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Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome (e.g. recurrence of disease), and are important tools in the management of cancer and many other diseases. Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because (sometimes conflicting) evidence relating to markers is often published across a number of studies. To investigate the practicality of this approach, an empirical investigation of a systematic review of tumour markers for neuroblastoma was performed; 260 studies of prognostic markers were identified, which considered 130 different markers.The reporting of these studies was often inadequate, in terms of both statistical analysis and presentation, and there was considerable heterogeneity for many important clinical/statistical factors. These problems restricted both the extraction of data and the meta-analysis of results from the primary studies, limiting feasibility of the evidence-based approach.Guidelines for reporting the results of primary prognostic marker studies in cancer, and other diseases, are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic reviews, meta-analysis and, ultimately, evidence-based practice. General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered, including poorly reported summary statistics and variability in cutoff level, outcome assessed and adjustment factors used. It would also limit the problem of reporting bias, although publication bias will remain a concern until studies are prospectively registered. Such changes in practice would help important evidence-based reviews to be conducted in order to establish the most appropriate prognostic markers for clinical use, which should ultimately improve patient care.

PURPOSE EWS-ETS fusion genes are the driving force in Ewing's sarcoma pathogenesis. Because of the variable breakpoint locations in the involved genes, there is heterogeneity in fusion RNA and protein architecture. Since previous retrospective studies suggested prognostic differences among patients expressing different EWS-FLI1 fusion types, the impact of fusion RNA architecture on disease progression and relapse was studied prospectively within the Euro-E.W.I.N.G. 99 clinical trial. PATIENTS AND METHODS Among 1,957 patients who registered before January 1, 2007, 703 primary tumors were accessible for the molecular biology study. Fusion type was assessed by polymerase chain reaction on frozen (n = 578) or paraffin-embedded materials (n = 125). The primary end point was the time to disease progression or relapse. Results After exclusion of noninformative patients, 565 patients were entered into the prognostic factor analysis comparing type 1 (n = 296), type 2 (n = 133), nontype 1/nontype 2 EWS-FLI1 (n = 91) and EWS-ERG fusions (n = 45). Median follow-up time was 4.5 years. The distribution of sex, age, tumor volume, tumor site, disease extension, or histologic response did not differ between the four fusion type groups. We did not observe any significant prognostic value of the fusion type on the risk of progression or relapse. The only slight difference was that the risk of progression or relapse associated with nontype 1/nontype 2 EWS-FLI1 fusions was 1.38 (95% CI, 0.96 to 2.0) times higher than risk associated with other fusion types, but it was not significant (P = .10). CONCLUSION In contrast to retrospective studies, the prospective evaluation did not confirm a prognostic benefit for type 1 EWS-FLI1 fusions.

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