Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases.
OBJECTIVE
To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma.


METHODS
Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed.


RESULTS
Among all 2,313 patients with stage III disease, 81% had micrometastases, and 19% had clinically detectable macrometastases. The 5-year overall survival was 63%; it was 67% for patients with nodal micrometastases, and it was 43% for those with nodal macrometastases (P < .001). Tremendous heterogeneity in survival was observed, particularly in the microscopically detected nodal metastasis subset (from 23% to 87% for 5-year survival). Multivariate analysis demonstrated that in patients with nodal micrometastases, number of tumor-containing lymph nodes, primary tumor thickness, patient age, ulceration, and anatomic site of the primary independently predicted survival (all P < .01). When added to the model, primary tumor mitotic rate was the second-most powerful predictor of survival after the number of tumor-containing nodes. In contrast, for patients with nodal macrometastases, the number of tumor-containing nodes, primary ulceration, and patient age independently predicted survival (P < .01).


CONCLUSIONS
In this multi-institutional analysis, we demonstrated remarkable heterogeneity of prognosis among patients with stage III melanoma, especially among those with nodal micrometastases. These results should be incorporated into the design and interpretation of future clinical trials involving patients with stage III melanoma.
Balch
Charles M
CM
Department of Surgery, Johns Hopkins Medical Institutions, 600 N Wolfe St, Osler 624, Baltimore, MD 21287, USA. balchch@jhmi.edu
Gershenwald
Jeffrey E
JE
Soong
Seng-Jaw
SJ
Thompson
John F
JF
Ding
Shouluan
S
Byrd
David R
DR
Cascinelli
Natale
N
Cochran
Alistair J
AJ
Coit
Daniel G
DG
Eggermont
Alexander M
AM
Johnson
Timothy
T
Kirkwood
John M
JM
Leong
Stanley P
SP
McMasters
Kelly M
KM
Mihm
Martin C
MC
Morton
Donald L
DL
Ross
Merrick I
MI
Sondak
Vernon K
VK
D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D016009:Chi-Square Distribution; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000401:mortality* / Q000556:secondary*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology*; D013997:Time Factors; D014481:United States / Q000453:epidemiology