Four RCTs (361 patients) and 13 non-controlled prospective studies (5,846 patients) were included.
All the included controlled studies scored C using Sackett's criteria, owing to the lack of blinding.
RCTs.
One RCT (88 patients, 81 patients analysed) found no significant difference between ALA-PDT and cryosurgery in the recurrence of BCC (diagnosed histologically by punch biopsy) after one year (25% versus 15%, P>0.05). It found that ALA-PDT significantly increased the need for re-treatment compared with cryosurgery: 30% (13 out of 44) versus 3% (1 out of 39) (P-value not reported). There were several methodological limitations: the analysis of recurrence did not account for the increased number of repeat treatments required by patients allocated to ALA-PDT, and the short duration of follow-up.
One RCT (96 patients, 48 in each treatment group) found that cryosurgery plus curettage increased recurrence at one year compared with surgical excision (3 out of 48 versus 0 out of 48), but the statistical significance was not reported. The authors found that patients reported better results with excision, but the differences were small: for excision versus cryosurgery, 48 versus 42 patients rated the results as 'good' and 0 versus 6 patients rated the results as 'fair' (P-value not reported). The patients reported no significant difference between treatments on a 10-point visual analogue scale (8.87 versus 7.58). A beautician found no significant difference between treatments in appearance post-treatment, but four clinical professionals rated excision much better than cryosurgery (the data for the beautician and one clinician were reported).
One RCT (84 patients) found that two freeze-thaw cycles reduced recurrence rates in facial BCCs compared with one cycle after follow-up ranging from 10 months to 7 years (4.7% versus 20.6%, P-value not reported on the review).
One RCT (93 patients) found that radiotherapy reduced recurrence at one year compared with cryosurgery: 4% (2 out of 49) versus 39% (17 out of 44) (P-value not reported in the review). Methodological limitations included no details of the type of BCC, and the study was conducted at a time when cryosurgical techniques were evolving.
Prospective studies.
The recurrence rates after cryosurgery ranged from 0% (one study with 222 patients followed up for 5 to 10 years; eyelid BCCs, from 0.3 to 3.5 cm in diameter) to 8.2% (one study with 171 patients entered and 84 patients followed up for more than 5 years; BCCs at any site, less than 10 cm in diameter).