Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
There is a wide range of treatment approaches, including excision, radiation therapy, cryosurgery, electrodesiccation and curettage, photodynamic or laser-beam light exposure, and topical therapies. Mohs micrographic surgery is a form of tumor excision that involves progressive radial sectioning and real-time examination of the resection margins until adequate uninvolved margins have been achieved, avoiding wider margins than needed. Each of these methods is useful in specific clinical situations. Depending on case selection, these methods have recurrence-free rates ranging from 85% to 95%.
Stage 0 melanoma is defined by the American Joint Committee on Cancer's TNM classification system:
Tis, N0, M0
Patients with stage 0 disease may be treated by excision with minimal, but microscopically free, margins.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 melanoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
A systematic review of 27 randomized controlled trials comparing various treatments for BCC has been published. Eighteen of the studies were published in full, and nine were published in abstract form only. Only 19 of the 27 trials were analyzed by intention-to-treat criteria. Because the case fatality rate of BCC is so low, the primary endpoint of most trials is complete response and/or recurrence rate after treatment. Most of the identified studies had short follow-up times (only one study had a follow-up as long as 4 years) and were not of high quality. Short follow-up periods will lead to overestimates of tumor control. A literature review of recurrence rates in case series with long-term follow-up after treatment of BCCs indicated that only 50% of recurrences occurred within the first 2 years, 66% after 3 years, and 18% after 5 years. A rule of thumb was that the 10-year recurrence rates were about double the 2-year recurrence rates.
This traditional surgical treatment usually relies on surgical margins ranging from 3 mm to 10 mm, depending on the diameter of the tumor. Re-excision may be required if the surgical margin is found to be inadequate on permanent sectioning. For example, in one trial, 35 of 199 (18%) primary BCCs were incompletely excised by the initial surgery and underwent a re-excision. In addition, many laboratories examine only a small fraction of the total tumor margin pathologically. Therefore, the declaration of tumor-free margins can be subject to sampling error.
Excision has been compared in randomized trials to radiation therapy, Mohs micrographic surgery, photodynamic therapy (PDT), and cryosurgery:
In a single-center trial, 360 patients with facial BCCs less than 4 cm in diameter were randomly assigned to excision or to radiation therapy (55% interstitial brachytherapy, 33% contact radiation therapy, and 12% conventional external-beam radiation therapy [EBRT]). Excisional margins, assessed during surgery by frozen section during the procedure in 91% of cases, had to be at least 2 mm, with re-excision if necessary. Thirteen patients were not treated and were dropped from the analysis.
At 4 years (mean follow-up of 41 months), the actuarial failure rates (confirmed persistent or recurrent tumor) were 0.7% and 7.5% in the surgery and radiation therapy arms, respectively (P = .003). The cosmetic results were also rated as better after surgery by both patients and dermatologists, and also by three independent judges. At 4 years, 87% of surgery patients rated cosmesis as good versus 69% of radiation therapy patients.[Level of evidence: 1iiDii]
In a two-center intent-to-treat analysis, 374 patients with 408 primary facial BCCs were randomly assigned to receive either surgical excision or Mohs micrographic surgery with at least a 3-mm margin around the visible tumor until there were no positive margins in either case.
After 30 months of follow-up, the recurrence rate was 5 out of 171 tumors (3%) in the excision group and 3 out of 160 (2%) in the Mohs micrographic surgery group (absolute difference = 1%; 95% confidence interval [CI], -2.5%-+3.7%; P = .724). There was no difference in complication rates, and overall cosmetic outcomes were similar. Total operative costs were nearly twice as high in the Mohs group (405.79 Euros vs. 216.86 Euros (P < .001).[Level of evidence 1iiDii]
In a multicenter randomized trial, 101 adults with previously untreated nodular skin BCCs, excluding lesions of the midface, orbital areas, and ears, were treated with either excision (at least 5-mm margins) or PDT using topical methyl aminolevulinate cream (160 mg/g) followed by red-light exposure (wavelength 570-670 nm, 75 J/cm2) twice, 7 days apart. A per-protocol-per-lesion analysis was performed on the 97 patients who had an excision or at least one cycle of PDT.
At 3 months, the complete response (CR) rate in the surgery group was 51 out of 52 lesions (98%) versus 48 out of 53 lesions (91%) in the PDT group (P = .25). CR rates assessed at 12 months were 96% versus 83% (P = .15).[Level of evidence: 1iiDiv] The investigators interpreted the results as noninferiority of PDT, but the study may have been underpowered. Both the investigators and the patients, however, rated the cosmetic results as either excellent or good in a higher proportion of PDT treatments at each time point of follow-up. At 12 months, patient ratings of excellent or good were 98% versus 84% (P = .03) and investigator ratings were 79% versus 38% (P = .001).
In a randomized single-center trial, 96 primary BCCs (patient number unclear) less than 2 cm in diameter involving the head and neck area were randomly assigned to excision with a 3-mm safe margin versus cryosurgery (i.e., curettage plus two freeze-thaw cycles by liquid nitrogen spray gun).
At 1 year, there were no recurrences in the excision group versus three in the cryosurgery group (P = NS), but this is a very short follow-up time. Patients and five independent professionals who were blinded to the treatment arm rated the cosmetic outcomes. Their overall assessments favored excision.[Level of evidence 1iiDiv]