Cancer

The voltaren has kicked in. Back pain has eased

Heather Cameron

In Australia, colorectal cancer is the second most frequently diagnosed cancer and one of the most common causes of cancer‐related death.1 Evidence that bowel cancer screening reduces mortality through early detection and treatment2 led to the introduction in 2006 of the Australian National Bowel Cancer Screening Program (NBCSP), offering faecal occult blood testing. The NBCSP has been progressively rolled out, from covering those aged 55 or 65 years in 2006 to screening every two years for all Australians aged 50–74 years by 2020.3 During 2016–17, 41% of people invited to participate in screening did so.4 A recent review of the NBCSP found that the risk of death from colorectal cancer was lower for invitees, and that those who had cancer were diagnosed at an earlier stage of disease.5 In Australia, jurisdictional cancer registries do not collect data on surgery‐related morbidity. However, the Binational Colorectal Cancer Audit (BCCA) (https://www.bowelcanceraudit.com) has collected information since 2007 on the diagnosis, management, and outcomes of surgically managed Australian and New Zealand patients with colorectal cancer, as well as whether patients were identified by the NBCSP. BCCA data are voluntarily collected by 435 registered surgeons at 138 participating hospitals across Australia and New Zealand, covering about 24% of newly diagnosed cases of colorectal cancer in 2019.6 We sought to determine whether patients with surgically managed colorectal cancer diagnosed through the NBCSP have better post‐operative outcomes than those diagnosed in other pathways. We undertook a cross‐sectional analysis of de‐identified BCCA data for patients aged 18 years or over who underwent surgery in Australia for colorectal cancer during January 2007 – December 2018. Outcome measures were inpatient and 30‐day mortality; surgical complications; medical complications; return to theatre; and hospital length of stay. We undertook binary logistic regression to assess associations between screening and binary outcomes. The association with length of stay was assessed in ordinary least squares linear regression models. The Monash University Human Research Ethics Committee (project, 19327) and the BCCA Operations Committee provided ethics approval for our study. Of 23 310 cases of colorectal cancer in the database, we could include 15 630 cases with data on cancer type and screening status in our comparison of demographic and clinical characteristics. A larger proportion of patients identified by the NBSCP than of otherwise identified patients were men (58% v 54%); their mean age (64 years, standard deviation [SD], 7 years v 69 years; SD, 14 years) was lower, and larger proportions had American Society of Anesthesiologists (ASA) scores in the low risk range (77% v 59%), were from lower socio‐economic status areas, had presented for elective surgery (96% v 85%), had less advanced cancer stage disease (stages 0–II: 69% v 63%), and underwent minimally invasive surgery (80% v 66%) (Box 1). Data on adjusting variables and outcomes were available for the 11 366 cases included in our logistic regression models. NBSCP‐detected patients were less likely to have post‐operative surgical (adjusted odds ratio [aOR], 0.83; 95% confidence interval [CI], 0.69–0.99) or medical complications (aOR, 0.75; 95% CI, 0.59–0.94); their length of stay was also briefer (adjusted mean difference, –1.56 days; 95% CI, –2.06 to –1.06 days). Post‐operative mortality and return to theatre rates were similar for screened and other patients (Box 2). Our analysis of BCCA data indicates that, in addition to the lower long term mortality associated with the NBCSP,5 short term post‐operative benefits are also evident that should be taken into account when promoting the program. Our study reinforces calls to improve participation rates in the national screening program by eligible participants to optimise the value of this critically important initiative. Box 1 – Demographic and clinical features of 15 730 patients who underwent surgery for colorectal cancer in Australia, 2007–2018, by diagnostic pathway Identification of patients Characteristic Total NBSCP Other P Number of patients 15 730 1357 14 373 Age at surgery (years) Mean (SD) 69 (13) 64 (7) 69 (14) < 0.001 Range 18–100 50–75 18–100 50 or under* 1556 (10%) 77 (6%) 1479 (10%) 51–60 2433 (15%) 385 (28%) 2048 (14%) 61–70 4192 (27%) 651 (48%) 3541 (25%) 71–80 4473 (28%) 244 (18%) 4229 (29%) over 80 3073 (20%) 0 3073 (21%) Missing data 3 0 3 Sex 0.003 Women 7142 (45%) 563 (42%) 6579 (46%) Men 8586 (55%) 792 (58%) 7794 (54%) Missing data 2 2 0 American Society of Anesthesiologists score < 0.001 1–2 (low risk) 9205 (60%) 1000 (77%) 8205 (59%) 3–5 (high risk) 6033 (40%) 294 (23%) 5739 (41%) Missing data 492 63 429 Socio‐economic status (IRSD quintile) < 0.001 1 (most disadvantaged) 2470 (16%) 224 (17%) 2246 (16%) 2 2385 (16%) 221 (17%) 2164 (16%) 3 2957 (20%) 278 (22%) 2679 (19%) 4 3107 (21%) 288 (22%) 2819 (20%) 5 (least disadvantaged) 4153 (28%) 282 (22%) 3871 (28%) Missing data 658 64 594 Cancer type 0.50 Colon 11 287 (72%) 963 (71%) 10 324 (72%) Rectal 4443 (28%) 394 (29%) 4049 (28%) Operative urgency < 0.001 Elective 13 457 (86%) 1310 (96%) 12 147 (85%) Emergency 999 (6%) 11 (1%) 988 (7%) Urgent 1248 (8%) 36 (2%) 1212 (8%) Missing data 26 0 26 Cancer stage < 0.001 0 (cancer in situ) 699 (5%) 92 (7%) 607 (4%) I (local disease) 3728 (24%) 535 (41%) 3193 (23%) II (local disease) 4689 (31%) 278 (21%) 4411 (32%) III (nodal spread) 4437 (29%) 347 (26%) 4090 (29%) IV (metastatic disease) 1625 (11%) 42 (3%) 1583 (11%) X (not identifiable) 121 (1%) 16 (1%) 105 (1%) Missing data 431 47 384 Operative approach < 0.001 Minimally invasive surgery† 10 498 (67%) 1082 (80%) 9416 (66%) Open 5140 (33%) 269 (20%) 4871 (34%) Missing data 92 6 86 IRSD = Index of Relative Socioeconomic Disadvantage (Australian Bureau of Statistics); NBSCP = National Bowel Cancer Screening Program; SD = standard deviation. * National screening program participants are aged 50 years or more. † Laparoscopic, hybrid, conversion of laparoscopic, robotic and transanal total mesorectal excision. table#t1 tbody td:nth-child(n+2) P. Pleft { text-align: center; } table#t2 tbody td:nth-child(n+2) P. Pleft { text-align: center; } Box 2 – Logistic and linear regression analysis of the association between screening and outcomes for 11 366 patients with colorectal cancer, Australia, 2007–2018 Identification of patients NBSCP v other Outcome NBSCP Other Univariate regression: OR (95% CI) Multivariate regression: aOR* (95% CI) Number of patients 843 10 523 30‐day mortality† 2 175 0.14 (0.02–0.44) 0.31 (0.05–1.01) Surgical complications‡ 171 2494 0.82 (0.69–0.97) 0.83 (0.69–0.99) Medical complications§ 89 1889 0.54 (0.43–0.67) 0.75 (0.59–0.94) Returned to theatre 52 658 0.99 (0.73–1.31) 1.02 (0.75–1.37) Mean difference (95% CI) Adjusted mean difference* (95% CI) Length of stay (days), mean (SD) 7.27 (6.17) 9.62 (8.02) –2.34 (–2.90 to –1.79) –1.56 (–2.06 to –1.06) aOR = adjusted odds ratio; CI = confidence interval; NBSCP = National Bowel Cancer Screening Program; OR = odds ratio; SD = standard deviation. * Adjusted for age, sex, socio‐economic status, screen category, cancer type, American Society of Anesthesiologists score. † Within 30 days of surgery. ‡ Abdominal/pelvic collection, anastomotic leak, entero‐cutaneous fistula, wound dehiscence, wound infection, sepsis, ileus, small bowel obstruction, urinary retention, ureteric injury, splenectomy, post‐operative haemorrhage. § Including chest infection, cardiac complications, deep vein thrombosis, pulmonary embolus.

Sasha Taylor · Farhad Salimi · Arul Earnest · Alexander G Heriot · John R Zalcberg · Susannah Ahern

More evidence is required to explain the differences in cancer treatment reported by data linkage studies

Ian N Olver

Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men

Xuan Rui S Ong · Dominic Bagguley · John W Yaxley · Arun A Azad · Declan G Murphy · Nathan Lawrentschuk

To the Editor: The recent discussion on chronic liver disease and ultrasonographic surveillance is welcome.1 Over two decades ago, investigators at Westmead Hospital in Sydney showed that ultrasonographic surveillance of 232 Australian patients with chronic liver disease (most of whom had cirrhosis) was superior to α‐fetoprotein in the detection of hepatocellular carcinoma (HCC).2 In this research, we detected six HCCs with ultrasound for an annual cohort incidence of 1.4%; we calculated that each HCC detected cost $US8472 (in 1998 dollar terms). Further, the superior detection of HCCs with ultrasonography did not translate into improved survival either because of tumour multicentricity, metastases at diagnosis, or patient comorbidity factors precluding surgery. Since that time, our technical expertise in liver screening with ultrasound has grown. Nevertheless, we remain concerned by the relatively poor sensitivity compared with computed tomography or magnetic resonance imaging. In addition, specialists in diagnostic imaging understand that the distorted liver architecture from cirrhosis and the presence of regenerating nodules pose significant challenges in distinguishing HCC from benign lesions. While published meta‐analyses3,4 offer some promise, they are by their very nature highly selective in the data evaluated and seldom consider the downstream costs of false positive tests. It is perhaps unsurprising that recent appropriateness criteria guidelines from the American College of Radiology sound a note of caution on the role of ultrasound in this context.5 Despite the above, there remains a need to perform a contemporary analysis of the potential benefits and costs of screening in patients with cirrhosis in Australian settings. However, as a recent Australian HCC surveillance study6 has concluded, it is difficult to interpret survival outcomes from selective retrospective studies, and conducting a randomised controlled trial may be nigh on impossible.

George Larcos

The involvement of patient advocates should ensure that guidelines are rigorously patient‐focused The fundamental objective of clinical management guidelines for any disease entity is to ensure that the information required to provide evidence‐based management recommendations to patients is readily available to their treating clinicians. It is well established that familiarity with guidelines by clinicians and adherence to them increases the number of patients receiving best‐practice care and improves outcomes.1 However, although management guidelines are intended primarily for clinicians, they must also reflect the patient perspective.2 Patient representation on the Melanoma Guidelines Working Party After identifying the need to produce new Australian guidelines on the management of melanoma, a multidisciplinary working party — under the auspices of Cancer Council Australia and the Melanoma Institute Australia — was established in 2014 to critically assess new evidence and update the previous national guidelines. In addition to clinicians and researchers, two patient advocates (consumer representatives), representing patients with melanoma from around Australia through their affiliations with patient advocacy and support networks, were invited to join the working party. These patient advocates had personal experience of melanoma diagnosis and treatment and extensive prior involvement in melanoma advocacy. This meant that they were able to make important contributions based on their experience as well as providing feedback from the patient networks they represented. Electronic publication Whereas the two previous editions of Australian melanoma guidelines, published in 1999 and 2008 respectively, were printed documents, each taking more than 4 years to compile,3,4 the new guidelines were electronic and were made available on Cancer Council Australia's Wiki platform.5 This publication format allowed individual sections to be published as they were completed and permitted selective updating as new evidence became available. Electronic publication has also meant that the guidelines are more readily accessible to both doctors and patients. They can simply search on their computer, tablet or smartphone for “Australian melanoma guidelines” or go directly to the guidelines website (https://wiki.cancer.org.au/australia/Guidelines:Melanoma).5 The level of evidence supporting each guideline recommendation is clearly documented, informing doctors and assisting patients in their decision‐making process. Patients’ expectations from their treating clinician When patients who are concerned about the possibility of having a primary melanoma consult a general practitioner, dermatologist or surgeon, they are entitled to expect that evidence‐based guidelines will be followed and therefore that the steps below will take place: if there are any suspicious skin lesions, they will be carefully examined; if the doctor suspects that a lesion may be a melanoma, the recommended form of biopsy will be carried out (usually complete excision biopsy with a 2–3 mm margin); if melanoma is diagnosed, the recommended treatment and likely outcome will be clearly explained; the melanoma will be staged correctly, appropriately wide surgical excision will be recommended, and the option of sentinel node biopsy will be discussed for melanomas 1 mm or greater in Breslow thickness or 0.8–1.0 mm in thickness with higher risk pathological features, so that prognosis can be estimated accurately and the eligibility for adjuvant post‐operative systemic therapy can be determined;6,7 and the potential benefits and possible side effects of adjuvant therapy will be discussed. When patients are given a diagnosis of metastatic melanoma in regional lymph nodes, or at a systemic site and are referred to a surgeon, medical oncologist or radiation oncologist, again, they should be able to expect that the following will happen: appropriate surgery will be recommended, and surgery that may be unnecessary (eg, completion lymph node dissection for sentinel node positivity8,9) will not be undertaken without a full discussion of the advantages and disadvantages; and if surgery is not considered appropriate, therapeutic systemic therapy options will be discussed, again with a realistic description of the likely benefits and possible side effects.10 Use of the guidelines While different stakeholders will use guidelines in different ways, they are intended to be useful to both clinicians and patients: to GPs, particularly those who work in skin cancer clinics; to dermatologists, who see many patients when they first present with a primary melanoma but who rarely manage patients with metastatic melanoma; to surgeons who treat patients with both primary and metastatic melanoma; to medical and radiation oncologists who are involved in the care of patients with metastatic disease; and importantly, to patients by providing a reliable source of information. It is hoped that by having access to guidelines based on the best available evidence, both treating clinicians and patients will be better informed, treatment options will be better understood, and patients will receive the most appropriate care. The ongoing involvement of patient advocates in the process of developing and updating the Australian melanoma guidelines should ensure that they are useful and relevant to patients and that the health care outcomes most valued by them are considered, resulting in guidelines that are rigorously patient‐focused, as they should be.

Alison E Button‐Sloan · John F Thompson

A recently developed national transport and cryopreservation service improves equity of access to fertility care for young people across Australia Loss of fertility, which is a well recognised complication of cancer treatment, has a significant impact on quality of life and is ranked as one of the top survivorship concerns.1 Improvements in survival (> 88% for adolescents and young adults) and expansion of fertility preserving options have stimulated rapid evolution of the fertility preservation landscape, aiming to decrease this devastating impact of cancer therapy.2 In addition to the gonadotoxic burden of cancer treatment, societal trends of delayed fertility mean that there are many young people who have not yet completed or even commenced trying for a family when diagnosed with a life‐threatening illness. Fertility discussion, and provision of services to preserve gametes or tissue, is no longer seen as a distraction or a luxury but is acknowledged as a mandatory part of cancer management.3 However, barriers to provision of fertility preservation care remain. These include the lack of education of health care providers about both the long term fertility consequences of cancer treatment and the clinical value of available options. There is also often a lack of clarity about whose role it is to educate patients about these options. Importantly, there can be significant logistic, geographic and economic barriers for patients, especially outside the major centres, such that only 4–50% of young people take up fertility preservation in a timely fashion.4 Established strategies to preserve fertility for the future include medical therapies to protect the primordial follicle pool, vitrification of oocytes and embryos, and ovarian tissue cryopreservation for females. Mature sperm freezing is undertaken in post‐pubertal males, and testicular tissue cryopreservation, while providing the only opportunity for pre‐pubertal boys, is still considered experimental.3 Gonadal tissue cryopreservation Ovarian tissue cryopreservation is the only option for prepubertal girls and may be the only or best option for women at high risk of infertility from cancer treatment, particularly if there are time constraints or safety concerns with other options. Ovarian tissue cryopreservation is no longer considered experimental by peak bodies,3 and there have been over 140 births worldwide following ovarian tissue grafting, including several in young women whose ovarian tissue was cryopreserved as pre‐pubertal children.5 Testicular tissue cryopreservation provides an experimental option for fertility preservation in pre‐pubertal boys at significant risk of azoospermia from gonadotoxic treatments. As boys do not produce mature sperm that can be frozen, a treatment involving testicular biopsy and cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is proposed to allow restoration of fertility.6 Recent publications of in vitro sperm maturation and live birth success using the primate animal model provide optimism, such that the joint international consensus statement of peak fertility bodies in 2015 recommended that testicular tissue cryopreservation should be offered for pre‐pubertal boys,3 despite the currently experimental nature of future use, especially as there are no other options. Testicular biopsy can be safely performed and often coordinated concomitantly with other medically necessary procedures without delaying the start of treatment.7 While cryopreservation of eggs, sperm and embryos is a routine part of assisted reproductive laboratory activity, the technique for cryopreservation of ovarian and testicular tissue is biophysically different, and very few centres nationally and internationally have established tissue cryopreservation laboratories with validated, published protocols and clinical success after thawing.8 Due to distance challenges within Australia and lack of resources to meet the needs of these patients, particularly those who reside in rural and remote areas, ovarian and testicular tissue cryopreservation is not accessible to over 70% of people who would benefit from this opportunity.4 Establishment of the National Ovarian and Testicular Transport and Cryopreservation Service To provide equity of access to fertility care, the Fertility Preservation Service at the Royal Women's Hospital in Melbourne has developed the National Ovarian and Testicular Transport and Cryopreservation Service, allowing collaboration between local units and specialised centres, with professional and patient education as part of the program. There are several successful international models for collaborative care with published protocols and data to support transportation and storage of gonadal tissue or gametes in a specialised centre with expertise, health and safety regulations.9 The live birth rates with and without overnight transportation are comparable.9 The Fertility Preservation Service, a partnership between the Royal Women's Hospital and Melbourne IVF, was established 30 years ago. It is the largest service of its kind in Australia, with clinical expertise in counselling, cryopreservation, testing, storage and transport procedures. It sees about 300 patients per year, managed by a multidisciplinary team of fertility specialists, nurses, research scientists, research managers, laboratory staff, counsellors and administrators. There have been increasing referrals each year, reflecting the increased demand. Eighty percent of these are cancer related, with serious medical conditions and gender dysphoria forming the remainder. The Fertility Preservation Service has built extremely strong relationships with cancer centres, both in Victoria and nationally, and collaborates closely with other fertility preservation units, including the Fertility and Research Centre in NSW and the Royal Children's Hospital Melbourne. It supports data collection for the Australasian Oncofertility Registry.10 Based on a recent Fertility Society of Australia survey,11 we believe that Victoria, possibly because of both the dedicated fertility preservation centre and the well developed collaborative relationships, has the highest rate of patients referred for fertility consultation. The service stores gonadal tissue from over 1000 patients. Ovarian tissue grafting has been performed in 40 patients, with five children born and a live birth rate of 20% per embryo transferred. There are also mature eggs and embryos which have been cryopreserved from ovarian tissue stimulation. Testicular tissue has been cryopreserved for 163 patients. The establishment of a centralised national tissue retrieval and transport program allows gonadal tissue harvesting to take place in a local centre with subsequent transportation to the central laboratory for processing, cryopreservation and storage. Communication with the National Ovarian and Testicular Transport and Cryopreservation Service team occurs via a paging service which is checked daily by a dedicated nurse, with treating clinician and, when appropriate, patient follow‐up by teleconference. Subsequently, ovarian tissue grafting may be performed at the Royal Women's Hospital or the tissue can be transported back to the local centres. The service also provides follow‐up and psychological support for patients, and educational resources to assist with all aspects of fertility preservation, both for patients and health practitioners. Fertility preservation is a mandatory part of cancer care; the National Ovarian and Testicular Transport and Cryopreservation Service program will improve equity of access to fertility preservation for young women and men around Australia.

Genia Rozen · Stephanie Sii · Franca Agresta · Debra Gook · Catharyn Stern

Cancer immunotherapy during the COVID‐19 pandemic presents management challenges from immune‐related toxicities, requiring careful patient selection The coronavirus disease 2019 (COVID‐19) pandemic has led to fundamental re‐evaluation of the benefits versus risks of treatment in oncology. Immunotherapy has had an expanding presence in oncology, becoming a primary systemic treatment option in diseases such as melanoma, lung, urothelial, renal, and head and neck cancers. Immune checkpoint inhibitor (ICI) therapy, namely anti‐programmed cell death protein 1 (anti‐PD‐1), anti‐programmed cell death ligand 1 (anti‐PD‐L1) and anti‐cytotoxic T‐lymphocyte‐associated protein 4 (anti‐CTLA‐4) antibodies, halt the negative regulatory checks of T lymphocytes, thus activating the immune response against tumours. Patients with cancer receiving these treatments are faced with a unique set of treatment‐related toxicities driven by an autoimmune mechanism. An association between immune‐related adverse events (irAEs) and severe COVID‐19 has been raised during the current outbreak. In particular, an overlap in the physiological insult from immunotherapy‐mediated pneumonitis and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐related interstitial pneumonia is hypothesised.1 Both conditions may present with lung parenchymal changes, and their coexistence may potentially aggravate the underlying interstitial inflammatory infiltrate and diffuse alveolar damage, leading to a common final pathway of respiratory failure. Pre‐existing lung pathology is expected to be a risk factor for COVID‐19 pneumonia, with higher incidence in patients with lung cancer and smokers.2 Whether prior thoracic radiation may have an impact on outcomes from COVID‐19 pneumonia is unknown. Parallels have been drawn between the cytokine storm driving COVID‐19‐associated acute respiratory distress syndrome and cytokine release syndrome as a complication following T cell‐engaging therapies, such as chimeric antigen receptor T cell and CD3‐based bispecific T cell engager therapies. It is known that interleukin (IL)‐6, IL‐10 and interferon (IFN)‐γ are key drivers behind cytokine release syndrome. Elevated circulating IL‐6 levels have been observed in patients with COVID‐19‐associated pneumonia.3 Patients with severe COVID‐19 have significantly higher circulating levels of pro‐inflammatory cytokines, including IL‐1B, IL‐6, IL‐8 and IL‐10, compared with milder cases of COVID‐19;3 and elevated IL‐6 has been shown to be a predictor of mortality risk. Patients with immune‐related toxicity have higher levels of 11 circulating cytokines, such as G‐CSF, GM‐CSF, IFN‐α‐2, IL‐1a, IL‐1B, IL‐2 and IL‐12,4 with some but incomplete overlap with the cytokine milieu seen in severe COVID‐19 cases.3 The outcomes of COVID‐19 in patients with cancer treated with immunotherapy remain under investigation, with some2,5 but not all6 studies suggesting a more severe outcome. In a multicentre study from China involving 105 patients with cancer infected with SARS‐CoV‐2, 6% received anti‐PD‐1 therapy within 40 days of COVID‐19 symptom onset and experienced increased risk of death and critical symptoms.2 Another series of 423 cancer patients with SARS‐CoV‐2 infection from New York City also reported that treatment with ICI therapy within 90 days was a predictor for admission to hospital and for severe respiratory illness, defined as the requirement for high flow oxygen supplementation or mechanical ventilation.5 Of interest, even after exclusion of patients with lung cancer, the ICI group experienced worse outcomes, inferring that the ICI therapy itself conferred inferior COVID‐19 outcomes without the confounding effect of lung cancer, which had been shown as an independent predictor of poor prognosis in COVID‐19. However, an interim analysis of the first 200 patients from the Thoracic Cancers International COVID‐19 Collaboration (TERAVOLT) registry of patients with thoracic malignancies did not observe a worse outcome among the 37% of patients receiving ICI therapy (23% ICI alone and 14% ICI plus chemotherapy), with data collection ongoing.6 Dual checkpoint inhibitor (anti‐CTLA4 with anti‐PD1 antibody) therapy has achieved high response rates in a number of cancer types,7,8 but is associated with greater incidence and severity of treatment‐related toxicity compared with monotherapy.7 This has several implications. Firstly, differentiating between immune‐mediated pneumonitis and COVID‐19‐associated pneumonia can be difficult due to similarities in clinical and radiological features. Earlier in the pandemic, there were concerns that this may cause delays in initiation of corticosteroids, which is the standard management of irAEs. However, emerging evidence for potential benefit of dexamethasone in severe cases of COVID‐199 reduces concerns for its empirical use in cases where immune‐mediated pneumonitis is a differential diagnosis. Secondly, patients with severe irAEs, such as immune‐mediated pneumonitis requiring intensive care support may face a health system already strained by demand from COVID‐19 cases. Finally, severe irAEs require treatment with high dose corticosteroid and, at times, additional immunosuppressive agents, such as infliximab and mycophenolate. To avoid rebound of the irAEs, corticosteroids are weaned over 6–8 weeks, subjecting patients to prolonged immunosuppression that can predispose them to opportunistic and nosocomial infections.10,11 This has the potential to add further burden to the health care system. The impact of cancer immunotherapy on microbial infection in general is not fully understood. A retrospective study of patients with metastatic melanoma receiving immunotherapy (mainly ipilimumab, an anti‐CTLA4 antibody) reported a 7.3% incidence of serious infections due to a variety of bacterial, viral, fungal or parasitic infections requiring hospitalisation or parenteral antimicrobials.10 Nonetheless, the study of this interaction is complex, with the receipt of corticosteroids for irAEs and having diabetes as a comorbidity10,12 associated with an increased risk of infection in patients with cancer receiving ICI therapy. Furthermore, immune checkpoint blockade can reactivate tuberculosis and viral infections. There are case reports of acute tuberculosis developing in patients with cancer receiving immunotherapy, without concurrent corticosteroid therapy.13 At least three of five cases were suspected to represent reactivation of latent tuberculosis, which may be directly mediated through PD‐1 inhibition driving an exaggerated immune response to tuberculosis infection. Another consideration for patients with cancer receiving immunotherapy is influenza vaccination during the COVID‐19 pandemic. While there is currently no vaccine specifically against COVID‐19, many health authorities encourage the uptake of influenza vaccination to reduce the concurrent burden from influenza illnesses, particularly for nations approaching winter facing the seasonal influenza period. Controversy surrounds whether influenza vaccination in patients receiving cancer immunotherapy heightens the risk of irAEs.14 Numerous retrospective series support the safety of inactivated influenza vaccine in recipients of anti‐PD‐1 monotherapy, with no increase in irAEs observed.15 Reassuringly, influenza vaccination had no adverse impact on the anticancer effect of ICI therapy.14,15 However, there may be heightened concerns for influenza vaccination in combination immunotherapy (anti‐PD‐1 with anti‐CTLA‐4) recipients, as they are more prone to irAEs, including rarer, but potentially fatal, complications such as immune‐mediated myocarditis. This potential concern for influenza vaccination in recipients of combination ICI can leave this patient population more vulnerable from influenza infection. For patients taking monotherapy ICI, current evidence supports the safety and efficacy for influenza vaccination. There are guidelines addressing the use of cancer immunotherapy in the COVID‐19 era.16,17 These call for careful considerations on the use of dual checkpoint inhibitor therapy depending on the local prevalence of community transmission and the capacity of the local health service to cope with demand.16 On a practical note, this requires individual patient risk–benefit assessment. Patient factors such as age, smoking and comorbidities (eg, diabetes and chronic obstructive pulmonary disease) may affect their recovery from irAEs and affect the outcomes from concomitant COVID‐19. Tumour factors for consideration include the burden and biology of disease. Combination immunotherapy may be justified, for example, in a young patient with metastatic melanoma with high disease burden and/or intracranial metastases. This is in contrast to a patient with underlying comorbidities who has low volume disease and/or disease characteristics, such as underlying B‐Raf proto‐oncogene (BRAF) V600K mutation or desmoplastic melanoma subtype, associated with higher likelihood of response to single‐agent anti‐PD‐1/anti‐PD‐L1 therapy. Current guidelines recommend ICI monotherapy to be delivered at increased dosing intervals, such as nivolumab four times per week and pembrolizumab six times per week.16 These approved alternate schedules have been shown to maintain therapeutic efficacy, while advantageous in reducing patient attendance at health care facilities, potentially reducing exposure and community transmission of COVID‐19. The timing of immunotherapy cessation in patients is another consideration. A number of trials in metastatic non‐small cell lung cancer had a 2‐year treatment duration for immunotherapy in responding patients.18 Data on metastatic melanoma support that cessation of anti‐PD‐1 after at least 6 months of therapy in patients achieving complete response can be feasible without adversely affecting outcome.19 Selection of patients with cancer suitable to stop immunotherapy may further reduce these patients’ hospital visits and may potentially reduce the chance of acquiring COVID‐19. There are international efforts to collate the clinical experience of COVID‐19 in patients receiving cancer immunotherapy.6 These registries will provide a valuable resource for further areas of research, such as assessing the impact of irAEs on COVID‐19. The data will also improve our understanding of the outcomes in this patient population to aid management decisions and counsel patients. Research on potential biomarkers of disease severity may also assist in patient triage. In this rapidly evolving area, it is helpful for practising clinicians to maintain current knowledge through regularly updated resources (Box). In summary, the increased role of ICI therapy in oncology calls for consideration of the impact of their use during the COVID‐19 pandemic. While these agents are not directly immunosuppressive, as with cytotoxic chemotherapy, ICI‐associated toxicities pose diagnostic and therapeutic challenges for management in the setting of a COVID‐19 outbreak. Overlapping clinical and radiographic features in immune‐mediated pneumonitis and COVID‐19‐associated pneumonia may cause diagnostic difficulties at initial presentation. Severe irAEs requiring corticosteroids and prolonged immunosuppression may predispose patients to opportunistic infections. Furthermore, there is a possibility of worse outcomes in the setting of COVID‐19 with underlying immune‐mediated pneumonitis and damaging inflammatory response from immune checkpoint blockade. Practical measures, namely prolonging treatment interval and careful patient selection for combination ICI therapy, may help minimise harm. Box – Practice points for cancer immunotherapy during the coronavirus disease 2019 (COVID‐19) pandemic Judicious use of combination anti‐CTLA-4 and anti‐PD-1/anti‐PD-L1 immunotherapy in patients requiring high tumour response rate with good organ functional reserve. Combination checkpoint therapy is associated with higher rate for immune‐related toxicities (eg, pneumonitis), which may potentially have an adverse impact on outcomes in patients with COVID‐19 Use of approved dosing schedule with longer duration between treatments (eg, nivolumab every 4 weeks, pembrolizumab every 6 weeks) Individualised assessment for pausing or cessation of immunotherapy in patients with controlled low disease burden Rapid assessment and COVID‐19 testing for patients receiving cancer immunotherapy who have clinical presentations with overlapping features for COVID‐19 and immune‐related adverse events Prevention of co‐infections: seasonal influenza vaccination for patients taking single‐agent immune checkpoint inhibitor (the use in combination checkpoint recipients should be individualised). Pneumocystis jirovecii prophylaxis for patients receiving prolonged corticosteroid therapy for immune‐mediated toxicities Maintain current knowledge through professional journals, dynamic resource links (examples below) and webinars sharing clinical knowledge and experience internationally: ▸ Clinical Oncology Society of Australia (https://www.cosa.org.au/publications/covid‐19-updates/articles/) ▸ American Society of Clinical Oncology (https://www.asco.org/asco-coronavirus‐information) ▸ European Society for Medical Oncology (https://www.esmo.org/covid‐19-and‐cancer/covid‐19-full‐coverage) ▸ Journal of Thoracic Oncology (https://www.jto.org/content/covid19) anti‐CTLA‐4 = anti‐cytotoxic T‐lymphocyte‐associated protein 4; anti‐PD‐1 = anti‐programmed cell death protein 1; anti‐PD‐L1 = anti‐programmed cell death ligand 1.

Yada Kanjanapan · Desmond Yip

Objective: To compare treatments for localised prostate cancer for men diagnosed in private and public health services in Victoria. Design: Retrospective analysis of Victorian Cancer Registry data linked to population‐based administrative health datasets. Setting, participants: 29 325 Victorian men diagnosed with prostate cancer during 2011–2017. Main outcome measures: Proportions of men in private and public health services receiving radical prostatectomy (with or without curative radiation therapy) or curative external beam radiation therapy alone within 12 months of diagnosis. Results: After adjusting for age, tumour classification and comorbidity, men diagnosed in private health services received radical treatment more frequently than men diagnosed in public health services (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.31–1.49). The proportion of private patients who underwent radical prostatectomy was larger than that for public patients (44% v 28%; OR, 2.28; 95% CI, 2.13–2.44) and the proportion of private patients who received curative external beam radiation therapy alone (excluding brachytherapy) was smaller (9% v 19%; OR, 0.45; 95% CI, 0.42–0.49). These differences were apparent for all International Society of Urological Pathology (ISUP) tumour grades. The magnitude of the difference for prostatectomy was greater for men aged 70 years or more; for radiation therapy alone, it was larger for those diagnosed before age 70. The differences between private and public services narrowed during 2011–2017 for men with ISUP grade 1 disease, but not ISUP grade 2–5 tumours. Conclusion: Prostate cancer treatment choices differ substantially between men diagnosed in private and public health services in Victoria. These differences are not explained by disease severity or comorbidity.

Luc te Marvelde · Roger L Milne · Colin J Hornby · Adam B Chapman · Graham G Giles · Ian E Haines

The challenge now is how to implement artificial intelligence technology safely into clinical practice Artificial intelligence is a branch of computer science that, in broad terms, deals with either decision making or classification. The aim of artificial intelligence is to surpass human cognitive functioning such that automated decisions can be made. Machine learning — an application of artificial intelligence — is commonly used in image recognition. In general, the machine, or algorithm, learns from exposure to a large dataset. Once learning has taken place, the algorithm can be applied to unseen data. The potential advantages of this approach in health care are clear: machines can learn from very large datasets in relatively short time frames and can apply themselves to new data without fatigue or intra‐observer replication error. Machine learning has recently demonstrated remarkable performance in image‐based diagnosis across various medical fields, including ophthalmology, radiology, pathology and dermatology. In dermatology, the primary focus has been on developing machine learning systems that facilitate classification and decision support for skin cancer management. Skin cancer (including melanocytic and keratinocytic malignancy) is the most common cancer in Australia and among Caucasian populations worldwide. Melanoma is responsible for the majority of skin cancer deaths in Australia and has various presentations.1,2 While dermoscopy has improved the accuracy of melanoma diagnosis, significant variability occurs and is largely a function of clinical expertise. Recent studies show that machine learning algorithms have the potential to surpass the diagnostic performance of experts, and the challenge now is how to implement this new technology safely into clinical practice. Although there are a number of machine learning algorithms that could be used in the dermatology setting, convolutional neural networks (CNNs) are the most promising. This is largely because they learn from data without any feature specification, and they are known to exhibit superior performance for image recognition in comparison with other machine learning algorithms.3 The aim of the CNN is to generalise its previously learned knowledge on unseen images beyond the training dataset. There are numerous parameters within a CNN that can be tweaked to maximise algorithm performance. Most of these parameters are adjusted automatically by the algorithm, without user input. Therefore, very little can be known, in principle, about why and how the algorithm reaches any particular decision. Currently, there are efforts underway to reduce the “black box” effect of CNNs. Some commercial software programs coupled to imaging devices will provide the user with comparable lesions to justify the algorithm's output and improve transparency. However, this retrieval system may fail for rare or unseen cases and does not provide a decision‐making process. While the black box phenomenon remains, there are two potentially negative implications for clinical practice: first, clinicians may have difficulty upskilling by following the algorithms’ outputs; and second, there exists the potential for deskilling and underperforming due to an over‐reliance on technology.4,5 The effect of a faulty system has been explored by manipulating a previously trusted algorithm to generate incorrect classifications and found that doctors of all experience levels were susceptible to being misled by the recommendation.5 Algorithm performance is dependent on both the size and quality of the training image dataset and on whether the algorithm is used in situations for which it was intended. Depending on the training set, the device may be limited in its ability to diagnose specific lesions (eg, non‐pigmented), or lesions in certain skin types (eg, darker skin) or sites (eg, scalp or acral). Retrospective image databases used to train algorithms may be associated with bias. In addition, artefacts (eg, hair, dermoscopic gel, air bubbles, rulers, pen markings, reflections) can distract from key features. However, if a CNN is trained on a large enough cohort, it can learn to deal with potential artefacts. Nonetheless, unbiased lesion selection and standardised image capture would invariably improve algorithm performance, and recent advances in three‐dimensional (3D) imaging modalities will enable this.6 Several studies have now shown that CNNs trained on retrospective image data collected at a single time point are capable of classifying skin cancer with sensitivities and specificities equal or superior to that of dermatologists (Box 1),5,7,8,9,11 and clinicians with less experience gain most from AI support under experimental conditions.5 Hypomelanotic and acral melanoma can be more challenging to diagnose clinically,1 and this could potentially present a challenge for automated classification. However, CNNs have achieved greater accuracy for hypopigmented and acral lesions in comparison with human experts, at least in silica.9,11 In addition to clinical images, CNNs have been applied to histopathological images of melanoma and benign naevi with promising results.10 The ground truth for lesion diagnosis The gold standard for melanoma diagnosis is histopathological assessment. However, there exists significant inter‐ and intra‐observer variability in histological diagnostic labels attributed to atypical melanocytic lesions.12 The existence of such variability in diagnoses poses the dilemma of whether the CNN has learnt from the correct set of diagnoses. Consensus diagnoses, if practical, may help overcome this problem. Molecular biomarkers may assist in establishing a diagnosis13 and identifying high risk biology,14 but they require extensive validation before clinical use. Pathologists and clinicians also rely on metadata (age, personal and family history, lesion symptoms, recent change), which may influence diagnostic likelihoods. Importantly, it is possible to incorporate different data types, including metadata, sequential image data coupled with histopathology, to train future CNN algorithms and improve diagnostic discrimination of borderline lesions (Box 2). Use of artificial intelligence for melanoma screening It is well known that the incidence of invasive melanoma in Australia has increased over the past 40 years. In addition, there has been a striking increase in incidence of in situ melanoma over the past decade, from 32 cases per 100 000 population in 2004 to 80 per 100 000 population in 2019, with age‐standardised mortality remaining fairly stable.2 The potential causes for the increase in incidence are complex, and involve a true increase, driven by poor sun exposure practices of individuals born before the SunSmart era, combined with increased awareness, excessive screening, and overdiagnosis. It has recently been estimated that 54% of melanomas (15% of invasive melanomas) are overdiagnosed.15 Artificial intelligence‐assisted targeted screening of high risk individuals is likely to be a more effective strategy to save lives than the current opportunistic approach. With sequential whole‐body image datasets linked to metadata, molecular biomarkers and clinical outcomes, our ability to identify lesions associated with sinister biological potential will improve (Box 2), thereby reducing unnecessary biopsies, minimising overdiagnosis and other potential harms associated with screening. Use of artificial intelligence in clinical practice There are advantages and disadvantages of introducing artificial intelligence at different points in the patient care pathway.16 An artificial intelligence system used as a triaging tool before clinician assessment would enable automated risk stratification of individuals and/or lesions (Box 2). This approach could dramatically improve clinician workload and timely access to specialist care for people requiring urgent attention. Alternatively, artificial intelligence consulted following an examination by the clinician may act as a second opinion to improve diagnostic sensitivity and reduce unnecessary biopsies.5 The latter is more closely aligned with current clinical workflows and therefore likely to be preferred while the field matures. There is potential for over‐reliance on artificial intelligence systems in both scenarios. A secondary support system may provide the clinician with a diagnosis or a management decision. Doctors are more likely to change their minds if they are uncertain of a diagnosis and an algorithm provides a conflicting result.5 It is thus important to consider how an algorithm might convey uncertainty to avoid false guidance. For example, a decision‐support output (eg, excise, monitor or reassure) avoids the diagnostic dilemma of differentiating between melanoma and dysplastic naevi. However, the problem is complex and arguments exist as to why, in many situations, a diagnostic probability output might be more desirable. Safe implementation of new technologies The Therapeutic Goods Administration (TGA) has developed an action plan to improve the processes by which new devices are approved for use in Australia, strengthen monitoring and follow‐up, and provide more information to consumers about the devices they use.17 International collaborations also exist with groups, such as the International Medical Device Regulators Forum, to establish better processes for medical device regulation globally. If software is classified as a medical device (ie, it is intended for diagnosis, prevention, monitoring, treatment or alleviation of disease), it must be registered on the Australian Register of Therapeutic Goods following TGA approval and before distribution within Australia. Consumers and clinicians need to be aware of the intended use of an application or device. There are several smartphone applications available to the general public, with functionality ranging from education to monitoring and tracking to skin lesion classification. Some of these provide skin lesion risk assessment, although they may state that they are not intended to be used as a diagnostic device. There is concern that, if this is not immediately obvious to the consumer, unregistered applications may be used in lieu of seeking medical advice. Unsupervised consumer‐operated diagnostic devices would require careful testing before they can be recommended. Conclusion As clinicians, we need to be aware of the limitations of any diagnostic tool and interpret outputs accordingly. Although the performance of artificial intelligence to date is promising, it remains to be seen how diagnostic devices in dermatology will influence decision making in the clinic and affect patient outcomes. Regardless of the specialty, any new technologies need to be rigorously tested before implementation and monitored after implementation. Ultimately, responsibility for patient care remains with the clinician and, as such, a high level of clinical acumen must be maintained. Nonetheless, artificial intelligence in dermatology is primed to become a powerful tool in skin cancer assessment. Box 1 – Comparison of skin cancer classification tasks by artificial intelligence (AI) systems and dermatologists/pathologists Study AI architecture Images Classification task Training dataset size Test dataset size AI Dermatologists/pathologists Sensitivity Specificity AUC/overall accuracy Sensitivity Specificity AUC/overall accuracy Tschandl5 ResNet34 CNN Clinical (dermoscopic) Benign v malignant v non‐neoplastic skin lesions 10 015 1412 0.81 (0.79–0.83)* 0.92 (0.90–0.93)* 0.73†(0.70–0.76)* 0.80 (0.78–0.83)* 0.80 (0.77‐0.82)* 0.60† (0.57–0.63)*,‡ 0.86 (0.84–0.88§)* 0.88 (0.87–0.90§)* 0.74† (0.71–0.77§)* Esteva7 GoogleNet Inception v3 CNN Clinical (macroscopic, dermoscopic) Benign v malignant v non‐neoplastic skin lesions 129 450 1942 na na 72.1%¶ ± 0.9% na na 66.0%¶ Haenssle8 GoogleNet Inception v4 CNN Clinical (macroscopic, dermoscopic) Benign melanocytic naevi v melanoma > 100 000 100 86.6%** 82.5%** 0.86** 86.6%** 71.3%** 0.79** 88.9%†† 82.5%†† 0.86†† 88.9%†† 75.7%†† 0.82†† Tschandl9 GoogleNet Inception v3 CNN Clinical (macroscopic, dermoscopic) Benign v malignant hypo‐pigmented lesions 13 724 2072 81% 53.5% 0.73 78% 51.3% 0.68 Hekler10 ResNet50 CNN Histopathology Benign naevus v melanoma 595 100 76% 60% na 51.8%‡‡ 66.5%‡‡ na Fujisawa11 GoogleLeNet DCNN Clinical (macroscopic) Benign v malignant skin lesions§§ 4867 1142 96.3% 89.5% 92.4%¶ ± 2.1% na na 85.3%¶ ± 3.7% AUC = area under the curve; na = not applicable. * 95% CI. † Youden statistic. ‡ Clinicians with varied experience and training. § Clinician accuracy with multiclass probabilistic AI support. ¶ Overall accuracy. ** Level I: AI and human readers provided with dermoscopic images only. †† Level II: AI provided with dermoscopic images only, human readers provided with dermoscopic images, macroscopic images and additional clinical information. ‡‡ Pathologist. §§ 52.6% of melanomas in this study were acral. Box 2 – Incorporation of different data types to train future convolutional neural network (CNN) algorithms and improve diagnostic discrimination of borderline lesions AI = artificial intelligence.

Miki Wada · ZongYuan Ge · Stephen J Gilmore · Victoria J Mar

To the Editor: The coronavirus disease 2019 (COVID‐19) pandemic has required rapid adjustments in health service delivery.1 The Victorian COVID‐19 Cancer Network (VCCN) is a joint initiative of the Victorian Comprehensive Cancer Centre and Monash Partners Comprehensive Cancer Consortium. Through expert groups, the VCCN aims to provide support and advice to clinicians and health care services treating cancer patients during the pandemic. The VCCN Telehealth Expert Working Group conducted a survey to understand the barriers and enablers to the rapid adoption of telehealth in health services during the first week of April 2020. Seventeen cancer services from across metropolitan and regional Victoria and Tasmania responded. Notably, all respondent cancer services had implemented some form of telehealth since the pandemic. Healthdirect, the Victorian Department of Health and Human Services’ supported telehealth platform, was used in 40% of services, with 25% using phone only and others using platforms such as Skype, FaceTime and doxy.me. With the unprecedented increase in the uptake of telehealth,2 there is a tremendous opportunity to integrate telehealth into routine practice, potentially improving inequities and inefficiencies in the delivery of cancer care for suitably selected patients. Our survey results suggest several areas for attention to support telehealth, including the need for further investment in information technology infrastructure across health services and administrative support to facilitate changes in practice and workflow (Box). The survey results also highlight the educational and training needs of consumers and health professionals during telehealth implementation. Aboriginal and Torres Strait Islanders, people from culturally and linguistically diverse backgrounds and of lower socio‐economic status, and older patients may have greater needs and will require additional support from both government and relevant organisations to ensure equity of access to cancer care via telehealth. We strongly advocate the need to establish evidence‐based, patient‐centred and sustainable telehealth in cancer management. Research into the experience of patients and clinicians should be prioritised to ensure the consistent quality of telehealth consultation with face‐to‐face consultation in appropriate clinical circumstances. Box – Barriers to implementing telehealth: survey results

Zee Wan Wong · Hannah L Cross

To the Editor: A recent article highlighted a case where self‐collection enabled detection of an early cervical adenocarcinoma and curative treatment in a previously underscreened woman.1 This case underlines the important benefits from self‐collection making cervical screening more accessible and acceptable to women who have previously declined or delayed screening. Unfortunately, self‐collection is currently very underutilised in Australia. Although it is currently restricted to women aged 30 years and over who are 2 or more years overdue for cervical screening, potentially around a million women are eligible.2 In contrast, data from Medicare, VCS Pathology, and the National Cancer Screening Register suggest that fewer than 6000 self‐collected tests were processed over 2018 and 2019, indicating that less than 1% of eligible women have had a self‐collected test. What drives this discrepancy? Self‐collection is highly acceptable to underscreened Australian women, and very high uptake can be achieved with appropriate clinical support.3 A recent survey reported that many practitioners, especially outside Victoria, do not yet feel comfortable discussing or recommending self‐collection, and lack confidence that self‐collection is a reliable test.4 Potentially, this is due to an initial delay in self‐collection being available, confusion about eligibility, and current restrictions giving the false impression that self‐collection is less sensitive. Self‐collection is now available to eligible women nationally (provided samples are sent to one of two accredited laboratories, which accept samples from anywhere in Australia), and updated evidence demonstrates that polymerase chain reaction‐based human papillomavirus (HPV) testing is equally sensitive for detecting pre‐cancer in self‐collected and clinician‐collected samples.5 Another barrier may be difficulties for providers in checking whether women are eligible. The rollout of the provider portal into the National Cancer Screening Register, allowing providers to view a woman's screening history at the point of care, will be important in addressing this issue. Many screening‐eligible women who have not had their first HPV test are now overdue and could be eligible for self‐collection. Self‐collection is a reliable test now available nationally to eligible women, which can have a transformative effect in the lives of underscreened women, as shown in the recent case study.

Megan Smith · Marion Saville · Karen Canfell

It has been reported that about 60% of patients commencing chemotherapy in Australia with curative intent and 47% of those receiving radiotherapy also use complementary medicine.1,2 Ingestible products are frequently used, but are often not discussed with the medical team, which increases the risk of interactions and other undesirable effects. Opportunity costs are another problem; while complementary medicine is typically used by people with cancer for supportive care and wellbeing, some use it to help treat cancer.2 Given the frequent use of complementary medicine by people with cancer, we surveyed Australian public and private hospitals with dedicated cancer services (1 May – 15 December 2016),3,4 to assess various aspects of cancer service coverage, particularly complementary medicine services. In this report, we describe hospital policies on complementary medicine and the availability of related information for patients. The study was approved by the human research ethics committees of the University of Western Sydney (reference, H11389), the University of Wollongong and Illawarra Shoalhaven Local Health District (reference, HREC/16/WGONG/178), and Calvary Health Care, Adelaide (reference, 16‐CHREC‐E011). One staff member from the cancer service of each participating hospital (262 of 282 invited hospitals, 93%) completed a 52‐item electronic survey (online Supporting Information). Chemotherapy was provided by 207 of the participating services (79%) and supportive and allied health care by 196 (75%), including 66 (25%) that provided at least one type of complementary medicine service. Palliative care was provided by 168 hospitals (64%), surgery by 143 (55%), and radiotherapy by 143 (34%). Ninety‐three responding hospitals (36%) could not provide responses to one or more of the five policy‐related survey questions. This was despite the option to complete the survey across several log‐in sessions and 223 of the respondents (85%) having administrator or management roles. Only 89 respondents (34%) were aware of the Council of Australian Therapeutic Advisory Groups (CATAG) position statement on complementary medicines,5 and only 31 of these respondents (35%) thought that their hospital policies were aligned with this statement. A substantial proportion of hospitals did not have policies regarding complementary medicine practitioners or patient‐initiated complementary medicine use (Box). Most hospitals (229, 87%) had policies for documenting complementary medicines: 76 (33%) documented all complementary medicines (including patient‐initiated products) on medication charts, 88 (38%) documented only complementary medicines approved by medical staff, and 48 (21%) documented complementary medicine use only in the clinical history. The policy at 17 hospitals (6%) was that complementary medicines were never permitted, despite CATAG advice.5 In an adjusted backward multinominal logistic regression analysis, hospitals with cancer services without complementary medicine services were significantly less likely to have policies on complementary medicine practitioners and documenting complementary medicines (Box). Further, only 123 services (47%) provided complementary medicine information for patients, and 23 respondents (9%) did not know whether such information was available. The differences in the awareness of and the availability of hospital policies and patient information about complementary medicine are concerning. Irrespective of whether a cancer service provides complementary medicine, consistent policies across Australian hospitals, and staff and patient awareness of these policies, are important because of the widespread use of complementary medicine. Stronger leadership is needed from peak bodies, such as the Australian Commission on Safety and Quality in Health Care and CATAG, to encourage Australian cancer services and hospitals to update or review their complementary medicine policies. Box – Hospital policies regarding complementary medicine products and visiting practitioners, based on survey responses from 262 hospitals with cancer services Complementary medicine (CM) cancer services available Hospitals without v with CM service: adjusted odds ratio* (95% CI) Policy type Number Yes No Total number of hospitals 262 66 (25%) 196 (75%) Documenting CM product use Hospital policy 229 (87%) 60 (91%) 169 (86%) — No policy 24 (9%) 1 (2%) 23 (12%) 10.4 (1.3–81) Unknown 9 (3%) 5 (8%) 4 (2%) 0.29 (0.07–12) Documenting patient‐initiated CM products Hospital policy 43 (16%) 15 (23%) 28 (14%) — No policy 133 (51%) 30 (45%) 103 (53%) 1.8 (0.84–4.0) Case‐by‐case 43 (16%) 9 (14%) 34 (17%) 1.2 (0.48–3.3) Unknown 43 (16%) 12 (18%) 31 (16%) 1.8 (0.68–5.0) Referrals to CM practitioners outside the hospital Hospital policy 25 (10%) 14 (21%) 11 (6%) — No policy 145 (55%) 27 (41%) 118 (60%) 5.2 (2.1–13) Case‐by‐case 43 (16%) 15 (23%) 28 (14%) 2.8 (0.99–8.0) Unknown 49 (19%) 10 (15%) 39 (20%) 4.4 (1.5–13) Scope of practice for visiting CM practitioners Hospital policy 54 (21%) 20 (30%) 34 (17%) — No policy 113 (43%) 16 (24%) 97 (49%) 3.3 (1.5–7.3) Case‐by‐case 34 (13%) 17 (26%) 17 (9%) 0.65 (0.26–1.6) Unknown 61 (23%) 13 (20%) 48 (24%) 2.1 (0.95–5.0) Credentialing for visiting CM practitioners Hospital policy 72 (28%) 32 (48%) 40 (20%) — No policy 103 (39%) 11 (17%) 92 (47%) 6.2 (2.8–14) Case‐by‐case 28 (11%) 11 (17%) 17 (9%) 1.4 (0.56–3.5) Unknown 59 (22%) 12 (18%) 47 (24%) 2.9 (1.3–6.6) CI = confidence interval. * Reference category: hospital has policy and its cancer service provides complementary medicine services. Derived by backward multinominal logistic regression, adjusted for survey responder's role (administration/management: 46 [18%], health care professional: 70 [27%], dual role: 146 [56%]); hospital ownership (public: 132 [50%], private for‐profit: 74 [28%], private not‐for‐profit: 56 [21%]; and Australian Bureau of Statistics remoteness classification (major cities: 117 [40%], inner/outer regional: 87 [30%], remote/very remote: 91 [31%]).

Jennifer Hunter · Suzanne Grant · Geoff P Delaney · Caroline A Smith · Kate Templeman · Jane Ussher

During the pandemic, cancer survivors are lost in transition

Bogda Koczwara

Advice for clinicians managing patients with cancer during the pandemic

Robert Weinkove · Zoe K McQuilten · Jonathan Adler · Meera R Agar · Emily Blyth · Allen C Cheng · Rachel Conyers · Gabrielle M Haeusler · Claire Hardie · Christopher Jackson · Steven W Lane · Tom Middlemiss · Peter Mollee · Stephen P Mulligan · David Ritchie · Myra Ruka · Benjamin Solomon · Jeffrey Szer · Karin A Thursky · Erica M Wood · Leon J Worth · Michelle K Yong · Monica A Slavin · Benjamin W Teh

Out‐of‐pocket expenses for cancer care are of growing concern for patients, clinicians, service providers, non‐governmental organisations, private insurers, and politicians. Contrary to popular belief, there is no direct link between the cost and quality of care. Out‐of‐pocket expenses are a particular problem for patients who live further from treatment centres, are younger, or have later stage disease.1 Adults (18 years or older) with pathologically confirmed colorectal, lung, prostate or breast cancer from four rural (Midwest, South West, Great Southern, Goldfields) and two outer metropolitan (Joondalup/Wanneroo and Rockingham/Peel) regions of Western Australia were identified in the WA Cancer Registry. Between 1 April 2014 and 31 April 2017, eligible patients were invited to complete questionnaires requesting demographic, financial, and treatment information, including all costs during treatment, as reported previously.2 We used log‐linked generalised linear models with gamma distribution, adjusted for age and sex, to estimate out‐of‐pocket expenses (with 95% confidence intervals [CIs]) for participant characteristics found to be significantly associated with out‐of‐pocket expenses in univariate analyses (online Supporting Information). The study was approved by the WA Country Health Service Ethics Committee (reference, 2014:10) and the Department of Health WA Human Research Ethics Committee (reference, 2014/26). One hundred and seventeen of the 119 outer metropolitan participants (98%) and 294 of the 308 rural participants (95%) incurred out‐of‐pocket expenses for their cancer care, chiefly for surgery, medical tests, and medical appointments. These costs ranged between $51 and $106 140 for outer metropolitan participants, and between $13 and $20 842 for rural participants. Fifty‐three rural participants (17%) and 39 outer metropolitan participants (33%) spent more than 10% of their household income on cancer care (data not shown). Among rural participants, mean out‐of‐pocket expenses were higher for men ($1988; 95% CI, $1605–$2461 v $1362; 95% CI, $1092–$1699), for people with private health insurance ($2455; 95% CI, $1973–$3053 v $1103; 95% CI, $877–$1386), and for people who were married ($2086; 95% CI, $1749–$2489 v $1297; 95% CI, $975–$1725), had undergone surgery ($1990; 95% CI, $1684–$2351 v $1360, 95% CI, $1005–$1839), or had worked prior to being diagnosed with cancer ($2084; 95% CI, $1643–$2644 v $1298; 95% CI, $1038–$1625) (Box). Among outer metropolitan participants, mean out‐of‐pocket expenses were higher for men ($5217; 95% CI, $3928–$6928 v $2247; 95% CI, $1756–$2875), for people with private health insurance ($4670; 95% CI, $3588–$6078 v $2510; 95% CI, $1853–$3401), and for those who had undergone surgery ($5434; 95% CI, $4260–$6932 v $2157; 95% CI, $1541–$3020), worked prior to being diagnosed with cancer ($5471, 95% CI, $3952–$7573 v $2143; 95% CI, $1643–$2794), resided in areas of high socio‐economic status ($4299; 95% CI, $3235–$5712 v low, $1859; 95% CI, $1374–$2516), or were receiving chemotherapy ($4286; 95% CI, $3162–$5810 v $2735; 95% CI, $2116–$3534) (Box). It is perhaps surprising that out‐of‐pocket expenses were higher for people in outer metropolitan areas, who presumably lived closer to treatment centres than rural residents. However, these findings are consistent with the recent report that out‐of‐pocket spending on non‐hospital Medicare‐subsidised services and specialist services was higher for metropolitan patients than for those in regional areas.4 The higher out‐of‐pocket expenses for people with private health insurance or undergoing surgery indicate the importance of health care funding arrangements and the magnitude of the costs borne by patients. The marked variation in out‐of‐pocket expenses reported here and by others5 highlights the need for easily accessible information about services, medical costs, and gap payments for all health care services. The Informed Financial Consent website coordinated by the Australian Medical Association,6 consumer organisation fact sheets, and professional body initiatives are steps in the right direction, but their impact is yet to be determined. Problems that still need attention in the unregulated private fee‐setting environment in Australia include price discrimination in some specialist sectors.7 Bundles of care for cancer treatment that would allow patients and their families to better understand and plan for expenses should be explored. Box – Estimated mean out‐of‐pocket expenses for cancer‐related health care (with 95% confidence intervals) for outer metropolitan and rural patients, by patient characteristics significantly associated with higher out‐of‐pocket expenses in univariate analyses* * For outer metropolitan patients, marital status, and for rural patients, socio‐economic status and chemotherapy were not significant predictors of out‐of‐pocket expenses, and were therefore not included in the final models. †Index of Relative Socio‐economic Disadvantage (IRSD):3 low (most disadvantaged), deciles 1–4; moderate, deciles 5–6; high (least disadvantaged), deciles 7–10.

Neli S Slavova‐Azmanova · Jade C Newton · Christobel M Saunders

Timely diagnosis of cirrhosis and HCC surveillance using ultrasound may help improve patient outcomes

Gary P Jeffrey · Louisa Gordon · Grant Ramm

The conventional treatment for brain metastases is whole brain radiotherapy (WBRT).1 But there has been a gradual move to managing limited brain metastases with stereotactic radiosurgery (SRS),2 and delaying or avoiding WBRT because of its effects on cognition and quality of life. Data on contemporary SRS practice for managing brain metastases in Australia are, however, very limited.3 We performed a population‐based linkage study, analysing data from the Victorian Cancer Registry and the Victorian Radiotherapy Minimum Data Set (VRMDS). We included all patients with solid tumours (ICD‐10 codes C00–C80), but excluding primary central nervous systems malignancies (ICD‐10 codes C69–72), who received brain radiotherapy in Victoria between 1 January 2012 and 31 December 2017. The primary outcome was the proportion of patients treated with SRS. Although SRS refers to large single fraction radiotherapy, patients treated with fractionated “stereotactic radiotherapy” were also classified as receiving SRS. In addition, because of potential coding inconsistencies, patients who had no more than four fractions of radiotherapy and were treated with “volumetric modulated arc therapy” or “intensity modulated radiation therapy” were also classified as receiving SRS. Differences in factors of interest by SRS use were assessed in Pearson χ2 (categorical variables) and Student t or Mann–Whitney U tests (continuous variables). Temporal changes were assessed with the Cochran–Armitage test for trend. Factors associated with SRS use were assessed by logistic regression, with year as an ordinal categorical variable; variables for which P < 0.10 in univariate analyses were included in the multivariate model. The study was approved by the Austin Health Human Research Ethics Committee (reference, LNR/18/Austin/34). A total of 3961 patients who received radiotherapy for brain metastases were included, of whom 1116 (28%) received SRS. The proportion of patients receiving SRS increased from 27% (105 of 388) in 2012 to 35% (287 of 821) in 2017 (for trend: P < 0.001). The mean age of patients who received SRS (63.5 years; standard deviation [SD], 12.5 years) was lower than for those who did not (65.2 years; SD, 12.5 years). Factors that influenced SRS use included socio‐economic status, primary cancer type (about half the patients with melanoma received SRS, and about one‐quarter of patients with other cancer types), treatment institution type (public institutions, 31%; private institutions, 24%), and location (metropolitan centres, 34%; regional centres, 5%). Remoteness of patients’ area of residence was not a significant factor. In multivariate analyses, age, primary cancer type, treatment centre type, and location were significant factors for SRS use (Box). While the VRMDS captures all radiotherapy delivered in Victoria, it does not include data on patients’ performance status, numbers of brain metastases, the extent of extracranial disease, and other factors that would allow evaluation of the appropriateness of SRS for individual patients. Another limitation is potential misclassification of radiotherapy classified as “SRS”, as the VRMDS did not include data on radiotherapy dose. As evidence supporting the use of SRS for managing brain metastases grows, we would expect SRS rates to rise.6,7 While SRS was less frequently used in regional centres, patients living in regional areas were as likely to receive SRS as patients living in metropolitan areas. It is nevertheless important to ensure easy and convenient access to SRS services for all cancer patients in Victoria. Box – Baseline characteristics of 3961 patients who received radiotherapy for brain metastases, Victoria, 2012–2017 Stereotactic radiosurgery Multivariable analysis: odds ratio (95%CI) P Received Not received Number of patients 1116 (28%) 2845 (72%) Age at first treatment for brain metastases (years) < 55 266 (33%) 543 (67%) 1 55–59 157 (32%) 331 (68%) 1.11 (0.86–1.44) 0.42 60–64 161 (28%) 419 (72%) 0.89 (0.69–1.14) 0.35 65–69 177 (26%) 502 (74%) 0.85 (0.67–1.08) 0.19 70–74 153 (25%) 448 (75%) 0.88 (0.68–1.14) 0.33 75 or more 202 (25%) 602 (75%) 0.78 (0.62–0.99) 0.045 Mean (SD) 63.5 (12.5) 65.2 (12.5) — — Sex Men 528 (28%) 1373 (72%) — — Women 588 (29%) 1472 (71%) — — Primary cancer type Lung 419 (24%) 1344 (76%) 1 Breast 203 (28%) 512 (72%) 1.24 (1.00–1.53) 0.05 Melanoma 252 (47%) 277 (52%) 2.89 (2.32–3.59) < 0.001 Gastrointestinal 93 (28%) 235 (72%) 1.37 (1.03–1.80) 0.028 Genitourinary 73 (28%) 189 (72%) 1.33 (0.97–1.80) 0.07 Other 76 (21%) 288 (79%) 0.80 (0.60–1.06) 0.12 Socio‐economic status (quintile) 1st (most disadvantaged) 188 (24%) 612 (77%) 1 2nd 189 (27%) 501 (73%) 1.12 (0.87–1.44) 0.39 3rd 202 (26%) 572 (74%) 1.02 (0.79–1.30) 0.90 4th 220 (26%) 618 (74%) 0.90 (0.70–1.14) 0.38 5th (least disadvantaged) 317 (37%) 542 (63%) 1.19 (0.94–1.50) 0.14 Remoteness classification5 Major city 780 (29%) 1949 (71%) — — Inner regional 261 (26%) 732 (73%) — — Outer regional/remote/very remote 75 (31%) 164 (69%) — — Treatment institution type Public 744 (31%) 1656 (69%) 1 Private 372 (24%) 1189 (76%) 0.10 (0.07–0.14) < 0.001 Treatment institution location Metropolitan 1071 (34%) 2071 (66%) 1 Regional 45 (5%) 774 (95%) 0.58 (0.49–0.68) < 0.001 Year of first brain metastasis treatment 2012 105 (27%) 283 (73%) 1 2013 111 (25%) 342 (76%) 1.01 (0.72–1.41) 0.95 2014 147 (25%) 439 (75%) 0.86 (0.63–1.18) 0.35 2015 207 (25%) 633 (75%) 0.79 (0.59–1.06) 0.12 2016 259 (30%) 614 (70%) 1.10 (0.83–1.47) 0.50 2017 287 (35%) 534 (65%) 1.41 (1.06–1.88) 0.017 CI = confidence interval; SD = standard deviation. * Index of Relative Socio‐Economic Disadvantage.4

Wee Loon Ong · Therese Ming Jung Kang · Gishan Ratnayake · Morikatsu Wada · Jeremy Ruben · Sashendra Senthi · Roger L Milne · Jeremy L Millar · Farshad Foroudi

A 74-year-old Caucasian woman was referred for hirsutism over the abdomen and was incidentally found to have a 21 × 25mm ulcerated nodule over the umbilicus

Tom Kovitwanichkanont · Shoba Joseph · Leona Yip

The skin has more disease processes than any other organ system in medicine, with over 3000 dermatological conditions described

Kirsty JL Wark · Saxon D Smith · Deshan F Sebaratnam

The balance between benefits and risks could be improved if effective risk-based screening protocols were developed

David M Roder · Elizabeth Buckley

Colorectal cancer is an important cause of morbidity and mortality in Australia.1 The National Bowel Cancer Screening Program (NBCSP) aims to detect the disease early by offering faecal occult blood testing (faecal immunochemical test, FIT) to people aged 50–74 years.2 The expansion of the NBCSP has been paralleled by increased numbers of FITs outside the program (community‐initiated FITs) for a number of reasons, including the presence of symptoms. We investigated whether colonoscopy services should provide endoscopies to patients with positive FIT results with the same priority, regardless of whether the test was instigated by the NBCSP, by analysing data from the Newcastle Direct Access Colonoscopy Service (DACS) for the period 2014–18. The DACS manages all patients in the same manner: a positive FIT result leads to assessment for colonoscopy.3,4 Ethics approval was granted by the Hunter New England Human Research Ethics Committee (reference, AU201608‐01). All data were recorded prospectively. Findings were categorised according to surveillance categories endorsed by the Gastroenterological Society of Australia and the Colorectal Surgical Society of Australia and New Zealand.5 Data accuracy was confirmed by reviewing the primary sources for 10% of patients. We identified 2693 patients referred for screening colonoscopy between 1 July 2014 and 30 June 2018; 1439 (53%) had had community‐initiated FITs (Box 1). After excluding 318 patients who did not attend or were lost to follow‐up (community‐initiated, 200; NBCSP, 118) and ten patients with poor bowel preparation and no follow‐up colonoscopy during the study period, 2365 complete screening colonoscopy outcomes were analysed: 1233 following community‐initiated and 1132 following NBCSP testing. With these sample sizes, the study had 80% power to detect differences in colonic neoplasia rate ranging from 16 percentage points (assumed prevalence, 50%) to two percentage points (assumed prevalence, 3%). Z‐tests were used to calculate P values, and Wald tests (two‐tailed) for calculating confidence intervals (CIs) for the differences between the two groups. Differences between the two groups in the proportion of patients with each specific finding are presented with 99% asymptotic CIs to control for multiple testing. Colonoscopy quality was high: the completion rate (defined as either caecal intubation, reaching an ileocolic anastomosis, or reaching an obstructing mass lesion) was 97.1% (community‐initiated, 1193 of 1233, 96.8%; NBCSP, 1104 of 1132, 97.5%), and the adenoma detection rate was 49%, exceeding international benchmarks for either symptomatic or screening patients (for screening: at least 25% in men and 15% in women;6 for populations enriched with patients with positive FIT results: 35%7). The rate of colorectal neoplasia (malignant or pre‐malignant) was similar in the two groups. Importantly, the difference in the rates of adenocarcinoma was not statistically significant (community‐initiated, 4.0%; NBCSP, 2.7%; difference, 1.3 percentage points [99% CI, –0.6 to 3.3 percentage points]; P = 0.09). The only statistically significant difference by type was that the incidence of high risk adenoma was slightly higher in the NBCSP group (22.9% v 17.2%; difference, 5.7 percentage points [99% CI, 1.4–10 percentage points]; P < 0.001) (Box 2). We found that the incidence and detection rates of colorectal neoplasia in people aged 50–74 years were similar for people with positive results for NBCSP or community‐initiated FITs. The large population in our study means that it provides colonoscopy providers strong evidence that evaluation should be performed equally promptly for patients with positive results from NBSCP and community‐initiated FITs. Box 1 – Demographic characteristics of the 2693 patients with positive faecal immunochemical test results and referred to the Newcastle Direct Access Colonoscopy Service for colonoscopy, 2014–18 Faecal immunochemical test Total Community‐initiated NBCSP Number of patients 1439 1254 2693 Sex Women 675 559 1234 Men 764 695 1459 Age (years), mean (SD) 62.9 (6.8) 63.2 (7.3) 63.1 (7.0) Numbers of patients 50–54 years 213 147 360 55–59 years 280 271 551 60–64 years 312 212 524 65–69 years 330 288 618 70–74 years 304 336 640 NBCSP = National Bowel Cancer Screening Program; SD = standard deviation. Box 2 – Differences in colonoscopy outcomes for people who had community‐initiated (1233 patients) or NBCSP (1132 patients) faecal immunochemical tests CI = confidence interval; NBCSP = National Bowel Cancer Screening Program. *Large sessile polyps (> 2 cm) or malignant polyps. † Between values for community‐initiated and NBCSP groups.

Simon Whitcher · Monique Magnusson · Jon Gani · Christopher Oldmeadow · Peter G Pockney