Strategy Review Workshop Malignant Melanoma Developing Clinical Practice S.Sinclair Consultant Plastic Surgeon A.Bro

1. Strategy Review Workshop(Malignant Melanoma)Developing Clinical PracticeS.Sinclair – Consultant Plastic SurgeonA.Brown – SpR Plastic SurgeryNorthern Ireland Plastic and Maxillofacial Service

2. Malignant Melanoma 13th most common cancer in males (2%). 9th most common in females (3%). Half of patients aged 57 or younger. Rapid increase in incidence between 1993 and 2001, specifically in males. Incidence rate in N.I. Is increasing faster than any other tumour. Accounts for only 7% of skin cancer cases, but almost all skin cancer deaths.

3. New staging system for melanoma adopted by the American Joint Committee on Cancer (AJCC) Stage Criteria IA Localized melanoma =0.75 mm or level II (T1a,N0,M0) IB Localized melanoma 0.76-1.5 mm or level III (T1b,T2a,N0,M0) IIA Localized melanoma 1.5-4.0 mm or level IV (T2b,T3a,N0,M0) IIB Localized melanoma >4 mm or level V (T3b,T4a,N0,M0) IIC T4b,N0,M0 IIIA T1-4a,N1a,M0 T1-4a,N2a,M0 IIIB T1-4b,N1,M0 T1-4b,N2a,M0 T1-4a,N1b,M0 T1-4a,N2b,M0 T1-4a/b,N2c,M0 IIIC T1-4b,N1b,M0 T1-4b,N2b,M0 Any T,N3,M0 IV Any T any N M1a, M1b or M1c

4. Management of Melanoma Multidisciplinary Team Plastic Surgery Dermatology Oncology Histopathology Radiotherapy Clinical Nurse Specialist

5. GP Referral of Suspicious Lesions 7-point list Change in size Change in shape Change in colour Diameter > 7mm Inflammation Oozing Change in sensation Referral One ‘major’ criteria Three ‘minor’ criteria

6. Referral System

7. Current Standard Patients seen within 2 weeks of referral Patients operated on within 2 weeks (primary excision)

8. Initial Assessment and Management Clinical Examination: - examination of lesion - full skin examination - lymph nodes / hepatomegaly Excision Biopsy of Lesion (if indicated): - 2mm margin

9. Definitive Management of Primary Lesion (based upon Breslow thickness) Less than 1mm: 1cm margin 1 – 2mm: 2cm margin 2 – 4mm: 2-3cm margin Greater than 4mm: 2-3cm margin - Veronesi (WHO 1998): no difference in survival b/n 1 and 3 cm margins - Balch (Intergroup Melanoma Trial): no diff in survival b/n 2 and 4cm margins - Aitken et al (1983): advises 3cm margin for > 4mm - BAPS / MSG Trial: no diff b/n 1cm and 3cm in survival. decrease in locoregional recurrence for 3 vs 1cm.

10. Follow-Up In situ: - self examination (mole surveillance) only. Less than 1mm: - 3 monthly for 3 years Greater than 1mm: - 3 monthly for 3 years - further 6 monthly for 2 years

11. Further Investigations Stage I and IIa: - clinical examination only Stage IIb and over: - FBP / LFT’s (inc.LDH) - CXR - USS or CT liver - ? MRI

12. Referral to Oncologist / Adjuvant Therapy II B and above referred to oncologist (local practice: refer if > 1mm) Offered treatment as part of trial No adjuvant therapy of proven benefit - ECOG 1684 – some benefit with IF alpha 2b - ECOG 1690- no increase in overall survival - Koops et al(1998) – no survival benefit with isolated limb perfusion.

13. Lymph Node Status / Management Importance of LN Status: - single most important predictor of survival when compared with other variables. (Gershenwald et al, J Clin Oncol 1999) Options for management: - Elective Lymph Node Dissection (ELND) - Therapeutic Lymph Node Dissection (TLND)

14. ELND – Is it of Benefit? ELND offers no overall survival benefit however survival is improved in patients who have histologically positive nodes. Evidence: - Cascinelli (Lancet, 1998) - Karbousis et al (1991) - Balch et al 1985 HENCE CASE FOR SENTINEL NODE BIOPSY

15. Sentinel Node Biopsy Means of identifying the first lymph node draining the skin in which melanoma arises. Usually performed at time of wider excision. Currently only a limited number of Plastic Surgery Units in UK performing procedure. Lens et al, Br J Plast Surg 2002.

16. Sentinel Node Biopsy Procedure is 95% accurate at identifying sentinel node if performed correctly. Detects 20% of patients with occult nodes

17. Procedure Pre-op lymphoscintigraphy Intra-op dye injection and gamma probe scan for node localisation Node dissection Histological processing

18. Procedure Pre-op lymphoscintigraphy - Inject radiolabelled (Technitium 99m) albumin at 4 points around tumour. - Obtain the plain gamma camera pictures. - Localise the SLN and mark its position on the skin. - The day before or the morning of surgery.

19. Procedure At time of surgery Inject blue dye (Patent V) (0.5ml –1.0ml) around the tumour Wait 10-15minutes. Scan the drainage area with the gamma probe. Incision over the point of maximum count. Identify blue nodes and check with the gamma probe. Excise node(s) and send for histology.

20. Procedure Await histology: If SLNB +ve: Completion lymph node dissection within 5 days If SLNB –ve : Observation policy

21. Benefits of Sentinel Node Biopsy Provides accurate staging information. Enables early recruitment to adjuvant therapy trials (beneficial?). Likely to be necessary for inclusion into studies (in America at present). Reassurance to patients following negative SLNB (psychological). ? Improves disease free survival. ? May show overall survival advantage.

22. Benefits of SNB / ELND vs TLND Studies suggesting survival advantage: Milton, Br J Surg 1982 Roses, Ann Surg 1985 Balch, J Clin Oncol 1988 Cascinelli, Lancet 1998 Balch, Ann Surg Oncol 2000 Balch, J Clin Oncol 2001 Morton, Ann Surg 2003 ** Retrospective, non-randomised**

23. Disadvantages of SNB Scar. May need general anaesthesia. May need overnight stay. Seroma, wound infection (3%) Increased risk of in-transit disease? Removal of tumour cells inhibits the development of an immune response? No long term outcome data available from prospective randomised trials. Funding and waiting list implications.

24. Indications for Sentinel Lymph Node Biopsy All intermediate thickness (1–4 mm) melanomas. ? Male patients with truncal melanoma <0.76 mm - have up to a 9% incidence of nodal metastases ? All patients with melanoma 0.76–1.0 mm - have a 5% incidence of nodal metastases and should be offered a choice of sentinel lymph node biopsy. ? Male patients with “thin” melanomas that are Clark level II or greater, ulcerated, regressed, or axial in location. - these patients are at greater risk for metastases and death at 5 years

25. Cost / Resource Implications Equipment Inpatient stay Theatre time Histology Outpatient care Complications Completion lymphadenectomy Staffing - Plastic Surgeon(s) - Theatre / Nursing staff - Pathologist / Laboratory staff

26. Cost/Resource Implications Analysis from UK Plastic Surgery Units performing SNB: - Royal Free Hospital, London - £4600 / patient - Royal Devon and Exeter Hospital - £5000 / patient

27. Positron Emission Tomography (PET) Scan FDG (fluoro-deoxyglucose). For detection and staging of melanoma patients. Highly sensitive and specific. Superior to CT for identifying mets to LN, liver and soft tissue. ‘Upstages’ patients, avoiding inappropriate surgery. Cost-effective.

28. PET scan Not routinely recommended / practised. Guidelines proposed by RCP/RCR/RCPath PET scans for: - pts with MM with known dissemination to assess exact extent of disease. - pts with MM in whom SNB could not be performed. Need to develop local guidelines.

29. Summary Rapid increase in numbers of MM patients referred to Plastic Surgery. Significant resource implications. Newer modalities of patient investigation / management should be explored to optimise patient care.

30. Summary Sentinel Node Biopsy - the best staging procedure available. - should be performed by Plastic Surgeon, as part of multidisciplinary team. - significant cost / resource implications (213 new cases of MM 2001).