High mitotic rate associated with poorer survival in primary melanoma

Thompson JF. J Clin Oncol. 2011;doi:10.1200/JCO.2010.31.5812.

Issue: May 25, 2011

Results from a review of data collected in the American Joint Committee on Cancer showed that mitotic rate was the second strongest prognostic factor, after tumor thickness, among the independent predictors of melanoma-specific survival.

Researchers analyzed the number of mitoses per millimeter squared in the primary melanoma for 13,296 patients with stage I and II disease. They found that there was an inverse correlation between survival and mitotic rate.

At 5 years, the survival rate was 97.8% for patients with zero mitosis/mm² compared with 59.4% for patients with at least 20 mitoses/mm². The pattern held at 10 years, with a survival rate of 93.2% for patients with a mitotic rate of 0/mm² vs. 47.6% for those with a mitotic rate of at least 20/mm².

Increase in tumor thickness correlated with an increase in mitotic rate and primary tumor ulceration. Researchers observed at least some mitotic activity in most patients with melanomas that were larger than 2.5 mm, but activity was uncommon in those with primary tumors smaller than 1 mm.

The 10-year survival rate was 97.1% for patients with a tumor thickness of 0.5 mm or smaller and less than one mitosis/mm² compared with 28.1% for those with a tumor thickness of larger than 6 mm and more than 10 mitoses/mm².

Increasing mitotic rate stayed highly correlated with increasing tumor thickness, even when ulceration was included as a third variable, especially in patients with equal tumor thickness in the presence of ulceration.

Cox multivariate analysis showed that, of the seven prognostic variables evaluated, mitotic rate was the second most powerful predictor of survival.

Writing in an accompanying editorial, Bruce J. Averbook, MD, associate professor of surgery with Case Western Reserve University, said mitotic rate should be incorporated into standard staging, added that patient age was the third-leading prognostic factor and cannot be ignored.

"Several studies in recent years have seen an impact of age on survival, and patient age should now be considered for incorporation into clinical staging. Classification and regression tree analysis would be one statistical method that could aid in delineating the best use of this information," he wrote. "Indeed, combining continuous data with ordinal data to arrive with some precision at cutoffs, percentages of risks of recurrence, and estimations of survival would give more precision to clinical decision-making and research group stratification."

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