THE RELATIONSHIP OF LOCAL AND DISTANT FAILURE FROM ENDOMETRIAL CANCER- DEFINING A CLINICAL PARADIGM

Purpose. Recently, statistical methods have been developed to rigorous ly assess the relationship between local and distant failures. Such me thodology has successfully been applied to a variety of tumors includi ng those arising in the prostate, breast, and cervix. To date, no publ ished data are available to generate a hypothesis to characterize the relationship between local and distant failure for endometrial cancer. The present analysis was undertaken to determine the effect of locore gional control on subsequent metastatic dissemination among women with pathologically staged endometrial cancer treated by hysterectomy foll owed by adjuvant radiotherapy. Methods. The series consisted of 394 pa tients with FIGO stages I-III endometrial cancer who were surgically s taged prior to irradiation [median external beam dose 45 Gy +/- brachy therapy (median vaginal surface dose, 30 Gy)]. The duration of follow- up ranged from 2 to 151 months, with a median of 62 months. Multiple f actors were evaluated to determine the associations with distant relap se including FIGO pathological stage, grade, histopathologic subtype ( adeno vs papillary/papillary-serous/clear cell), depth of myometrial p enetration, age, and local disease status. Time-dependent survival mod els were generated to assess the influence of local failure on distant metastases. Results. For the entire series, the 5-year actuarial rate s of local and distant failures were 9 and 20%, respectively. Women wh o failed locally had nearly a fourfold risk of failing distantly compa red to those who remained locally controlled (P = 0.02). Moreover, the earlier a local failure developed (e.g., within 1 year vs within 3 ye ars), the more likely it was to be associated with distant metastases (P < 0.05). The univariate correlations of other factors with the 5-ye ar rate of freedom from distant relapse also disclosed significant ass ociations for grade, histology (adenoca vs papillary/papillary-serous/ clear cell), and FIGO path stage. In multivariate analysis, only local control, low grade (grade 1 and 2), and early pathological stage were independently related to the likelihood of achieving freedom from dis tant relapse. Conclusions. Distant dissemination of endometrial cancer may develop secondary to local failure. Optimization of local control is therefore necessary if long-term cure is to be achieved. The limit s of the current database cannot establish whether local failure is a cause of distant spread or a high-risk marker for metastases; however, ongoing national cooperative trials may resolve this controversy. (C) 1997 Academic Press.