Fluorouracil and Other Predictors of Morpheaform Basal Cell Carcinoma Among High-Risk Patients: The Veterans Affairs Topical Tretinoin Chemoprevention Trial

Abstract

Although basal cell carcinoma (BCC) overall is less aggressive than other forms of skin cancer, the morpheaform subtype is particularly concerning because of its benign appearance and aggressive subclinical spread. We sought to evaluate risk factors for its development on the face or ears in a high-risk population of veterans with at least 2 prior keratinocyte carcinomas in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial. Methods | The VATTC Trial included 1131 high-risk veterans followed up for 2 to 6 years, as described elsewhere. 1 We determined risk factors for time to first morpheaform BCC (mBCC)

Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial

“…The 5 year follow-up data from the SINS study do not suggest a progressive rise in BCC recurrences between years 3 to 5, nor do they suggest that recurrences in the imiquimod group were difficult to spot, or that they had transformed from superficial to morphoeic forms as is the concern with some other topical treatments such as PDT (Bernabo et al, 2016;Xiong et al, 2014). Most treatment failures with topical imiquimod occurred in the first year of treatment, a finding that throws light on the possible mechanisms of topical immunotherapy for skin cancer -suggesting that once an immunological response has occurred, such a response is sustained.…”

“…We previously called this phenomenon "submarine lesions" (Williams HC, 2014). There are additional concerns that some forms of topical chemotherapy such as 5-fluorouracil, may alter the biological behaviour of BCC from a simple to a more difficult to treat lesion such as a morphoeic BCC (Xiong et al, 2014). For these reasons, it is important to follow up BCC trial participants for at least 5 years.…”

Advances in the management of basal cell carcinoma

“…It is important to note that most BCCs occurring on the head and neck are not of the superficial histologic subtype (more commonly found on the trunk) but rather are nodular and would be more appropriately treated surgically if not medically contraindicated. Notably, a recent finding from the Veterans Affairs Topical Tretinoin Chemoprevention Trial, which included 1,131 high-risk veterans who were followed for 2 to 6 years, revealed that one of the predictors of the development of a morpheaform BCC was a history of the use of fluorouracil, although fluorouracil use was not associated with an increased risk of BCC overall [ 54 ]. The authors of that trial postulated that the efficacy of fluorouracil in eliminating superficial BCCs while not fully eradicating morpheaform BCCs may be responsible for this association or that the fluorouracil may be treating cancer cells on the surface of BCCs, leaving a deeper component to proliferate.…”

Characteristics of Keratinocyte Carcinomas and Patients with Keratinocyte Carcinomas Following a Single 2–4 Week Course of Topical 5-fluorouracil on the Face and Ears

“…Meghan BEATSON [1][2][3] , Alexander D. MEANS 1,2,4 , Nicholas F. LEADER 1,2 , Leslie ROBINSON-BOSTOM a smaller number of SCCs in the 5-FU group vs. control group, but the reliability of either of these findings is uncertain given the multiple comparisons and small numbers (Table II). There were no differences between the 5-FU and control groups for mean age of development, mean size, and anatomic location of the tumor.…”

“…It was recently reported that 5-fluorouracil (5-FU) is effective for prevention of squamous cell carcinoma (SCC) for one year, but not for basal cell carcinoma (BCC) (1). Additionally, a history of 5-FU exposure has been associated with more aggressive BCC subtypes, and we wanted to confirm this finding prospectively by determining the influence of 5-FU on the histopathologic characteristics of BCC and SCC (2). We evaluated whether 5-FU was effective for prevention of specific subtypes of BCC or SCC or was effective in specific subpopulations of our high risk group of veterans with at least 2 prior keratinocyte carcinomas (KCs) in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial.…”