Endometrial Cancer in Reproductive-Aged Females: Etiology and Pathogenesis.

Endometrial cancer is the most common gynecologic malignancy in developed countries, and the incidence is rising in premenopausal females. Type I EC is more common than Type II EC (80% vs. 20%) and is associated with a hyperestrogenic state. Estrogen unopposed by progesterone is considered to be the main driving factor in the pathogenesis of EC. Studies show that BMI > 30 kg/m2, prolonged duration of menses, nulliparity, presence of polycystic ovarian syndrome, and Lynch syndrome are the most common causes of EC in premenopausal women. Currently, there are no guidelines established to indicate premenopausal patients who should be screened. This review aims to synthesize current data on the etiology, risk factors, presentation, evaluation, and prognosis of endometrial cancer in this population.

Role of lymphadenectomy in endometrial cancer with nonbulky lymph node metastasis: Comparison of comprehensive surgical staging and sentinel lymph node algorithm.

OBJECTIVES: To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). METHODS: Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004-2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006-2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. RESULTS: The study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79-5.58; P = 0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05-1.42; P = 0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60-2.67; P =0 .53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. CONCLUSIONS: In EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.

Multicenter study comparing oncologic outcomes between two nodal assessment methods in patients with deeply invasive endometrioid endometrial carcinoma: A sentinel lymph node algorithm versus a comprehensive pelvic and paraaortic lymphadenectomy.

OBJECTIVES: To compare oncologic outcomes in the staging of deeply invasive endometrioid endometrial carcinoma (EEC) using a sentinel lymph node algorithm (SLN) versus pelvic and paraaortic lymphadenectomy to the renal veins (LND); to compare outcomes in node-negative cases. METHODS: At two institutions, patients with deeply invasive (≥50% myometrial invasion) EEC were identified. One institution used LND (2004-2008), the other SLN (2005-2013). FIGO stage IV cases were excluded. Clinical characteristics and follow-up data were recorded. RESULTS: 176 patients were identified (LND, 94; SLN, 82). SLN patients were younger (p = 0.003) and had more LVSI (p < 0.001). 9.8% in the SLN and 29.8% in the LND cohorts, respectively, received no adjuvant therapy (p < 0.001). There was no association between type of assessment and recurrence; adjusted hazard ratio (aHR; LND vs. SLN) 0.87 (95%CI 0.40, 1.89) PFS. After controlling for age and adjuvant therapy, there was no association between assessment method and OS (aHR 2.54; 95%CI 0.81, 7.91). The node-negative cohort demonstrated no association between survival and assessment method: aHR 0.69 (95%CI 0.23, 2.03) PFS, 0.81 (95%CI 0.16, 4.22) OS. In the node-negative cohort, neither adjuvant EBRT+/-IVRT (HR 1.63; 95%CI 0.18, 14.97) nor adjuvant chemotherapy+/-EBRT+/-IVRT (HR 0.49; 95%CI 0.11, 2.22) were associated with OS, compared to no adjuvant therapy or IVRT-only. CONCLUSION: Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome.

Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.

OBJECTIVE: To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma. METHODS: Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. RESULTS: We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76). CONCLUSIONS: SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND.

Impact of Robotic Platforms on Surgical Approach and Costs in the Management of Morbidly Obese Patients with Newly Diagnosed Uterine Cancer.

BACKGROUND: Minimally invasive surgery (MIS) is associated with decreased complication rates, length of hospital stay, and cost compared with laparotomy. Robotic-assisted surgery-a method of laparoscopy-addresses many of the limitations of standard laparoscopic instrumentation, thus leading to increased rates of MIS. We sought to assess the impact of robotics on the rates and costs of surgical approaches in morbidly obese patients with uterine cancer. METHODS: Patients who underwent primary surgery at our institution for uterine cancer from 1993 to 2012 with a BMI ≥40 mg/m(2) were identified. Surgical approaches were categorized as laparotomy (planned or converted), laparoscopic, robotic, or vaginal. We identified two time periods based on the evolving use of MIS at our institution: laparoscopic (1993-2007) and robotic (2008-2012). Direct costs were analyzed for cases performed from 2009 to 2012. RESULTS: We identified 426 eligible cases; 299 performed via laparotomy, 125 via MIS, and 2 via a vaginal approach. The rates of MIS for the laparoscopic and robotic time periods were 6 % and 57 %, respectively. The rate of MIS was 78 % in this morbidly obese cohort in 2012; 69 % were completed robotically. The median length of hospital stay was 5 days (range 2-37) for laparotomy cases and 1 day (range 0-7) for MIS cases (P < 0.001). The complication rate was 36 and 15 %, respectively (P < 0.001). The rate of wound-related complications was 27 and 6 %, respectively (P < 0.001). Laparotomy was associated with the highest cost. CONCLUSIONS: The robotic platform provides significant health and cost benefits by increasing MIS rates in this patient population.

The role of adjuvant therapy in uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo-oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. Here we summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years.

Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes.

Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands, and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31 to 73 y). All patients presented at stage IIIC or IV and underwent complete surgical staging followed by chemotherapy. All 37 HGSC-BRCA cases showed either pushing pattern metastases (30; 81%) or infiltrative micropapillary metastases (7; 19%). No HGSC-BRCA case exhibited metastases composed solely of mixed infiltrative patterns. Among the 7 infiltrative micropapillary cases, 6 had a BRCA1 germline mutation versus 1 with a BRCA2 mutation. The median time of follow-up was 26 months (range, 13 to 49 mo). All 7 patients with infiltrative micropapillary metastases either experienced recurrence or died of disease (5 recurrences and 2 deaths), which was significantly worse than what was seen in patients with predominantly pushing pattern metastases, of whom 16 of 30 (53%) experienced recurrence (n=14) or died of disease (n=2) (P=0.03). In conclusion, the recognition of different invasion patterns of metastatic extrauterine HGSC-BRCA has prognostic implications. The infiltrative micropapillary pattern is associated with poor outcomes and is more frequently seen in BRCA1-associated HGSC than in BRCA2 cases.

Low-Volume Lymph Node Metastasis Discovered During Sentinel Lymph Node Mapping for Endometrial Carcinoma.

PURPOSE: The aim of this study was to characterize treatment patterns and oncologic outcomes in patients with low-volume lymph node metastasis (isolated tumor cells [ITCs] and micrometastasis [MM]) discovered during sentinel lymph node (SLN) mapping for endometrial carcinoma. METHODS: We identified endometrial cancer cases treated surgically from September 2005 to April 2013 in which SLN mapping was performed. MM was defined as tumor within a lymph node measuring >0.2 mm but <2.0 mm, and ITCs were those measuring ≤0.2 mm. RESULTS: Overall, 844 patients, with a median age of 61 years (range 30-90), met the inclusion criteria. Histology was as follows: endometrioid, 724 (85.8 %) patients; serous, 104 (12.3 %) patients; and clear cell, 16 (1.9 %) patients. The median number of lymph nodes resected was six (range 0-60), and the median number of SLNs was two (range 0-15). Overall, 753 (89.2 %) patients were node-negative, 23 (2.7 %) had ITCs only, 21 (2.5 %) had MM only, and 47 (5.6 %) had macrometastasis. Adjuvant chemotherapy was administered to 106 (14 %) of 753 node-negative patients, 19 (83 %) of 23 patients with ITCs, 17 (81 %) of 21 patients with MM, and 42 (89 %) of 47 with macrometastasis. Median follow-up was 26 months (range 0-108). Three-year recurrence-free survival was as follows: node-negative patients, 90 % (±1.5); ITCs only, 86 % (±9.4); MM only, 86 % (±9.7); and macrometastasis, 71 % (±7.2) [p < 0.001]. CONCLUSIONS: Patients with ITCs and MM frequently received adjuvant chemotherapy and had improved oncologic outcomes in comparison to those with macrometastasis to the lymph nodes. Further prospective study is needed to determine optimal post-resection management in patients with ITCs or MM alone.

Menopause education: needs assessment of American obstetrics and gynecology residents.

OBJECTIVE: This study aims to understand the current teaching of menopause medicine in American obstetrics and gynecology residency programs. METHODS: A Web-based survey was e-mailed to all American obstetrics and gynecology residency directors, with a request that they forward it to their residents. RESULTS: Of 258 residency program directors contacted, 79 (30.6%) confirmed forwarding the survey. In all, 1,799 people received the survey, with 510 completions, for a response rate of 28.3%. Most residents reported that they had limited knowledge and needed to learn more about these aspects of menopause medicine: pathophysiology of menopause symptoms (67.1%), hormone therapy (68.1%), nonhormone therapy (79.0%), bone health (66.1%), cardiovascular disease (71.7%), and metabolic syndrome (69.5%). Among fourth-year residents who will be entering clinical practice soon, a large proportion also reported a need to learn more in these areas: pathophysiology of menopause symptoms (45.9%), hormone therapy (54.2%), nonhormone therapy (69.4%), bone health (54.2%), cardiovascular disease (64.3%), and metabolic syndrome (63.8%). When asked to rate the most preferred modalities for learning about menopause, the top choice was supervised clinics (53.2%), followed by case presentations (22.2%), formal lectures (21.3%), small groups (14.7%), Web-based learning (7.8%), and independent reading (5.2%). Only 20.8% of residents reported that their program had a formal menopause medicine learning curriculum, and 16.3% had a defined menopause clinic as part of their residency. CONCLUSIONS: It seems that some American residency programs do not fulfill the educational goals of their residents in menopause medicine. A curriculum would be beneficial for increasing knowledge and clinical experience on menopause issues.