A Phase III, Multi-Centre Randomised Control Trial Investigating 1cm v 2cm Wide Excision Margins for Primary Cutaneous Melanoma
Why is this study necessary?
In melanoma, a wider excision around the original biopsy scar is performed to reduce risk of local recurrence and improve patient outcomes. While this 2-stage procedure is the fundamental international standard of care for all melanomas, surprisingly the detail of the wide excision is still highly controversial.
In the first stage, a doctor, usually a dermatologist or skin specialist, removes some of the growth in order to evaluate the tissue and make a diagnosis. A pathologist examines the growth to confirm that it is a melanoma and to see if the entire tumour has been removed. The second stage, known as a “wider excision”, involves removing an extra “safety margin” of healthy skin surrounding the original melanoma site to ensure that any remaining scattered melanoma tumour cells are removed that may have been left behind after the first operation. This is done to reduce the chance of your melanoma returning. Depending on the country you are living in, current guidelines recommend a safety margin of between 1 and 3cm of healthy skin all around your melanoma is removed.
Evidence from previous research suggests that a 1cm excision is enough to reduce a patient’s risk of the melanoma coming back in the same area; however a trial is needed to prove this theory.
Other advantages of a reduced surgical margin include:
- A smaller margin could mean less surgery which means a smaller scar and potentially less scar tissue.
- A smaller margin could mean that extra surgery to repair the wound, such as a skin graft or other reconstruction, is no longer necessary.
- A smaller margin could reduce the time it takes for patients to recover from their surgery, possibly resulting in a reduced stay in hospital post operatively. Less time in hospital may make it easier for patients to return to their normal routine as well as being more affordable overall.
- Reducing the pain that patients may feel immediately after their operation and in the longer term.
- Using a smaller margin may reduce the length of time it takes surgeons to perform the surgery, allowing them to see more patients in a day and increasing the availability of the surgeons so they can treat more people.
This study will also look at the costs and effects of having surgery for both patients and the health system. In addition, this study will look at the financial impact of melanoma on patients’ households. By finding out if patients and their families are suffering from financial hardship, this information will help policy makers to address out-of-pocket costs for melanoma patients.
What does participation in this trial involve?
You will be participating in a randomised controlled clinical trial. Sometimes we do not know which treatment is best for treating a condition. To find out we need to compare different treatments. We put people into groups and give each group a different treatment. The results are compared to see if one is better. To try to make sure the groups are the same, each participant is put into a group by chance (random). In this way, we will be able to compare the results of the different margins and therefore determine which is the more effective in melanoma. This research project has been designed to make sure the researchers interpret the results in a fair and appropriate way and avoids study doctors or participants jumping to wrong conclusions. Randomisation means that you are put into a group by chance. Neither you nor your doctor can choose the group you will be in. In this study you will have a 50% chance of receiving 1cm or 2cm margin, much like if you flipped a coin.
Treatment:
You will be assigned to receive either a:
- 1cm Wider Excision of your primary melanoma lesion
- 2cm Wider Excision of your primary melanoma lesion
What do I have to do?
For this trial you will be asked to attend regular visits with a doctor involved in this research. These visits are normal for patients with your condition; are recommended by your doctor and align with the national treatment guidelines.
Am I eligible to Participate?
Here are the criteria that patients have to fulfil in order to be enrolled onto the study. Please ask your doctor, cancer nurse specialist or research nurse if you are unsure of these criteria:
Inclusion criteria:
- Patients must have a primary invasive cutaneous melanoma of Breslow thickness greater than 1 millimetre as determined by diagnostic biopsy (narrow excision, incision or punch biopsy) and subsequent histopathological analysis.
- Patients must have had the primary completely excised, including the invasive any in situ component but excluding melanocytic atypia, with a narrow margin, either in one stage or more than one stage in the case where an incision or punch biopsy has previously been performed. This information, including measured margins of lateral and deep clearance must be documented on the pathology report.
- Must have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm, sole).
- An uninterrupted 2cm margin must be technically feasible around biopsy scar or primary melanoma.
- Randomisation and the primary study intervention, including staging sentinel node biopsy, must be completed by 120 days of original diagnosis.
- Patients must be 18 years or older at time of consent.
- Patients must be able to give informed consent and comply with the treatment protocol and follow-up plan.
- Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI.
- Patients must have an ECOG performance score between 0 and 1.
- A survivor of prior cancer is eligible provided that ALL of the following criteria are met and documented...
- The patient has undergone potentially curative therapy for all prior malignancies,
- There has been no evidence of recurrence of any prior malignancies for at least FIVE years (except for successfully treated cervical or non-melanoma skin cancer with no evidence of recurrence), and
- The patient is deemed by their treating physician to be at low risk of recurrence from previous malignancies.
- Uncertain diagnosis of melanoma i.e. so-called ‘melanocytic lesion of unknown malignant potential’.
- Patient has already undergone wide local excision at the site of the primary index lesion.
- Patient unable or ineligible to undergo staging sentinel lymph node biopsy of the primary index lesion
- Desmoplastic or neurotropic melanoma.
- Microsatellitosis as per AJCC 2009 definition
- Subungual melanoma
- Patient has already undergone a local flap reconstruction of the defect after excision of the primary and determination of an accurate excision margin is impossible.
- History of previous or concurrent (i.e., second primary) invasive melanoma.
- Melanoma located distal to the metacarpophalangeal joint, on the tip of the nose, the eyelids or on the ear, mucous membranes or internal viscera.
- Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic melanoma.
- Patient has undergone surgery on a separate occasion to clear the lymph nodes of the probable draining lymphatic field, including sentinel lymph node biopsy, of the index melanoma.
- Any additional solid tumour or haematologic malignancy during the past 5 years except T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine/cervical cancer.
- Melanoma-related operative procedures not corresponding to criteria described in the protocol.
- Planned adjuvant radiotherapy to the primary melanoma site after Wide Local Excision is not permitted as part of the protocol and any patients given this treatment would be excluded from the study.
- History of organ transplantation.
- Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at any time during study participation or within 6 months prior to enrolment.
Study Documents:
Trial Protocol
Patient Information Sheet