A Review of Immunocryosurgery and a Practical Guide to Its Applications

Abstract

Immunocryosurgery is a minimally invasive combinational therapeutic procedure that has been designed, developed, and evaluated in the Dermatology Department of the University of Ioannina from 2004. In a fixed time protocol, this approach combines immune stimulatory therapy with imiquimod and cryosurgery, i.e., cryosurgery is applied during continuous imiquimod treatment. Laboratory findings in tissue and blood level credit the efficacy to the synergy of imiquimod and cryosurgery. The synergy has been established through clinical trials and the excellent feasibility and efficacy demonstrated in clinical practice. Immunocryosurgery has extensive proof of excellent efficacy, comparable to surgery, in the treatment of basal cell carcinoma. It has also been evaluated in cases of Bowen’s disease, keratoacanthoma, Merkel cell carcinoma, lentigo maligna, and cutaneous squamous cell carcinoma with or without the addition of adjuvants. The aims of this review are to detail the immunocryosurgery protocol with the addition of daily practice clinical tips, compile data on the mechanism of action of immunocryosurgery, and delineate indications and possible future applications. Most of the available data originate from the treatment of BCC, of all histological types and localizations, and the principles reported mainly reflect on evidence related to the treatment of this common skin cancer.

The Feasibility of Immunocryosurgery in the Treatment of Non-Superficial, Facial Basal Cell Carcinoma That Relapsed after Standard Surgical Excision: An Experience Report from Two Centers

“…In all cases, treatment started with a standard 5–week immunocryosurgery cycle that involved the daily application of imiquimod for 5 weeks and a relatively mild cryosurgery session (liquid N 2 , open spray, two cycles of 15 s each) at day 14. The cryosurgery technique has recently been described in detail [ 1 , 11 ]. Incomplete responses and relapses after immunocryosurgery were scheduled to be treated with (repeat) immunocryosurgery cycles [ 11 ]; however, surgery or radiotherapy was also offered according to patient preferences.…”

“…Ιmmunocryosurgery is a minimally invasive therapeutic approach that utilizes the synergistic potential of a fixed timing combination of cryosurgery and topical imiquimod. A standard immunocryosurgery treatment cycle consists of once-daily 5% imiquimod cream application for 5 weeks and a rather mild cryosurgery session at day 14 of the imiquimod course [ 1 ]. Immunocryosurgery has demonstrated efficacy in the treatment of primary, non-superficial, basal cell carcinomas (BCC) with cure rates comparable to that of standard surgery [ 1 , 2 , 3 , 4 ].…”

“…A standard immunocryosurgery treatment cycle consists of once-daily 5% imiquimod cream application for 5 weeks and a rather mild cryosurgery session at day 14 of the imiquimod course [ 1 ]. Immunocryosurgery has demonstrated efficacy in the treatment of primary, non-superficial, basal cell carcinomas (BCC) with cure rates comparable to that of standard surgery [ 1 , 2 , 3 , 4 ]. Thus, after only one treatment cycle with immunocryosurgery, the 5-year recurrence rate of primary BCC with a maximal diameter ≤2 cm was 91.4 ± 2.8% for the per protocol and 87.7 ± 3.1% for the per intention to treat analyses [ 3 ].…”

“…Due to its satisfactory feasibility including the treatment of older and frail patients and the excellent safety profile, immunocryosurgery is gaining recognition and is used in the outpatient setting in addition to the treatment of BCC and Bowen’s disease in immunocompetent and immunocompromised patients [ 9 , 10 , 11 ] as well as in the therapy of selected cases of lentigo maligna [ 12 , 13 ], Merkel cell carcinoma [ 14 ], and squamous cell carcinoma [ 15 ]. Of note, immunocryosurgery is a tissue sparing modality whose efficacy is not really limited by the tumors’ localization, tumor histology, or patients’ overall health condition [ 1 , 16 ].…”

A Conservative Combined Laser Cryoimmunotherapy Treatment vs. Surgical Excision for Basal Cell Carcinoma

“…Classic immunocryosurgery comprises imiquimod applications and cryosurgery. While imiquimod stimulates local activation of potent antigen-presenting cells, the cryosurgical insult promotes necrosis of the residual tumoral cells [ 18 ]. The novel EADO classification for the BCC provides a five-group classification of difficult-to-treat BCCs based on five patterns of clinical circumstances [ 19 ]; future treatments should be guided by this current position statement.…”