Sentinel Lymph Node Mapping in Presumed Low- and Intermediate-Risk Endometrial Cancer Management (SLIM): A Multicenter, Prospective Cohort Study in The Netherlands.

The aim was to investigate the incidence of sentinel lymph node (SLN) metastases and the contribution of SLN mapping in presumed low- and intermediate-risk endometrial cancer (EC). A multicenter, prospective cohort study in presumed low- and intermediate-risk EC patients was performed. Patients underwent SLN mapping using cervical injections of indocyanine green and a minimally invasive hysterectomy with bilateral salpingo-oophorectomy. The primary outcome was the incidence of SLN metastases, leading to adjusted adjuvant treatment. Secondary outcomes were the SLN detection rate and the occurrence of complications. Descriptive statistics and univariate general linear model analyses were used. A total of 152 patients were enrolled, with overall and bilateral SLN detection rates of 91% and 61%, respectively. At final histology, 78.9% of patients (n = 120) had truly low- and intermediate-risk EC. Macro- and micro-metastases were present in 11.2% (n = 17/152), and three patients had isolated tumor cells (2.0%). Nine patients (5.9%) had addition of adjuvant radiotherapy based on SLN metastases only. In 2.0% of patients with high-risk disease, adjuvant therapy was more limited due to negative SLNs. This study emphasizes the importance of SLN mapping in presumed early-stage, grade 1 and 2 EC, leading to individualized adjuvant management, resulting in less undertreatment and overtreatment.

Cost-effectiveness of laparoscopy as diagnostic tool before primary cytoreductive surgery in ovarian cancer.

OBJECTIVE: To evaluate the cost-effectiveness of a diagnostic laparoscopy prior to primary cytoreductive surgery to prevent futile primary cytoreductive surgery (i.e. leaving >1cm residual disease) in patients suspected of advanced stage ovarian cancer. METHODS: An economic analysis was conducted alongside a randomized controlled trial in which patients suspected of advanced stage ovarian cancer who qualified for primary cytoreductive surgery were randomized to either laparoscopy or primary cytoreductive surgery. Direct medical costs from a health care perspective over a 6-month time horizon were analyzed. Health outcomes were expressed in quality-adjusted life-years (QALYs) and utility was based on patient's response to the EQ-5D questionnaires. We primarily focused on direct medical costs based on Dutch standard prices. RESULTS: We studied 201 patients, of whom 102 were randomized to laparoscopy and 99 to primary cytoreductive surgery. No significant difference in QALYs (utility=0.01; 95% CI 0.006 to 0.02) was observed. Laparoscopy reduced the number of futile laparotomies from 39% to 10%, while its costs were € 1400 per intervention, making the overall costs of both strategies comparable (difference € -80 per patient (95% CI -470 to 300)). Findings were consistent across various sensitivity analyses. CONCLUSION: In patients with suspected advanced stage ovarian cancer, a diagnostic laparoscopy reduced the number of futile laparotomies, without increasing total direct medical health care costs, or adversely affecting complications or quality of life.

Laparoscopy to Predict the Result of Primary Cytoreductive Surgery in Patients With Advanced Ovarian Cancer: A Randomized Controlled Trial.

Purpose To investigate whether initial diagnostic laparoscopy can prevent futile primary cytoreductive surgery (PCS) by identifying patients with advanced-stage ovarian cancer in whom > 1 cm of residual disease will be left after PCS. Patients and Methods This multicenter, randomized controlled trial was undertaken within eight gynecologic cancer centers in the Netherlands. Patients with suspected advanced-stage ovarian cancer who qualified for PCS were eligible. Participating patients were randomly assigned to either laparoscopy or PCS. Laparoscopy was used to guide selection of primary treatment: either primary surgery or neoadjuvant chemotherapy followed by interval surgery. The primary outcome was futile laparotomy, defined as a PCS with residual disease of > 1 cm. Primary analyses were performed according to the intention-to-treat principle. Results Between May 2011 and February 2015, 201 participants were included, of whom 102 were assigned to diagnostic laparoscopy and 99 to primary surgery. In the laparoscopy group, 63 (62%) of 102 patients underwent PCS versus 93 (94%) of 99 patients in the primary surgery group. Futile laparotomy occurred in 10 (10%) of 102 patients in the laparoscopy group versus 39 (39%) of 99 patients in the primary surgery group (relative risk, 0.25; 95% CI, 0.13 to 0.47; P < .001). In the laparoscopy group, three (3%) of 102 patients underwent both primary and interval surgery compared with 28 (28%) of 99 patients in the primary surgery group ( P < .001). Conclusion Diagnostic laparoscopy reduced the number of futile laparotomies in patients with suspected advanced-stage ovarian cancer. In women with a plan for PCS, these data suggest that performance of diagnostic laparoscopy first is reasonable and that if cytoreduction to < 1 cm of residual disease seems feasible, to proceed with PCS.

Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study.

BACKGROUND: Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. METHODS/DESIGN: Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.

Distinguishing benign and malignant pelvic masses: the value of different diagnostic methods in everyday clinical practice.

OBJECTIVE: To optimize referral to specialized gynaecologists for surgical treatment of ovarian cancer by improving preoperative discrimination between benign and malignant pelvic tumours. STUDY DESIGN: In a prospective multicentre study 143 patients with a pelvic mass were included. At several occasions during the diagnostic work-up the gynaecologist estimated the chance of malignancy (educated guess/expert opinion). MRI in the local setting was suggested for uncertain cases. All MRI images were reviewed by an expert radiologist. The datasheet designed for the study further allowed for determining the risk of malignancy index (RMI). RESULTS: The diagnostic accuracy of the gynaecologist's final estimation of the chance of malignancy and the calculated RMI were comparable (area under the ROC curve of 0.87 and 0.86). MRI did not improve the accuracy of the diagnostic work-up for the study population as a whole. Subgroup analysis did however show improved diagnostic accuracy in cases with an estimated chance of malignancy between 20 and 80% when the MRI was read by an expert radiologist. CONCLUSION: Patient selection for surgery of a pelvic mass should be based on the chance of malignancy as assigned by the referring gynaecologists. In case of uncertainty MRI improves diagnostic accuracy, when judged by an expert.

Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma.

BACKGROUND: Consultant gynecologic oncologists from the regional Comprehensive Cancer Center assisted community gynecologists in the surgical treatment of patients with ovarian carcinoma when they were invited. For this report, the authors evaluated the effects of primary surgery by a gynecologic oncologist on treatment outcome. METHODS: The hospital files from 680 patients with epithelial ovarian carcinoma who were diagnosed between 1994 and 1997 in the northern part of the Netherlands were abstracted. Treatment results were analyzed according to the operating physician's education by using survival curves and univariate and multivariate Cox regression analyses. RESULTS: Primary surgery was performed on 184 patients by gynecologic oncologists, and on 328 patients by general gynecologists. Gynecologic oncologists followed surgical guidelines more strictly compared with general gynecologists (patients with International Federation of Gynecology and Obstetrics [FIGO] Stage I-II disease, 55% vs. 33% [P=0.01]; patients with FIGO Stage III disease, 60% vs. 40% [P=0.003]) and more often removed all macroscopic tumor in patients with FIGO Stage III disease (24% vs. 12%; P=0.02). When patients were stratified according to FIGO stage, the 5-year overall survival rate was 86% versus 70% (P=0.03) for patients with Stage I-II disease and 21% versus 13% (P=0.02) for patients with Stage III-IV disease who underwent surgery by gynecologic oncologists and general gynecologists, respectively. The hazards ratio for patients who underwent surgery by gynecologic oncologists was 0.79 (95% confidence interval [95%CI], 0.61-1.03; adjusted for patient age, disease stage, type of hospital, and chemotherapy); when patients age 75 years and older were excluded, the hazards ratio fell to 0.71 (95% CI, 0.54-0.94) in multivariate analysis. CONCLUSIONS: The surgical treatment of patients with ovarian carcinoma by gynecologic oncologists occurred more often according to surgical guidelines, tumor removal more often was complete, and survival was improved.