Nicole W.J. Kelleners-Smeets

Photodynamic therapy versus topical imiquimod versus topical fluorouracil for treatment of superficial basal-cell carcinoma: a single blind, non-inferiority, randomised controlled trial

BACKGROUND Superficial basal-cell carcinoma is most commonly treated with topical non-surgical treatments, such as photodynamic therapy or topical creams. Photodynamic therapy is considered the preferable treatment, although this has not been previously tested in a randomised control trial. We assessed the effectiveness of photodynamic therapy compared with imiquimod or fluorouracil in patients with superficial basal-cell carcinoma. METHODS In this single blind, non-inferiority, randomised controlled multicentre trial, we enrolled patients with a histologically proven superficial basal-cell carcinoma at seven hospitals in the Netherlands. Patients were randomly assigned to receive treatment with methylaminolevulinate photodynamic therapy (MAL-PDT; two sessions with an interval of 1 week), imiquimod cream (once daily, five times a week for 6 weeks), or fluorouracil cream (twice daily for 4 weeks). Follow-up was at 3 and 12 months post-treatment. Data were collected by one observer who was blinded to the assigned treatment. The primary outcome was the proportion of patients free of tumour at both 3 and 12 month follow up. A pre-specified non-inferiority margin of 10% was used and modified intention-to-treat analyses were done. This trial is registered as an International Standard Randomised controlled trial (ISRCTN 79701845). FINDINGS 601 patients were randomised: 202 to receive MAL-PDT, 198 to receive imiquimod, and 201 to receive fluorouracil. A year after treatment, 52 of 196 patients treated with MAL-PDT, 31 of 189 treated with imiquimod, and 39 of 198 treated with fluorouracil had tumour residue or recurrence. The proportion of patients tumour-free at both 3 and 12 month follow-up was 72.8% (95% CI 66.8-79.4) for MAL-PDT, 83.4% (78.2-88.9) for imiquimod cream, and 80.1% (74.7-85.9) for fluorouracil cream. The difference between imiquimod and MAL-PDT was 10.6% (95% CI 1.5-19.5; p=0.021) and 7.3% (-1.9 to 16.5; p=0.120) between fluorouracil and MAL-PDT, and between fluorouracil and imiquimod was -3.3% (-11.6 to 5.0; p=0.435. For patients treated with MAL-PDT, moderate to severe pain and burning sensation were reported most often during the actual MAL-PDT session. For other local adverse reactions, local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with MAL-PDT. In the MAL-PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting. INTERPRETATION Topical fluorouracil was non-inferior and imiquimod was superior to MAL-PDT for treatment of superficial basal-cell carcinoma. On the basis of these findings, imiquimod can be considered the preferred treatment, but all aspects affecting treatment choice should be weighted to select the best treatment for patients. FUNDING Grant of the Netherlands Organization for Scientific Research ZONMW (08-82310-98-08626).

Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials

Background  Several noninvasive treatment modalities are available for superficial basal cell carcinoma (sBCC).

Fractionated 5-aminolaevulinic acid-photodynamic therapy vs. surgical excision in the treatment of nodular basal cell carcinoma: Results of a randomized controlled trial

Background  Skin cancer incidence rates have been increasing for decades and this increase is expected to continue. Surgical excision (SE) is the treatment of first choice for nodular basal cell carcinoma (nBCC). Photodynamic therapy (PDT) has proven to be an effective treatment for superficial basal cell carcinoma. Its long‐term efficacy in nBCC has not yet been established.

Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe.

Unmet needs exist in actinic keratosis (AK) treatment. Daylight photodynamic therapy (DL‐PDT) has shown good efficacy and safety results compared to conventional PDT (c‐PDT) in a recent Phase III multi‐centre randomised controlled trial in Australia among 100 subjects with AKs.

Fractionated 5-aminolevulinic acid photodynamic therapy after partial debulking versus surgical excision for nodular basal cell carcinoma: A randomized controlled trial with at least 5-year follow-up

BACKGROUND Although effective in superficial basal cell carcinoma (BCC), the treatment effect of photodynamic therapy (PDT) in nodular BCC (nBCC) is still questionable. The relation between tumor thickness and PDT failure is unclear. OBJECTIVE We sought to compare long-term effectiveness of fractionated 20% 5-aminolevulinic acid (ALA)-PDT with prior partial debulking versus surgical excision in nBCC. The effect of tumor thickness on ALA-PDT failure was analyzed. METHODS 173 primary, histologically proven nBCCs in 151 patients were randomized to fractionated ALA-PDT (n = 85) or surgical excision (n = 88). Two PDT illuminations were performed with a 1-hour interval. Follow-up was at least 5 years posttreatment. Clinical recurrences were confirmed histologically. RESULTS A total of 171 nBCCs were treated and had a median follow-up of 67 months (range 0-106). At 60 months, 23 tumors had recurred in the ALA-PDT group and 2 tumors in the surgical excision group. Cumulative recurrence probabilities 5 years posttreatment were 30.7% (95% confidence interval [CI] 21.5%-42.6%) for ALA-PDT and 2.3% (95% CI 0.6%-8.8%) for surgical excision (P < .0001). Two tumors in the ALA-PDT group recurred at 72 and 91 months posttreatment. Cumulative probability of recurrence-free survival post-PDT was 65.0% (95% CI 51%-76%) for nBCC measuring greater than 0.7 mm in thickness and 94.4% (95% CI 67%-99%, P = .018) for tumors less than or equal to 0.7 mm. LIMITATIONS Tumor thickness on punch biopsy specimen might differ from the total lesion thickness. CONCLUSIONS In nBCC, 5-year cumulative probability of recurrence after surgical excision is lower than after fractionated ALA-PDT with prior debulking. Although surgical excision remains the gold standard of treatment, PDT might be an alternative for inoperable patients with thin (≤0.7 mm) nBCC.

Trends in the incidence of basal cell carcinoma by histopathological subtype

Background  As a result of the high prevalence, basal cell carcinoma (BCC) causes a significant and expensive health care problem.

Correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent basal cell carcinoma

BACKGROUND The type of treatment for a basal cell carcinoma (BCC) depends on the histologic subtype. Histologic examination is usually performed on incisional biopsy specimens. In primary BCC, the histologic subtype is correctly identified with a punch biopsy in 80.7% of cases. In recurrent BCC, correct identification is more difficult because of discontinuous growth caused by scar formation. Because an aggressive histologic subtype has a significantly higher risk for recurrence in these tumors, the histologic subtype is at least as important in recurrent BCC as it is in primary BCC. OBJECTIVE To investigate the correlation between histologic findings on punch biopsy specimens and subsequent excision specimens in recurrent BCC. Furthermore, we sought to clarify how often an aggressive histologic subtype was missed, based on the punch biopsy specimen. METHODS We compared the histologic subtype in a punch biopsy specimen with the subsequent excision specimen in recurrent BCC. All BCCs were coded and judged randomly by the same dermatopathologist. RESULTS In 24 of 73 investigated BCCs (32.9%), the histologic subtype of the initial biopsy did not match with the histologic subtype of the subsequent excision. Of the 37 excised BCCs with an aggressive histologic subtype, 7 (19%) were missed by the initial punch biopsy. LIMITATIONS Intraobserver variation may have affected the results of this study. CONCLUSIONS Discriminating tumors with any aggressive growth is relevant for treatment. However, in recurrent BCC, the histology of the biopsy specimen does not always correlate with the histology of the definitive excision. This may have important therapeutic implications.

Histology-based Treatment of Basal Cell Carcinoma

Basal cell carcinoma is the most common type of skin cancer and its incidence is still rising. In recent years, new treatment modalities have been developed and existing modalities refined. The aim of this article is to give a histology-based overview of the available evidence-based research. The literature was searched for randomized controlled trials from which the efficacy of investigated treatments was obtained. Where possible, treatment modalities were evaluated specifically. Selection criteria were histological subtype, primary or recurrent basal cell carcinoma and tumour localization. Although surgery remains the preferred treatment for most basal cell carcinomas, patient and tumour characteristics should be taken into account when choosing the most suitable treatment.

Agreement between histological subtype on punch biopsy and surgical excision in primary basal cell carcinoma

Background  Diagnosis of clinically suspected basal cell carcinoma (BCC) by histological confirmation with punch biopsy has been recommended before treatment. Even shave biopsy has been proposed as useful to predict the correct subtype in primary BCC in 76–81%, whereas the agreement between histological BCC subtype on punch biopsy and subsequent excision specimens in recurrent BCC is 67.1%. However, no large studies on the agreement between histological BCC subtype seen on punch biopsy and the following surgical excision are performed in primary BCC.

Differentiation between basal cell carcinoma and trichoepithelioma by immunohistochemical staining of the androgen receptor: an overview

Clinical and histopathological differentiation between basal cell carcinoma (BCC) and trichoepithelioma (TE) is a frequent problem. Attempts have been made to identify immunohistochemical markers helpful in differentiating them. A correct diagnosis is important because the tumours are treated differently. Recent studies showed the absence of androgen receptor (AR) expression in benign hair follicle tumours like TE. This study examines whether AR immunostaining is a useful diagnostic test to differentiate between BCC and TE. We randomly selected 75 cases with histological diagnoses of either BCC (subtypes: superficial, nodular or infiltrative) or TE (subtypes: classic or desmoplastic) from the database of the pathology department of Maastricht University Medical Centre. The available haematoxylin & eosin (H&E) slides were reviewed by three independent investigators using predetermined characteristics. Fifty-six slides (38 BCC and 18 TE) with unequivocal histological characteristics of either tumour were used for immunohistochemistry with AR antibodies. Any nuclear expression within the tumour was considered positive. AR expression was present in 5/8 classic TE, 0/10 desmoplastic TE, 22/23 superficial or nodular BCC and in 10/15 infiltrative BCC. Immunohistochemical stain for AR is useful to differentiate between TE and BCC; particularly in desmoplastic TE versus infiltrative BCC (specificity and positive predictive value of 100%).