Immunocryosurgery for Non-superficial Basal Cell Carcinoma: A Pro­spective, Open-label Phase III Study for Tumours ≤ 2 cm in Diameter

Abstract

Cryosurgery and topical imiquimod are established mono-therapies for superficial basal cell carcinoma (BCC) but are often insufficient for thicker BCCs. We present here a phase III, prospective, interventional, single-arm (cases only) study (trial registration: NCT01212562) to evaluate the feasibility and efficacy of cryosurgery (liquid nitrogen, open spray, 2 × 15 s; day 14) during 5 weeks' imiquimod ("immunocryosurgery") for primary, non-superficial BCC, ≤ 2 cm in diameter. Ninety-one consecutive patients with 134 basal cell carcinoma were evaluated. A total of 83 patients (124 tumours) started treatment, and 79 patients (119 tumours) completed at least one cycle of immunocryosurgery (feasibility: 95.2%; follow-up: 18-60 months). The efficacy after one treatment cycle was 95 ± 2% stable complete remissions (116/119 tumours cleared, 3/116 tumours relapsed: 6 treat-ment "failures"). Neither tumour size (p = 0.865) nor localization (p = 0.233) predicted outcome. Repeat immunocryosurgery controlled 5/6 treatment failures (overall efficacy: 99%). Lack of a conventionally treated control group is a limitation of this study. However, the results show a high therapeutic efficacy of immunocryosurgery in a large series of primary non-superficial BCC.

Symposia

“…One 5-week treatment cycle resulted in 95 AE 2% relapse free rate of primary, non-superficial BCC, with ≤2 cm maximal diameter at 18 months follow-up. 2 With repeat treatment cycles the overall efficacy reached 99% and this is confirmed in the 5-year follow-up data. 4 Relapsing tumors respond to repeat treatments while larger BCC (>2 cm maximal diameter or even extensive ones up to 30 cm 2 ) 5 might require extended or repeated treatment cycles.…”

“…We used a bioinformatics approach described by BIndea et al (1) to categorize primary tumour subtypes in terms of their immune status. 6 subtypes were identified, one of which had evidence of profound T cell exclusion which was associated with evidence of increased catenin signaling as described by Spranger et al (2). This subtype was associated with significantly worse outcome.…”

“…Subsequently extensive experience has been acquired in the treatment of BCC and standardized treatment cycles have been attested in 2 clinical trials. 2,3 A standard immunocryosurgery cycle consists of 5 weeks daily application of imiquimod on the tumor area and a relatively mild cryosurgery session (open spray, liquid N 2 , 2 freeze-thaw cycles, 15sec active freezing each) at day 14 of treatment. One 5-week treatment cycle resulted in 95 AE 2% relapse free rate of primary, non-superficial BCC, with ≤2 cm maximal diameter at 18 months follow-up.…”

A neglected basal cell carcinoma in a young patient: successful treatment with immunocryosurgery

“…In one of authors' departments the combination of cryosurgery during continuous daily imiquimod (immunocryosurgery) has been established as an efficient, office-compatible, tissue sparing treatment for BCC <2 cm in maximal diameter, including tumor relapses. 5,6 Meanwhile this protocol has been adapted to treat certain cases of larger (quite >2 cm), invasive tumors. 7,8 Herein we present the case a young female patient with a giant, neglected BCC that was successfully treated with a course of five immunocryosurgery cycles.…”

Cryosurgery during Imiquimod (Immunocryosurgery) for Periocular Basal Cell Carcinomas: An Efficacious Minimally Invasive Treatment Alternative

“…Elaborate protocols for this combination modality are now offered within the framework of approved clinical trials to patients with BCC attending the dedicated dermato-oncology clinic of our department, as a therapeutic alternative to surgery or when the latter is considered inappropriate. Meanwhile, we have demonstrated in 2 trials the significance of the timing of cryosurgery [7] and the high efficacy of this combinational modality for tumors with a maximal diameter ≤20 mm [8]. Furthermore, a previous pilot study claimed promising feasibility and efficacy of immunocryosurgery in 3 cases that were difficult to treat with conventional pBCC methods [9].…”