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Nadeem R. Abu-Rustum

Most patients with endometrial cancer will present with early-stage disease. Although the rate of metastasis in these patients is low, proffering excellent prognoses, the standard of treatment in many practices still includes a complete or selective pelvic and para-aortic lymphadenectomy for staging; and accurate surgical staging is the most important prognostic factor. Many patients will undergo a comprehensive lymphadenectomy despite having disease confined to the uterus, resulting in prolonged operating time, additional cost, and potential side effects, such as lower extremity lymphedema. However, recent studies show that a complete lymphadenectomy may have no therapeutic benefit in patients with early-stage endometrial cancer. Sentinel lymph node (SLN) mapping, which has been used in other cancer types, may be an acceptable surgical strategy between a complete lymphadenectomy and no nodal evaluation in patients with endometrial cancer. SLN mapping is based on the concept that lymph node metastasis is the result of an orderly process; that is, lymph drains in a specific pattern away from the tumor, and therefore, if the SLN, or first node, is negative for metastasis, then the nodes after the SLN should also be negative. This approach can help patients avoid the side effects associated with a complete lymphadenectomy, although disease must be thoroughly staged for accurate prognosis and determination of appropriate treatment approach. Surgeon experience, adherence to an SLN algorithm, and the use of pathologic “ultrastaging” are key factors for successful SLN mapping.

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Nadeem R. Abu-Rustum and Yukio Sonoda

This article describes the surgical and pathologic findings of fertility-sparing radical trachelectomy using a standardized surgical technique, and reports the rate of posttrachelectomy outcomes. The authors analyzed a prospectively maintained database of all patients with FIGO stage IA1–IB1 cervical cancer admitted to the operating room for planned fertility-sparing radical abdominal trachelectomy. Sentinel node mapping was performed through cervical injection. Between November 2001 and May 2010, 98 consecutive patients with FIGO stage IA1–IB1 cervical cancer and a median age of 32 years (range, 6–45 years) underwent a fertility-sparing radical trachelectomy. The most common histology was adenocarcinoma in 54 patients (55%) and squamous carcinoma in 42 (43%). Lymph-vascular invasion was seen in 38 patients (39%). FIGO stages included IA1 (with lymph-vascular invasion) in 10 patients (10%), IA2 in 9 (9%), and IB1 in 79 (81%). Only 15 (15%) needed immediate completion radical hysterectomy because of intraoperative findings. Median number of nodes evaluated was 22 (range, 3–54), and 16 (16%) patients had positive pelvic nodes on final pathology. Final trachelectomy pathology showed no residual disease in 44 (45%) cases, dysplasia in 5 (5%), and adenocarcinoma in situ in 3 (3%). Overall, 27 (27%) patients needed hysterectomy or adjuvant pelvic radiation postoperatively. One (1%) documented recurrence was fatal at the time of this report. Cervical adenocarcinoma and lymph-vascular invasion are common features of patients selected for radical trachelectomy. Most patients can undergo the operation successfully with many having no residual invasive disease; however, nearly 27% of all selected cases will require hysterectomy or postoperative chemoradiation for oncologic reasons. Investigation into alternative fertility-sparing adjuvant therapy in patients with node-positive disease is needed.

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Rajmohan Murali, Deborah F. Delair, Sarah M. Bean, Nadeem R. Abu-Rustum and Robert A. Soslow

Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.

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Edward E. Partridge, Nadeem Abu-Rustum, Anna Giuliano, Stewart Massad, Joan McClure, Mary Dwyer and Miranda Hughes

These NCCN Guidelines Insights focus on recent recommendations for cervical cancer screening and management of abnormal screening tests. When the NCCN Panel convened to update the NCCN Guidelines for Cervical Cancer Screening, they decided to adopt and endorse guidelines from other organizations to avoid duplication of effort. Therefore, in July 2013, after review and validation of consensus guidelines from the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology, the NCCN Guidelines for Cervical Cancer Screening were discontinued.

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Edward E. Partridge, Nadeem R. Abu-Rustum, Susan M. Campos, Patrick J. Fahey, Michael Farmer, Rochelle L. Garcia, Anna Giuliano, Howard W. Jones III, Subodh M. Lele, Richard W. Lieberman, Stewart L. Massad, Mark A. Morgan, R. Kevin Reynolds, Helen E. Rhodes, Diljeet K. Singh, Karen Smith-McCune, Nelson Teng, Cornelia Liu Trimble, Fidel Valea and Sharon Wilczynski

Overview Despite a significant decrease in the incidence and mortality of cervical carcinoma in the United States, an estimated 12,200 women will be diagnosed with the disease in 2010, with 4210 expected deaths.1 High-risk groups include women without access to health care and those who have immigrated to the United States from countries where cervical cancer screening is not routinely performed.2 Because cervical cytology screening is the current method for early detection of this neoplasm, the purpose of these guidelines is to provide direction for the evaluation and management of cervical cytology. These guidelines include recommendations on screening techniques, initiation, and frequency of screening, and management of abnormal screening results including colposcopy. Cervical cytology screening techniques include liquid-based cytology or conventional Papanicolaou (Pap) smears. Unless specifically noted, these techniques are collectively referred to as cervical cytology in this discussion. Human papillomavirus (HPV) DNA testing for primary cervical cancer has been approved by the FDA; several diagnostic tests are available (e.g., HPV high-risk and HPV 16/18 DNA tests, Hybrid Capture 2 HPV DNA test). However, HPV DNA testing is not recommended in women younger than 21 years.3 HPV DNA testing for high-risk virus types can also be used as a component of both primary screening and workup of abnormal cytology results; it is not useful to test for low-risk virus types.3 (See HPV DNA Testing on page 1378 for more detail about these tests.) Colposcopy, along with colposcopically directed biopsies, is the primary method for evaluating women with abnormal cervical cytologies....
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Benjamin E. Greer, Wui-Jin Koh, Nadeem Abu-Rustum, Michael A. Bookman, Robert E. Bristow, Susana M. Campos, Kathleen R. Cho, Larry Copeland, Marta Ann Crispens, Patricia J. Eifel, Warner K. Huh, Wainwright Jaggernauth, Daniel S. Kapp, John J. Kavanagh, John R. Lurain III, Mark Morgan, Robert J. Morgan Jr, C. Bethan Powell, Steven W. Remmenga, R. Kevin Reynolds, Angeles Alvarez Secord, William Small Jr and Nelson Teng

Uterine Neoplasms Clinical Practice Guidelines in Oncology NCCN Categories of Evidence and Consensus Category 1: The recommendation is based on high-level evidence (e.g., randomized controlled trials) and there is uniform NCCN consensus. Category 2A: The recommendation is based on lowerlevel evidence and there is uniform NCCN consensus. Category 2B: The recommendation is based on lowerlevel evidence and there is nonuniform NCCN consensus (but no major disagreement). Category 3: The recommendation is based on any level of evidence but reflects major disagreement. All recommendations are category 2A unless otherwise noted. Clinical trials: The NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Overview Adenocarcinoma of the endometrium is the most common malignancy in the female genital tract in the United States. An estimated 40,100 new diagnoses of uterine cancer and 7470 deaths from this disease will occur in 2008.1 Uterine sarcomas are uncommon and account for approximately 1 in 12 of all uterine cancers.2 These guidelines describe epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management (see page 500). By definition, these guidelines cannot incorporate all possible clinical variations and are not intended to replace good clinical judgment or individualization of treatments. Exceptions to the rule were discussed among panel members during the process of developing these guidelines. For patients with suspected uterine neoplasms, initial preoperative evaluation includes a history and physical examination, endometrial biopsy, chest radiograph, a CBC,...
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Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, David Cohn, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, David K. Gaffney, Robert L. Giuntoli II, Ernest Han, Warner K. Huh, John R. Lurain III, Lainie Martin, Mark A. Morgan, David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Nicole R. McMillian and Miranda Hughes

These NCCN Clinical Practice Guidelines in Oncology for Cervical Cancer focus on early-stage disease, because it occurs more frequently in the United States. After careful clinical evaluation and staging, the primary treatment of early-stage cervical cancer is either surgery or radiotherapy. These guidelines include fertility-sparing and non-fertility-sparing treatment for those with early-stage disease, which is disease confined to the uterus. A new fertility-sparing algorithm was added for select patients with stage IA and IB1 disease..

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Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, David Cohn, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, Amanda Nickles Fader, Christine M. Fisher, David K. Gaffney, Suzanne George, Ernest Han, Warner K. Huh, John R. Lurain III, Lainie Martin, David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr, Nelson Teng, Todd Tillmanns, Fidel A. Valea, Nicole McMillian and Miranda Hughes

Adenocarcinoma of the endometrium (also known as endometrial cancer or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. An estimated 49,560 new uterine cancer cases will occur in 2013, with 8190 deaths resulting from the disease. Uterine sarcomas (stromal/mesenchymal tumors) are uncommon malignancies, accounting for approximately 3% of all uterine cancers. The NCCN Guidelines for Uterine Neoplasms describe malignant epithelial carcinomas and uterine sarcomas; each of these major categories contains specific histologic groups that require different management. This excerpt of these guidelines focuses on early-stage disease.

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Benjamin E. Greer, Wui-Jin Koh, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, John Chan, Kathleen R. Cho, Larry Copeland, Marta Ann Crispens, Nefertiti DuPont, Patricia J. Eifel, David K. Gaffney, Warner K. Huh, Daniel S. Kapp, John R. Lurain III, Lainie Martin, Mark A. Morgan, Robert J. Morgan Jr., David Mutch, Steven W. Remmenga, R. Kevin Reynolds, William Small Jr., Nelson Teng and Fidel A. Valea

Overview An estimated 12,200 new cases of cervical cancer will be diagnosed in the United States in 2010, and 4200 people will die of the disease.1 Cervical cancer rates are decreasing among women in the United States, although incidence remains high among Hispanic/Latino, black, and Asian women.2–5 However, cervical cancer is a major world health problem for women. The global yearly incidence of cervical cancer for 2002 was 493,200; the annual death rate was 273,500. It is the third most common cancer in women worldwide,6,7 with 78% of cases occurring in developing countries, where cervical cancer is the second most frequent cause of cancer death in women. Persistent human papillomavirus (HPV) infection is regarded as the most important factor contributing to the development of cervical cancer. A relationship seems to exist between the incidence of cervical cancer and the prevalence of HPV in the population. The prevalence of chronic HPV in countries with a high incidence of cervical cancer is 10% to 20%, whereas its prevalence in low-incidence countries is 5% to 10%.6 Immunization against HPV prevents infection with certain types of HPV and, thus, is expected to prevent specific HPV cancer in women (see NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines] for Cervical Cancer Screening, in this issue; to view the most recent version of these guidelines, visit the NCCN Web site at www.NCCN.org).8–12 Other epidemiologic risk factors associated with cervical cancer are a history of smoking, parity, contraceptive use, early age at onset of coitus, larger number...
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Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, Kathleen R. Cho, Christina Chu, David Cohn, Marta Ann Crispens, Don S. Dizon, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain III, Andrea Mariani, David Mutch, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Fidel A. Valea, Catheryn M. Yashar, Nicole R. McMillian and Jillian L. Scavone

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.