Cancer of the Uterus PDF

Preface

Cancers of the uterine corpus represent the most common gynecologic malignancies, with an estimated yearly incidence of 40,000 new cases in the United States, which is among the highest worldwide. A substantial increase in uterine cancers may be seen in the near future as a result of the epidemic of obesity and diabetes in the Western world. These statistics create a pressing need to understand the molecular basis of uterine cancers, improve their prevention and optimize their therapy.

We are extremely excited and humbled by the opportunity to invite a group of distinguished scientists and clinicians to discuss systematically the important basic, translational and clinical advances made in this field and review the many controversies still surrounding the management of uterine cancers. Dr. Goodfellow and colleagues discuss the current understanding of the molecular events underlying endometrial cancer and the identification of two distinct molecular phenotypes of endometrial cancer. Dr. Bandera reviews the role of the environmental and genetic factors modulating the risk of uterine cancer and discusses the counseling of women at risk for uterine cancer based on molecular epidemiology data. The molecular characterization of uterine cancers has unveiled novel targets for molecular therapy. Dr. Coukos and colleagues discuss these in relation to current compounds emerging from the industry pipeline. Understanding endometrial cancer and uterine sarcomas at the molecular level forces a rethinking of their pathologic classification, as it will be discussed by Drs. Kurman and colleagues and Dr.

Kempson, respectively. Although the role of steroid hormones in the pathogenesis of endometrial neoplasia is well established, the significance of steroid receptors as prognostic or disease classification biomarkers guiding therapy remains controversial and is discussed by Dr. Leslie and colleagues. Finally, Dr. Barakat reviews the effects of tamoxifen and other selective estrogen receptor modulators on the uterus and the management of patients receiving these drugs.

Important controversies remain in the clinical management of uterine cancers. Dr. Cooper and colleagues review the work up and management of abnormal uterine bleeding, while Dr. Randall and Bowman argue the case of conservative management of early endometrial cancer and its precursor lesions. Dr. Chu reviews the prognostic factors affecting outcome in patients with early stage endometrial cancer and discusses the rationale for surgical staging and different surgical approaches to define the optimal surgical management of early endometrial cancer. The public demand for minimally invasive surgical approaches has created a pressing need to define the value of laparoscopic approaches to uterine cancer surgery. Dr. Walker and colleagues review these issues in detail and present outcome evidence from recent studies.

Although high survival rates are attainable in early stage endometrial cancer, approximately 20% of newly diagnosed patients will have regional or distant spread of disease. Dr. Bristow and colleagues discuss the rationale and outcomes relevant to primary cytoreductive surgery for patients with stage III and IV disease. In addition, they review the recent literature addressing the surgical management of uterine papillary serous carcinoma, making the case that this histotype warrants aggressive management even in early stage.

One of the most controversial topics in the field of gynecologic oncology is the postoperative management of patients with endometrial cancer and uterine sarcomas. Dr. Grisby reviews radiation therapy recommendations for patients who are surgically staged and for those who have incomplete surgical staging, based on the results of existing prospective randomized studies or retrospective studies. He also describes the use of irradiation alone for medically inoperable patients and provide the techniques for both external irradiation and high dose rate brachytherapy.

The restored life expectancy of patients with early stage uterine cancer poses important questions on the safety of estrogen replacement therapy in this population. Dr. Runowicz and colleagues review the risks and benefits of estrogen replacement therapy in endometrial cancer survivors.

Recurrence is not uncommon in patients presenting initially with high risk early stage or advanced disease. There is a recognized role for surgery in carefully selected patients. Dr. Penalver and colleagues review the indications, technique, outcome, and complications of exenterative surgery for recurrent endometrial cancer in previously irradiated patients, and discuss palliative surgery approaches. In addition, Dr. Lu and colleagues discuss the medical management of recurrent endometrial cancer, reviewing the evidence on chemotherapy and hormonal therapy. Finally, Dr. Harris and colleagues review the postoperative radiation treatment of advanced and recurrent endometrial carcinoma, discuss palliative radiation therapy, and discuss the role of high dose radiation in this setting.

Uterine sarcomas represent a challenging group of tumors owing to their rarity and heterogeneity. Dr. Sutton and colleagues review the management of mixed müllerian mesodermal tumors, endometrial stromal sarcoma and leiomyosarcoma. They discuss the role of staging for apparently early disease and that of debulking for advanced sarcomas. They also discuss adjuvant therapies for early stage disease and the management of advanced disease.

We are grateful to all colleagues, friends, and authors for their time, wisdom, and technical expertise. We hope that this monograph will fill an important gap in the field of translational and clinical gynecologic oncology and provides the reader useful information for the management of these tumors.