Actinic keratoses can appear as single lesions or involve extensive skin areas (field cancerization) and are amenable to treatment with both cryosurgery and imiquimod [11]. Many authors regard cryosurgery as a first line modality for the treatment of most AK. Immunocryosurgery is highly effective in AK. Due to its vast efficiency and the involvement of large skin areas, we adapted the standard treatment protocol in order to minimize side effects and improve feasibility without reducing efficacy. Imiquimod is applied every other night for 2 weeks, with the patient applying it also the day prior to the cryosurgery session (Fig. 20.1b). Subsequently, mild cryosurgery is applied (open spray, liquid N₂, 2 freeze-thaw cycles of 10 s each effective freezing time), and imiquimod is continued for another week on alternate days on the treated area, starting at the day of cryosurgery, i.e., for additional four times (a total of 11 imiquimod applications). In practice, this is guaranteed by providing the patients with a detailed calendar plan of imiquimod application. The patient is followed up, and treatment is repeated on persisting lesions. As in the case of BCC (see discussion later in this chapter), in the absence of inflammation, a local retinoid can be added as an adjuvant, once daily in the morning for the duration of the treatment.

A standard immunocryosurgery protocol has been used to treat cases of solar cheilosis (Spyridonos et al. 2014). Data with sufficient follow-up periods ≥1 year are available in 8 patients and demonstrate both feasibility and efficacy of the method. However, lip treatment with immunocryosurgery imparts a significant burden on the patient’s quality of life for the duration of treatment as local inflammation can prevent the patient from the consumption of solid food for the remaining period after the cryosurgery session. Based on our current experience, this approach is suggested exclusively for highly motivated patients and only after explicit explanation of the transient, yet significant, burden of the side effects of therapy.

Both cryosurgery and imiquimod are moderately effective modalities for Bowen’s disease [12]. However, immunocryosurgery achieves excellent treatment outcomes in this condition (Fig. 20.2a–f) [13]. BD can sometimes be quite extensive or involve difficult-to-treat localizations, like the fingers [14], and immunocryosurgery can offer sufficient field therapy with excellent outcomes in these cases. Relatively small BD lesions are treated with the standard 5-week immunocryosurgery protocol. When larger areas are involved, especially on the head, the diseased area can be treated in subsections of 4–5 cm². Monomodal cryosurgery can be employed for small sites of residual disease or recurrences within the treated area (up to 0.5 cm in diameter); for more extensive lesions immunocryosurgery can be repeated. In the literature, there is some concern about the possibility of BD progression to invasive SCC during imiquimod treatment [15]; however, to date such cases have not been observed with immunocryosurgery.

Immunocryosurgery might offer an efficacious alternative in the treatment of keratoacanthoma. Treatment with add-ins is suggested. Intralesional injection of 5-fluorouracil (50 mg in 1 ml solution) on day 0 followed by subsequent treatment with immunocryosurgery has been quite efficacious in inducing disease involution (unpublished data).

To date, most experience with the use of immunocryosurgery is in the treatment of locally confined BCC (Fig. 20.3a–h) [3–5, 8]. With one standard immunocryosurgery cycle, initial tumor clearance can be achieved in up to 97.5 % of unselected BCC with macroscopic diameter ≤2 cm, i.e., for the vast majority (80–90 %) of all BCC at the time of reference for treatment [25, 26]. Treatment is performed as detailed earlier in this chapter, with 15–20 s effective freezing time, and follow-up visits are scheduled at 1, 3, and 6 months after the end of treatment (end of imiquimod application), every 6 months for the rest first 2 years, and yearly thereafter. For comparing effectiveness with other treatment modalities, this single immunocryosurgery cycle can be considered as the equivalent of a conventional surgical excision with at least comparable therapeutic efficiency. In the few cases of incomplete (partial) responses with the repetition of this treatment cycle, tumor clearance is essentially achieved in all cases (>99 %) of primary and relapsed BCC ≤2 cm (Fig. 20.4a–f) [4]. This high clearance rate is coupled by the equally high cure rates with relapse free >97 % of the treated tumors 3 years after treatment. This effectiveness is significantly higher than (a) that reported for either monomodal imiquimod (<65 %; [27]) or cryosurgery (based on common experience probably <50 % for the herein applied treatment parameters; [compare: [28, 29]) and also (b) anticipated for the simple additive action of the two modalities [2]. It is worth noting that the core reasons for the reference of a BCC for Mohs’ surgery, i.e., recurrent tumor with poorly defined margins and located in a so-called high risk area [25], are no limitations for the application of immunocryosurgery [4]. Moreover, relapse rate profile compares successfully with corresponding outcomes after conventional surgery, after which relapse rates of 5–10 % are expected during follow-up [30].