Prognostic Classification

The expectation of cure for the majority of patients with germ cell tumors (often with therapy that may cause death or major long-term morbidity) mandates a careful assessment of prognosis to allow appropriate tailoring of management to the individual. An understanding of the variation in the use of prognostic factors is also essential to the interpretation of the published literature. Until the mid-1990s, the lack of accepted definitions of good and poor prognoses prevented the accurate comparison of clinical trials that used a variety of criteria to assess prognosis, and delayed the identification of optimal therapy for poor-prognosis patients.

The use of pretreatment characteristics to determine the most appropriate treatment program was proposed early in the development of effective chemotherapy.36,47,48 Factors reported to have prognostic value included tumor bulk, tumor extent or number of metastatic sites, pretreatment serum tumor marker levels, primary site, visceral organ involvement, pure seminoma versus NSGCT, histologic subtypes, delay in treatment, age, and performance status. A number of reports considering reasonable numbers of patients receiving cisplatin-based chemotherapy and assessing some or all of these factors in multivariate statistical analyses have been published.49-54 Although most analyses were in general agreement, many trial groups or individual centers developed and used their own prognostic classification systems exclusively. Bajorin and colleagues demonstrated that the use of different criteria to assign prognostic categories has clinically important effects on patient selection for therapy and on the results of treatment trials.55

In the early 1990s, an international group of investigators was brought together by the Medical Research Council (MRC) to develop a prognostic classification system for all germ cell tumors through shared data and a consensus process. The resulting classification was published in 199756 and has been widely accepted and implemented. This classification should be used in clinical practice to select treatment and in all reports of treatment trials in order to improve interpretation and the comparability of the achieved outcomes (it is described in greater detail in Chapter 8). The definition of a good-prognosis nonseminomatous tumor is shown in Table 13-1. Of the 5,202 cases of nonseminoma considered in the original analysis, 56% were classified in the good-prognosis group. This group achieved an 89% 5-year progression-free survival rate and an overall survival rate of 92%. Given the recognized pattern, over time, of more frequent presentation with earlier-stage disease,57,58 both the proportion of patients classified in the good-prognosis category and the proportion of survivors are likely to have improved since the data used in this analysis were collected.

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