Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

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.

A comparative analysis of prediction models for complete gross resection in secondary cytoreductive surgery for ovarian cancer.

OBJECTIVE: We sought to examine compliance and outcomes using Memorial Sloan Kettering "(MSK) criteria" to predict complete gross resection (CGR) and compare them with the validated Tian and AGO models. METHODS: Patients who underwent SCS for recurrent platinum-sensitive ovarian cancer from 5/2001-6/2014 were identified. The AGO and Tian models were applied to the study population; appropriate statistical tests were used to determine ability to predict CGR. RESULTS: 214 SCS cases were identified. Since the implementation of MSK criteria, the CGR rate has been 86%. The AGO model had a 49% accuracy rate in predicting CGR, and predicted gross residual disease (RD) in 51%; however, CGR was achieved in 86%. The Tian model had an 88% accuracy rate. Of the 4% scored as Tian high risk for gross RD, 33% achieved a CGR. Comparing models, McNemar's p-value was 0.366 between the Tian and MSK models and <0.001 between AGO and MSK criteria. Median PFS was 21.3 (95%CI, 18.2-24.5), 22.5 (95%CI, 19.4-25.3), and 14.1months (95%CI, 9.7-22.1) for the entire cohort, for those achieving CGR, and for those left with RD, respectively (p=0.013). OS was 82.2 (95%CI, 60.2-123.3), 95.6 (95%CI, 63.6-NE), and 57.5months (95%CI, 27.5-113.9), respectively (p=0.014). CONCLUSION: CGR during SCS is associated with extended PFS and OS. We report a high rate of CGR using MSK criteria. There was good concordance between the Tian and MSK models; however, the latter has fewer variables and is more user-friendly. Tian criteria may be applied to intermediate MSK cases for further stratification.

Impact of Obesity on Sentinel Lymph Node Mapping in Patients with Newly Diagnosed Uterine Cancer Undergoing Robotic Surgery.

PURPOSE: The aim of this study was to determine the impact of obesity on the rate of successful sentinel lymph node (SLN) mapping in patients with uterine cancer undergoing robotic surgery, and compare SLN detection rates using indocyanine green (ICG) versus blue dye. METHODS: We reviewed robotic cases undergoing SLN mapping with a cervical injection from January 2011 to December 2013 using either blue dye or ICG with near-infrared (NIR) fluorescence imaging. Data were stratified by body mass index (BMI) and the dye used. Appropriate statistical tests were applied. RESULTS: Overall, 472 cases were identified. Bilateral mapping was successful in 352 cases (75 %), and unilateral mapping was successful in 73 cases (15 %). Bilateral mapping was achieved in 266 (85 %) of 312 ICG cases compared with 86 (54 %) of 160 blue-dye cases (p < 0.001). Cases with successful bilateral mapping had a median BMI of 29.8 kg/m(2) (range 16.3-65.3 kg/m(2)); cases with no mapping had a median BMI of 34.7 kg/m(2) (range 21.4-60.4 kg/m(2)) (p = 0.001). With increasing BMI, there was a significant decrease in successful bilateral mapping rates for both the ICG (p < 0.001) and blue-dye groups (p = 0.041); however, the use of ICG resulted in better bilateral (p = 0.002) and overall (p = 0.011) mapping rates compared with the use of blue dye in all BMI groups. CONCLUSIONS: ICG results in a higher overall and bilateral SLN detection than blue dye in women with uterine cancer. Successful mapping decreases with increasing BMI irrespective of the dye used; however, it is significantly improved with the use of ICG and NIR fluorescence imaging compared with blue dye.

Neoadjuvant chemotherapy and primary debulking surgery utilization for advanced-stage ovarian cancer at a comprehensive cancer center.

OBJECTIVE: The aim of this study was to evaluate the use of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) before and after results from a randomized trial were published and showed non-inferiority between NACT and PDS in the management of advanced-stage ovarian carcinoma. METHODS: We evaluated consecutive patients with advanced-stage ovarian cancer treated at our institution from 1/1/08-5/1/13, which encompassed 32 months before and 32 months after the randomized trial results were published. We included all newly diagnosed patients with high-grade histology and stage III/IV disease. Associations between the use of NACT and clinical variables over time were evaluated. RESULTS: Our study included 586 patients. Median age was 62 years (range, 30-90); 406 patients (69%) had stage III disease, and 570 (97%) had disease of serous histology. Twenty-six percent (154/586) were treated with NACT and 74% (432/586) with PDS. NACT use increased significantly from 22% (56/256) before 2010 (at which point the results of the randomized trial were published) to 30% (98/330) after 2010 (p=0.037). Although patients who underwent PDS were more likely to experience grade 3/4 surgical complications than those who underwent NACT, those selected for PDS had a median OS of 71.7 months (CI, 59.8-not reached) compared with 42.9 months (CI 37.1-56.3) for those selected for NACT. CONCLUSIONS: In this single-institution analysis, the best survival outcomes were observed in patients who were deemed eligible for PDS followed by platinum-based chemotherapy. Selection criteria for NACT require further definition and should take institutional surgical strategy into account.

Elevated plasma growth differentiation factor-15 correlates with lymph node metastases and poor survival in endometrial cancer.

PURPOSE: The study objective was to investigate and validate plasma growth differentiation factor-15 (GDF-15) as a predictor of lymph node metastasis and a poor prognosis in primary endometrial cancer. EXPERIMENTAL DESIGN: Plasma samples from 510 women treated for endometrial cancer in a primary investigation cohort (n = 44) and a secondary validation cohort (n = 466) were analyzed for GDF-15. Plasma from healthy premenopausal (n = 20) and postmenopausal (n = 20) women, women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125) were used for comparison. RESULTS: Median plasma GDF-15 concentration for the endometrial cancer group was elevated (1,077 ng/L) as compared with pre- and postmenopausal controls (590 and 684 ng/L) and women with benign (591 ng/L) or borderline ovarian tumors (718 ng/L; all P < 0.001), but similar to the ovarian cancer group. In the large validation cohort of endometrial carcinomas, high plasma GDF-15 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease, nonendometrioid histology, high grade, older age, postmenopausal status, and lymph node metastases (all P ≤ 0.001). High GDF-15 was also an independent predictor of poor disease-specific and recurrence-free survival. CONCLUSIONS: Based on findings indicated in a primary investigation set and confirmed in the large secondary validation set, we report for the first time plasma GDF-15 as a biomarker for endometrial cancer phenotype, including presence of lymph node metastasis and reduced survival. Its applicability as a predictor of metastatic nodes and in monitoring treatment of endometrial cancer needs to be further studied.