High-risk endometrial cancer subgroups: candidates for target-based adjuvant therapy☆
Introduction
In the United States, endometrial cancer is the most common malignancy of the female reproductive tract and is exceeded annually in overall frequency only by breast, colon, and lung cancers. It is estimated that during calendar year 2004, 40,320 new cases of endometrial cancer will be diagnosed and 7090 women will die of this disease [1]. This neoplasm generally becomes manifest early in its natural history, resulting in approximately 80% of patients presenting with stage I disease. Nevertheless, nearly one of every three women who die of endometrial cancer presents with presumed localized disease.
The majority of treatment failures and the accompanying compromised longevity are the result of the failure to recognize sites of occult extrauterine dissemination at the time of primary treatment. Furthermore, adjuvant therapy has generally been dictated by traditional preferences (modality-based) rather than target-based algorithms as determined by patterns of recurrence.
The natural history of epithelial corpus cancer includes four potential routes of metastasis: contiguous extension, hematogenous dissemination, lymphatic embolization, and exfoliation with intraperitoneal spread. The associated recurrences for each of these diverse routes of spread would presuppose different adjuvant treatment strategies. In addition, such target-based therapies are predicated on the cataloging of specific pathologic or molecular factors that identify patients at high risk for harboring occult disease disseminated via one or more of these routes.
In a preliminary analysis, we reported independent risk factors for recurrence based on hematogenous [2], [3], lymphatic [4], and intraperitoneal [5] routes of dissemination in endometrial cancer (Table 1).
The objective of the present study was to identify subgroups of patients with predictable regional or distant patterns of recurrence who might potentially benefit from target-based adjuvant therapies.
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Materials and methods
From 1984 to 1996, 1109 patients with endometrial cancer were managed surgically at Mayo Clinic (Rochester, MN). Based on data from their medical records, 915 patients with epithelial endometrial cancer met the following inclusion criteria: (1) treatment included hysterectomy and removal of existing adnexal structures and (2) no other malignancy was diagnosed within 5 years before or after the diagnosis of endometrial cancer (except for carcinoma in situ or skin cancer other than melanoma).
Results
The mean age ± SD of the 915 patients was 64.5 ± 11.0 years (range, 22–95 years). The clinical and pathologic characteristics of the patients are summarized in Table 2.
Overall, lymph node dissection was performed in 514 patients (56%), specifically, pelvic lymphadenectomy in 497 (54%) and paraaortic lymphadenectomy in 152 (17%) (paraaortic lymphadenectomy only in 12 and concomitant pelvic and paraaortic lymphadenectomy in 140); the site from which the nodes were harvested was not identified in
Discussion
Approximately 70% to 80% of patients with endometrial cancer present with localized disease that potentially can be cured with surgery alone. However, approximately one of every three women dying of endometrial cancer was considered to have early-stage locoregional disease [1]. The main reason for treatment failure after traditional modality-based therapy is the presence of documented or occult extrauterine systemic disease and our inability to recognize and treat it successfully.
Traditional
Acknowledgments
Supported by the Mayo Cancer Center (P30CA15083) and the Rochester Research Committee, Mayo Foundation.
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Presented at the 13th International Meeting of the European Society of Gynaecological Oncology (ESGO), Brussels, Belgium, April 6–10, 2003.
No conflicts of interest exist for this manuscript.