A three-year randomised controlled clinical trial in the Netherlands found that two topical creams are effective in most primary, low-risk superficial basal cell carcinoma (BCC), comparing favourably with photodynamic therapy.
Basal cell carcinoma is one of the most common cancers and its incidence is increasing worldwide, putting a significant burden on health services. Topical treatments are available for superficial basal cell carcinoma (BCC) but there has a lack of long-term follow-up data to guide treatment decisions.
More than 80% of all skin cancers are BCC, arising from the basal cells (small, round cells found in the lower layer of the epidermis). There are over 2m cases a year in the U.S. and the lifetime risk of developing a BCC before the age of 85 years is one in five people. The prognosis is excellent, but it can cause significant disfigurement by invading surrounding tissues.
While most types of BCC require surgery, superficial BCC can be treated topically with non-invasive treatments such as PDT, imiquimod cream, fluorouracil cream, cryosurgery or electrodessication and curettage.
Investigators in the Netherlands report the results of a three-year follow-up of a randomised controlled trial that compared three non-invasive treatments that included imiquimod and fluorouracil cream. “The main advantages of non-invasive treatments are good cosmetic outcome, preservation of surrounding tissue, and potential for home application of either creams,” explained lead investigator Marieke Roozeboom of the department of dermatology, Maastricht University Medical Centre in the Netherlands. “Throughout the last two decades there has been a growing interest in these non-surgical therapies, which offer the possibility of avoiding surgery and reducing demands on busy medical practices.”
However, prior to this study there has been a lack of randomised controlled trials with a long-term follow-up that compare the effectiveness of non-invasive treatments. Consequently, there is no consensus in international BCC guidelines on the first choice of non-invasive therapy for superficial BCC.
A total of 601 patients with a superficial BCC participated in this study: 202 patients were treated with methylaminolevulinate photodynamic therapy (MAL-PDT), 198 with imiquimod cream, and 201 with fluorouracil cream. The three study groups had a similar distribution of baseline characteristics, with the exception of tumour size.
Around 80% of patients with superficial BCC were tumour free after imiquimod treatment after three years. The clearance rate was 68% for patients treated with fluorouracil and 58% for individuals receiving PDT.
“Based on our findings, both imiquimod and fluorouracil are effective non-invasive treatments in most primary, low-risk superficial BCC, but the data provide no definite evidence for superiority of imiquimod to fluorouracil,” commented Roozeboom. “Both creams have an equal cosmetic outcome and risk of local adverse events. Fluorouracil has the advantage of being less expensive than imiquimod. However, between one- and three-year follow-up, more recurrences were diagnosed in the fluorouracil group compared with the imiquimod group.”
“When choosing a treatment for an individual patient with a superficial BCC, other factors like age, compliance, and patient preferences should always be taken into account. For example, we have found that in superficial BCC on the lower extremities in older patients, PDT should be prescribed rather than imiquimod. Our evidence indicates that a personalised treatment approach is necessary,” added Roozeboom.
A randomized controlled trial including 601 patients previously showed that the effectiveness of imiquimod and fluorouracil cream were not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) in patients with superficial basal cell carcinoma after 1 year of follow-up. We now present the 3-year follow-up results. The probability of tumor-free survival at 3 years post-treatment was 58.0% for MAL-PDT (95% confidence interval [CI] = 47.8–66.9), 79.7% for imiquimod (95% CI = 71.6–85.7), and 68.2% for fluorouracil (95% CI = 58.1–76.3). The hazard ratio for treatment failure comparing imiquimod with MAL-PDT was 0.50 (95% CI = 0.33–0.76, P = 0.001). Comparison of fluorouracil with MAL-PDT and fluorouracil with imiquimod showed hazard ratios of 0.73 (95% CI = 0.51–1.05, P = 0.092) and 0.68 (95% CI = 0.44–1.06, P = 0.091), respectively. Subgroup analysis showed a higher probability of treatment success for imiquimod versus MAL-PDT in all subgroups with the exception of elderly patients with superficial basal cell carcinoma on the lower extremities. In this subgroup, the risk difference in tumor-free survival was 57.6% in favor of MAL-PDT. In conclusion, according to results at 3 years post-treatment, imiquimod is superior and fluorouracil not inferior to MAL-PDT in treatment of superficial basal cell carcinoma.
Marieke H Roozeboom, Aimee HMM Arits, Klara Mosterd, Anja Sommer, Brigitte AB Essers, Michette JM de Rooij, Patricia JF Quaedvlieg, Peter M Steijlen, Patty J Nelemans, Nicole WJ Kelleners-Smeets