What do the AAD's new non melanoma skin cancer guidelines say?

By Abby S. Van Voorhees, MD, February 1, 2018

In this month's Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Murad Alam, MD, and Christopher Bichakjian, MD, about their recent Journal of the American Academy of Dermatology articles, "Guidelines of care for the management of basal cell carcinoma" and "Guidelines of care for the management of cutaneous squamous cell carcinoma." 

Dr. Van Voorhees: The updated guidelines for both BCC and cSCC recommend several key elements be provided to the dermatopathologist. These include patient demographic information, anatomic location, prior treatments at the site, size of lesion, and additional risk factors. Why is this thought to be helpful in these tumors?

Dr. Alam: It is recommended that biopsy tissue being submitted to dermatopathologists for evaluation be accompanied with patient demographic information as well as relevant detail regarding tumor location, size, and other risk factors, such as history of radiation, immunosuppression, and organ transplantation. A dermatopathologist who is expert in both the clinical manifestations of skin tumors as well as their histopathologic features can consider this supplemental information in formulating an accurate and precise diagnosis via so-called clinical-pathologic correlation. Additionally, tumor history and risk factors can impact prognosis, and higher risk tumors may motivate the dermatopathologist to perform additional targeted assessments of tumor morphology and aggressiveness that can in turn help the clinician guide future management.

Dr. Van Voorhees: Has the recommended margin of uninvolved skin for an excision of a BCC and cSCC changed? How does this vary with the risk of the tumor?

Dr. Bichakjian: When developing guidelines for treatment of BCC and cSCC, it is humbling to learn how often therapeutic decision-making is based on standard clinical practice, rather than evidence-based data. No randomized controlled trials have been done to evaluate surgical excision margins for BCC or cSCC. Treatment recommendations are based on extrapolation from retrospective studies and consensus expert opinion. For low-risk tumors, as defined by criteria such as tumor size and location, histologic growth pattern, recurrent nature, history of prior radiation therapy, immunosuppression, and perineural invasion, surgical margins of 4 mm for BCC and 4-6 mm for cSCC are recommended. While Mohs micrographic surgery is generally recommended for high-risk tumors, there are clinical scenarios in which it is reasonable to treat a high-risk tumor with standard excision (e.g. 1.2 cm cSCC on the neck, or 8 mm infiltrative BCC on the trunk). The workgroup agrees that too many variables preclude a standard margin recommendation for these situations, and advises clinicians to exercise caution given the risk of subclinical tumor extension.

Dr. Van Voorhees: Thankfully metastatic BCC is fairly rare. What do these guidelines recommend, however, for patients with metastatic disease? What about those with metastatic cSCC?

Dr. Bichakjian: Metastatic BCC is indeed exceedingly rare, but when it occurs it is associated with a poor prognosis. If metastatic disease is limited to the regional lymph nodes, surgery and/or radiation therapy are considered first-line therapy. For distant metastatic disease, oral hedgehog pathway inhibitors (e.g. vismodegib, sonidegib) achieve better response rates than traditional platinum-based chemotherapy and are considered first-line therapy. However, response rates for metastatic BCC are less than 40% and all responses are partial, with a median duration of objective response of 7.6 months.

Metastatic cSCC is more common than metastatic BCC, particularly among immunosuppressed individuals, including solid organ transplant recipients. Very limited data on the treatment of patients with metastatic cSCC exist and few advances have been made in recent years. The use of immune checkpoint inhibition for metastatic cSCC is currently being evaluated in clinical trials, which are being followed with great interest based on favorable anecdotal reports.

Dr. Van Voorhees: What is the risk of metastasis for cutaneous SCC? How does it vary in those who are immunosuppressed? Does that impact the appropriate choice for handling a cSCC?

Dr. Bichakjian: The development of an accurate risk assessment model and universally accepted staging system for cSCC remains a work in progress. NCCN risk stratification of high versus low risk primary tumors is based primarily on the risk of local tumor recurrence and indication for comprehensive surgical margin control. The consensus of the workgroup from the current guidelines is that the Brigham and Women’s Hospital (BWH) staging system currently provides the most accurate and clinically useful prognostication for patients with localized cSCC. While the recent 8th edition of the Staging Manual of the American Joint Committee on Cancer (AJCC) includes a chapter on cSCC, the data is limited to the head and neck and includes all carcinomas, excluding Merkel cell carcinoma. Based on BWH staging, the risk of nodal metastasis from tumors with no (T1) or 1 risk factor (T2a) is very low (0.1-3%). The risk increases significantly for tumors with 2-3 (T2b 21%) and 4 risk factors or bone invasion (T3 69%). BWH risk factors include tumor diameter > 2 cm, poorly differentiated histology, perineural invasion, and tumor invasion beyond subcutaneous fat. While it is well known that immunosuppressed patients are at risk for developing cSCC, there is insufficient data to support that immunosuppression is associated with poor outcomes, which is therefore not included in the BWH and AJCC staging systems. For high-risk tumors (e.g. BWH ≥  T2b), nodal evaluation with cross-sectional imaging or sentinel lymph node biopsy may be considered, although the effect on outcome is unknown.

Dr. Van Voorhees: What is the probability of a recurrence after a person has had a NMSC? Does this change over time? Are there specific recommendations for appropriate follow up for our patients?

Dr. Alam: Once a patient has had a NMSC, there is good evidence that they have an elevated risk of another such NMSC in the future. The likelihood of a second NMSC after a first one has been reported to be as high as 40-50%. The risk of another NMSC rises with time elapsed from diagnosis of the previous primary tumor, and the future risk is also higher once a patient has had more than one NMSC. Prospective cohort data suggests that the 5-year probability of a subsequent NMSC after more than one previous tumor is 82%, or twice as high as the probability after a single NMSC. Risk edges up over time, and by 10 years, the risk of a second primary after a first is almost 60% and that of another primary after more than one preceding NMSC is in excess of 90%. Patients should be counseled that if they have had one NMSC there is a greater than 50% chance they will have another one at some point, and if they have had several NMSCs, more are almost inevitable.

Fortunately, most tumors in most patients can be managed safely and effectively without long-term sequelae if they are detected early, while they are small. To facilitate early detection, patients with history of NMSC should be counseled regarding the need for in-office screening. Such screenings assess the patient for not only NMSC but also melanoma, and are scheduled at appropriate intervals based on patient and tumor-specific risk factors, but no less often than once a year. Additionally, self-screening at home by the patient or family members may help speed detection of new or changing lesions.

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