Advances in Surgical Management of Primary Melanoma: Identifying Patients Who Need More than Conventional Wide Local Excision Christopher J. Miller, MD Director of Penn Dermatology Oncology Center Associate Professor of Dermatology
I have no conflicts of interest or relevant ties with industry.
We are not going to talk about well-defined trunk and proximal extremity melanomas Stage IA melanoma 0.3 mm No ulceration No mitoses
Consensus guidelines provide clear surgical treatment recommendations for T&E melanomas
We re going to talk about melanomas that challenge consensus guidelines Tis/ Stage 0
Excision with 0.6 mm margin Immediate reconstruction
Upstaged from MIS to IIA Positive margins 1.62 mm, 1 mit/mm2, no ulceration T2b/Stage IIA *Upstaged to SLNB candidacy
P E N N D E R M ATO L O G Y O N C O L O G Y C E N T E R P I G M E N T E D L E S I O N C L I N I C M O H S A N D R E C O N S T R U C T I V E S U R G E R Y C L I N I C H I G H - R I S K S K I N C A N C E R C L I N I C F O R O R G A N T R A N S P L A N T A N D I M M U N O - S U P P R E S S E D P A T I E N T S R A R E & I N H E R I T E D S K I N C A N C E R C L I N I C
Specialty-site melanomas Rule of 10s Head and neck, hands and feet, genitals, pretibial leg 10+% 10x Upstaging Positive excision margins Local recurrence Complex reconstruction
Challenge #1 Upstaging from partial preoperative biopsies
57 yo woman How would you biopsy? Diagnosis: Melanoma, 4.3 mm
46 yo woman. How would you biopsy? Diagnosis: Lentigo maligna
Partial preoperative biopsies are often a practical necessity Physicians employ a wide variety of biopsy techniques for melanoma Excision Punch Shave Incision Curettage Tadiparthi S et al. Ann R Coll Surg Engl 2008;90:322-325
PennDOC Data (Etzkorn J., Miller CJ et al. manuscript in progress) 1345 melanomas treated with conventional wide local excision at Penn between 2008-2013 Age, y Range Mean Median Sex Male Female Diagnostic biopsy T stage TIS T1A T1B T2A T2B T3A T3B T4A T4B Location Trunk and proximal extremity Pretibial leg Head and neck Hands and feet Genitals Total Number of Biopsies Range Mean Median Totals 18-94 60.85 62 57.6% (775/1345) 42.4% (570/1345) 34.1% (458/1345) 36.7% (493/1345) 12.8% (172/1345) 7.2% (97/1345) 1.9% (25/1345) 3.4% (46/1345) 2.2% (29/1345) 0.9% (12/1345) 1.0% (13/1345) 79.3% (1067/1345) 1.9% (26/1345) 15.4% (207/1345) 3.0% (41/1345) 0.3% (4/1345) 1-7 1.09 1 Stages and locations reflect populationbased data
Rates of upstaging of melanoma Overall 3.9% (52/1332) Head, neck, hands, feet, genitals, pretibial leg 12% (32/277) Trunk and proximal extremities 1.8% (19/1055) Etzkorn JR, Miller CJ et al. Frequency of and risk factors for tumor upstaging after WLE of primary cutaneous melanoma. JAAD 2016. Under revision
Anatomic location is most powerful predictor of upstaging Risk factor Anatomic location on head, neck, hands, feet, genitals, or pretibial leg Extension of melanoma to base of biopsy specimen Odds Ratio (multivariate analysis with step-wise regression) P-value 7.06 <0.001 3.24 <0.001 Multiple preoperative biopsies 1.89 0.004 Older age 1.03 (per year) 0.002 Non-LM histologic subtype 3.6 0.003 12% (32/272) risk of upstaging at specialty sites (versus 1.8% [19/1055] on T&E) Etzkorn JR, Miller CJ et al. Frequency of and risk factors for tumor upstaging after WLE of primary cutaneous melanoma. JAAD 2016. Under revision
Upstaging may affect surgical management Chance that upstaged tumor will change margin recommendations Chance that upstaged tumor will qualify for SLNB 62% (32/52) 27% (14/52)
Challenge #1: Upstaging due to partial preoperative biopsies Upstaging complicates: Patient counseling Margin determination Sentinel lymph node biopsy Preoperative staging: T1a Melanoma, 0.22 mm Postoperative staging: T2a Melanoma, 1.65 mm Recon delayed for SLNB
Challenge #2 Positive margins due to inaccurate clinical and surgical margins
Melanoma, 0.30 mm What margin would you excise?
Inaccurate clinical margins = Inaccurate surgical margins Diagnosis: MIS What margin would you excise?
Recommended margins were used in only 67.8% of standard excisions of melanomas on the head neck Insufficient margin of excision (i.e., less than recommended) independently associated with tumor location on the head and neck Specialty of surgeon did not affect compliance with recommended margins Livingstone E et al. European J of Cancer 2011;47:1977-1989
PennDOC Data (Etzkorn J., Miller CJ et al. manuscript in progress) 1345 melanomas treated with conventional wide local excision at Penn between 2008-2013 Age, y Range Mean Median Sex Male Female Diagnostic biopsy T stage TIS T1A T1B T2A T2B T3A T3B T4A T4B Location Trunk and proximal extremity Pretibial leg Head and neck Hands and feet Genitals Total Number of Biopsies Range Mean Median Totals 18-94 60.85 62 57.6% (775/1345) 42.4% (570/1345) 34.1% (458/1345) 36.7% (493/1345) 12.8% (172/1345) 7.2% (97/1345) 1.9% (25/1345) 3.4% (46/1345) 2.2% (29/1345) 0.9% (12/1345) 1.0% (13/1345) 79.3% (1067/1345) 1.9% (26/1345) 15.4% (207/1345) 3.0% (41/1345) 0.3% (4/1345) 1-7 1.09 1
Rates of positive margins after WLE Overall 4.2% (56/1345) Head, neck, hands, feet, genitals, pretibial leg 11.5% (32/278) Trunk and proximal extremities 2.2% (24/1067) Etzkorn JR, Miller CJ et al. Risk factors for positive or equivocal margins after WLE of 1345 cutaneous melanomas. JAAD 2016. Under revision
Predictors of positive margins on conventional WLE Risk factor Non-compliance with recommended margins Anatomic location on head, neck, hands, feet, genitals, or pretibial leg Odds Ratio (multivariate analysis with step-wise regression) P-value 5.57 0.002 5.07 <0.001 Histologic regression 2.78 0.007 Melanoma in situ 2.27 0.011 Multiple preoperative biopsies 1.92 (per biopsy) 0.004 Older age 1.049 (per year) <0.001 11.5% (32/278) risk of positive margins at specialty sites (versus 2.2% [24/1067] on T&E)
Challenge #3 Local recurrence due to inaccurate pathologic margins
Local recurrence of melanoma Head and neck 13% (388/2984) Trunk and extremities 1.7% (144/8400) Historical data from Table IV in Etzkorn JR, Miller CJ et al J Am Acad Dermatol 2015;72:840-50
Local recurrence rates are higher for specialty-site MM 1.7% (144/8400) Range: 0.8-12.4% 13% (388/2984) Range (2.8-28%) Etzkorn JR, Miller CJ et al J Am Acad Dermatol 2015;72:840-50
Local recurrence is more common for specialty site melanoma Positive margins complicate: Patient counseling Margin determination Timing of reconstruction Persistent lentigo maligna melanoma in graft Defect after excision of recurrence/persistence
Challenge #4 Timing of reconstruction relative to margin determination
10x greater likelihood of complex reconstruction for specialty site melanomas Anatomic location Frequency of flap or graft reconstruction Odds Ratio (95% CI) P-value Specialty site 53.7% (275/512) 10.3 (4.86-21.8) 0.0001 Trunk and proximal extremity 10.1% (8/79) 1 (reference) Etzkorn JR, Miller CJ et al. Dermatol Surg 2016;42:471-476
MIS Preoperative Mohs defect
Complex reconstruction is 10 times more likely for specialty-site melanomas 4 months postoperative
Previously treated melanomas are significantly more likely to require more complex reconstruction Etzkorn JR, Miller CJ et al. Dermatol Surg 2016;42:471-476 Linear scar previous surgery 10/11/2011 Final Mohs defect 4 stages
People place highest priority on restoring normalcy of specialty sites Borah GL, Rankin MK. Plast Reconstr Surg 2010;125:873
Conditions for optimal surgery of melanomas Accurate pathologic staging prior to reconstruction Clear microscopic margins Reconstruction in tumor-free skin
JAAD 2015 First 597 melanomas of >1800 cases since 2006 Two outcome measures Accuracy of staging prior to recon: 99.8% (596/597) Local recurrence rate: 0.34% (2/597) average f/u: 2.8 years
Combine breadloaf sectioning of central tumor with Mohs margin assessment prior to reconstruction
H&E and MART-1 frozens on all sections of debulk and Mohs layer MART-1 Debulk Excision Vertical Sections H&E
melanocyte keratinocyte H&E frozen section MART-1 frozen section
Mohs surgery video
Did we meet the 3 conditions for optimal surgery of melanomas? Accurate pathologic staging prior to reconstruction Clear microscopic margins Reconstruction in tumor-free skin
Treatment goal #1: Accurate pathologic staging prior to reconstruction 99.8% accurate (596/597) Breadloaf sectioning of the central tumor prior to reconstruction
34/614 (5.5%) patients upstaged AJCC T category 8 97% (33/34) detected by Mohs surgeon prior to reconstruction
23.5% (8/34) upstaged to criteria qualifying for SLNB 3 patient elected to undergo SLNB (1 was positive) Melanoma, 0.22 mm Melanoma, 1.65 mm Recon delayed for SLNB
Treatment goal #2: -Clear microscopic margins 100% microscopic margin assessment of the Mohs layer with MART-1 frozen section immunostains
Local recurrence rate 0.34% (2/597) (Mean follow time: 2.8 years)
Comparison historical rates of local recurrence after conventional surgery 0.8-12.4% 2.8-28% 10%
Estimated local recurrence rate after conventional surgery (historical published data) 2/597 (0.34%) 60/597 (10%) Penn local recurrence rate (published Penn data)
Treatment goal #3: -Reconstruction in tumor-free field 100% microscopic margin assessment of the Mohs layer with MART-1 frozen section immunostains
Complex reconstruction in tumor-free skin >55% of head and neck melanomas were repaired with either a flap or graft 80 70 60 Chart Title 76.4 50 45.4 40 38.6 30 20 10 0 11 Flap 3.9 0 Flap and graft 7.4 7.1 5.5 0.6 0.4 1.6 2.1 0 0 Graft Linear Linear + graft Linear + second intent Second intent 0 Referred out Head and neck Trunk and extremity
Specialty-site melanomas Rule of 10s Head and neck, hands and feet, genitals, pretibial leg 10+% 10x Upstaging Positive excision margins Local recurrence Complex reconstruction
Combine breadloaf sectioning of central tumor with Mohs margin assessment prior to reconstruction
Mohs Surgery for Melanoma at Penn Dermatology Oncology Center