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Nabil Wasif MD, MPH Associate Professor of Surgery Mayo ... · Median f/u . 7.5 years . 10 years :...
Transcript of Nabil Wasif MD, MPH Associate Professor of Surgery Mayo ... · Median f/u . 7.5 years . 10 years :...
Nabil Wasif MD, MPH Associate Professor of Surgery
Mayo Clinic in Arizona
Disclosures
Relevant Financial Relationship(s) None
Off Label Usage
None
Learning Objectives
• Discuss controversies in surgical margins for melanoma excision
• Examine the indications for sentinel node biopsy for melanoma
• Discuss controversies in the management of node positive melanoma
• Analyze the role of surgery for stage IV melanoma
Centrifugal lymph permeation
Surgical Margins in Melanoma
Surgical Margins in Melanoma
Balch CM, Houghton AN, Sober AJ, Soong S. Cutaneous Melanoma. St Louis QMP 1998
Randomized trials on Surgical Margins
WHO Intergroup Swedish European UK
# patients 612 740 989 326 900
Thickness <2 mm 1-4 mm 0.8-2 mm <2.1 mm >2 mm
Median f/u 7.5 years 10 years 11 years 16 years 5 years
Margins 1 cm vs 3 cm 2 cm vs 4 cm 2 cm vs 5 cm 2 cm vs 5 cm 1 cm vs 3 cm
LRR 9% vs 9% 2.5% vs 3.5% 1% 13% vs 20% HR 1.26
DFS 82% vs 84% 80% 85% vs. 83% NS
OS 90% vs 90% 70% vs 77% 85% 87% vs 86% NS
Conclusion 1 cm for <1 mm 2 cm for 1-4 mm
2 cm for > 0.8 mm
2 cm for < 2.1 mm
1 cm NOT for >2 mm
Current Guidelines for Surgical Margins of Excision
Controversies • There has never been a comparison of 1 vs. 2cm for
intermediate and thick melanomas • 1cm margin for all?
• None of the randomized trials showed any difference in survival or local recurrence
• What about Mohs surgery?
Mohs surgery for H&N Melanoma
Zitelli. J Am Acad Dermatol. 2005 Jan;52(1):92-100
• Not randomized
• Used historical controls
Mohs surgery for melanoma • No randomized trials • National Comprehensive Cancer Network (NCCN)
does not make any recommendations • Journal of the American Academy of Dermatology
(JAAD) takes a pass on the issue
• Reasonable to use for tricky anatomic locations • Also reasonable for melanoma in situ
Courtesy of JC Martinez, MD.
Should All Melanomas Undergo
SLNB? Tumor Total No. Positive SLN Thickness Patients All Non-Ulcerated
Ulcerated (mm) (N) (%) (%) (%) < 1.00 326 4.2 3.9 12.5 1.01-2.00 490 11.4 10.8 21.2 2.01-4.00 310 28.5 23.1 37.0 4.01+ 190 45.5 34.2 55.4 Total 1316 17.4 11.9 37.0
Ross, MI. Clin Cancer Res. 2006;12: 2312s-2319s.
Incidence of Positive SLN: AJCC Stage Grouping
0
10
20
30
40
50
60
Perc
ent P
ositi
ve S
LN
3.9%
11.4%
22.1%
35.3%
55.4%
Ia Ib IIa IIb IIc
AJCC Stage
Guidelines for SLNB for Melanoma SSO/ASCO and NCCN published guidelines
Intermediate thickness melanoma
• Recommended for Breslow thickness 1-4 mm of any anatomic site
Thick melanomas
• May be recommended for staging and to facilitate regional disease control >4 mm melanomas
Thin melanomas
• Insufficient evidence to support routine SLNB for melanomas <1 mm in Breslow thickness, although it may be considered in high-risk patients
Coit DG, et al. Melanoma clinical practice guidelines in oncology. J Natl Compre Cancer Netw. 2012;10:366-400.
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609. doi: 10.1056/NEJMoa1310460.
Breslow thickness: - 1.2 – 3.5 mm - >3.5 mm
Efficacy and Value of SLNB: Multi-center Selective Lymphadenectomy Trial - I
Randomization: - WLE and observe - WLE and SLNB
1661 randomized - 1347 intermediate - 314 thick
• Within SLNB group,melanoma specific survival differed significantly between positive and negative SLN patients in both intermediate and thick groups
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609. doi: 10.1056/NEJMoa1310460.
SLN status most powerful predictor of survival
Significant prognostic value for evaluating SLN status for intermediate group
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599-609. doi: 10.1056/NEJMoa1310460.
5-year disease-free survival 73.1% vs 78.3%, p=0.009
• Median follow-up 59.8 months
• However no difference in melanoma specific survival was seen between the two arms at 5 years
86.6% vs. 87.1, p = 0.58
Morton et al. N Engl J Med. 2006;355:1307
Impact of Sentinel Node Biopsy on Relapse-Free Survival
SLNB for Thin Melanoma
• 70% of newly diagnosed melanomas are ≤1 mm and have 10-year survival rates of ~90%
• Controversy exists • Subset of thin melanoma patients do poorly with 5-
10% developing regional recurrences and these patients may benefit from nodal staging
• Low incidence of nodal metastasis • Uncertain prognostic value
• Several high-risk factors for nodal disease in thin melanomas reported with no consensus
AAD Guidelines for SLN Biopsy • Status of SLN is most important prognostic indicator for disease-
specific survival in patients with primary cutaneous melanoma; impact of SLNB on overall survival remains unclear.
• SLNB is not recommended for patients with melanoma in situ or T1a melanoma.
• SLNB should be considered in patients with melanoma >1 mm in tumor thickness.
• In patients with T1b melanoma 0.76-1.00 mm in tumor thickness, SLNB should be discussed
• In T1b melanoma, with tumor thickness ≤0.75 mm, SLNB should generally not be considered, unless other adverse parameters in addition to ulceration or increased mitotic rate are present, such as angiolymphatic invasion, positive deep margin, or young age
Strength of Recommendations: B Level of Evidence: I,II,III
• SLN positivity more common in the younger patients • Elderly have a higher incidence of in-transit
metastases
Lymph Node Status and Age
SLN+
<70 years
>70 years
P value
Entire Cohort
15%
11%
0.02
T1/T2 T3/T4
9%
33%
6%
18%
0.02
MacDonald JB, J Cancer, 2011;2:538-543
Deep Positive Margins on Initial Biopsy
• Retrospective analysis of 609 patients
• 60% had a positive margin • Shave (81%) vs. Punch (64%) or Excision (23%)
• 39% were found to have residual disease at excision
• Only 10% of patients had a T category upstage at excision
• No difference in overall or disease free survival
• Change in surgical management should be based upon clinical judgment Egnatios GL, Am J Surg;2011:202:771-778
Desmoplastic Melanoma
• DM is a biologically distinct form of melanoma • Higher incidence of local recurrence • Very low risk of regional metastasis
• Mayo Arizona 0/35 SLN+ • Overall thickness greater than other cutaneous
melanomas • Lymph node staging may be avoided in this
subgroup of patients
Wasif N, J Surg Oncol, 2011;103:158-62
• Gene Sequencing and Prediction of Nodal Status
• Noninvasive gene expression profile (GEP) test
• AAD 2014 and ASCO 2105
• Prediction of metastatic risk in patients with negative SLNB
• Improves risk stratification independent of SLN and ulceration
Should Any Melanoma Undergo SLNB?
Surgical Management of Positive SLNB
• Approximately 15-20% of patients with +SLNB have additional disease
• Patients with minimal sentinel node tumor burden appear to have outcomes similar to sentinel node negative patients
• Only 2% patients with subcapsular metastases (<0.1 mm) had additional positive nodes and 10-year MSS of 95%
• No clear survival benefit for CLND
Van der Ploeg, J Clin Oncol 2011
White, Ann Surg 2002
Prognostic Impact of Positive Lymph Nodes
Does Every Positive SLN Case Require CLND? MSLT-II
Morton DL, et al. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg. 2005;242:302-11; discussion 311-3.
• 80-85% of positive SLN cases with no additional nodal metastasis outside of SLN disease
• 70-80% of positive SLN patients only have 1 node with metastasis
Surgical Resection for Stage IV melanoma
• Multiple series indicate 15-28% 5-year survival can be achieved in a small proportion of highly selected patients with a few sites of distant metastases that can be completely resected.
• For isolated GI metastases, can reach up to 40% with surgical resection alone.
• Recent multicenter SWOG study had similar results – 25% 5-year survival, median survival of 21 months
Surgical Resection for Stage IV melanoma
Currently, randomized trial comparing surgery to best medical therapy.
Surgical Resection for Stage IV melanoma
Wasif N et al. Does metastasectomy improve survival in patients with Stage IV melanoma? A cancer registry analysis of outcomes. J Surg Oncol. 2011
• Margins • Melanoma in situ and thick melanoma
• SLNB • Thin and thick melanoma
• Positive SLNB • Completion dissection
• Surgery for Stage IV melanoma • In select cases
Summary