Do age at diagnosis, tumour thickness and tumour site explain sex differences in melanoma survival? A causal mediation analysis using cancer registry data.

Women diagnosed with melanoma have better survival than men, but little is known about potential intervention targets to reduce this survival gap by sex. We conducted a population-based study using Victorian Cancer Registry data including 5833 women and 6780 men aged 15 to 70 years when diagnosed with first primary melanoma between 2007 and 2015. Deaths to the end of 2020 were identified through linkage to the Victorian and national death registries. We estimated the effect of age at diagnosis, tumour thickness and tumour site on reducing the melanoma-specific survival gap by sex (ie, interventional indirect effects [IIEs]) on risk difference (RD) scale. Compared to women, there were 211 (95% CI: 145-278) additional deaths per 10 000 in men within 5 years following diagnosis. We estimated that 44% of this gap would be reduced by a hypothetical intervention shifting the distribution of melanoma thickness in men to be the same as that observed for women (IIEthickness RD 93 [95% CI: 75-118] per 10 000) and 20% by an intervention on tumour site (head and neck/trunk vs upper limb/lower limb; IIEsite RD 42 [95% CI: 15-72] per 10 000), while an intervention on age at diagnosis would have a negligible effect. Tumour thickness, tumour site and age at diagnosis mediated 65% of the effect of sex on 5-year melanoma survival in Victoria. Of these factors, tumour thickness had the most considerable mediating effect, suggesting that effective promotion of earlier detection of melanoma in men could potentially nearly halve the gap in melanoma-specific survival by sex.

Assessing the genetic risk of nodular melanoma using a candidate gene approach.

BACKGROUND: Nodular melanoma (NM) is a challenge to diagnose early due to its rapid growth and more atypical clinical presentation, making it the largest contributor to melanoma mortality. OBJECTIVES: Our study aim was to perform a rare-variant allele (RVA) analysis of whole-exome sequencing of patients with NM and non-NM (minor allele frequency ≤ 1% non-Finnish European) for a set of 500 candidate genes potentially implicated in melanoma. METHODS: This study recruited 131 participants with NM and 194 with non-NM from South-east Queensland and patients with NM from Victoria to perform a comparative analysis of possible genetic differences or similarities between the two melanoma cohorts. RESULTS: Phenotypic analysis revealed that a majority of patients diagnosed with NM were older males with a higher frequency of fair skin and red hair than is seen in the general population. The distribution of common melanoma polygenic risk scores was similar in patients with NM and non-NM, with over 28% in the highest quantile of scores. There was also a similar frequency of carriage of familial/high-penetrant melanoma gene and loss-of-function variants. We identified 39 genes by filtering 500 candidate genes based on the greatest frequency in NM compared with non-NM cases. The genes with RVAs of greatest frequency in NM included PTCH1, ARID2 and GHR. Rare variants in the SMO gene, which interacts with PTCH1 as ligand and receptor, were also identified, providing evidence that the Hedgehog pathway may contribute to NM risk. There was a cumulative effect in carrying multiple rare variants in the NM-associated genes. A 14.8-fold increased ratio for NM compared with non-NM was seen when two RVAs of the 39 genes were carried by a patient. CONCLUSIONS: This study highlights the importance of considering frequency of RVA to identify those at risk of NM in addition to known high penetrance genes.

Examining labelling guidelines for AI-based software as a medical device: A review and analysis of dermatology mobile applications in Australia.

In recent years, there has been a surge in the development of AI-based Software as a Medical Device (SaMD), particularly in visual specialties such as dermatology. In Australia, the Therapeutic Goods Administration (TGA) regulates AI-based SaMD to ensure its safe use. Proper labelling of these devices is crucial to ensure that healthcare professionals and the general public understand how to use them and interpret results accurately. However, guidelines for labelling AI-based SaMD in dermatology are lacking, which may result in products failing to provide essential information about algorithm development and performance metrics. This review examines existing labelling guidelines for AI-based SaMD across visual medical specialties, with a specific focus on dermatology. Common recommendations for labelling are identified and applied to currently available dermatology AI-based SaMD mobile applications to determine usage of these labels. Of the 21 AI-based SaMD mobile applications identified, none fully comply with common labelling recommendations. Results highlight the need for standardized labelling guidelines. Ensuring transparency and accessibility of information is essential for the safe integration of AI into health care and preventing potential risks associated with inaccurate clinical decisions.

Minimum labelling requirements for dermatology artificial intelligence-based Software as Medical Device (SaMD): A consensus statement.

BACKGROUND/OBJECTIVES: Artificial intelligence (AI) holds remarkable potential to improve care delivery in dermatology. End users (health professionals and general public) of AI-based Software as Medical Devices (SaMD) require relevant labelling information to ensure that these devices can be used appropriately. Currently, there are no clear minimum labelling requirements for dermatology AI-based SaMDs. METHODS: Common labelling recommendations for AI-based SaMD identified in a recent literature review were evaluated by an Australian expert panel in digital health and dermatology via a modified Delphi consensus process. A nine-point Likert scale was used to indicate importance of 10 items, and voting was conducted to determine the specific characteristics to include for some items. Consensus was achieved when more than 75% of the experts agreed that inclusion of information was necessary. RESULTS: There was robust consensus supporting inclusion of all proposed items as minimum labelling requirements; indication for use, intended user, training and test data sets, algorithm design, image processing techniques, clinical validation, performance metrics, limitations, updates and adverse events. Nearly all suggested characteristics of the labelling items received endorsement, except for some characteristics related to performance metrics. Moreover, there was consensus that uniform labelling criteria should apply across all AI categories and risk classes set out by the Therapeutic Goods Administration. CONCLUSIONS: This study provides critical evidence for setting labelling standards by the Therapeutic Goods Administration to safeguard patients, health professionals, consumers, industry, and regulatory bodies from AI-based dermatology SaMDs that do not currently provide adequate information about how they were developed and tested.

Evaluation of dynamic dermoscopic features of melanoma and benign naevi by sequential digital dermoscopic imaging and total body photography in a high-risk Australian cohort.

BACKGROUND/OBJECTIVES: Sequential digital dermoscopic imaging (SDDI) and total body photography (TBP) are recommended as a two-step surveillance method for individuals at high-risk of developing cutaneous melanoma. Dermoscopic features specific to melanoma have been well described, however, dynamic changes on serial imaging are less understood. This study aims to identify and compare dermoscopic features in developing melanomas and benign naevi that underwent SDDI and TBP to understand which dermoscopic features may be associated with a malignant change. METHOD: Histopathology reports from a private specialist dermatology clinic from January 2007 to December 2019 were reviewed. Histopathologically confirmed melanoma and benign naevi that underwent SDDI and TBP with a minimum follow-up interval of 3 months were included. RESULTS: Eighty-nine melanomas (38.2% invasive, median Breslow thickness 0.35 mm, range: 0.2-1.45 mm) and 48 benign naevi were evaluated by three experienced dermatologists for dermoscopic changes. Features most strongly associated with melanoma included the development of neovascularisation, asymmetry and growth in pigment network, additional colours, shiny white structures, regression, structureless areas and change to a multi-component pattern. The presence of atypical vessels (p = 0.02) and shiny white structures (p = 0.02) were significantly associated with invasive melanoma. CONCLUSION: Evaluation for certain evolving dermoscopic features in melanocytic lesions monitored by SDDI and TBP is efficient in assisting clinical decision making. SDDI with TBP is an effective tool for early detection of melanoma.

Informing a position statement on the use of artificial intelligence in dermatology in Australia.

Artificial Intelligence (AI) is the ability for computers to simulate human intelligence. In dermatology, there is substantial interest in using AI to identify skin lesions from images. Due to increasing research and interest in the use of AI, the Australasian College of Dermatologists has developed a position statement to inform its members of appropriate use of AI. This article presents the ACD Position Statement on the use of AI in dermatology, and provides explanatory information that was used to inform the development of this statement.

Impact of chronic lymphocytic leukaemia on melanoma outcomes: A retrospective case-control study.

With new, effective treatments for chronic lymphocytic leukaemia (CLL) the impact of second malignancies is increasingly important. We performed a retrospective case-controlled study examining the effect of CLL and its treatment on melanoma-specific survival and recurrence. A total of 56 patients with melanoma with CLL were matched 1:1 to patients without CLL for age, date of diagnosis, gender and melanoma tumour, node, metastasis (TNM) stage. Multivariate analysis found CLL was associated with significantly worse melanoma-specific mortality (hazard ratio [HR] 2.46, 95% confidence interval [CI] 1.27-4.74, p = 0.007) and recurrence (HR 3.44, 95% CI 1.79-6.63, p < 0.001). Patients with CLL had poor immunotherapy tolerance and prior CLL treatment was not associated with melanoma outcomes.

Yield of baseline imaging for distant metastases in high-risk primary melanoma.

BACKGROUND: The yield of baseline imaging in patients presenting with higher risk primary tumours, at least American Joint Committee on Cancer 8th edition stage IIC or III melanoma, is unclear. METHODS: This retrospective study included patients referred to the Victorian Melanoma Service from January 2017 to April 2020, diagnosed with at least stage IIC or stage III melanoma. Patients with a T4b tumour and no sentinel lymph node biopsy were included as 'T4bNX'. RESULTS: One hundred and sixty-four patients (median age 65 years) with baseline imaging (T4bNX: 19, IIC: 30, IIIA: 21, IIIB: 43, IIIC: 50, IIID: 1) were included. The majority were male (73%), and those with T4bNX melanoma tended to be older (median age 79 years). Distant metastases were detected in 21% (4/19) of T4bNX, 3% (1/30) of stage IIC, 0% (0/21) of stage IIIA, and 6% (6/94) of stages IIIB-D melanoma patients. All stage III patients with distant metastases had palpable lymphadenopathy a presentation. Two patients had brain metastases, both of whom had T4bNX melanoma and synchronous extra-cranial metastases. CONCLUSIONS: Compared to stage IIC, baseline imaging detects higher rates of extra-cranial distant disease in stages IIIB-D and T4bNX melanoma. Intracranial imaging has greater yield in patients with distant extra-cranial disease.

Legal and ethical considerations of artificial intelligence in skin cancer diagnosis.

Artificial intelligence (AI) technology is becoming increasingly accurate and prevalent for the diagnosis of skin cancers. Commercially available AI diagnostic software is entering markets across the world posing new legal and ethical challenges for both clinicians and software companies. Australia has the highest rates of skin cancer in the world and is poised to be a significant benefactor and pioneer of the technology. This review describes the legal and ethical considerations raised by the emergence of artificial intelligence in skin cancer diagnosis and proposes recommendations for best practice.

Sensitivity of two Australian melanoma risk tools to identify high-risk individuals among people presenting with their first primary melanoma.

AIMS: Regular skin examinations for early detection of melanoma are recommended for high-risk individuals, but there is minimal consensus regarding what constitutes 'high-risk'. Melanoma risk prediction models may guide this. We compared two online melanoma risk prediction tools: Victorian Melanoma Service (VMS) and Melanoma Institute Australia (MIA) risk tools; to assess classification differences of patients at high-risk of a first primary melanoma. METHODS: Risk factor data for 357 patients presenting with their first primary melanoma were entered into both risk tools. Predicted risks were recorded: 5-year absolute risk (VMS tool and MIA tool); 10-year, lifetime, and relative risk estimates (MIA tool). Sensitivities for each tool were calculated using the same high-risk thresholds. The MIA risk tool showed greater sensitivity on comparison of 5-year absolute risks (90% MIA vs 78% VMS). Patients had significantly higher odds of being classified as high or very-high risk using the MIA risk tool overall, and for each patient subgroup. Using either tool, patients of male gender or with synchronous multiple first primary melanomas were more likely to be correctly classified as high- or very-high risk using 5-year absolute risk thresholds; but tumour invasiveness was unrelated to risk. Classification differed when using the MIA risk categories based on relative risk. CONCLUSIONS: Both melanoma risk prediction tools had high sensitivity for identifying individuals at high-risk and could be used for optimising prevention campaigns. The choice of which risk tool, measure, and threshold for risk stratification depends on the intended purpose of risk prediction, and ideally requires information on specificity.

Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study.

BACKGROUND: Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty-six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry. METHODS: Potential clinical quality indicators were identified by examining the literature, including Australian and international melanoma guidelines, and by consulting with key melanoma and registry opinion leaders. A modified two-round Delphi survey method was used, with participants invited from relevant health professions routinely managing melanoma as well as relevant consumer organisations. RESULTS: Nineteen participants completed at least one round of the Delphi process. 12 of 13 proposed clinical quality indictors met the validity criteria. The clinical quality indicators included acceptable biopsy method, appropriate excision margins, standardised pathology reporting, indications for sentinel lymph node biopsy, and involvement of multidisciplinary care and referrals. CONCLUSION: This study provides a multi-stakeholder consensus for important clinical quality indicators that define optimal practice that will now be used in the Australian Melanoma Clinical Outcomes Registry (MelCOR).

Dermoscopic Evaluation of Inflammatory Nail Disorders and Their Mimics.

Nail dermoscopy (onychoscopy) is a valuable diagnostic tool for evaluating diseases in the nail apparatus. It is non-invasive, allowing clinicians to prioritize particular nails for biopsy. Thus, it can improve diagnostic accuracy and expedite treatment. Evaluating inflammatory nail disorders using onychoscopy is a relatively new approach to clinical assessment and has the potential to augment clinical care. This review highlights key dermoscopic features of major inflammatory nail disorders, including trachyonychia, nail psoriasis, nail lichen planus, onychotillomania, nail lichen striatus and allergic contact dermatitis due to artificial nails. It also illustrates their management and differential diagnoses, including onychomycosis, onycholysis, nail dystrophy due to systemic amyloidosis and malignant nail tumours. Limitations of this review included the low amount of literature on this topic and non-standardized terminology used among research-ers. As onychoscopy is a relatively new technique, further studies and standardization of terminology are warranted to consolidate the role of dermoscopy in evaluating inflammatory nail disorders.

Diagnostic tools used for melanoma: A survey of Australian general practitioners and dermatologists.

BACKGROUND/OBJECTIVE: Diagnostic tools such as dermoscopy, sequential digital dermoscopy imaging (SDDI), total body photography (TBP) and automated diagnostic tools are available to assist in early melanoma diagnosis. The use, accessibility and barriers of dermoscopy have been well studied; however, there are few similar studies regarding SDDI, TBP and automated diagnostic tools. We aim to understand the use of these diagnostic aids amongst Australian general practitioners (GPs) and dermatologists. METHODS: Between June 2019 and January 2020, GPs and dermatologists across Australia were invited to participate in an online survey. Surveys were distributed through GP and dermatology organisations. RESULTS: A total of 227 survey responses were received, 175 from GPs and 52 from dermatologists. Amongst GPs, 44.6% worked in a skin cancer clinic. Dermoscopy was used at least occasionally by 98.9% of all GPs. SDDI was used by 93.6% of skin cancer GPs, 80.8% of dermatologists and 45.3% of generalist GPs. TBP was used or recommended by 77.1% of generalist GPs, 82.3% of skin cancer GPs and 86.5% of dermatologists. The most common barriers to the use of TBP were cost, limited accessibility, poor patient compliance, and time required for both patients and doctors. Very few clinicians reported using automated diagnostic tools. There was an interest in future diagnostic aids for melanoma in 88% of GPs and dermatologists. CONCLUSION: Dermoscopy, SDDI and TBP were commonly used by responding Australian skin cancer GPs and dermatologists in this survey. Automated diagnostic tools were not reported to be used routinely. Several barriers were identified for use of TBP.

The impact of incomplete clinical information and initial biopsy technique on the histopathological diagnosis of cutaneous melanoma.

BACKGROUND/OBJECTIVES: Increased rates of histopathological misdiagnosis of melanoma have been associated with incisional punch more so than shave biopsy when compared with complete excisional biopsy. It is unknown how the increasing utilisation of shave biopsy may impact melanoma diagnosis. The extent to which the provision of clinical information to the pathologist may improve diagnostic accuracy remains unclear. This study assessed the impact of both initial biopsy technique and provision of adequate clinical information to pathologists on the accuracy of histopathological diagnosis of melanoma and disease progression. METHODS: We conducted a retrospective cohort with nested case-control study of all histopathological false-negative and false-positive melanoma diagnoses from January 2014 to May 2019 from the Victorian Melanoma Service electronic database. Cases were assessed for the initial biopsy type, provision of clinical information on pathology request forms and disease progression associated with false-negative diagnosis. RESULTS: Partial shave biopsy had higher odds of false-negative (OR 5.19, 95% CI 2.89-9.32; P < 0.001) and false-positive diagnoses (OR 1.95, 95% CI 1.45-2.63; P < 0.001) of melanoma when compared with elliptical excisional biopsy. These odds ratios were comparable with those found with incisional punch biopsy. Providing the suspected clinical diagnosis to pathologists also reduced the odds of false-negative diagnosis with melanoma progression by 3.8-fold (P = 0.02). CONCLUSION: The choice of initial biopsy technique and providing the suspected clinical diagnosis to pathologists are important for correct histopathological diagnosis of cutaneous melanoma and prevention of further disease progression.

Knowledge and attitudes of Australian dermatologists towards sentinel lymph node biopsy for melanoma: a mixed methods study.

BACKGROUND/OBJECTIVES: In melanoma management, sentinel lymph node biopsy (SLNB) is used to stage patients and to indicate prognosis. More recently, it has been used to select patients for adjuvant therapy. This study aimed to report knowledge of and attitudes towards SLNB for patients with melanoma among Australian dermatologists. METHODS: Mixed methods study using cross-sectional questionnaires (n = 88) and semi-structured interviews (n = 13), May-September 2019. RESULTS: Of the dermatologists surveyed, 56% thought SLNB had an important role in melanoma management, 26% were unsure and 18% thought SLNB unimportant. Of the 92% who would discuss SLNB with their patients, the main stated value of SLNB was for assessing eligibility for adjuvant therapies (79%); only 60% indicated SLNB was of value for providing prognostic information, and just over half (53%) thought it could improve staging. Interview data indicated that attitudes towards SLNB are shifting among dermatologists, driven by data from landmark clinical trials and the influence of professional networks. Accordingly, interviewees adopted one of three positions in relation to SLNB: (a) believed in utility of SLNB and adhered to the guidelines; (b) were unconvinced about utility of SLNB but adhered to the guidelines; and (c) were unconvinced about utility of SLNB and did not adhere to the guidelines. CONCLUSION: Although most of the dermatologists surveyed were familiar with and follow the SLNB recommendations, some disagreement with and distrust of the recommendations was evident. Greater acceptance of the SLNB recommendations appeared to be driven by the improved outcomes demonstrated in stage III patients receiving adjuvant systemic therapy.

Long-term deaths from melanoma according to tumor thickness at diagnosis.

There is little long-term follow-up information about how the number of melanoma deaths and case fatality vary over time according to the measured thickness of melanoma at diagnosis. This population-based longitudinal cohort study examines patterns and trends in case fatality among 44,531 people in Queensland (Australia) diagnosed with a single invasive melanoma (International Classification of Diseases for Oncology, third revision [ICD-O-3], C44, Morphology 872-879) between 1987 and 2011, including 11,883 diagnosed between 1987 and 1996, with up to 20 years follow-up (to December 2016). The 20-year case fatality increased by thickness, with the percentage of melanoma deaths within 20 years of diagnosis being up to 4.8% for melanomas with measured thickness <0.80 mm, 10.6% for tumors 0.8 to <1.0 mm and generally more than 30% for melanomas measuring 3 mm and more. For melanomas <1.0 mm, most deaths occurred between 5 and 20 years after diagnosis, whereas for thicker melanomas the reverse was true with most deaths occurring within the first 5 years. Five-year case fatality decreased over successive calendar time periods for melanomas <1.0 mm, but not for melanomas ≥1.0 mm. These findings demonstrate that the time course for fatal melanomas varies markedly according to tumor thickness at diagnosis. Improved understanding of the patient factors and characteristics of melanomas, in addition to tumor thickness, which increase the likelihood of progression, is needed to guide clinical diagnosis, communication with patients and ongoing surveillance pathways of patients with potentially fatal lesions.

Think before you shave: Factors influencing choice of biopsy technique for invasive melanoma and effect on definitive management.

BACKGROUND/OBJECTIVE: Partial biopsies are sometimes used for melanoma diagnosis with anticipated time and cost savings compared to excisional biopsy. However, their impact on subsequent melanoma management is unknown. Determine factors related to choice of partial over excisional biopsy to diagnose invasive melanoma and examine the effect of partial biopsies on definitive melanoma management. METHOD: Retrospective repeated cross-sectional population-based study through the Victorian Cancer Registry of diagnosed melanomas in 2005, 2010 and 2015. A random sample of 400 patients per year, stratified by tumour thickness, was selected. RESULTS: A total of 1200 patients had 833 excisional and 337 partial biopsies. Omission of suspected diagnosis on pathology requests affected 46% (532/1151) of all diagnostic biopsies. Diagnostic suspicion did not influence preference for partial over excisional biopsy [Odds Ratio (OR) 1.2, 95%CI 0.8-1.7; P = 0.40]. The partial:excisional biopsy usage ratio was higher in patients aged > 50 years than patients aged <50 years [relative risk ratios (RRR) 1.5; 95%CI 1.0 to 2.2; P = 0.03]. In 34% and 17% of tumours diagnosed with punch and shave, respectively, three procedures were required for definitive excision instead of two, compared with 5% of excisional biopsies When partial biopsy was used, patients were at greater risk of requiring three-staged excisions when controlled for age, anatomical site, melanoma subtype and thickness (RRR 6.7; 95%CI 4.4-10.1; P < 0.001). CONCLUSION: Diagnostic suspicion does not appear to be a major factor influencing choice of biopsy technique. Using partial biopsy to diagnose melanoma often leads to an extra procedure for definitive treatment compared with excisional biopsy.

The increasing use of shave biopsy for diagnosing invasive melanoma in Australia.

OBJECTIVE: To assess changes in the choice of skin biopsy technique for assessing invasive melanoma in Victoria, and to examine the impact of partial biopsy technique on the accuracy of tumour microstaging. DESIGN: Retrospective cross-sectional review of Victorian Cancer Registry data on invasive melanoma histologically diagnosed in Victoria during 2005, 2010, and 2015. SETTING, PARTICIPANTS: 400 patients randomly selected from each of the three years, stratified by final tumour thickness: 200 patients with thin melanoma (< 1.0 mm), 100 each with intermediate (1.0-4.0 mm) and thick melanoma (> 4.0 mm). MAIN OUTCOME MEASURES: Partial and excisional biopsies, as proportions of all skin biopsies; rates of tumour base transection and T-upstaging, and mean tumour thickness underestimation following partial biopsy. RESULTS: 833 excisional and 337 partial diagnostic biopsies were undertaken. The proportion of partial biopsies increased from 20% of patients in 2005 to 36% in 2015 (P < 0.001); the proportion of shave biopsies increased from 9% in 2005 to 20% in 2015 (P < 0.001), with increasing rates among dermatologists and general practitioners. Ninety-four of 175 shave biopsies (54%) transected the tumour base; wide local excision subsequently identified residual melanoma in 65 of these cases (69%). Twenty-one tumours diagnosed by shave biopsy (12%) were T-upstaged. With base-transected shave biopsies, tumour thickness was underestimated by a mean 2.36 mm for thick, 0.48 mm for intermediate, and 0.07 mm for thin melanomas. CONCLUSION: Partial biopsy, particularly shave biopsy, was increasingly used for diagnosing invasive melanoma between 2005 and 2015. Shave biopsy has a high rate of base transection, reducing the accuracy of tumour staging, which is crucial for planning appropriate therapy, including definitive surgery and adjuvant therapy.

Tumour mutation status and melanoma recurrence following a negative sentinel lymph node biopsy.

BACKGROUND: A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours. METHODS: Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded. Multivariate Cox proportional hazards regression models estimated the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the association between mutation status and development of recurrence following a negative-SLNB. RESULTS: Overall, 344/477 (72.1%) patients had a negative SLNB. Of these, 54 (15.7%) developed subsequent recurrence. The risk of disease recurrence following a negative SLNB was increased for patients with either a BRAF or NRAS mutant tumour compared to wild-type tumours (aHR 1.92, 95% CI: 1.02-3.60, p = 0.04). CONCLUSION: Melanoma patients with BRAF or NRAS mutant tumours had an increased risk compared to patients with BRAF/NRAS wild-type tumours of developing disease recurrence following a tumour-negative SLNB. The findings also confirm the importance of continued surveillance to monitor for disease recurrence among SLNB-negative patients.