1. The Natural History and Surgical Treatment of Primary Melanoma 2011 Phoenix Surgical Symposium John M. Kane III, MD Chief-Melanoma/Sarcoma Roswell Park Cancer Institute

2. Melanoma Facts estimated 68,130 cases in 2010 –8700 deaths 6 th most common adult cancer –second only to leukemia for loss of life- years –one death per hour in U.S. lifetime risk approaching 1 in 55

3. ABCDE’s of a Suspicious Lesion Aasymmetry Bborder irregularity Ccolor differences Ddiameter > 6 mm E evolution

4. Biopsy of a Suspicious Lesion thickness of tumor most important –full thickness punch biopsy –excisional biopsy –limitations of shave biopsy consider need for more surgery –small rim of normal skin (1-2mm) –arms/legs-longitudinal –chest/abdomen/back-transverse –small biopsy of large lesion

7. Melanoma Staging: Primary Tumor Breslow thickness (mm) –≤ 1, 1.01-2, 2.01-4, >4 ulceration mitotic index –# mitoses/mm 2 –< vs. ≥ 1 Clark level no longer relevant

8. Melanoma Staging: Lymph Nodes micro versus macrometastases number of positive nodes concept of in transit disease AJCC melanoma staging 2010

9. 2010 AJCC Melanoma Staging

10. AJCC TNM Staging Balch et al. J Clin Oncol 2001

11. Additional Prognostic Information Balch et al. J Clin Oncol 2001

12. Additional Prognostic Information Balch et al. J Clin Oncol 2001

13. AJCC Melanoma Nomogram www.melanomaprognosis.org/

14. Preoperative Melanoma Workup biopsy pathology history and physical exam focused studies from H&P no proven benefit to routine CXR, CT, PET, or laboratory studies –CXR: <0.3% true +; 3-15% false + –CT or PET: <1.3% true +; 16-37% false +

16. Surgical Treatment historical “wide local excision” with 5 cm margins –single patient pathology description –circular defect with skin graft current margin recommendations –melanoma in situ: 5mm –< 2 mm: 1 cm –≥ 2mm: 2 cm full thickness skin/SQ to fascia for melanoma ignore lines of Langer < 20% will require skin graft local recurrence rate 1-2%

18. Melanoma Lymph Node Metastases and Prognosis # lymph nodes 1 microscopic 1 visible 2-3 microscopic 2-3 visible > 4 5 year survival 50-70% 30-60% 50-65% 25-50% 20-30%

19. Lymphatic Basins at Risk lymphoscintigraphy –59% of lymphatic drainage not predicted by Sappey’s lines –89% of midline lesions drained bilaterally –evidence of orderly lymphatic drainage

20. Sentinel Lymph Node (SLN) Biopsy outpatient procedure for finding occult tumor in the regional nodes success rate > 95% minimal complications –<2% risk lymphedema completion lymphadenectomy if sentinel node is positive

21. SLN Biopsy 10-40% are positive –risk increases with primary tumor thickness NOT for every melanoma patient –≥ 10% risk for nodal metastases –no major medical co-morbidities –reasonable life expectancy –less predictive in older patients “As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients—all poor prognostic factors. Incongruously, however, the frequency of SLN metastasis declines with increasing age.” Chao C, Martin RCG II, Ross MI, et al. Correlation between prognostic factors and increasing age in melanoma. Ann Surg Oncol 2004;11:259–64.

22. Lessons from Lymph Node Mapping

25. The $1,000,000 Question Does early detection and removal of clinically occult nodal metastatic melanoma using SLN biopsy/completion node dissection (CLND) improve survival?

26. Multicenter Selective Lymphadenectomy Trial (MSLT) 1,347 patients with melanoma 1.2-3.5 mm 3:2 randomized WE/SLN Bx vs. WE/OBS median follow-up 59 months positive nodes: 16% vs. 15.6% 5 yr melanoma specific survival –87.1% vs. 86.6% (n.s.) 90.2% if negative SLN Bx 72.3% if positive SLN Bx Mean # positive nodes: 1.4 vs. 3.3

27. Multicenter Selective Lymphadenectomy Trial (MSLT)

28. Benefits of SLN Biopsy accurate nodal staging in all patients high chance for obtaining regional control of positive nodal basin variable most predictive for survival guide adjuvant therapy decisions identifies a homogeneous patient population for clinical trials IS A MARKER FOR BUT NOT THE CAUSE OF DISTANT METASTASES!!!IS A MARKER FOR BUT NOT THE CAUSE OF DISTANT METASTASES!!!

29. Melanoma Surveillance 50% recurrences in first 2 years –90% by 5 years –2% recur 15+ years history and physical –Q3-6 mos X 2 yrs, Q6 mos X 3 yrs, Q yr X 5 yrs no proven benefit to routine surveillance imaging or bloodwork –occasional pelvic CT to assess iliac LNs after only superficial groin LND for a positive SLN biopsy dermatologic skin surveillance –5% lifetime risk for second primary melanoma

30. Special Situations thick primary children elderly pregnancy unknown primary atypical Spitz/unknown biologic potential congenital nevus

31. Thick Primary and Sentinel Node Biopsy Gershenwald et al., Ann Surg Onc, 2000 126 patients SLN biopsy 4-22 mm thick melanoma 39% positive SLN predictors of survival SLN status ulceration

32. Melanoma in Children 2% melanomas < age 20 risks: congenital nevus, DNS, xeroderma 80% early stage outcome similar to adults –+/- shorter time to recurrence treatment same as adults Spitz nevus

33. Elderly Melanoma Patient negative survival results of MSLT-I medical comorbidities –anticipated survival –risks of anesthesia –? candidate for adjuvant therapy “As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients—all poor prognostic factors. Incongruously, however, the frequency of SLN metastasis declines with increasing age.” wide excision +/- SLN biopsy (selective) Chao C, Martin RCG II, Ross MI, et al. Correlation between prognostic factors and increasing age in melanoma. Ann Surg Oncol 2004;11:259–64.

34. Melanoma, Pregnancy, and Estrogen melanoma biology not worse during pregnancy no increased risk with subsequent pregnancy –timing based upon recurrence risk no increased risk with OCP’s or HRT no prospective randomized trials, but good case/control studies Schwartz et al., Cancer, 2003

35. Surgical Treatment of Melanoma During Pregnancy SLN biopsy –information extremely valuable –does not improve survival –anesthetic/dye risks –accuracy does not decrease after wide excision  Perform wide excision and delay sentinel node biopsy until after delivery

36. Unknown Primary concept of regression –hypopigmentation/Wood’s light exam 2.6% of 2485 patients 43% presented with nodal disease –5 yr OS 38.7% no survival difference stage for stage vs. historical controls Katz et al., Melanoma Research, 2005

37. Atypical Spitz Tumor atypical features not sufficient to call melanoma treat as if melanoma WLE consider SLN biopsy –up to 50% positive inverse with age not necessarily a poor prognosis Dahlstrom et al., Pathology, 2004

38. Large Congenital Nevus 1:1,000-20,000 births melanoma risk 2-20% –1/3 childhood melanoma –1/2 by age 10 consider prophylactic excision –full thickness to fascia

39. Melanoma Summary evaluation of suspicious lesion –full thickness biopsy –smallest biopsy possible –think about need for additional surgery wide excision is primary therapy importance of regional lymph node status –sentinel lymph node biopsy –removal of all lymph nodes for clinical disease or positive sentinel node need for long-term follow-up