Indications for Mohs Surgery Chrys Schmults, MD, MSCE Christine Liang, MD

Overview Brief review of Mohs technique and how it differs from standard excision Review of data comparing outcomes with Mohs vs. standard excision 2010 NCCN guidelines Cost-effectiveness of Mohs as compared to excision Indications for Mohs Too small Too big Just right Enough to share (multidisciplinary approach) Role of Mohs surgeon as cutaneous oncologist/care coordinator, especially for large and complex cases

What is Mohs surgery? Technique for removing skin cancer Developed by Frederick Mohs, M.D. beginning in 1930’s 2 key features: Nearly 100% of surgical margin is evaluated microscopically The surgeon is also the pathologist If another pathologist makes call on margin, it’s not Mohs and should not be billed as such

Mohs Surgery Advantage All of peripheral & deep margin examined microscopically Less than 1% is examined in standard vertical sections

Mohs Surgery Advantage

Mohs Surgery Procedure Debulk visible tumor Hatch marks made on skin for orientation

Mohs Surgery Procedure Tumor excised with small (1mm - 2mm) border

Mohs surgery procedure Tissue is placed on map preserving orientation Tissue is inked Locations and colors of ink replicated on map Tissue inked Corresponding Mohs map

Mohs Surgery Procedure Tissue is frozen so it can be cut in thin layers (frozen sections)

Mohs Surgery Procedure Tissue pieces stained with hematoxylin and eosin

Mohs Surgery Procedure Positive areas are recorded on the map

Mohs Surgery Procedure Additional tissue is taken from positive areas

Mohs Surgery Procedure Tissue is again inked, mapped, frozen, cut, and read by surgeon Process repeated until margins are clear

Mohs Surgery Procedure Wound is reconstructed so as to minimize scarring

Why is Mohs surgery used? Highest reported cure rates (97-99% overall) for many types of skin cancer due to complete margin evaluation Spares normal tissue so the wound is as small as possible while still fully removing cancer

Do we miss valuable information by not looking at entire tumor? No. Clear margins are the crucial factor. Used to look at debulk but stopped as almost never added information beyond the biopsy Only evaluate debulk if Diagnosis was in question Biopsy location is in question It is an unusual tumor (though looking at biopsy slides is usually sufficient to assess tumor appearance) Mohs’ high cure rates have been established by looking only at the margins

Data comparing Mohs vs. excision and NCCN treatment guidelines regarding Mohs

BCC

Recurrence Rates for the Treatment of Primary Basal Cell Carcinoma Rowe et al. J Dermatol Surg Oncol, 1989.

Summary of Recurrence Rates for Treatment of Recurrent BCC Rowe et al. J Dermatol Surg Oncol, 1989.

RCT Mohs vs Excision of facial BCC 5 year local recurrence rate Lesion Mohs surgery Excision Primary BCC n=408 2.5% 4.1% Recurrent BCC n=204 2.4% 12.1% (p=0.01) Mosterd et al, Lancet Oncol 2008

SCC

Mohs vs non-Mohs treatments in SCC 5 year local recurrence rate Location Mohs surgery Non-Mohs treatment Lip 2.3% (952) 10.5% (7022) Ear 5.3% (337) 18.7% (214) Recurrent SCC 10.0% (151) 23.3% (34) (surgical excision) From Rowe et al JAAD 1992

Overall cure rates for SCC: Mohs vs. non-Mohs treatments Tumor factor Mohs surgery Non-Mohs treatments Size > 2cm 75% (652) 58% (1205) Poorly differentiated 67% (387) 46% (222) From Rowe et al JAAD 1992

Treatment outcomes for perineural SCC (determinate cases) Mohs surgery Surgical excision Local recurrence rate 0% (17) 47% (72) Metastatic rate 8% (24) 47% (112) **Surgical clearance of tumor is critical and may require head and neck surgeon to pursue tumor into parotid or cranium From Rowe et al JAAD 1992

2010 NCCN treatment guidelines for BCC and SCC

2010 NCCN Guidelines Consensus category 2A –based on lower level evidence/NCCN uniform consensus

2010 NCCN treatment guidelines High risk BCC and SCC can only be treated with standard excision (using 1cm clinical margin) if: it’s on trunk/extremities AND diameter ≥2cm is only risk factor AND it can be closed primarily Otherwise, Mohs or complete circumferential peripheral and deep margin assessment with frozen or permanent sections (CCPDMA) is indicated

Use of Mohs in other tumors Dermatofibroma sarcoma protuberans Microcystic adnexal carcinoma Extramammary paget’s disease Atypical fibroxanthoma Merkel cell carcinoma Lentigo maligna, melanoma in situ Standard of care for some tumors, controversial for others

Dermatofibromasarcoma protuberans Study Study Design Results Meguerditchian et al., 2010 Retrospective cohort 28 WLE (50 mo f/u) 20 Mohs (40 mo f/u) Recurrence rate -Wide local excision: 3.6% -Mohs: 0% (p = 1.0) Paradisi et al., 2008 38 WLE (4.8 yr f/u) 41 Mohs (5.4 yr f/u) -Wide local excision: 13% -Mohs: 0% (p = 0.015) Gloster et al., 1996 39 WLE (36 mo f/u) 15 Mohs (40 mo f/u) -Wide local excision: 12.8% -Mohs: 6.6% 2010 study positive margins in 21% with WLE than mohs, but recurrence rates similar NCCN treatment guidelines- excision with clear surgical margins, given significant subclinical extension – mohs, modified mohs, 30

Microcystic adnexal carcinoma Study Study Design Results Chiller, et al, 2000 Retrospective cohort 26 Excision 22 Mohs Recurrence rate (3 yr mean f/u) -Excision 1.5% pp/yr -Mohs: 2.4% pp/yr MMS exhibited a clear benefit over simple excision in that 30% of tumors treated with simple excision required at least another office visit Leibovitch et al 2005 Prospective cohort 20 Mohs Recurrence rate (5 yr f/u) -Mohs: 5% (Local recurrence rates of up to 30-47% have been reported with standard surgical excision) MMS treatment of choice and is excellent for following the subclinical extension and tracing perineural involvement The size of the defect can be up to 6 times the clinical appearance of the lesion1 In a series of 48 pts, MMS showed a clear benefit vs standard excision, with 30% of standard surgical excisions requiring at least another procedure to clear the margins4 Recurrence rates for standard excision range from 40-60%, compared to 0-12% after MMS Some have suggested the use of an additional layer for permanents after complete clearance of margins with MMS for further histologic control, as frozen sections can be more difficult to interpret.5 No outcome data exist for this method 31

Extramammary Paget’s Disease Study Study Design Results Lee et al., 2008 Retrospective cohort 22 wide excision 11 Mohs Recurrence rate (mean f/u 62 months) -Wide excision: 36.4% -Mohs: 18.2%   O’Connor et al, 38 WLE 41 Mohs Recurrence rate -Wide local excision: 22% -Mohs: 8% Study of 22 patients with EMPD retrospective study using radiotherapy, The 2- and 5-year local progression-free rates were 91% and 84%, respectively. Morbidity of the surgery is considerable, so radiotherapy may be highly considered. No comparison of radiotherapy to surgical treatment. Recurrence with Mohs is still high and surgery can carry a very high morbidity in this disease Superficial (electron beam) radiation warrants further study and has been used with success in our experience 32

Atypical fibroxanthoma Study Study Design Results Ang et al, 2009 Retrospective cohort 23 wide excision 59 Mohs Recurrence rate -Wide excision: 8% (8.7 yr) -Mohs: 0% (4.5 yr f/u)   Treatment of choice in AFX 33

Merkel Cell Carcinoma Study Study Design Results O’Connor et al., 1997 Retrospective cohort 41 wide local excision 13 Mohs Local recurrence rate -Wide local excision: 31.7% -Mohs: 8.3%   Regional metastasis rate -Wide local excision: 48.8% -Mohs: 33.3% Boyer et al 2002 25 Mohs alone 20 Mohs +XRT Mohs alone: 16% (28 mo f/u) Mohs+XRT =0% (27 mo f/u)

Lentigo Maligna/MMIS Study Study Design Results Walling et al., 2007 Retrospective cohort 41 staged excision 16 Mohs Recurrence rate -Staged excision: 7.3% (mean f/u 95 months) -Mohs: 33% (p < 0.025) (mean f/u 117 months) Bene et al., 2008 Prospective study 167 MIS pts 116 LM pts Recurrence rate 1.8% Frozen sections accurate 95.1% compared to paraffin sections Controversy over the data for LM/MIS – no prospective RCTs, all data is single institution retrospective data. Reliability of Interpretation of frozen sections an issue – rates vary depending on operator (Zitelli, coldiron >95% accuracy), vs 60-80% by other authors. Recurrence rates following excisional surgery for MIS have ranged from 6 to 20% in studies with a follow-up period of 3 years or more (Table 2). Mohs surgery offers significantly improved recurrence rates of 0% to 3.6% over a minimum follow-up period of 18 months Multiple studies showing that MART-1 staining helpful, now there is a 16 minute MART-1 that is effective. 35

Cost Considerations

Is Mohs cost-effective? When something is more effective and cheaper/equivalent in price, it is superior When something is both less effective and more expensive, it is inferior If something is more effective but also more expensive, when is it cost-effective? Available data indicate Mohs is more effective in curing non-melanoma skin cancer Is it cost-effective?

Cost of Mohs vs. excision for 1cm tumor on cheek (2010 BWH Medicare professional + technical) 11643 (2-3cm excision) $249 + $664 13132 (Complex repair >2.5cm) $513 +$366 88305 (path) $154 +$311 (plus $176 + $310 for each immunostain if needed) Total for excision: $2,257 Mohs: 99214 (Level 4 established) $82 (+ ? technical) 17311 (stage 1) $417 (+ ?$644 technical) Total for Mohs: $2,022

Is Mohs cost-effective? YES! When something is both more effective and cheaper/equivalent in price, it is superior Mohs is in this category since reimbursement was cut 2 years ago

Indications for Mohs Too small (or too superficial) Used to be lesions less than 2cm on trunk and proximal extremities Now this is more case by case with cost equivalency But the tumor should require surgery Avoid biopsy of AK/SCCIS Usually lie on a field of histologically similar damage Hard to locate biopsy site When is it “clear”? Try cryotherapy (with light curettage) or topical 5FU Biopsy and refer for surgery only if fails to clear with non-invasive treatment

Indications for Mohs Too big? Extremely large tumors may require large excisions, bone removal, and reconstructions difficult to perform under local anesthesia Still, we prefer to evaluate as we have experience in managing difficult tumors assessing need for nodal staging, pre-op imaging, adjuvant therapy coordination of multidisciplinary care via DFCI relationships and tumor board

Team Approach for Extensive Tumors Recurrence after multiple standard excisions Involvement of bone on CT Mohs established peripheral margin to level of periosteum Complete excision including bone performed by Head and Neck and Neurosurgery

Team Approach for Extensive Tumors Recurrent SCC s/p excision and adjuvant XRT MRI w/ bone involvement Mohs for peripheral margin including periosteum Neurosurgery removed bone Head and neck reconstructed with free flap

Team Approach for Extensive Tumors Mohs for peripheral margin including periosteum Head and neck excised deep margin including bone Patient opted for prosthesis

Indications for Mohs In summary, no case is too big but some are too small Please send us all invasive non-melanoma skin cancer (BCC, SCC, DFSP, AFX, MAC sebaceous carcinoma, etc.) meeting NCCN guidelines On head, neck, hands, genitalia, below knees 2cm tumors on trunk/extremities Deeper than dermis/4mm Recurrent (including SCCIS that failed non-invasive treatment) Moderate-poorly differentiated, infiltrative, micronodular, perineural/vascular/lymphatic invasion Immunocompromised patient (CLL, RA, transplant) Any others you don’t want to excise

Regarding Merkel Though Mohs may be excellent in controlling primary tumors ≤2cm, SLN biopsy is standard care for almost all cases This is currently difficult to coordinate at Faulkner

Regarding melanoma We do not do Mohs on invasive melanoma (due to skip areas) Happy to do wide excisions on melanomas that do not need SLN No mitoses and <1mm We currently do staged excision with en fasse margins for lentigo maligna and malignant melanoma in situ May consider Mohs with MART1 in future

Staged excision “Slow Mohs” for lentigo maligna Clear margin after 2 stages Slow Mohs = staged excision Use sutures or ink to orient tissue Margins read by pathologist Not closed until clear margins obtained 7 days after rotation flap

“Slow Mohs” for lentigo maligna 3 months post-op