Surgical and systemic management of endometrial cancer: an international survey.

PURPOSE: To ascertain the spectrum of clinical management of endometrial carcinoma (EC) the largest international survey was conducted to evaluate and identify differences worldwide. METHODS: After validation of a 15-item questionnaire regarding surgical and adjuvant treatment of EC in Germany, an English-adapted questionnaire was put online and posted to all the major gynecological cancer Societies worldwide for further distribution commencing in 2010 and continued for 26 months. RESULTS: A total of 618 Institutions around the world participated: Central Europe (CE), Southern Europe (SE), Northern Europe (NE), Asia and USA/Canada/UK. Both a therapeutic and staging value was attributed to systematic pelvic and paraaortic lymph node dissection (LND) in CE (74.6%) and in Asia (67.2%), as opposed to USA/UK where LND was mainly for staging purposes (53.5%; p < 0.001). LND was performed up to the renal veins in CE in 86.8%, in Asia in 80.8%, in USA/UK in 51.2% and in SE in 45.1% (p < 0.001) of cases. In advanced disease, centers from Asia were treated most with adjuvant chemotherapy alone (93.6%), as opposed to centers in SE, CE and UK/USA that employed combination chemo-radiotherapy in 90.9% (p < 0.001) of cases. Paclitaxel/carboplatin was mostly used followed by doxorubicin/cisplatin (75 vs. 23.3%; p < 0.001). In total, 94% of all participants supported the concept of treating EC patients within appropriate clinical trials. CONCLUSIONS: There is broad range in both the surgical and adjuvant treatment of EC across different countries. Large-scale multicenter prospective trials are warranted to establish consistent, evidence-based guidelines to optimize treatment worldwide.

Long-term clinical outcome of pelvic exenteration in patients with advanced gynecological malignancies.

BACKGROUND AND OBJECTIVES: We evaluated the outcome of pelvic exenteration in women with locally advanced primary or recurrent gynecological malignancies. METHODS: All pelvic exenteration procedures performed between 01/2003 and 06/2009 were evaluated. Extent of surgical radicality, operative techniques, and outcome were evaluated. Kaplan-Meier curves were calculated for Overall (OS) and progression-free survival (PFS). RESULTS: Forty-seven patients (median age: 52.5 years) were evaluated. Ten of 47 patients (21.3%) had a primary and 37(78.7%) a relapsed cancer. Most common (80.8%) site of origin was the cervix. Patients (80.8%) had undergone previous pelvic irradiation. A total exenteration was performed in 32/47 patients (68%). A complete tumor resection was obtained in 23 patients (49%). Thirty-three patients (70.2%) had at least one major complication, including ileus (8.5%), intestinal-fistula (29.8%), ureteral anastomotic insufficiency (6.4%), abscess (6.4%), and cardiothrombotic events (23.4%). At a median follow-up of 7 months (range: 1-42), 22/47 patients (46.8%) died and 22/47 (46.8%) experienced a relapse. Median OS was 4 months (range: 0.1-16) and 22 months (range: 6-42) for patients with versus without postoperative tumor residuals, respectively (P = 0.0006), while median PFS was 4 months (range:0.1-16) versus 12 months (range: 6-42) (P < 0.0001). CONCLUSIONS: Radical pelvic exenteration due to advanced pelvic malignancies may be associated with a high morbidity. Complete tumor resection is associated with a significantly higher overall and PFS.

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study.

PURPOSE: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance. MATERIALS AND METHODS: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator. RESULTS: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1-48), while median progression-free survival was 5 months (range: 0.5-34). CONCLUSIONS: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.

Systematic pelvic and aortic lymphadenectomy in intermediate and high-risk endometrial cancer: lymph-node mapping and identification of predictive factors for lymph-node status.

OBJECTIVE: To systematically assess the metastatic pattern of intermediate- and high-risk endometrial cancer in pelvic and para-aortic lymph-nodes and to evaluate risk factors for lymph-node metastases. STUDY DESIGN: Between 01/2005 and 01/2009 62 consecutive patients with intermediate- and high-risk endometrial cancer who underwent a systematic surgical staging including pelvic and para-aortic lymphadenectomy were enrolled into this study. Patients' characteristics, histological findings, lymph-node localization and involvement, surgical morbidity and relapse data were analyzed. Univariate analysis was performed to define risk factors for lymph-node metastasis. RESULTS: Of the 13 patients (21%) with positive lymph-nodes (N1), 8 (61.5%) had both pelvic and para-aortic lymph-nodes affected, 2 (15.4%) only para-aortic and 3 (23%) only pelvic lymph-node metastases. Overall, 54% of the N1-patients had positive lymph-nodes above the inferior mesenteric artery (IMA) to the level of the renal veins. Univariate analysis revealed lymph vascular space invasion (p-value: <0.001), vascular-space-invasion (p-value: <0.001) and incomplete tumor resection (p-value: 0.008) as significant risk factors for N1-status. Overall and progression-free survival was not significantly different between N1- and N0-patients. CONCLUSIONS: Since the proportion of N1-endometrial cancer patients with positive para-aortic lymph-nodes is, at 76%, considerably high, and more than half of them have affected lymph-nodes above the IMA-level, lymphadenectomy for endometrial cancer should be extended up to the renal veins, when indicated. The therapeutic impact of systematic lymphadenectomy on overall and progression-free survival has still to be evaluated in future prospective randomized studies.