WoW - Single- vs Two-staged Excisions of Thin Melanoma (WoW)

Wise vs Wide: A National, Multicenter, Prospective, Randomized and Controlled, Parallel Group, Non-inferiority Study to Compare Single- vs Two-staged Excisions of Thin Melanoma

The overall aim of this national, multicenter, prospective, randomized, and controlled study is to enhance the management of patients with thin melanoma (≤1 mm Breslow thickness). The investigators hypothesize that wide local excisions (WLEs) following complete excision of thin melanoma do not affect the risk of recurrence, defined as the occurrence of local, regional, distant disease, or melanoma-specific death during a 5- to 10-year follow-up period.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Procedure: Surgery; Other: No Surgery

Detailed Description

Melanoma is one of the most common forms of skin cancer and has become the third most common type of cancer among men and the fourth most common among women in Sweden.

The mortality associated with melanoma is strongly linked to the thickness of the original tumor. Thicker tumors generally have a worse prognosis compared to thinner tumors. In melanoma in situ (MIS), the tumor is confined to the epidermis and cannot spread. In invasive melanoma, the tumor has grown into the dermis. The thickness of these invasive melanomas is measured using the "Breslow thickness." Thinner invasive melanomas with a Breslow thickness of ≤1.0 mm constitute the majority of cases in Sweden and have an excellent prognosis with a 10-year disease-specific survival rate of 97%.

Melanoma represents a significant economic burden with increasing healthcare costs. Early detection and cost-effective treatment strategies are therefore important to improve prognosis, reduce costs, and avoid unnecessary overtreatment.

Surgical methods for treating melanoma vary depending on the thickness of the tumor. Traditionally, a two-step procedure has been used. Initially, a diagnostic excision (surgery to remove the tumor) with a narrow clinical margin is performed. Once melanoma is confirmed, a second wide local excision (WLE) is performed around the surgical scar with a 1-2 cm clinical margin depending on the exact Breslow thickness. This method has evolved over time, and narrower clinical margins are now used in the WLE than previously. However, researchers have begun to question whether a WLE is necessary at all for thin melanomas if the tumor is completely removed during the initial diagnostic excision.

Researchers are now exploring a more personalized treatment strategy that considers histopathological margins instead of a standardized clinical margin. For well-defined melanomas, a clinical margin of 3-5 mm may be sufficient to ensure that the melanoma is removed with an acceptable histopathological margin (≥1.5 mm). The hypothesis is that this margin may be adequate and that the WLE does not reduce the risk of local, regional or distant disease nor melanoma-specific death. If the hypothesis is proven, unnecessary surgery, patient suffering, risk of complications, resource utilization, and healthcare costs could be reduced.

The investigators now want to investigate whether there is a difference in the risk of recurrence, spread, and/or death for patients with thin melanomas (≤1mm Breslow thickness) treated with only one excision compared to the current standard of two excisions.

• Study Type: Interventional
• Enrollment (Estimated): 2486
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: John Paoli, Professor; Phone Number: 0730404044; Email: john.paoli@vgregion.se

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Recruiting
    • Sahlgrenska University Hospital
    • Contact: John Paoli, Professor; Phone Number: +46730404044; Email: john.paoli@vgregion.se
    • Principal Investigator: John Paoli, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Patients need to fulfill all criteria listed below:

• Has recently been diagnosed with a primary invasive cutaneous melanoma of Breslow thickness ≤1.0 mm (pT1) as determined by a diagnostic excision with subsequent histopathological analysis that:

  1. Is located on a body location in which a WLE with a 10-mm clinical margin is feasible and would have been planned according to current standard of care.
  2. Had histopathologically verified free margins of at least 1.5 mm.
• Is 18 years or older at time of consent.
• Is able to give informed consent and comply with the treatment protocol and follow-up plan.
• Has a life expectancy of ≥5 years from the time of diagnosis.

Exclusion Criteria:

If any of the listed criteria below are present, the patient is ineligible for study participation.

The study lesion:

• was partially biopsied prior to the diagnostic excision.
• was diagnostically excised with a clinical margin >5 mm.
• was a melanoma of desmoplastic or lentiginous (i.e. lentigo maligna or acral lentiginous) subtype.
• was located on digits in which amputation is necessary.

The patient:

• had a previous or concurrent MIS or invasive melanoma (cutaneous or non-cutaneous).
• had physical, clinical, radiographic or pathologic evidence of microsatellite, satellite, in-transit, regional or distant metastatic melanoma.
• had a previous or intercurrent treated solid tumor or hematologic malignancy during the past 5 years except cutaneous squamous cell carcinoma or basal cell carcinoma.
• has planned adjuvant radiotherapy to the primary melanoma site after WLE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Wide - With wide local excision - Control group; Standard treatment with a wide local excision (i.e. reexcision of the diagnostic excision scar with a lateral clinical surgical margin of 10 mm and a deep clinical surgical margin down to the muscular fascia as recommended by the Swedish national guidelines).	Procedure: Surgery; Wise or wide excision
Experimental: Wise - Without wide local excision - Experimental group; No wide local excision.	Other: No Surgery; No wide local excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate at 5 years.	Recurrence is defined as any presence of local/regional/distant disease or melanoma-specific death.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate at 10 years.	Recurrence is defined as any presence of local/regional/distant disease or melanoma-specific death.	10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications	Determine the frequency of postoperative complications in both treatment groups.	3 months
Direct and indirect costs per patient	Calculate and compare costs per patient in the experimental and control groups.	5 years
All-cause mortality	Overall all-cause mortality incidence in both treatment groups.	5 years
All-cause mortality	Overall all-cause mortality incidence in both treatment groups.	10 years
Biomarkers	Differences in biomarkers of recurrent and non-recurrent melanomas.	10 years
Scar length, width and quality	Measurement of the scar length and width as well as the scar quality assessed by both patient and clinician (measured with the Patient and Observer Scar Assessment Scale, POSAS). The POSAS consists of two subscales: the Patient Scale and the Observer Scale, each ranging from 6 to 60, where a lower score indicates a better scar outcome.	1 year
Scar length, width and quality	Measurement of the scar length and width as well as the scar quality assessed by both patient and clinician (measured with the Patient and Observer Scar Assessment Scale, POSAS). The POSAS consists of two subscales: the Patient Scale and the Observer Scale, each ranging from 6 to 60, where a lower score indicates a better scar outcome.	3 years
Patient satisfaction	The Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - Patient Satisfaction questionnaire (FACIT-TS-PS) is to be completed electronically or in clinic. The FACIT-TS-PS assesses patient satisfaction with treatment, with total scores ranging from 0 to 36, where higher scores indicate greater satisfaction with treatment.	3 months
Patient satisfaction	The Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - Patient Satisfaction questionnaire (FACIT-TS-PS) is to be completed electronically or in clinic. The FACIT-TS-PS assesses patient satisfaction with treatment, with total scores ranging from 0 to 36, where higher scores indicate greater satisfaction with treatment.	1 year
Patient satisfaction	The Functional Assessment of Chronic Illness Therapy - Treatment Satisfaction - Patient Satisfaction questionnaire (FACIT-TS-PS) is to be completed electronically or in clinic. The FACIT-TS-PS assesses patient satisfaction with treatment, with total scores ranging from 0 to 36, where higher scores indicate greater satisfaction with treatment.	2 years
Patients' quality of life	The Quality of Life (QoL) questionnaire Functional Assessment of Cancer Therapy - Melanoma (FACT-M) is to be completed electronically or in clinic. The FACT-M assesses quality of life in melanoma patients, with total scores ranging from 0 to 172, where higher scores indicate better quality of life.	3 months
Patients' quality of life	The Quality of Life (QoL) questionnaire Functional Assessment of Cancer Therapy - Melanoma (FACT-M) is to be completed electronically or in clinic. The FACT-M assesses quality of life in melanoma patients, with total scores ranging from 0 to 172, where higher scores indicate better quality of life.	1 year
Patients' quality of life	The Quality of Life (QoL) questionnaire Functional Assessment of Cancer Therapy - Melanoma (FACT-M) is to be completed electronically or in clinic. The FACT-M assesses quality of life in melanoma patients, with total scores ranging from 0 to 172, where higher scores indicate better quality of life.	2 years

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Region Östergötland; Region Skane; Region Stockholm; Dalarna County Council, Sweden; Region Örebro County; Region Västerbotten; Blekinge County Council Hospital
• Investigators: Principal Investigator: John Paoli, Professor, Dept. of Dermatology and Venereology, Sahlgrenska Academy, University of Gothenburg, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2025
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2039

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Surgery; Recurrence; Melanoma; Death; Metastasis; Wide local excision
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma
• Other Study ID Numbers: WoW - Wise or wide

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data will be shared upon reasonable request.
• IPD Sharing Time Frame: Data will be available 6 months after publication of study results (start date) and 1 year after this (end date).
• IPD Sharing Access Criteria: Data will be shared upon reasonable request and accessed by contacting john.paoli@gu.se.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No