Improvement of survival in sex cord stromal tumors - an observational study with more than 25 years follow-up.

OBJECTIVE: To highlight aspects of malignant ovarian sex cord stromal tumors, effects of treatment, and developments over the past 28 years. DESIGN: Population-based cohort study. SETTING: Gynecological departments within the catchment-area of the Munich Cancer Registry and associated with the project group 'Malignant Ovarian Tumors' of the Munich Cancer Center. SAMPLE: One hundred and forty-five women with an invasive single sex cord stromal tumor diagnosed between 1978 and 2005. METHODS: Overall survival was estimated with the Kaplan-Meier method, relative survival was computed by the ratio of observed to expected survival rate. The impact of age, International Federation of Gynecology and Obstetrics (FIGO)-stage, residual tumor, and chemotherapy was examined by multivariate analysis (Cox regression model). MAIN OUTCOME MEASURES: Overall and relative survival and multivariate adjusted overall survival. RESULTS: Survival data showed a five-/10-year overall survival of 55.8%/42.8% (relative survival 58.6%/49.2%) for women diagnosed before 1988 and 89.1%/78.3% (relative survival 92.7%/85.2%) for women diagnosed after 1988. After adjustment for age and FIGO-stage, the following hazard ratios and 95% confidence intervals (95% CI) for treatment methods resulted: 3.3 (95% CI 1.5-7.0) for women with compared to women without residual tumor and 2.2 (95% CI 1.2-4.2) for women with chemotherapy compared to women where no chemotherapy was given. CONCLUSIONS: Improvements in survival may be attributed to a stage-shift toward more favorable stages at diagnosis and to advances in treatment such as improved surgery without residual tumor. There is no evidence for any benefit of adjuvant chemotherapy. Surgery remains the cornerstone of treatment, yet the benefit of postoperative therapy is still under debate.

Minimal residual disease in breast cancer and gynecological malignancies: phenotype and clinical relevance.

In breast cancer, about 35% of patients without any clinical signs of overt distant metastases already have disseminated tumor cells in bone marrow aspirates at the time of primary therapy. A significant prognostic impact of these disseminated tumor cells has been shown by many international studies: patients with tumor cells in their bone marrow have a significantly worse prognosis than those without them. Even in malignancies where the skeletal system is not a preferred location for distant metastasis, such as ovarian cancer, early presence of minimal residual disease (MRD) is correlated with poor patient outcome. Thus, besides analysis of the primary tumor, detection of MRD can be used for assessment of patient prognosis and for prediction or monitoring of response to systemic therapy. Disseminated tumor cells are also the targets for novel tumor biological therapy approaches such as specific antibody-based therapies against target cell-surface antigens such as HER2, Ep-CAM (17-1A), and uPA-R. In breast cancer, a first antibody-based tumor therapy against HER2 (Herceptin) has already been approved for clinical use in recurrent disease. However, patient selection for such tumor biological therapies becomes rather difficult due to phenotype changes, which may manifest themselves as differences between primary lesion and disseminated tumor cells. Therefore, not only identification of disseminated tumor cells but even more so their characterization at the protein and gene levels have become increasingly important. In conclusion, characterization of tumor biological properties of disseminated tumor cells allows identification of patients with breast cancer or gynecological malignancies at risk for relapse who are likely to benefit from systemic treatment and/or novel tumor biological therapy approaches.