Needs Assessment for Mohs Micrographic Surgery

Background

Mohs micrographic surgery (MMS) is a surgical treatment for skin cancer that couples tissue conservation with complete microscopic margin control allowing for superior cure rates while minimizing deformity.¹ The utility of MMS is based on the observation that skin cancers often grow contiguously, with fingerlike projections that can invade deeply or laterally from the clinically visible tumor. Unlike traditional methods of tumor excision, which involve removal of the clinically visible tumor along with an additional margin of normal-appearing tissue, the advantage of MMS is that it allows minimal removal of normal appearing tissue. This is because MMS involves immediate histological evaluation of excised tumor tissue using horizontal frozen sections, which allows for rapid visualization of 100% of the surgical margins, as opposed to the traditional bread-loaf technique, which reveals <1% of the interface between the specimen and the patient.² With MMS, the performing physician renders both the surgical and pathological services, and the tissue is sampled until it is determined to bee tumor-free. MMS has become the treatment of choice for NMSCs (consisting of BCCs and SCCs) with a high risk for local recurrence.

Indications

MMS is often indicated for NMSCs at high risk for local recurrence or possible significant functional or cosmetic impairment. Clinical morphology, anatomic location and size, histology, (including level of invasion), patient immunity, and recurrence after previous treatment are criteria that can be used to determine the appropriate use of MMS for treating a cutaneous neoplasms. The indications for MMS, as outlined in the clinical guidelines currently adapted by Medicare for reimbursement³ include the following:

1. BCC in anatomic locations where they are prone to recur including the mask area of the face which are mainly embryonic fusion planes (central face, eyelids, eyebrows, periorbital areas, nose, lips, chin, mandible, periauricular areas, ear, temple), scalp, forehead, cheeks, and neck, genitalia, hands & feet.

2. NMSCs that have one or more of the following features: recurrent or positive margin on recent excision, aggressive pathology in the hands and feet, genitalia, and nail unit/periungual, large size (2.0 cm or greater), poorly defined borders, age < 40, radiation-induced, immunocompromised host, arising in an old scar (e.g., a Marjolin's ulcer); associated with xeroderma pigmentosum; deeply infiltrating lesion or difficulty estimating depth of lesion; perineural invasion on biopsy.

3. SCCs exhibiting any of the following: Undifferentiated to poorly differentiated, adenoid (acantholytic), adenosquamous, desmoplastic, infiltrative, perineural, periadnexal, or perivascular, and verrucous. Subtypes including Bowen's disease (squamous cell carcinoma in situ), Erythroplasia of Queryrat, and verrucous carcinoma. Although tumors treated with excision have a cure rate of 80%, the reported cure rate with Mohs surgery approaches 98%. (Pugliano-Mauro 2010)

4. Basal cell nevus syndrome.

5. Other cutaneous neoplasms: Aside from BCCs and SCC, MMS can successfully treat a variety of cutaneous tumors, as outlined below. While its use and application is clear in most instances, its use for the some tumors is controversial due to tumor characteristics (multifocality, discontinuous growth patterns) or technique limitations (inherent disadvantages of frozen sections vs permanent sections).

   1. Keratoacanthoma (KA):^4–6 KAs are rapidly-growing, solitary, cutaneous tumors that can often spontaneously regress, but can cause significant local tissue destruction prior to regressing. Some KA subtypes, such as giant KA (greater than 20–30 mm in diameter), KA centrifugum marginatum, and subungual KA, can be difficult to surgically treat with a standard excision. Furthermore, some KAs can show aggressive histologic features, such as perineural invasion.⁴ Predicting which KAs will behave aggressively (grow rapidly, cause extensive local tissue damage, invade nerves) is not always possible. Because of the unpredictability of spontaneous regression and their potentially destructive nature, recurrent KAs and KAs near vital structures (where tissue conservation is warranted) are ideally treated with MMS.⁵ As a cautionary note, eruptive KAs can sometimes arise as a complication of skin excision including Mohs,⁶ and in the case of eruptive KAs following surgery, other treatment modalities, such as intralesional methotrexate or oral retinoids should also be considered.

   2. Dermatofibrosarcoma protuberans (DFSP):^7–9 DFSP is an uncommon, slow-growing, fibrohistiocytic tumor which can be locally aggressive with distant subclinical extension. It is often treated with wide local excision with a margin of at least 3 cm down to the fascia. Despite the wide surgical margins, multiple recurrences are frequently reported, with a recurrence rate of approximately 49%. Histologic identification of the tumor margin can be difficult using frozen sections, because malignant cells may resemble normal fibroblasts. The supplemental use of CD 34 immunostain or excision of a conservative additional margin for permanent section can be useful in helping to delineater tumor clearance. MMS Mohs micrographic surgery is well established for the treatment of primary and recurrent DFSPs and is suggested as the treatment of choice for DFSP.

   3. Microcystic adnexal carcinoma (MAC)^10–14 also referred to as sclerosing sweat duct carcinoma, is a more recently described, uncommon, malignant eccrine tumor that is known for its aggressive local invasion of tissue. MAC rarely metastasizes; however, it usually involves deep soft tissue and dermis and has a propensity for perineural invasion.¹⁵ Because MAC grows contiguously, it is well suited for removal with Mohs micrographic surgery. Local recurrences after traditional excisional surgery approach 47%, usually within the first 3 years.¹¹ Five-year recurrence rate for MMS is far less (0–22%).¹⁰ Mohs micrographic surgery should be strongly considered as a first-line modality for the treatment of MAC.

   4. Atypical fibroxanthoma (AFX):^16–17 AFX is a low-grade malignancy that is most often seen in actinically damaged skin on the head and neck of elderly patients. Compared to excision, MMS has been shown to provide superior cure rates for AFX. On average, the available follow-up for AFX treated with MMS is approximately 30.7 months; the average recurrence rate is 3%.¹⁷ Fewer recurrences are seen with MMS compared with excision, suggesting that MMS may have better cure rates for this rare tumor.

   5. Melanoma:^18–20 Use of MMS in melanoma is still controversial because of the inherent difficulty in distinguishing melanoma cells from benign melanocytic proliferations on frozen section, and its use is mostly limited to anatomical locations that preclude use of conventional excision with appropriate margins. The use of melanoma-specific immunostains (including S-100, HMB-45, Mart-5, and Melan-A) has helped overcome this barrier, but the time and cost of immunostains has limited widespread adoption of MMS for treatment of melanoma.

   6. Other rare tumors: Many other cutaneous neoplasms listed below are treated by using MMS either alone, or in as part of an overall treatment approach for these unusual neoplasms. However, the small number of such cases precludes any conclusions about the utility of this technique.

      • Angiosarcoma²¹

      • Sebaceous gland carcinoma^22–23

      • Extramammary Paget's disease^24–25

      • Malignant fibrous histiocytoma²⁶

      • Leiomyosarcoma or other spindle cell neoplasms of the skin²⁷

      • Adenocystic carcinoma of the skin^28–29

      • Apocrine or eccrine carcinoma of the skin³⁰

      • Merkel cell carcinoma^31–32

Utilization

Mohs surgery is performed on over 876,000 tumors per year in the United States³³ and that rate is rapidly rising.³⁴ Approximately half of all MMS cases are performed on Medicare beneficiaries.³⁴ Analysis of Medicare claims data can therefore yield very useful information on time trends in MMS utilization. Although the minority of NMSCs in the Medicare population are treated with MMS, its utilization is increasing at a much faster rate than the use of other treatment modalities, such as excision. The rate of Mohs surgery per 1,000 Medicare beneficiaries increased by 236% between 1999 and 2009, while excisions and destructions of lesions increased by approximately 20%. It is unclear to what extent the increasing rate of Mohs surgery utilization is due to the epidemic increase in the incidence of nonmelanoma skin cancer over time, and to the increasing availability of Mohs surgeons, who were in short supply until 10–20 years ago. It has been suggested that prior lower utilization rates were associated with a lack of availability of Mohs surgery services. Mohs surgery was more likely than surgical excision on the face and less likely elsewhere. Tumor location was associated with MSS utilization with 47% of facial lesions and 15% of lesions on the rest of the body treated with MMS. Patient age, race, and geographic region were also significantly associated with the likelihood of Mohs surgery. The use of Mohs for these cancers decreased with patient age (from 41% of patients aged 67–69 years to 34% of patients 85 years or older). Mohs was used in 37% of white patients, 23% of black patients, and 29% of patients of other races. Areas with high densities of Mohs surgeons were likely to have higher rates of MMS, however, some areas with low densities still had high rates of Mohs utilization.³⁴ There was wide variation in regional MMS utilization and geographical disparity that warrants further investigation.

Use of Curettage Prior to Mohs

There is no standardized procedure for determining tumor margins prior to removing the first stage during MMS. Some Mohs surgeons perform light curettage of the tumor, which not only debulks the friable tumor tissue to facilitate tissue processing, but more importantly, can potentially help delineate its margins. Preoperative curettage has the potential to reduce the number of Mohs surgical stages required for tumor clearance, potentially increasing practice efficiency and decreasing cost of care.³⁵ Several studies have examined the effectiveness of curettage in delineating tumor margins prior to MMS and have yielded different conclusions.^36–38 Jih³⁸ el al studied 150 previously biopsied BCCs and SCCs <1.5 cm in size divided the study into 3 parts (1) a retrospective study of 50 tumors curetted prior to MMS by a surgeon who routinely curettes preoperatively (2) a prospective study in which a surgeon who routinely does not curette preoperatively curetted 50 tumors prior to MMS; and (3) a comparative historical group of 50 non-curetted tumors treated with Mohs' surgery by the latter surgeon. Histologic evaluation of the curetted tissue revealed that only 50% had tumor in the curettings, but in 76% of these, the curette left residual tumor at the surgical margins. Of the remaining 50% in which the curette removed only non-cancer-containing skin, 34% had tumor present at the surgical margin. Overall, the curette removed tumor, leaving no residual tumor at the surgical margins in only 12% of lesions. Comparison with historical non-curetted tumors operated on by the same surgeon showed that curettage did not affect the mean number of stages or the proportion of tumors requiring more than one stage for histologic clearance.

A prospective evaluation of 599 patients with biopsy-proven BCCs treated with MMS examined preoperative tumor size, curetted dimensions before the first surgical stage, proposed excisional margins before each surgical stage, and the final defect dimensions after each surgical stage were measured.³⁶ Results showed that the curetted margin exceeded the observed extent of each tumor in the majority of cases. A 1-mm excisional margin taken in the first stage of Mohs surgery without first performing curettage would have necessitated an extra surgical stage in 99.0% of the cases. These authors concluded that careful presurgical curettage significantly reduces the number of Mohs surgical stages required for BCC treatment.³⁶

A recent study³⁷ compared visual inspection, curettage, and dermoscopy in determining tumor extent before initial margins are taken for MMS. They randomized 54 patients into three groups to delineate residual tumor (visual inspection, curettage, or dermoscopy) before MMS for basal cell carcinomas on the nose and recorded the final number of stages and postoperative defect sizes. They found no statistically significant differences for the final number of stages (p=.20) or the final defect sizes (p=.47) between the three arms.

Part of the discrepancy between these studies lays in their design. In the study by Jihn et al, 100 of the 150 tumors studied were from the practice of one Mohs surgeon who, in all likelihood, did not value the use of curettage prior to MMS because he did not routinely use it in his practice. Results from a single surgeon, or a study where one surgeon dominates the findings may be prone to bias because of different value on the use of curettage and variation in technique (differential application of pressure during curettage, number of passes, etc). Also, in all studies, the outcome measures were not recorded by blinded observers, leading to the potential for further bias. To better answer this question, a study design where Mohs surgeons (balanced among those who favor and do not favor preoperative curettage) are randomized to curettage or none a priori and rigorous blinded methodologies are employed to measure outcomes. Until then, the value of preoperative curettage for MMS is to be determined.

Use of Prophylactic Antibiotics

There is considerable practice variation in the use of prophylactic antibiotics for MMS. MMS is considered a clean surgical procedure (unless a tumor is secondarily colonized and infected) with an overall very low rate of surgical site infection estimated at around 0.7–2.5%.^39-41 Similarily, the rate of bacteremia during dermatologic proceudures is low, estimated around 1.9% (Wright et al, 2008). Yet prophylactic antibiotics may be administered to MMS patients despite a low risk of bactermia and surgical site infections in most patients. There are some indications for prophylactic antibiotics that are clear (including history of immunosuppression (solid organ transplant recipeint, HIV with low CD4 count, chronic lymphocytic leukemia). However, some Mohs surgeons routinely use prophylactic antibiotics for patients with a history of prostheses (valves or joints), nonphysiologic heart murmurs or valvular disease, or repair type (skin graft or large flap) where the data are not supportive.

With regard to cardiac indications, the American Heart Association (AHA) released updated guidelines for antibiotic prophylaxis in 2007⁴² which recommends their use to prevent bactermia in dental, oral, upper respiratory tract, and some genitourinary and gastrointestinal procedures, in patients with high- or moderate-risk cardiac conditions. MMS does not usually fall into any of the above categories, unless oral or respiratory mucosa is breached during the procedure. However, if MMS is planned on the lip or on the nose where breach of the nasal mucoas is anticipated, antibiotic prophylaxis would be indicated for the following cardiac conditions:

• Prior infective endocarditis

• Prosthetic cardiac valves

• Unrepaired cyanotic congenital heart defects, including palliative shunts and conduits

• Congenital heart defects completely repaired with prosthetic material or a device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure

• Repaired congenital defects with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device

• Cardiac transplants and development of cardiac valvulopathy

Patient groups that may have received routine antibiotic prophylaxis in the past but are no longer candidates for it include those with mitral and aortic valve disease, rheumatic heart disease, or structural disorders like ventricular or atrial septal defects or hypertrophic cardiomyopathy, according to the AHA statement. Thus, prophylactic antibiotics are rarely necessary for patients who have cardiac disease undergoing MMS.

In general, systemic prophylactic antibiotics are not indicated in patients undergoing MMS who have vascular grafts, or orthopedic prostheses. However, there are certain instances where their use may be warranted. A recently published Advisory Statement for antibiotic prophylaxis in dermatologic surgery³⁹ suggests their use in Mohs performed on the lower extremity/groin area in individuals with a total hip or knee replacement because of the documented increased risk of surgical site infection on the lower extremities. Mohs surgeons can utilize guidelines in formulating their approach based on individual patient characteristics and needs.

If antibiotic prophylaxis is deemed necessary, the most commonly used antibiotics for prophylaxis include dicloxacillin and cephalexin (2 g by mouth 1 hour prior to surgery). For patients who are allergic to penicillin, this author uses either cefdinir (600 mg by mouth 1 hour prior to surgery, unless the patient had an anaphylactic reaction to penicillin), azithromycin (500 mg by mouth 1 hour prior to surgery) or clindamycin (600 mg by mouth 1 hour prior to surgery). However, Mohs surgeons should strive to decrease unnecessary use of antimicrobials by avoiding them in situations wherein good evidence indicates that they are ineffective.

Managing anticoagulants

The use of anticoagulant medications such as aspirin, non-steriodal anti-inflammtory medications, warfarin, clopridogel and dipyramidol, and supplements with anticoagulant effect such as vitamin E, ginger, and ginko has increased in recent years. The risk of post-operative complications depends on the anticoagulant agent and regimen. Complication rates with aspirin appear to be low.^43–44 Numerous studies have compared the rate of hemorrhagic complications in patients using aspirin and other NSAIDs. A review of these published reports reveals that there is no increased risk of severe bleeding complications in patients using aspirin and other NSAIDS.⁴⁴

In contrast, us some anticoagulants clearly increase the risk of post-operative bleeding. Continuous treatment with clopridogel, a thienopyridine class antiplatelet agent used to inhibit clotting, appears to be increase risk of complications.⁴⁵ Post-operative bleeding complications appear to be increased seven-to-eight fold among patients taking warfarin^46–47 compared to controls. The risk of bleeding appears to be independent of their international normalized ratio (INR) at the time of surgery.⁴⁷

Mohs surgeons must weigh the risk of post-operative complications against the risk of thrombotic complications when deciding how to manage perioperative anticoagulation. The trend in Mohs surgery has been to continue medically necessary anticoagulants while performing skin surgery,⁴⁸ but there is considerable variation in management of anticoagulants among Mohs surgeons. More adequately powered prospective studies are needed to better quantify the risk of postoperative bleeding and other complications attributable to anticoagulation therapy, especially examining the type, dose and effect of combination anticoagulant therapy as well as herbal agents with anticoagulant properties on post-operative complications after MMS.

Outcomes

Recurrence

Observational studies have consistently demonstrated that MMS has a low recurrence rate^49–50 often much lower than surgical excision, especially facial NMSCs.⁵¹ The recurrence rate for MMS is estimated at between 1–3% for primary BCCs and 5–7% for recurrent BCCs. This compares favorably to reported rates for treatment with surgical excision, which are estimated at 3–10% in primary BCC and >17% in recurrent BCCs.^52–54 The only randomized trial performed to date, which evaluated the rates of recurrence of 397 primary and 201 recurrent facial BCCs randomized to MMS vs. excision found that after 30 months of follow-up, five (3%) of the primary BCCs recurred after excision compared with three (2%) after MMS. For recurrent tumors, three (3%) recurred after excision compared to none after MMS during 18 months of follow-up.⁵⁰ After five years of follow-up, there were 7 (4·1%) recurrences in primary BCCs treated with surgical excision compared with four (2·5%) in patients treated with MSM, a statistically non-significant difference. However, for recurrent BCCs, only 2 (2·4%) treated with MMS recurred, versus 10 (12·1%) in the excision treated patients. This difference significantly favored MMS for recurrent BCC.⁵⁵

This trial has been criticized as having several methodological issues including bias in treatment assignment (patients were not strictly randomized due to patient or physician preference) and possible misclassification (some patients who were randomized to excision crossed over to MMS but were analyzed with the excision group).⁵⁶ However, it is the only trial data available that directly compares MMS to surgical excision. For now, it is safe to say that MMS is the treatment of choice for recurrent facial BCCs. There is a need for more data from future randomized controlled trials for both BCCs and SCCs arising on the head and neck with sufficient follow-up where the randomization process is more strictly enforced.

Patient satisfaction

Patient satisfaction is an important outcome measure, especially for conditions, such as skin cancer, where multiple viable options are available. Patient satisfaction can be influenced by numerous variables including sociodemographic factors, health status, tumor characteristics and previous experience with the disease. For MMS, satisfaction may also be influenced by intraoperative variables (number of stages, defect diameter, repair type) as well as postoperative variables (complications, time lost for treatment, perceived involvement in care). As an outcome measure, patient satisfaction has been associated with several other important outcomes including health status, quality of life (QOL), adherence to medical advice, and initiation of complaints.^57–60 In order to improve patient satisfaction, it is important for clinicians to understand the factors that impact it.

In a recently published prospective cohort study of 339 patients treated with Mohs, the relationship of pre-, intra- and postoperative variables that influence short-term (at one week) and long-term (at one year) satisfaction were explored.⁶¹ Preoperative skin QOL and number of intraoperative Mohs stages were both found to be associated with short-term and long-term satisfaction. Some variables, such as postoperative bother from bleeding or perception of shared decision making were significant predictors for short-term satisfaction, and others, such as marital status, were predictors of long-term satisfaction. The temporal changes in the variables that predict patient satisfaction suggest that attention should be paid to the time frame during which measures of satisfaction are ascertained.⁶² For patients presenting for surgical treatment, questions about satisfaction asked at different time points may yield slightly different outcomes. It may be important to measure skin-related QOL in patients undergoing MMS in order to help clinicians identify patients at risk for being unsatisfied. Further studies may help determine which skin-related QOL factors are amenable to intervention(s) and possible improvement.

In comparing patient satisfaction across different treatments for NMSC, a recently published study examined short-term and long-term satisfaction among 834 consecutive patients at two centers before and after three treatments: electrodessication and curettage, excision and MMS. In multivariable regression models adjusting for patient, tumor, and care characteristics, higher long-term satisfaction was independently associated with younger age, better pre-treatment mental health and skin-related quality of life, and treatment with Mohs surgery.⁵⁷ Thus, patients treated with Mohs compared to other treatments, tend to be more satisfied long-term. This information, along with other outcome measures, such as quality of life and risk of recurrence, may help guide clinicians in treatment selection.

Cost Effectiveness

MMS can be a cost-effective treatment in certain cutaneous malignancies where there is high risk of incomplete tumor excision or recurrence. The cost of MMS is largely driven by the reconstruction method used for repair.⁶³ Cost may also be driven higher if reconstruction is performed by a different specialist, or if a large number of Mohs stages per tumor are required for clearance. Many studies have compared costs across different treatments for NMSC, including MMS,^{50, 64–72} many with conflicting findings. Cook and Zitelli⁷³ found that taking into account treatment and 5 year follow-up MMS was 7% more expensive than excisions with permanent sections, but 11% cheaper than excisions with frozen sections. Their study did not include tumors that were actually treated with excision but relied on expert opinion to estimate resource utilization for excision from an MMS-treated sample. Using the older Medicare costing rules, Welch found for procedure costs only, MMS was about $130 more than for a like tumor treated with excision in a military population, and they suggested that MMS could be cheaper than excision if differences in recurrence rates were factored into cost analysis.⁷⁴ Bentkover et al⁷⁰ examined the costs of the physician and facility fee using Medicare prevailing rates for BCC removal by MMS, compared with excision with rapid cross-sectional frozen section. They found that MMS cost $400–$600 more than excision depending on number of stages or frozen sections done. Bialy et al⁶⁸ compared the costs for the treatment of facial and auricular NMSC, using a single MMS-treated sample of 98 patients. Excision costs for this same sample were estimated by an otolaryngologist based on a theoretical treatment plan. They used CPT codes and Connecticut Medicare reimbursement rates for 2002 and found that cost differences were sensitive to type of repair chosen and number of frozen sections and positive margins. Blasquez et al did a cost-analysis study comparing MMS to excision in Spain and reported no difference in cost in patients with high-risk facial BCC. The differences in these observational study findings may be attributable to do with methodologic shortcomings (failure to account for treatment selection bias), differing costs depending on country of origin of the study, and different cost structures (microcosting vs. total cost of care).

Using microcosting techniques, the randomized controlled trial conducted in the Netherlands of facial BCCs treated with MMS and excision found that the surgical costs alone of MMS were almost twice that of excision.⁵⁰ Their costs included time spent by the staff directly involved in the procedures, the actual prices of the materials used, and the prices of processing and examination of histopathological slides. There is a need for well-done comparative effectiveness and cost-effectiveness studies to ascertain the relative value of MMS in treating subtypes of NMSCs.

Conclusion

MMS is a unique technique that has the potential to offer the highest cure rates and maximum tissue conservation in the management of specific primary and recurrent skin cancers. Yet there are many areas of controversy that surround MMS, including appropriate indications for its use, technical quandries (use of curretage, antibiotic prophylaxis, management of anticoagulants), and outcomes (recurrence, patient-oriented outcomes, cost). This needs assessment summarized recent efforts into these areas in an attempt to identify research gaps in MMS to help fuel further work. The utility of MMS and its methods for delivery need more stringent, evidence-based, rigourous study.