Melanoma Margins Trial-II: 1cm v 2cm Wide Surgical Excision Margins for AJCC Stage II Primary Cutaneous Melanoma

Inclusion Criteria:

Patients may be included in the study if they meet ALL of the following criteria:

1.

1. Patients must have a Stage II primary invasive cutaneous melanoma (pT2b-pT4b,AJCC 8th edition) with Breslow thickness >1.0mm to 2.0mm; >2.0mm to 4.0mm or >4.0mm with ulceration, or >2.0mm to 4.0mm; or >4.0mm without ulceration (Table

1. as determined by diagnostic biopsy (narrow excision, incision, shave orpunch biopsy) and subsequent histopathological analysis.

2. Must have a primary melanoma that is cutaneous (including head, neck, trunk,extremity, scalp, palm or sole).

3. An uninterrupted 2cm margin must be technically feasible around biopsy scar orprimary melanoma.

5. Surgical intervention (which refers to the staging -SLNB and WLE as these areboth to be done on the same day) must be completed within 120 days of theoriginal diagnosis. Surgical intervention must also be performed within 28 daysof randomisation.

6. Patients must be 18 years or older at time of consent.

7. Patient must be able to give informed consent and comply with the treatment protocoland follow up plan.

8. Life expectancy of at least 5 years from the time of diagnosis, not considering themelanoma in question, as determined by the PI.

9. Patients must have an ECOG performance score between 0 and 1 at screening.

10. A survivor of prior cancer is eligible provided that ALL of the following criteriaare met and documented:

• The patient has undergone potentially curative therapy for all priormalignancies,

• There has been no evidence of recurrence of any prior malignancies for at leastFIVE years (with the exception of successfully treated uterine/cervical ornon-melanoma skin cancers (SCCs/BCCs) with no evidence of recurrence), and

• The patient is deemed by their treating physician to be at low risk ofrecurrence from previous malignancies.

Exclusion Criteria:

Patients will be excluded from the study for ANY of the following reasons:

1. Uncertain diagnosis of melanoma i.e., so-called 'melanocytic lesion of unknownmalignant potential'.

2. Patient has already undergone WLE at the site of the primary index lesion.

3. Patient unable or ineligible to undergo staging SLNB of the primary index lesion.

4. Perineural invasion or neurotropic melanoma: Neurotropism or perineural invasion inany type of melanoma is an exclusion. Perineural invasion does not includeentrapment of nerves within the main primary tumour mass.

5. Desmoplastic melanoma: with any patient where pathology determines melanoma as PUREdesmoplastic (as per WHO definition of >90% desmoplasia), they are not eligible forthis study. However melanomas with less than 90% desmoplasia or mixed desmoplasticsubtypes are eligible unless there is neurotropism present (perineural invasion).

6. Microsatellitosis (a nest of metastatic tumour cells found to be growing away fromthe primary tumour) as per AJCC 8th edition definition is an exclusion.

7. Subungual melanoma

8. Patient has already undergone a local flap reconstruction of the defect afterexcision of the primary and determination of an accurate excision margin isimpossible.

9. History of previous or concurrent (i.e. >1 primary melanoma) invasive melanoma.

10. Melanoma located distal to the metacarpophalangeal joint; on the tip of the nose;the eyelids or on the ear; genitalia, perineum or anus; mucous membranes or internalviscera.

11. Physical, clinical, radiographic or pathologic evidence of satellite, in-transit,regional, or distant metastatic melanoma.

12. Patient has undergone surgery on a separate occasion to clear the lymph nodes of theprobable draining lymphatic field, including -SLNB, of the index melanoma.

13. Any additional solid tumour or hematologic malignancy during the past 5 years (withexception of non- melanoma skin cancers (T1 skin lesions of squamous cell carcinoma (SCCs), basal cell carcinoma (BCCs)), or uterine/cervical cancer).

14. Melanoma-related operative procedures not corresponding to criteria described in theprotocol.

15. Planned adjuvant radiotherapy to the primary melanoma site after wide local excisionis not permitted as part of the protocol and any patients given this treatment wouldbe excluded from the study.

16. History of organ transplantation.

17. Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) atenrolment or within 6 months prior to enrolment.

Pregnancy is not a specific exclusion criterion for this trial, though it may not be clinically appropriate to perform a wide excision and SLNB until the pregnancy has been completed, which may exclude the patient due to violation of inclusion criterion 4. We would advise careful counselling of the patient prior to enrolling the patient, which would include a discussion at the treating centre's multidisciplinary team meeting or tumour board. We would strongly advise contacting the central trial office to discuss the case prior to enrolling on the study.