 20 years ago, a significant barrier to their integration has been the ability of the health system to operationalise routine collection and response to PROs data. In 2020, we finally have technology for efficient, real‐time collection, reporting of, and response to PROs through customisable portals and dashboards and integration with the electronic medical records. But technology alone is not sufficient and its roll‐out, especially with regards to electronic medical records, has been slow and fragmented. Similar to the approach to multidisciplinary care,2 it is time to articulate the principles and outcomes necessary to integrate PROs into the routine clinical workflow (Box 1). Where multidisciplinary care called for a core team of experts, the PROs collection requires a core dataset. While a dataset using a generic PROs measure, such as the Edmonton Symptom Assessment System Revised (ESAS‐r) used in Canada, may be most appropriate for screening for unmet needs in any clinical setting, more specific measures may be required for assessment of different cancer types, different phases of disease (ie, at diagnosis v end of life) or for different populations, such as Indigenous patients.13 There is a need for a clear communication framework involving relevant heath care providers in a timely fashion, with feedback communicated to the patient. The process must be accessible to patients irrespective of technology, rurality, remoteness or language barriers. Lastly, the collection of PROs needs to be underpinned by agreed standards that clearly articulate and support the role of the patient in this process. While the barriers to adoption of PROs in clinical practice are significant,14 they are not insurmountable. System redesign may be required to integrate PROs collection and feedback into the routine workflow, with clear pathways to inform a standardised approach. PROs collection should not become an additional task but rather be considered part of a realignment of workload and services to meet patients’ needs, reduce care variation, and optimise resource utilisation. A systematic approach to identification of needs is critical to supporting self‐management, an essential component of patient care, as it assists the patient in knowing what symptoms are unexpected, what to report, and how to seek support when needed.15 Data from existing PROs systems show that rapid, real‐time feedback to health care providers facilitates timely response, reducing the likelihood of issues escalating or remaining unaddressed. In many cases, this response may only require reassurance and/or advice on self‐management, with only the more severe issues necessitating referral and/or hospital admission. With advances in technology, patients and health care providers can obtain visual summaries of trends over time that may assist further in decision making, while aggregated data derived from individual cases can be used to drive health system improvement and plan services to meet demand. Are we ready for this final frontier? PROs can become an important part of value‐based care delivery with support through relevant drivers, such as reimbursement and accreditation. But we need to build capacity through training and a community of practice to share learnings, resources and tools. Many tools already exist (Box 2), with technology fully capable to support rapid processing of data and linkage to electronic health records; although it is important to note that PROs collection can be achieved using paper‐based surveys or simple reporting such as text messaging. As we reflect on the 20 years of multidisciplinary cancer care in Australia, it is worth remembering that multidisciplinary care is not just about multidisciplinary meetings. Similarly, PROs are not just about PROs collection tools. Together, these two complementary approaches put into practice the principle of personalised care. It is the focus on the patient that enables us to realise the full potential of the multidisciplinary care through framing multidisciplinary recommendations in the context of what the patient identifies as their main issues, needs or concerns. It is time to reach this final frontier and make personalisation of cancer care through PROs an achievable standard in Australia. Box 1 – Principles of clinical use of patient‐reported outcomes (PROs) in cancer care Principle Outcome Core data Agreed core dataset appropriate for patient, population or setting Communication framework Relevant information is communicated to relevant team members in a timely fashion through agreed channels Access Systems established to ensure access for all users irrespective of distance, technology, language, literacy level, or completion method Standards of care Patients and clinicians are aware of PROs and support their use at key points in clinical care pathway through: best practice protocols; stratified alert systems; reporting framework; professional development opportunities; adequate resourcing to allow collection, scoring, review, response and feedback and re‐screening; and feedback and co‐design opportunities Patient involvement Information and education Self‐management support Feedback and co‐design opportunities Box 2 – Examples of clinical practice resources for patient‐reported outcomes (PROs) use in routine care Australian Commission on Safety and Quality in Health Care (https://www.safetyandquality.gov.au/our-work/indicators-measurement-and-reporting/patient-reported-outcome-measures) General information on PROs, including list of validated measures and guides for implementation International Consortium for Health Outcomes Management (https://www.ichom.org/) Multiple resources and standard datasets for multiple conditions including cancer Cancer Care Ontario, Patient Reported Outcomes and Symptom Management Program (https://www.cancercareontario.ca/en/cancer-care-ontario/programs/clinical-services/patient-reported-outcomes-symptom-management) A system of PROs screening for patients with cancer, including clinical pathways and guides for patients and health care providers Clinical Oncology Society of Australia, PROs Think Tank report (https://www.cosa.org.au/media/332504/cosa_pros_think_tank_report_final.pdf) An overview of evidence, current practice and recommendations for PROs uptake into cancer care in Australia

Clinical Oncology Society of Australia (COSA) Patient Reported Outcomes Working Group

Liver disease and liver cancer incidence and mortality are unacceptably high among Indigenous Australians

Jessica Howell · James S Ward · Jane Davies · Paul J Clark · Joshua S Davis

Objectives: To describe patterns of care in New South Wales for men with prostate cancer, and to ascertain factors associated with receiving different types of treatment. Design: Individual patient data record linkage study. Setting, participants: 4003 New South Wales men aged 45 years or more enrolled in the population‐based 45 and Up Study in whom prostate cancer was first diagnosed during 2006–2013. Main outcome measures: Prostate cancer treatment type received; factors statistically associated with treatment received; proportions of patients who consulted radiation oncologists prior to treatment. Results: In total, 1619 of 4003 patients underwent radical prostatectomy (40%), 893 external beam radiotherapy (EBRT) (22%), 183 brachytherapy (5%), 87 chemotherapy (2%), 373 androgen deprivation therapy alone (9%), and 848 no active treatment (21%). 205 of 1628 patients who had radical prostatectomies (13%) had radiation oncology consultations prior to surgery. Radical prostatectomy was more likely for patients aged 45–59 years, with regional stage disease, living 100 km or more from the nearest radiotherapy centre, having partners, or having private health insurance, while lower physical functioning, obesity, and living in areas of greater socio‐economic disadvantage reduced the likelihood. EBRT was more likely for patients aged 70–79 years, with non‐localised or unknown stage disease, living less than 100 km from the nearest radiotherapy centre, or not having private health insurance, while the likelihood was lower for patients aged 45–59 years or more than 80 years and for those who had several comorbid conditions. Conclusions: Men with prostate cancer were twice as likely to have radical prostatectomy as to receive EBRT, and fewer than one in seven had consulted radiation oncologists prior to prostatectomy. The treatment received was influenced by several socio‐demographic factors. Given the treatment‐specific side effects and costs, policies that affect access to different treatments for prostate cancer should be reviewed.

Mei Ling Yap · Dianne L O'Connell · David E Goldsbury · Marianne F Weber · David P Smith · Michael B Barton

To the Editor: Palliative radiotherapy is effective for symptomatic management of bone metastases in cancer patients. However, it may take 2–4 weeks after completion of radiotherapy to achieve maximal clinical response.1 Radiotherapy can be delivered as a single fraction treatment (SFRT), or over a more protracted course of multifraction treatment (MFRT).2 Randomised trials have consistently shown that SFRT and MFRT provide equally effective symptom control,3 and SFRT is associated with lower medical and societal cost,4 allowing for better health services utilisation. Hence, in patients with poor prognosis, the use of SFRT over MFRT should be encouraged to minimise the time patients spend on treatment at the end of life without compromising efficacy. Using the population‐based Victorian Cancer Registry data linked to the Victorian Radiotherapy Minimum Data Set, we evaluated the use of SFRT for bone metastases at the end of life. The study sample included all cancer patients who received radiotherapy for bone metastases between 2013 and 2016, and died within 30 days of commencing radiotherapy. The primary outcome was SFRT use and the associated factors. The Cochrane–Armitage test for trend was used to evaluate temporal changes in SFRT use over time. Logistic regression was used to evaluate factors associated with SFRT use; variables with a P value below 0.1 in univariate analyses were included in multivariate model, which employed the robust standard error, with analyses clustered on patient identifiers to allow for clustering of patients who had multiple courses of radiotherapy. The study was approved by the Austin Health Human Research Ethics Committee (LNR/18/Austin/34). A total of 1069 patients received 1359 courses of radiotherapy for bone metastases at the end of life, of which 396 courses (29%) were SFRT, and 963 (71%) were MFRT (Box). There was no significant change in SFRT use over time: from 30% in 2013 to 32% in 2016. SFRT was more commonly used closer to death: 49%, 29% and 25% of radiotherapy courses delivered within 7 days, 8–14 days, and 15–30 days of death, respectively. There were large institutional provider variations in SFRT use: 33% and 19% of radiotherapy delivered in public and private institutions, respectively. In multivariate analyses, the site of bone metastases, time between radiotherapy and death, and treatment institution type were independently associated with SFRT use. Overall, in this large Victorian population‐based study, less than one in three courses of radiotherapy for bone metastases at the end of life were SFRT, and about one in two courses of radiotherapy delivered in the last week of life were MFRT, meaning that these cancer patients spent multiple days in their final week of life receiving radiotherapy. Acknowledging that estimation of prognosis towards the end of life can be difficult, there are models (eg, the TEACHH model)5 that can be useful in guiding clinicians in this process. Nonetheless, given the large body of evidence supporting the use of SFRT for bone metastases, there is a need to raise awareness of the recommendation to use of SFRT instead of MFRT, especially at the end of life, among radiation oncologists, other health professionals and patients. This can be achieved through health education initiatives such as the Choosing Wisely campaign (https://www.choosingwisely.org.au/). Box – Factors associated with single fraction palliative radiotherapy (SFRT) for bone metastases at the end of life in Victoria, 2013–2016 (1359 courses of radiotherapy) Variable SFRT (n = 396, 29%) MFRT (n = 963, 71%) Multivariate analysis (odds ratio [95%CI]) P Age (years) Mean (SD) 71.7 (11.9) 70.1 (12.3) < 60 62 (24%) 192 (76%) 1 60–69 95 (27%) 252 (73%) 1.04 (0.67–1.61) 0.9 70–79 149 (32%) 312 (68%) 1.29 (0.83–1.99) 0.3 ≥ 80 90 (30%) 207 (70%) 1.17 (0.73–1.88) 0.5 Sex Men 247 (28%) 622 (72%) Women 149 (30%) 341 (70%) Primary cancer type Lung 163 (30%) 373 (70%) Prostate 49 (29%) 118 (71%) Breast 32 (29%) 77 (71%) Gastrointestinal 53 (28%) 138 (72%) Melanoma 21 (25%) 62 (75%) Other 78 (29%) 195 (71%) Target site of radiotherapy Spine 202 (27%) 545 (73%) 1 Skull 9 (6%) 147 (94%) 0.15 (0.06–0.38) <0.001 Rib 35 (51%) 33 (49%) 3.82 (2.10–6.95) <0.001 Shoulder 35 (49%) 36 (51%) 2.80 (1.44–5.42) 0.002 Hip 19 (36%) 34 (64%) 1.67 (0.78–3.54) 0.2 Pelvic bone 20 (27%) 54 (73%) 1.10 (0.57–2.14) 0.8 Extremities 42 (52%) 39 (48%) 3.04 (1.74–5.29) <0.001 Multiple site 34 (31%) 75 (69%) 1.25 (0.73–2.14) 0.4 Time between radiotherapy start date and death 1–7 days 92 (49%) 97 (51%) 1 8–14 days 99 (29%) 246 (71%) 0.40 (0.25–0.65) < 0.001 15–30 days 205 (25%) 620 (75%) 0.33 (0.21–0.51) < 0.001 Socio‐economic status 1st quintile (most disadvantaged) 103 (35%) 194 (65%) 1 2nd quintile 63 (32%) 137 (69%) 0.88 (0.55–1.40) 0.6 3rd quintile 70 (26%) 203 (74%) 0.73 (0.46–1.17) 0.2 4th quintile 55 (22%) 194 (78%) 0.63 (0.39–1.02) 0.06 5th quintile (least disadvantaged) 105 (31%) 235 (69%) 1.00 (0.62–1.61) 0.9 Remoteness of area of residency Major city 262 (28%) 668 (72%) Inner regional 109 (31%) 241 (69%) Outer regional/ remote 25 (32%) 54 (68%) Treatment institution type Public 317 (33%) 633 (67%) 1 Private 79 (19%) 330 (81%) 0.44 (0.29–0.65) < 0.001 Treatment institution location Metropolitan 280 (27%) 746 (73%) 1 Regional 116 (35%) 217 (65%) 1.02 (0.71‐1.47) 0.9 Year of radiotherapy 2013 115 (30%) 262 (70%) 2014 93 (28%) 243 (72%) 2015 84 (26%) 241 (74%) 2016 104 (32%) 217 (68%) MFRT = multifraction radiotherapy.

Wee Loon Ong · Farshad Foroudi · Roger L Milne · Jeremy L Millar

A 49-year-old woman presented with severe dyspnoea and respiratory distress

Huizhen Fan · Lei Yu

Medicare Benefits Schedule (MBS) data indicated that there were 37% fewer screening procedures for breast cancers and 55% fewer for colorectal cancers in April than in March 2020.1 We examined the temporal relationship between coronavirus disease 2019 (COVID‐19)‐related restrictions in Victoria during 1 April – 15 October 2020 and cancer pathology notifications to the Victorian Cancer Registry (VCR), to estimate their impact on cancer diagnoses. Victorian legislation requires pathology services to notify reportable cancer diagnoses to the VCR.2 The E‐Path system, installed in all Victorian pathology services during 2013–2018,3 automatically transmits notifications to the VCR together with pathologist report authorisations. During 2019, 97 313 of 104 025 cancer pathology notifications to the VCR (94%) were received via E‐Path (data supplied by author LB). Changes to the E‐Path system during 2019 meant that we were unable to directly compare notification numbers for 2019 and 2020. We therefore modelled cancer incidence during 2014–2018 by Poisson regression. A spline function was fitted to VCR cancer incidence data for weeks 1–52, adjusted for day type (working or non‐working day/public holiday) and year, and the fitted curve used to predict daily incidence during 7 January – 15 October 2020. Predicted incidence was re‐scaled to estimate expected notification numbers; the scale factor was the number of notifications during the baseline period — 1 February – 16 March 2020, allowing a two‐week washout period before restrictions were formally announced — divided by the predicted incidence during this period. Observed and predicted notification numbers were compared using Poisson regression, with the expected number as an offset term, enabling estimation of relative reductions with 95% confidence intervals (CIs). Differences between predicted and actual notification numbers were estimated, both overall and for specific groups (eg, by tumour or age group), based on the pertinent incidence data. As a single cancer diagnosis can be associated with several pathology notifications, the number of undiagnosed cancers was estimated by multiplying the difference in notification numbers by the ratio of newly diagnosed tumours to pathology notifications in 2018 (Supporting Information, table 1). The confidence interval for the number of undiagnosed cases was based on the Poisson model, keeping the ratio of newly diagnosed tumours to pathology notifications constant. In sensitivity analyses, data were fitted to polynomial models, different baseline periods were used, or data were restricted to reportable cancer diagnoses. The study was exempted from formal ethics review by the human research ethics committee of Cancer Council Victoria. During 1 April – 15 October 2020, there were 5446 fewer notifications of new cancer diagnoses than predicted by our primary model (predicted, 54 609 v observed, 49 163; relative reduction, –10.0%; 95% CI, –10.8% to –9.2%) (Supporting Information, figure 1); we estimated that there were 2530 undiagnosed cancers (95% CI, 2327–2731). The relative reduction was greatest during 1 April – 4 May 2020 (Box 1). By tumour group, the relative reductions were most marked for prostate cancer, head and neck tumours, melanoma, and breast cancer; they were greater for men, people aged 50 years or more, and for people in areas of higher socio‐economic position (Box 2). The pattern of difference in notifications varied between tumour groups (Supporting Information, figure 2). The 6.5‐month period of COVID‐19‐related restrictions in Victoria was accompanied by a 10% reduction in cancer pathology notifications; we estimated that about 2530 cancer diagnoses were either delayed or missed. The impact of delayed diagnosis is greatest for patients with aggressive cancers. Changes in care delivery during the restrictions, including suspension of screening services and outpatient clinics and postponed surveillance of existing cancers, may have affected notification numbers for some tumour groups and consequently the estimated number of delayed diagnoses. Planning for a possible surge in cancer diagnoses over the coming 6–12 months, and media campaigns encouraging people to not further delay seeking medical attention, may ameliorate any negative impact of delayed cancer diagnosis. Box 1 – Cancer pathology notifications to the Victorian Cancer Registry, January–October 2020: observed (red) and predicted numbers (green), by day type LOESS = locally estimated scatterplot smoothing. The grey area marks the baseline period, the vertical dotted lines the analysis period for predicted notifications. A state of emergency was declared in Victoria on 16 March 2020. Stage 3 movement restrictions were applied from 30 March, eased on 13 May, and re‐applied from 8 July. The state of emergency was renewed on 2 August, together with application of stage 4 restrictions to metropolitan Melbourne until their easing from 19 October. For further details, see the footnote to figure 2 in the online Supporting Information. Box 2 – Cancer pathology notifications and estimated numbers of undiagnosed reportable cancers, 1 April – 15 October 2020* table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Notifications Relative difference (95% CI) Absolute difference (a) Tumour to notification ratio (b) Estimated number of undiagnosed tumours (a*b) Characteristic Predicted Observed All notifications 54 609 49 163 –10.0% (–10.8% to –9.2%) –5446 0.465 2530 Sex† Males 15 458 14 190 –8.2% (–9.7% to –6.7%) –1268 0.427 541 Females 10 408 10 367 –0.4% (–2.3% to 1.5%) –41 0.434 18 Age at diagnosis (years) < 50 9981 9674 –3.1% (–5.0% to –1.1%) –307 0.454 139 50–74 30 949 27 555 –11.0% (–12.0% to –9.9%) –3394 0.447 1516 ≥ 75 13 697 11 934 –12.9% (–14.4% to –11.3%) –1763 0.514 906 Tumour group Breast 7923 7130 –10.0% (–12.1% to –7.9%) –793 0.380 301 Colorectal 5063 4838 –4.4% (–7.1% to –1.7%) –225 0.501 113 Haematologic 10 011 9321 –6.9% (–8.8% to –5.0%) –690 0.234 162 Melanoma 7168 6217 –13.3% (–15.4% to –11.1%) –951 0.538 511 Lung 2967 3062 3.2% (–0.4% to 6.9%) 95 0.483 –46 Head and neck 1363 1155 –15.3% (–20.0% to –10.3%) –208 0.504 105 Bladder 2159 2009 –6.9% (–10.9% to –2.8%) –150 0.370 56 Prostate 6417 4770 –25.7% (–27.8% to –23.5%) –1647 0.560 922 All other 11 931 10 661 –10.6% (–12.3% to –8.9%) –1270 0.546 693 Socio‐economic position (quintile)‡ 1 (most disadvantaged) 10 334 9789 –5.3% (–7.1% to –3.4%) –545 0.453 247 2 10 378 9447 –9.0% (–10.8% to –7.1%) –931 0.456 425 3 10 192 9624 –5.6% (–7.4% to –3.7%) –568 0.488 277 4 10 925 9463 –13.4% (–15.1% to –11.6%) –1462 0.455 665 5 (least disadvantaged) 11 385 9714 –14.7% (–16.4% to –13.0%) –1671 0.460 769 Remoteness¶ Major cities 37 506 33 753 –10.0% (–11.0% to –9.0%) –3753 0.461 1731 Inner regional 13 414 12 031 –10.3% (–11.9% to –8.7%) –1383 0.472 652 Outer regional/remote 2553 2457 –3.8% (–7.5% to 0.1%) –96 0.472 45 CI = confidence interval. * Poisson regression (spline function, adjusted for day type [working day or non‐working day/public holiday] and year; baseline period: 1 February – 16 March 2020). † For cancers common in both sexes (melanoma, colorectal cancer, lung, head and neck cancers, haematological malignancies). ‡ Based on residential address, using the Google Geocoding API (https://developers.google.com/maps/documentation/geocoding/overview), spatially joined to Australian Bureau of Statistics Statistical Area 1 (SA1) polygons.4 Area‐based socio‐economic quintiles were based on 2016 Australian Bureau of Statistics census data.5 ¶ Accessibility and Remoteness Index of Australia.6

Luc te Marvelde · Rory Wolfe · Grant McArthur · Louis A Blake · Sue M Evans

An 81-year-old woman presented with subacute chorea as a paraneoplastic neurological syndrome

Rebecca Nothrop · Will Lee · Denise Lee · Amanda K Gilligan

A 58-year-old man presented with shortness of breath on exertion and cough.

Mike M Nguyen · Melissa M Moore

To the Editor: In 1996, two articles showed that bowel cancer screening in subjects aged 45–741 and 45–752 years, recruited in the early 1980s, led to a significant reduction in mortality; since then, the age range in Australia’s screening program remains at 50–74 years. Between 1981 and 2015–2017, the mean life expectancy at birth for men and women in Australia rose by 9.3 and 6.3 years respectively.3 In 2016–2018, the mean life expectancy at 75 years was 12.3 and 14.3 years for men and women respectively, and even at 80 years, the mean life expectancy was 9.1 and 10.6 years respectively,3 suggesting a reduction in morbidity in the 75–79 years cohort over the 1981–2017 period. In 2015, the estimated bowel cancer incidence and mortality rates for Australians in the 75–79 years range were 28% and 82% higher than in the 70–74 years range.4 In the United States, in adults aged 65 years and older, the prevalence of screening was higher than 80% in nine states.5 In Australia, mean participation in the National Bowel Cancer Screening Program (NBCSP) increased with age cohort6 (Box). Although there is an increased risk of complications from colonoscopy with increasing age, a prospective observational study compared the risks in the 75–79 with the 70–74 years range and found no increase in perforation rates.7 A US study found that colorectal cancer screening was cost‐effective at ages 79 and 80 years even in persons with severe comorbid conditions.8 A recent Australian microsimulation study9 suggested that the cost‐effectiveness of screening the 50–79 and 50–74 year groups would be almost identical, although the advantage of a likely high participation in the 75–79 age range was not addressed. It found that the number of immunochemical faecal occult blood tests and colonoscopies would increase by 10–16% and 21–30% respectively if the screening cessation age were extended to 79 years, both of which should be welcomed. Facilities in Australia can cope with such an increase in colonoscopies. In view of the above, the NBCSP age range should be extended to 79 years. At a minimum, a pilot study of such an extension should be undertaken. Box – Australian National Bowel Cancer Screening Program participation Age (years) Participation rates (%) 2014–2015 2015–2016 2016–2017 2017–2018 Mean 50–54 28.5 28.1 29.8 31.9 29.6 55–59 36.8 35.5 35.5 37.3 36.3 60–64 43.2 42.7 43.1 43.7 43.2 65–69 43.5 44.2 47.5 49.6 46.2 70–74 52.5 52.5 52.6 53.1 52.7

Donald J Frommer

Objectives: To investigate causes of death of people with cancer alive five years after diagnosis, and to compare mortality rates for this group with those of the general population. Design, setting, participants: Retrospective cohort study; analysis of South Australian Cancer Registry data for all people diagnosed with cancer during 1990–1999 and alive five years after diagnosis, with follow‐up to 31 December 2016. Main outcome measures: All‐cause and cancer cause‐specific mortality, by cancer diagnosis; standardised mortality ratios (study group v SA general population) by sex, age at diagnosis, follow‐up period, and index cancer. Results: Of 32 646 people with cancer alive five years after diagnosis, 30 309 were of European background (93%) and 16 400 were males (50%); the mean age at diagnosis was 60.3 years (SD, 15.7 years). The median follow‐up time was 17 years (IQR, 11–21 years); 17 268 deaths were recorded (53% of patients; mean age, 80.6 years; SD, 11.4 years): 7845 attributed to cancer (45% of deaths) and 9423 attributed to non‐cancer causes (55%). Ischaemic heart disease was the leading cause of death (2393 deaths), followed by prostate cancer (1424), cerebrovascular disease (1175), and breast cancer (1118). The overall standardised mortality ratio (adjusted for age, sex, and year of diagnosis) was 1.24 (95% CI, 1.22–1.25). The cumulative number of cardiovascular deaths exceeded that of cancer cause‐specific deaths from 13 years after cancer diagnosis. Conclusions: Mortality among people with cancer who are alive at least five years after diagnosis was higher than for the general population, particularly cardiovascular disease‐related mortality. Survivorship care should include early recognition and management of risk factors for cardiovascular disease.

Bogda Koczwara · Rosie Meng · Michelle D Miller · Robyn A Clark · Billingsley Kaambwa · Tania Marin · Raechel A Damarell · David M Roder

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at‐risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators. Methods and recommendations: This statement has been developed by specialists in hepatology, radiology, surgery, oncology, palliative care, and primary care, including medical practitioners and nurses. The statement addresses four main areas relevant to HCC management: epidemiology and incidence, diagnosis, treatment, and patient management. A modified Delphi process was used to reach consensus on 31 recommendations. Principal recommendations include the adoption of surveillance strategies, use of multidisciplinary meetings, diagnosis, treatment options and patient management. Changes in management as a result of this statement: This consensus statement will simplify HCC patient management and reduce clinical variation. Ultimately, this should result in better outcomes for patients with HCC.

John S Lubel · Stuart K Roberts · Simone I Strasser · Alexander J Thompson · Jennifer Philip · Mark Goodwin · Stephen Clarke · Darrell HG Crawford · Miriam T Levy · Nick Shackel