To examine whether urokinase-type plasminogen activator (uPA) and type 1 plasminogen inhibitor (PAI-1), DNA ploidy, and S-phase fraction (SPF) add supplementary prognostic information relative to stage and Fuhrman's grade in renal cell carcinoma.

A total of 100 patients with primary renal adenocarcinoma treated by nephrectomy were followed up for a median of 42 months. Of the 100 patients, 78 with Stage M0N0-Nx tumors were studied by multivariate analysis. The study population was dichotomized on the basis of the median cytosolic uPA and PAI-1 concentrations (30 pg/mg protein and 12.7 ng/mg protein, respectively). DNA content was measured by flow cytometry (FCM) on multiple tumor samples from each patient. DNA aneuploidy was observed in 67% of cases. The SPF was calculated for aneuploid samples.

An FCM classification based on a combination of DNA content and SPF was obtained. High-risk patients were those with aneuploid tumors and high SPF values (greater than 1.7%) and included 23% of patients with M0N0-Nx tumors. Cytosolic uPA and PAI-1 levels were not predictive of metastasis. The stage, grade, SPF, and FCM classification were statistically significant prognostic factors in the univariate analysis, in both the overall population and the M0N0-Nx subgroup. In multivariate analysis, tumor grade and the FCM classification were the only independent predictors of disease-free survival (P = 0.018 and P = 0.046, respectively).

We defined a group of M0N0-Nx patients with aneuploid tumors and high SPF values who are at a high risk of metastasis and who may benefit from closer long-term follow-up.