Clinical trial NCT06363591: WoW - Single- vs Two-staged Excisions of Thin Melanoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Melanoma
Keywords: Melanoma
Surgery
Wide local excision
Recurrence
Metastasis
Death
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Region Stockholm
name: Region Skane
name: Region Västerbotten
name: Region Örebro County
name: Blekinge County Council Hospital
name: Region Östergötland
name: Dalarna County Council, Sweden
First posted: 2024-04-12
Enrollment: 2486
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients with thin (≤1.0 mm) invasive melanomas excised with a histopathological margin ≥1.5 mm will be offered to participate following informed consent and randomization (1:1) to either:

1. Standard treatment with a WLE 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.

   or
2. Experimental treatment with no WLE.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence rate at 5 years.
timeFrame: 5 years
Secondary outcomes:
measure: Recurrence rate at 10 years.
timeFrame: 10 years
Other outcomes:
measure: Postoperative complications
timeFrame: 3 months
measure: Scar length, width and quality
timeFrame: 1 year
measure: Scar length, width and quality
timeFrame: 3 years
measure: Patient satisfaction
timeFrame: 3 months
measure: Patient satisfaction
timeFrame: 1 year
measure: Patient satisfaction
timeFrame: 2 years
measure: Patients' quality of life
timeFrame: 3 months
measure: Patients' quality of life
timeFrame: 1 year
measure: Patients' quality of life
timeFrame: 2 years
measure: All-cause mortality
timeFrame: 5 years
measure: All-cause mortality
timeFrame: 10 years
measure: Direct and indirect costs per patient
timeFrame: 5 years
measure: Biomarkers
timeFrame: 10 years
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Dept. of Dermatology and Venereology, Sahlgrenska Academy, University of Gothenburg, Sweden
name: John Paoli, Professor
role: PRINCIPAL_INVESTIGATOR
References: