Wise or wide (WoW) study protocol: a national, multicentre, prospective, randomised and controlled, parallel group, non-inferiority study to compare single-staged versus two-staged excisions of thin invasive (<=1.0 mm) melanoma

Background
Sweden has one of the highest incidence rates of cutaneous melanoma globally, and the incidence is rapidly increasing. Melanoma mortality is linked to the thickness of the primary tumour, with thicker melanomas having a poorer prognosis. Thin invasive melanomas (≤1.0 mm Breslow thickness) have excellent prognosis. Traditionally, the surgical approach for melanoma involves a two-step procedure of a diagnostic excision followed by a wide local excision (WLE) with 10 mm clinical margins. The WLE aims to remove potential microsatellites and residual melanoma, which in theory would prevent loco-regional recurrence and could improve survival. However, recent research questions the necessity of WLE for thin invasive melanomas, given their favourable prognosis, minimal risk of microsatellitosis and low rates of residual melanoma found in WLE tissue specimens.

Methods and analysis
This multicentre, non-inferiority, randomised controlled trial seeks to enrol 2486 patients with thin invasive melanomas that are completely excised with ≥1.5 mm histopathological margins following the diagnostic excision. Patients will be randomly assigned to either a control group that will undergo a WLE with 10 mm clinical margins according to current clinical routine or an experimental group without a WLE. The primary and secondary endpoints are recurrence-free survival at 5 and 10 years, respectively, with tertiary aims including postoperative complications, scar quality, patient satisfaction and quality of life, healthcare resource utilisation as well as differences in biomarkers of recurrent and non-recurrent melanomas. Patients will be assessed at clinical follow-up visits at 3 months as well as at 1, 2, 3, 5 and 10 years.

Ethics and dissemination
Approval of this study was obtained from the Swedish Ethical Review Authority (2024-03274-01). The findings of the study will be presented at international scientific meetings and published in peer-reviewed academic journals.

Trial registration number
NCT06363591.

Leggi
Aprile 2025

Real-world outcomes in patients with melanoma brain metastasis: a US multisite retrospective chart review study of systemic treatments

Objective
This study examined real-world treatment patterns and outcomes in patients with melanoma brain metastasis (MBM) treated with first-line immunotherapy consisting of nivolumab plus ipilimumab or anti-programmed death-1 (PD-1) monotherapy (nivolumab or pembrolizumab) or targeted therapy consisting of BRAF/MEK inhibitors.

Design
Retrospective chart review study.

Setting
Academic medical centres, community hospitals and private practice offices.

Participants
Included patients diagnosed with melanoma with brain metastasis in the USA.

Outcome measures
The statistical analysis was descriptive in nature. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared between treatments in a univariate Cox proportional hazards model.

Results
In total, 472 patients with MBM who received first-line nivolumab plus ipilimumab (n=246), anti-PD-1 monotherapy (n=112) or BRAF/MEK inhibitors (n=114) were identified. Patients receiving nivolumab plus ipilimumab, compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors, had favourable baseline prognostic factors, such as younger age, fewer or smaller brain metastases, better Eastern Cooperative Oncology Group performance status and less frequently elevated lactate dehydrogenase. Median follow-up times were 15.4 months (range 0.1 to 37.0), 13.3 months (range 0.3 to 36.6) and 13.9 months (range 1.9 to 36.5), respectively. Numerically longer OS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.47, 95% CI 0.34 to 0.67) or BRAF/MEK inhibitors (HR 0.72, 95% CI 0.50 to 1.04) and numerically longer PFS was observed with nivolumab plus ipilimumab versus anti-PD-1 monotherapy (HR 0.74, 95% CI 0.53 to 1.02) or BRAF/MEK inhibitors (HR 0.82, 95% CI 0.60 to 1.12). With nivolumab plus ipilimumab, anti-PD-1 monotherapy and BRAF/MEK inhibitors, 1-year OS rates were 79%, 60% and 72%, respectively; 1-year PFS rates were 68%, 58% and 59%.

Conclusions
In this real-world study, first-line nivolumab plus ipilimumab appeared to provide benefit versus anti-PD-1 monotherapy and BRAF/MEK inhibitors in patients with MBM, consistent with pivotal trial data. However, the observed benefit may have been due to confounding and selection bias, given that patients receiving nivolumab plus ipilimumab had favourable baseline prognostic factors compared with patients receiving anti-PD-1 monotherapy or BRAF/MEK inhibitors.

Leggi
Gennaio 2025

Characterising melanoma diagnostic pathways for patients in routine practice using administrative health data in Ontario, Canada: a population-based study

Objective
To characterise diagnostic pathways for patients with melanoma in routine practice and compare patient, disease and diagnostic interval (DI) characteristics across pathways.

Design
Descriptive cross-sectional study using administrative health data.

Setting
Population-based study in Ontario, Canada.

Participants
Patients with melanoma diagnosed from 2007 to 2019.

Main outcome measures
We used latent class cluster analysis to create clusters of patients with similar diagnostic experiences to characterise diagnostic pathways in routine practice. Indicator variables characterised the patient’s keratinocyte carcinoma and dermatologist history, presentation pattern, procedure types, number of visits and procedures, and the activity on the diagnosis date. 2 tests and Pearson residuals were used. We characterised clusters by the lengths of their DI, primary care subinterval and specialist care subinterval.

Results
There were 33 371 patients diagnosed with melanoma from 2007 to 2019. We identified four diagnostic pathways: ‘primary care only’ (n=6107), ‘referred to specialist with immediate action’ (n=8987), ‘multiple visits and procedures in specialist care’ (n=11 893) and ‘specialist care only’ (n=6384). Patient, disease and DI characteristics varied across pathways. Pathway types varied regionally. A higher proportion in the ‘primary care only’ pathway lived in rural areas whereas a higher proportion in the ‘referred to specialist for immediate action’ and the ‘specialist care only’ pathways lived in major urban centres. Across pathways, the median DI varied from 1 to 67 days, the median primary care subinterval varied from 1 to 30 days and the median specialist care subinterval varied from 1 to 25 days. Patients in the ‘primary care only’ pathway experienced the shortest DIs, and patients in the ‘multiple visits and procedures in specialist care’ pathway experienced the longest DIs.

Conclusions and relevance
We identified four melanoma diagnostic pathways. The shortest DI, the ‘primary care only’ pathway, highlights the important role of primary care and the need to reduce the wait for specialists. Diagnostic processes varied across geographical locations. Future research should address reasons for these differences, including whether they are associated with inefficient or inappropriate care.

Leggi
Gennaio 2025

Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study

Introduction
A diagnosis of melanoma in situ presents negligible risk to a person’s lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients’ management choices and anxiety levels.

Methods and analysis
This study is a between-subjects randomised online experiment, using hypothetical scenarios. Following consent, eligible participants will be randomised 1:1:1 to three labels: ‘melanoma in situ’ (control), ‘low-risk melanocytic neoplasm’ (intervention 1) and ‘low-risk melanocytic neoplasm, in situ’ (intervention 2). The required sample size is 1668 people. The co-primary outcomes are (1) choice between no further surgery or further surgery to ensure clear histological margins greater than 5 mm and (2) choice between patient-initiated clinical follow-up when needed (patient-led surveillance) and regular routinely scheduled clinical follow-up (clinician-led surveillance). Secondary outcomes include diagnosis anxiety, perceived risk of invasive melanoma and of dying from melanoma and management choice anxiety (after surgery choice and follow-up choice). We will make pairwise comparisons across the three diagnostic label groups using regression models (univariable and multivariable).

Ethics and dissemination
The study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000740594). Ethics approval has been received from The University of Sydney Human Research Ethics Committee (2024/HE000019). The results of the study will be published in a peer-reviewed medical journal, and a plain language summary of the findings will be shared on the Wiser Healthcare publication page (https://www.wiserhealthcare.org.au/category/publications/).

Trial registration number
Australian New Zealand Clinical Trials Registry (ID 386943).

Leggi
Dicembre 2024