New data adds to prognostic factors for thin melanoma

October 1, 2007

Researchers have come up with a broader set of prognostic factors for thin melanomas to enhance American Joint Committee on Cancer (AJCC) staging and improve clinical decision-making. Their findings support the consensus that tumor cell mitotic rate should be incorporated into the next iteration of AJCC staging.

Keypoints:

Philadelphia - In what researchers call the most extensive investigation of patients with thin melanomas of its kind, a broader set of prognostic factors has been produced to enhance American Joint Committee on Cancer (AJCC) staging and improve clinical decision-making.

Researchers pulled together data from 26,291 patients with thin melanomas in the U.S. population-based Surveillance, Epidemiology and End Results (SEER) cancer registry (1988 to 2001), and 2,389 patients in the University of Pennsylvania's Pigmented Lesion Group (PLG; 1972-2001).

The researchers first developed a SEER-based classification tree using AJCC core prognostic factors of thickness, anatomic level, ulceration, site, sex and age, says Phyllis Gimotty, Ph.D., lead author on the study and professor of biostatistics at the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania School of Medicine.

The researchers found that the SEER-based classification tree identified additional criteria to explain survival heterogeneity among patients with thin, nonulcerated lesions, showing that 10-year survival rates ranged from 89.1 percent to 99 percent.

The new PLG-based tree identified groups using level, tumor cell mitotic rate and sex; with survival rates from 83.4 percent to 100 percent, it had better discrimination.

"Using the potential prognostic factors available in SEER, a recursive partitioning computer algorithm was used that allowed us to identify the optimal prognostic factors to predict survival," Dr. Gimotty says.

"We then looked at the PLG data to see if patients in the groups that were defined by the selected factors (prognostic profiles) had similar survival rates, (and) they did, validating both the current AJCC and our expanded AJCC classification," she tells Dermatology Times.

"Since the expanded classification is more accurate than AJCC staging in predicting outcome, and since we validated it in a separate population (the patients managed by the PLG), it can be used now by clinicians and researchers," Dr. Gimotty adds.

Study analysis

The findings offer important updated information to the current AJCC staging system, which is limited in that it was originally validated on a multi-institutional cohort of 17,600 patients that was not population-based and in which only 40 percent of patients had thin melanomas.

New classification tree

In developing the new PLG-based classification tree, four additional prognostic factors were tested: invasive radial growth phase (RGP) or vertical growth phase (VGP), RGP regression, VGP mitogenicity and tumor infiltrating lymphocytes. Two of the prognostic factors, level and sex, were in the expanded AJCC classification, and VGP mitogenicity represented a new factor.

Since mitogenicity can represent the biology of tumor progression, it holds significance beyond factors currently used to stage thin melanomas.

"We have shown that tumor progression in primary melanomas may be characterized by three stages: a phase of rapid tumor cell proliferation in the epidermis (the in situ RGP), followed by a phase of invasion into the dermis and decreased proliferation (the invasive RGP), and then by a phase in which higher proliferative rates resume in the dermis as the VGP ensues," the authors explain.

Tumor cell mitotic rate has already been widely validated and demonstrated to be an independent prognostic factor for disease-free survival and metastasis among patients with thin melanomas. Researchers emphasize that mitogenicity should be included in the next version of AJCC staging for melanoma.

"We have developed a profile of factors that can be used now in patients with thin melanomas to more accurately identify those with excellent prognosis and those with high risk of melanoma-related death," she says.

Clinical participants

"Patients with excellent prognoses do not need sentinel node biopsies and might be followed as infrequently as once a year," says DuPont Guerry M.D., co-author on the study, professor of medicine and director of the Abramson Cancer Center's Melanoma Program at the University of Pennsylvania School of Medicine.

"High-risk patients would be excellent candidates for a clinical study of the frequency of positivity and the impact on survival (with or without adjuvant therapy) of sentinel node biopsies," Dr. Guerry says.

"High-risk patients should be followed closely for evidence of relapse; once the 'new' classification is validated, it, too, can be used in this fashion."