Centre of Research Excellence (CRE) in Melanoma

The CRE in Melanoma is an Australian collaboration of clinicians, researchers and implementation scientists from melanoma centres and universities in New South Wales (Melanoma Institute Australia; The University of Sydney; and the Australian Institute of Health Innovation, Macquarie University) and Victoria (Peter MacCallum Cancer Centre; Victorian Melanoma Service Alfred Hospital; The University of Melbourne; Monash University and the Skin and Cancer Foundation), Australia, and is funded by the Australian National Health and Medical Research Council (NHMRC). The Melanoma CRE, like all Australian government-funded CREs, is tasked with three primary objectives: pursuing collaborative research; developing capacity; and promoting translation of research outcomes into policy and practice. This third objective is the focus of the mixed-methods study outlined in this protocol paper, in particular to understand the structural, contextual and cultural factors affecting implementation of the recently updated national clinical practice guidelines for SLNB for melanoma patients in Australia.

Prioritisation of SLNB uptake as a key implementation goal

One of the rationales behind embedding implementation science expertise within the Melanoma CRE is to support the transfer of evidence-based, effective and efficient patient-centred care across and beyond the Melanoma CRE research sites so that all melanoma patients, regardless of location in Australia, can benefit from its generation of knowledge. A necessary first step in the implementation process is to identify and prioritise interventions with the greatest potential to impact positively on the quality of care for patients with melanoma. Between December 2018 and February 2019, meetings of Melanoma CRE members systematically mapped CRE projects across the melanoma care continuum (online supplementary file 1) and identified two in which implementation science had the greatest potential to identify pathways to practice change. One of these, ‘SLNB for patients with melanoma’, is outlined in this protocol paper.

Melanoma diagnosis and staging

Melanoma is the fourth most common cancer diagnosis in Australia.1 In 2019, it is estimated that 15 229 people will be diagnosed with invasive melanoma and that 1725 people will die from it.1 Between 2011 and 2015, an individual diagnosed with melanoma had a 91% chance of surviving for 5 years.1 Survival is influenced by the stage of the melanoma at diagnosis. Staging takes into account tumour thickness and ulceration and whether the melanoma has spread regionally (to the lymph nodes) or more distantly (to other parts of the body) (table 1).2 3 Accurate staging is a fundamental prerequisite for optimal melanoma management. From the perspective of the individual patient, staging provides important prognostic information, guides management and clinical decision making, including whether a patient may benefit from adjuvant systemic therapy, shapes communication between the patient, their clinician and the patient’s family and may determine the patient’s eligibility for clinical trials.4 From a public health perspective, staging also facilitates standardised reporting, centralised cancer registry reporting, the design and conduct of clinical trials, and the analysis of clinical trial data.2

Sentinel lymph node biopsy (SLNB)

An important primary melanoma staging tool is SLNB, a multiphase procedure involving cutaneous lymphatic mapping with lymphoscintigraphy in the nuclear medicine department, surgical removal of the localised SLNs and pathological assessment of the SLNs for the presence of metastatic disease. The procedure has a high degree of accuracy for identifying patients with melanoma who have clinically occult metastases in their regional lymph nodes.5 6

Prior to the introduction of SLNB by Morton et al in 1992,5 the only way to detect spread from the primary tumour site to the regional lymph nodes was through clinical examination of the patient’s lymph nodes or by performing an elective lymph node dissection with its attendant morbidity. Elective lymph node dissection was routinely offered to patients who were considered to be at risk of relapse in the belief that removal of all lymph nodes in the lymph node field would prevent distant spread of the melanoma to other parts of the body. However, as only a small proportion (about 20%) of those at-risk patients who had an elective lymph node dissection actually had nodal metastases, the procedure resulted in considerable unnecessary morbidity, primarily lymphoedema.

SLNB avoided this unnecessary morbidity by using nuclear medicine and vital blue dyes to identify the SLN, that is, the lymph node receiving direct lymphatic drainage from the primary melanoma site.5 The rationale (which Morton referred to as the incubator hypothesis or stepwise model of disease progression) was that the most likely site of early metastases, the SLN, could then be removed and tested pathologically for clinically occult melanoma cells, and if found, a completion lymph node dissection was performed. Conversely, if the SLN was clear of metastatic disease, then it was reasoned that it was unlikely that other, more distant nodes would be diseased, thereby saving the patient from an unnecessary lymph node dissection. In this context, SLNB has been reported to be cost-effective for the management of intermediate-thickness melanoma.7

Contemporary melanoma management

Based on the results of two recent randomised controlled trials,8 9 it is now widely accepted that a completion lymph node dissection in patients who are SLN positive does not provide an overall survival benefit. Consequently, the role SLNB plays in contemporary melanoma management is changing. In Australia and in many other countries, in addition to providing staging and prognostic information, SLNB is now being used to identify patients who might benefit from adjuvant systemic therapy. Adjuvant systemic therapies, such as immunotherapies (in which the patient’s own immune system is activated to target cancer cells) and BRAF-directed targeted molecular therapies (which block the growth and spread of cancer by interfering with specific abnormal molecules within the tumour cells themselves), have been developed on the basis of recent advances in our understanding of the molecular and immune biology of melanoma. These adjuvant systemic therapies have been shown to significantly prolong survival in patients with unresectable stage III and stage IV melanoma10 and have also been shown to improve recurrence-free survival when administered as adjuvant therapy in patients with resected stage III melanoma.11–13 However, they are not yet publicly funded in the adjuvant melanoma setting in Australia. Consequently, access is often restricted to clinical trials, eligibility for which requires staging via SLNB, and compassionate access schemes.

International (American Joint Committee on Cancer (AJCC) staging system) and national (Australian) guidelines for SLNB

The AJCC Staging Manual has become the benchmark for classifying patients’ disease stage, outlining prognosis and establishing the best treatment approaches.14 The recently updated eighth edition recommends that lymphatic mapping and SLNB should be routinely used as a staging procedure for patients with T1b, T2, T3 or T4 primary cutaneous melanomas (ie, melanomas ≥0.8 mm with or without ulceration or <0.8 mm with ulceration) and who have clinically negative regional lymph nodes.3 Likewise, the 2018 Australian Clinical Practice Guidelines for the Diagnosis and Management of Melanoma recommend that ‘SLNB should be considered for all patients with melanoma >1 mm in thickness and for patients with melanoma >0.8 mm with other high risk pathological features to provide optimal staging and prognostic information and to maximise management options for patients who are node positive’.15

Rates of SLNB in Australia and internationally

The limited data that exist for rates of SLNB for melanoma in Australia indicate that these rates may be lower than expected. Rates of SLNB are likely to be related to the guidelines in place at that point in time. In Australia, the 1999 guidelines stated ‘Lymphatic mapping and sentinel node biopsy should be considered for all melanomas >1 mm thick provided they can be done in the context of a controlled clinical trial and by surgeons trained in these procedures’; the 2008 guidelines stated ‘Patients with a melanoma >1.0 mm in thickness should be given the opportunity to discuss sentinel lymph node biopsy to provide staging and prognostic information’. A population-based study in Queensland between 2010 and 2014 reported rates of SLNB of 33% (261 of 787 study patients) for stage 1b and stage 2 melanoma patients.16 The 2006 New South Wales Melanoma Patterns of Care Study reported that SLNB was performed in 45% of patients diagnosed with a melanoma >0.75 mm thick.17 SLNB rates in Australia are roughly comparable with rates reported internationally. Data from the US Surveillance Epidemiology and End Results database for 2004–2006 indicate that 53% of eligible patients received an SLNB,18 while data from a population-based study in the northeast of France indicated that 34% of patients with a melanoma >1 mm in thickness received an SLNB.19 Factors associated with having an SLNB included patient age <50 years,17 primary tumour on upper limb,17 treatment in an urban setting17 19–23 and hospital size (>50 beds).24 Recent international data indicate that rates of SLNB are increasing: in the Netherlands, the SLNB rate increased from 39.0% in 2003 to 47.8% in 2014.25 The authors suggested that changes in rates of SLNB may be related to evolving views on SLNB as a staging or therapeutic procedure, changes to the AJCC staging system and less acceptance of the stepwise model of disease progression.

Challenges relating to implementation of clinical practice guidelines

Clinical practice guidelines synthesise and summarise complex research evidence into easily understandable recommendations. Clinical practice guidelines were initially heralded as a means of overcoming the knowledge gaps perceived to be behind observed variations in clinical practice.26 However, even guidelines that are based on rigorous evidence rarely penetrate medical practice as intended.26 It is now accepted that the distillation and summary of evidence into clinical practice guidelines, although a necessary step, is not in and of itself sufficient for the translation of research evidence into routine clinical practice.26

Successful adoption and implementation of guidelines require an understanding of the technical, social, political, economic, cultural, structural and psychological barriers to the use of research evidence.27 As Greenhalgh and colleagues28 noted in 2004, clinicians are not passive recipients of innovations (such as guidelines). Instead they ‘seek innovations, experiment with them, evaluate them, find (or fail to find) meaning in them, develop feelings (positive or negative) about them, challenge them, worry about them, complain about them, “work around” them, gain experience with them, modify them to fit particular tasks, and try to improve or re-design them—often through dialogue with other users’. In addition, as Ferlie and colleagues29 noted in 2001, the research evidence for a particular practice is often ambiguous and contested. Consequently, the evidence base ‘must be continually interpreted and reframed in accordance with the local context, a process that often involves power struggles among various professional groups’.29 For their widespread acceptance, guidelines need to be perceived as authoritative, credible and professional documents that help healthcare professionals improve their practice, traits closely tied to the provenance of the guidelines.26

Theoretical framework

The Tailored Implementation for Chronic Disease (TICD) Checklist is a comprehensive, integrated checklist that was designed to be used as a tool to identify determinants of practice that warrant further in-depth investigation.30 Although originally designed to be used in the chronic disease setting, the authors advise that it can be used more broadly.31 Determinants of practice are the barriers and facilitators that might impact on implementation of an intervention. The TICD Checklist includes 57 potential determinants of practice grouped into seven domains. These seven domains are: guideline factors; individual health professional factors; patient factors; professional interactions; incentives and resources; capacity for organisational change; and social, political and legal factors.

The TICD Checklist was selected for a number of reasons, specifically: (1) the TICD Checklist is a single comprehensive, integrated checklist of determinants of practice that was created through the systematic identification and synthesis of 12 previously published checklists, frameworks, taxonomies and classifications of determinants of healthcare professional practice; (2) the TICD Checklist focuses on provider behaviour rather than patient behaviour; (3) in addition to identifying determinants of practice, the TICD Checklist can also be used to inform the design of implementation strategies; and (4) the TICD Checklist includes a comprehensive range of worksheets designed to support its use.

The knowledge generated in this project will be used to inform future implementation strategies to support effective and widespread melanoma guideline implementation in Australia. A greater awareness of the guidelines, and the melanoma patients to whom they apply, should in turn lead to improved melanoma management and outcomes for patients, including more accurate information about prognosis and access to systemic adjuvant therapies such as immunotherapy or targeted molecular therapy for eligible patients with melanoma.