Treatments for non-metastatic squamous cell carcinoma of the skin

Squamous cell carcinoma (SCC) of the skin is the second most common skin cancer in people of white origin, most frequently occurring on sun-exposed areas of the body. People with fair skin and those with certain genetic conditions or an impaired immune system are at greater risk of developing SCC of the skin. Clinically, SCC often appears as a persistent red, scaly patch which may bleed if traumatised although lesions may also look like warts or non-healing sores. Occasionally SCC of the skin returns, even after apparently successful treatment and may spread to other parts of the body. However, it rarely causes death. Most skin SCCs are treated surgically, either by cutting out the cancer with a margin of normal-looking skin, or occasionally by Mohs micrographic surgery in which visible tumour is removed and examined under the microscope, with further stages of excision and microscopic examination until all the tumour has gone. If surgery is not possible, radiotherapy may be used as a treatment. Other treatments sometimes used include curettage and cautery (where tumour is scraped off and the wound sealed with a small electrical current to stop bleeding and destroy remaining cancer cells), and cryotherapy, in which cancer cells are destroyed by freezing. Sometimes combinations of treatment are used for more aggressive skin SCC that has a high risk of recurring and spreading. Other more novel treatments have also been used but are not generally recommended.

We searched for studies where people with primary non-metastatic SCC had been randomised to receive one or another treatment for their disease. Our primary aim was to ask which treatment method is associated with the lowest levels of recurrence of disease and the best quality of life. We also aimed to compare treatments in terms of discomfort to the individual and appearance of the area treated. Only one study was found which compared the recurrence of cancer in people with aggressive skin SCC (exhibiting characteristics making it at high risk of recurrence or spread) who were treated with either added chemotherapy after initial surgical treatment, or who did not receive any added chemotherapy. The evidence from this trial suggested that adding chemotherapy had no significant effect on time to recurrence. As no further randomised studies were found comparing the different interventions, we could not find enough evidence to answer these questions in this review. This highlights the need for more well-designed randomised studies in this field in order to provide more reliable evidence for the management of people with this condition.

Authors' conclusions: 

Little evidence from RCTs comparing the efficacy of different interventions for primary cutaneous SCCs exists. There is a clear need for well-designed randomised studies in order to improve the evidence base for the management of this condition.

Read the full abstract...

Squamous cell carcinoma (SCC) is the second most common skin cancer, and is becoming increasingly common around the world. Left untreated, it may spread to other parts of the body, and, although the risk is low, it may ultimately lead to death. Surgical excision is the first line of treatment for most skin SCCs, although other forms of treatment are also used depending upon the nature and site of the tumour and individual participant factors. A multi-professional approach is therefore required for the management of people with this condition.


To assess the effects of treatments for primary non-metastatic squamous cell carcinoma of the skin.

Search strategy: 

In February 2010 we searched for relevant trials in The Cochrane Skin Group Specialised Register, The Cochrane Library (Issue 1, 2010), MEDLINE, EMBASE, PsycINFO, AMED, LILACS, and the ongoing trials registries.

Selection criteria: 

We only included randomised controlled trials (RCTs) of interventions for primary SCC of the skin. Inclusion criteria were: adults with one or more histologically proven primary SCCs of the skin which had not metastasised. The primary outcome measures were time to recurrence one to five years after treatment, and quality of life. Secondary outcomes included early treatment failure within six months, number of adverse events by the end of treatment, aesthetic appearance as assessed by the participant and clinician, discomfort to the participant during and after treatment, and death.

Data collection and analysis: 

Two authors (LL, FB-H) independently carried out study selection and assessment of methodological quality and data extraction.

Main results: 

One trial involving 65 people was included. This compared the time to recurrence in participants with aggressive skin SCC who were randomised to receive either adjuvant 13-cis-retinoic acid and interferon alpha after surgery with or without radiation treatment, or no adjuvant therapy after their initial treatment. There was no significant difference in time to recurrence of tumour between the two groups (hazard ratio 1.08, 95% confidence intervals 0.43 to 2.72).

Most studies identified from the searches were excluded as they were either uncontrolled case series, did not include participants with invasive primary SCC, or included only participants with recurrent or metastatic disease.