New NMSC Guidelines Highlight Options and Need for More Research
The latest guidelines of care for SCC and BCC endorse the standard of care and show we need additional, high-quality research into non-surgical options.
Basal cell carcinoma (BCC) is the most common form of human cancer, and cutaneous squamous cell carcinoma (SCC) is the second most common form of human cancer. Collectively, more than 3.3 million individuals in the US are affected by non-melanoma skin cancers (NMSC) each year. The incidence of both BCC and SCC has been increasing in the US over several decades, and there is no clear evidence of a change in the trend. The AAD has published updated guidelines for the management of BCC and SCC, emphasizing surgical treatment as the most effective option for most cases of NMSC. By and large, most dermatologists in the US probably already hew to the guidelines in their day-to-day practice. However, the guidelines point out some areas ripe for additional research.
According to the guidelines, surgical treatment—excision, Mohs surgery, or curettage and electrodessication—is the most effective option for most cases of NMSC. The new guidelines stress that, “A treatment plan that considers recurrence rate, preservation of function, patient expectations, and potential adverse effects is recommended.”
Primary Approaches to BCC. The guidelines emphasize that, given the slow growing nature of BCC, special attention was paid to follow-up periods in reported trials, so as to best assess long-term efficacy.
For the management of BCC, the guidelines indicate that, “Recurrence rates following surgical excision were uniformly significantly lower than those following treatment with topical therapy, radiation therapy, or destructive modalities. Only Mohs micrographic surgery (MMS) was superior to standard excision for the treatment of primary and recurrent facial BCC after five and 10 years of follow-up. When cosmetic outcome following various treatment modalities were evaluated, the appearance after standard excision was consistently judged more favorable than that after C&E or cryotherapy.”
Primary Approaches to SCC. In the case of SCC, the guidelines indicate that, “Given the limited available data, the work group recommends standard excision with a 4-6mm margin of uninvolved skin around the tumor and/or biopsy site to a depth of the mid-subcutaneous adipose tissue with histologic margin assessment for low-risk primary cSCC.”
Some SCC may be considered aggressive. “There is a subset of tumors with increased risk for local recurrence, perineural spread, and even nodal or distant metastasis, particularly in immunocompromised individuals,” the guideline authors note. “Unfortunately, a systematic review of the literature reveals a complete absence of RCTs and a general paucity of prospective trials assessing the effectiveness of primary surgical interventions for cSCC.”
The guidelines do not recommend treating NMSC with laser therapy or electronic brachytherapy, as there was not enough evidence available for the work group to make an informed decision.
BY THE NUMBERS
Number of NMSC cases treated in over 3.3 million people in the US in 2012.
1 in 5.
Number of Americans who will develop skin cancer by age 70.
Annual cost of treating skin cancers in the US; about $4.8 billion for NMSC
Metastatic BCC Management. Metastatic BCC is rare, with an estimated incidence of 0.0028-0.55 percent. There is good evidence to support the use of relatively new SMO inhibitors in appropriate patients with locally advanced or metastatic BCC. “When metastatic disease is limited to the regional lymph node basin, surgery and/or radiation therapy remain the most appropriate treatment, when possible,” the guidelines indicate. “For patients with distant metastases, multidisciplinary consultation is recommended to consider systemic therapy with hedgehog pathway inhibitors. If this is not feasible, platinum-based chemotherapy may be considered.” The guidelines also advise that patients with advanced disease be provided with or referred to best supportive and palliative care.
Metastic SCC Management. There are limited data available to inform guidelines on management of metastatic SCC; clinicians are encouraged to review the guideline recommendations for this group of patients.
NMSC Follow up and Prevention. In addition to providing recommendations on NMSC treatment, the guidelines recommend at least annual skin exams for any individual diagnosed with BCC or SCC. Patients should be educated on the conduct of skin self exams and should be encouraged to perform these regularly. The AAD also recommends strategies to reduce UV exposure and skin cancer risk including seeking shade, wearing protective clothing, and using a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.
Of note, the guidelines cite strong evidence against the use of topical or oral retinoids and dietary supplementation with selenium or beta-carotene for the reduction of risk for recurrence of BCC. However, there is evidence to support the use of celecoxib, a-difluoromethylornithine, and oral nicotinamide for reduction of recurrence of BCC.
When it comes to SCC, there is evidence to support the use of acetretin to reduce the risk for recurrence in solid organ transplant recipients only. Otherwise, the guidelines conclude that the evidence is against use of topical or oral retinoids, cehomprevention with celecoxib, Symbol -difluoromethylornithine, and oral nicotinamide, or dietary supplementation with selenium or beta-carotene.
Behind the Grading System
A. Recommendation based on consistent and good-quality patient-oriented evidence.
B. Recommendation based on inconsistent or limited-quality patient-oriented evidence.
C. Recommendation based on consensus, opinion, case studies, or disease-oriented evidence.
I. Good-quality patient-oriented evidence (i.e., evidence measuring outcomes that matter to patients: morbidity, mortality, symptom improve- ment, cost reduction, and quality of life).
II. Limited-quality patient-oriented evidence.
III. Other evidence, including consensus guide- lines, opinion, case studies, and disease- oriented evidence (i.e., evidence measuring intermediate, physiologic, or surrogate end points that may or may not reflect improvements in patient outcomes).
Evidence-based medicine is an important development in modern medical care. However, the quality of guidelines is, by definition, limited by the quality of the evidence. The current guidelines are valuable in buttressing what has emerged as the standard of care for NMSC—namely excisional techniques. From a clinical standpoint, the challenge for most dermatologists is identifying the best approach to managing patients who are not candidates for excision. Any number of factors may lead the dermatologist to consider non-surgical or non-destructive modalities for a given patient. While concerning trends suggest that patients are developing melanomas and NMSC at younger ages, the majority of cases of NMSC still occur in older patients. In this older patient population, preexisting medical conditions, ongoing chronic blood thinner use, or even inability to adhere to wound care guidelines are all possible factors that limit the feasibility of surgical management.
For nonsurgical management of BCC, the evidence is stronger than for SCC. Grade A recommendations are given for imquimod (Level I), as well as ALA-PDT (Level I, II) and MAL-PDT (Level I, II). Traditional and superficial radiation therapies earn a B recommendation (Level I, II) as does 5-FU (Level I, II). Electronic brachytherapy (Level II, III) and laser therapy (Level II) each earn C recommendations.
For the nonsurgical management of SCC, traditional and superficial radiation therapy has a B recommendation with level of evidence II and III. Electronic surface brachytherapy earns a C, with level III data. The use of imiquimod, 5-FU, and laser therapy alone all earn C ratings, with level II evidence. The recommendation against PDT alone has a B rating with level II evidence.
These recommendations offer some guidance to clinicians in choosing among non-surgical options. However, it is important to note that future research may yet support the role of some technologies and therapies for management of NMSC. The need for additional, high-quality studies may inspire additional trials to inform treatment decisions.
Diagnose, Treat, Follow
The key message from the current guidelines is that NMSC is a treatable disease with good outcomes and favorable prognosis in the vast majority of cases. However, the low relative risk of metastasis and mortality should not lead to complacency on the part of patients.
Dermatologists must take an active role in educating patients about skin cancer risks, encouraging skin self-exams, providing timely assessment of suspicious lesions, and implementing therapy when NMSC is diagnosed.
Surgical modalities are the primary treatment option for most SCC and BCC and is in most cases curative. When surgery is not an option, clinicians may consider alternatives based on the specific presentation. In light of the lower quality of evidence for some nonsurgical interventions, patients who receive these treatments may require more frequent and more aggressive assessment for recurrence of NMSC.
“Guidelines of care for the management of basal cell carcinoma” and “Guidelines of care for the management of cutaneous squamous cell carcinoma” appear in Journal of the American Academy of Dermatology and are available through the AAD website.
Jonathan Wolfe, MD is an Associate Professor of Dermatology at the University of Pennsylvania.