More Skin Cancer Lesions, More Risk

The presence of multiple squamous-cell skin cancer lesions significantly increased the likelihood of local recurrence and lymph node metastasis, a retrospective cohort study showed.

As compared with a single lesion, two to nine squamous-cell cancers almost doubled the risk of local recurrence and tripled the likelihood of nodal invasion. The few patients who had 10 or more lesions, most of whom were immuno suppressed, had a fourfold greater risk of local recurrence and nodal metastasis.

Although the absolute risk associated with multiple squamous-cell skin cancers remained modest, the findings emphasize the need for frequent follow-up, Chrysalyne D. Schmults, MD, of Brigham and Women's Hospital in Boston, and colleagues concluded in an article published online in JAMA Dermatology.

"These findings substantiate the importance of close follow-up for dermatologic patients with multiple cutaneous squamous-cell carcinomas (CSCCs), especially those with many tumors, and highlight the necessity for dermatologists to document prior CSCC sites, examine the scar sites of prior CSCCs, and perform lymph node examinations in those patients," the authors concluded. "Larger studies are required to determine which factors affect multiple tumor formation and subsequent outcomes."

The findings reflect a clinical scenario analogous to Russian roulette: "The more 'bullets in the chamber,' the higher the risk for local recurrence and spread to local lymph nodes," said Dominic Ricci, MD, of Baylor Scott & White Healthcare in Round Rock, Texas.

"The surprising thing, however, was that this high risk existed even if the original tumors weren't particularly aggressive," Ricci, who wasn't involved in the study, told MedPage Today in an email.

"Follow-up is extremely important for these patients," he added. "For patients with more than 10 cutaneous squamous cell carcinomas, they should be seen probably every 3 to 4 months by a dermatologist, and their exam should include a check of the lymph nodes in the region of their skin cancers. For patients with two to nine lesions -- depending on over what time period the skin cancers have occurred -- they should probably been seen every 6 months, at least yearly."

Despite the well-documented association between sun exposure and skin cancer, an estimated 400,000 to 700,000 new cases of CSCC arise each year in the United States, second only to basal-cell skin cancer. Although most cases are curable, patients do die of CSCC, with the estimated annual mortality ranging from 4,000 to 8,800 cases. In some parts of the southern and central U.S., deaths attributable to CSCC may exceed the number of deaths caused by other types of cancer, including melanoma.

Large cohort studies have identified factors associated with poor outcome in CSCC: larger tumor diameter, depth of invasion, poor differentiation, perineural invasion, lymphovascular invasion, desmoplasia, immunosuppression, and location on the ear, temple, or lip.

By the Brigham and Women's Hospital (BWH) tumor staging system, the presence of two or more risk factors define high-stage CSCC, conferring an elevated risk of nodal metastases and death. The staging system comprises diameter ≥2 cm, tumor invasion beyond subcutaneous fat, poorly differentiated histologic features, and large-caliber nerve invasion ≥0.1 mm.

A few studies have examined the risk of subsequent CSCC formation in patients with a history of the lesions, the authors continued. However, only a single study has examined the impact of lesion number on subsequent risk and outcomes, and that investigation employed a cutoff of three or more lesions versus fewer than three.

"There are no studies, to our knowledge, that specifically evaluate CSCC outcomes in individuals who form multiple versus single CSCCs," Levine and colleagues noted in their introduction.

To address the risk of multiple versus single CSCC lesions, investigators searched an electronic medical record database to identify patients treated for "dermally invasive (non-in situ) primary CSCC" from Jan. 1, 2000 through Dec. 31, 2009. The query identified 985 patients: 727 who had one CSCC, 239 who had two to nine lesions, and 19 who had 10 or more CSCCs. All but four of the patients with 10+ lesions were immunosuppressed.

The primary outcomes of interest were local recurrence (LR) and nodal metastasis (NM). During a median follow-up of 50 months, patients with two to nine CSCCs had a risk of LR and NM of 1.8 times (95% CI 1.1-4.3) and 3.0 times greater (95% CI 1.4-6.5) than did patients with a single lesion. The small group of patients with 10 or more lesions had a subhazard ratio of 3.8 for LR (95% CI 1.4-10.0) and 4.2 for NM (95% CI 1.4-10.4).

The 10-year cumulative incidence of LR and NM increased with the number of CSCCs:

•    One CSCC - LR 3.0%, NM 2.3%
•  Two to nine - 6.7%, 5.9%
• ≥10 - 36.8%, 26.3% 

  
CSCC-related mortality did not differ among patients with a single lesion (2.2%), two to nine lesions (2.0%), or ≥10 lesions (0%). Local recurrence and nodal metastasis were associated with higher tumor stage, irrespective of the number of lesions. Immunosuppression was significantly associated with high-stage tumors (P=0.04).

Authors of an invited review of the study, published online in JAMA Oncology, said the findings "confirm what is clinically intuitive -- that rates of local recurrence or nodal metastasis rise significantly as the number of CSCCs increases. The study's principal weakness -- acknowledged by the authors -- is that "increasing risk of poor outcomes in patients with multiple tumors may be merely an additive effect, as each additional CSCC is an independent event conferring additional risk," said Simon Yoo, MD, of Feinberg School of Medicine at Northwestern University in Chicago, and coauthors.
Source from : http://www.medpagetoday.com/Dermatology/SkinCancer/54032