Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation.

PURPOSE: To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial. PATIENTS AND METHODS: Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities. RESULTS: Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis. CONCLUSION: In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.

Sex differences in incidence and mortality of bladder and kidney cancers: national estimates from 49 countries.

OBJECTIVES: In the United States, among patients diagnosed with bladder cancer (BC), women have increased disease-specific mortality compared with men. The main objective of this study was to determine whether this pattern is also present in other countries. For comparison, similar analyses were performed for kidney cancer (KC). METHODS AND MATERIALS: Data for this study were obtained from the GLOBOCAN 2008 database. A total of 49 countries with available information on BC and KC incidence and mortality were included in the analysis, representing all major geographic regions except Africa. For each country, we computed the sex-specific ratio of the total number of deaths from a given cancer to the total number of diagnoses in the year 2008 (the mortality-to-incidence ratio [MIR]). The relative MIR was computed for each country as a ratio of MIR in women to MIR in men. A relative MIR of more than 1 would indicate that the number of cancer-specific deaths relative to the number of cancer-specific diagnoses is greater in women than in men. RESULTS: For BC, the relative MIRs were significantly more than 1 in 26 countries (53%), significantly less than 1 in 2 countries (4%), and not significantly different from 1 in 21 countries (43%). The median relative MIR was 1.21 (interquartile range: 1.04-1.41). For KC, the relative MIRs were significantly more than 1 in 4 countries (8%), significantly less than 1 in 3 countries (6%), and not significantly different from 1 in 42 countries (86%). The median relative MIR was 1.00 (interquartile range: 0.94-1.06). CONCLUSION: Among BC patients, increased disease-specific mortality in women compared with men appears to be a common (although not a universal) phenomenon. This pattern may potentially be explained by differences between the sexes in the biology of disease, time to diagnosis, treatment decisions, and other factors. In contrast, among KC patients, no significant differences in disease-specific mortality were seen between the 2 sexes in the overwhelming majority of the countries.