Incidence of lymphedema in the lower limbs and lymphocyst formation within one year of surgery for endometrial cancer: A prospective longitudinal multicenter study

Objective. The study aimed to determine the incidence of lower limb lymphedema (LLL) after surgery for endometrial cancer (EC) by means of three methods, and to determine the incidence of lymphocysts after one year. Methods. A prospective longitudinal multicenter study was conducted in 14 hospitals in Sweden. Two-hundred-and-thirty-five women with EC were included; 116 underwent surgery that included lymphadenectomy (+LA) and 119 were without lymphadenectomy ( -LA). Lymphedema was assessed objectively on four occasions; preoperatively, at 4-6 weeks, six months and one year postoperatively using systematic measurement of leg circumferences, enabling calculation of leg volumes, and a clinical grading of LLL, and subjectively by the patients perception of lymphedema measured by a lymphedema-specific quality-of-life instrument. Lymphocyst was evaluated by vaginal ultrasonography. Results. After one year the incidence of LLL after increase in leg volume adjusted for body mass index was 15.8% in +LA women and 3.4% in -IA women. The corresponding figures for clinical grading were 24.1% and 11.8%, and for patient-reported perceived LLL 10.7% and 5.1%. The agreement between the modalities revealed fair to moderate correlation between patient-reported LLL and clinical grading, but poor agreement between volume increase and patient-reported LLL or clinical grading. Lymphocysts were found in 43% after one year. Conclusions. Although the incidence of ILL and lymphocysts after surgery for EC including LA seemed to be relatively high the study demonstrated significant variations in incidence depending on the measurement modality. This emphasizes the need for a gold standard of measurement of LLL in clinical practice and research. (C) 2020 Elsevier Inc. All rights reserved.Funding Agencies|Swedish Cancer Society [Cancerfonden]Swedish Cancer Society [CAN2013/620]; Medical Research Council of Southeast Sweden [FORSS-308611, FORSS-391311, FORSS-662141, FORSS-858611]; Uppsala-Orebro Regional Research Council [LUL-349271]; Scientific Council of the Region Halland; County Council of Ostergotland; Linkoping University</p

Risk factors for lymphedema and method of assessment in endometrial cancer : a prospective longitudinal multicenter study

OBJECTIVE: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer. METHODS: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI). RESULTS: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading. CONCLUSION: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors.Funding: Swedish Cancer Society (Cancerfonden)Swedish Cancer Society [CAN2013/620]; Medical Research Council of Southeast SwedenUK Research &amp; Innovation (UKRI)Medical Research Council UK (MRC) [FORSS-308611, FORSS-391311, FORSS-662141, FORSS-858611]; Uppsala-Orebro Regional Research Council [LUL-349271]; Scientific Council of the Region Halland; County Council of Ostergotland; Linkoping University</p

Robot-assisted approach to cervical cancer (RACC) : An international multi-center, open-label randomized controlled trial

Background Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival. Primary Objective To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy. Study Hypothesis Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes. Trial Design Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden. Major Inclusion/Exclusion Criteria Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years. Primary Endpoint Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer. Sample Size The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1-β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients. Estimated Dates for Completing Accrual and Presenting Results Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter. Trial Registration The trial is registered at ClinicalTrials.gov (NCT03719547)

Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) study

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.Funding Agencies|Swedish Cancer Society</p

Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) study

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.Funding Agencies|Swedish Cancer Society</p

Lymphovascular space invasion as a predictive factor for lymph node metastases and survival in endometrioid endometrial cancer - a Swedish Gynecologic Cancer Group (SweGCG) study

Background: The aim of this study is to evaluate the impact of lymphovascular space invasion (LVSI) on the risk of lymph node metastases and survival in endometrioid endometrial adenocarcinoma. Material and methods: As regard the study design, this is a cohort study based on prospectively recorded data. Patients with endometrioid endometrial adenocarcinoma registered in the Swedish Quality Registry for Gynecologic Cancer 2010-2017 with FIGO stages I-III and verified nodal status were identified (n = 1587). LVSI together with established risk factors, namely DNA ploidy, FIGO grade, myometrial invasion and age, were included in multivariable regression analyses with lymph node metastases as the dependent variable. Associations between the risk factors and overall and relative survival were included in multivariable models. Estimates of risk ratios (RR), hazard ratios (HR), excess mortality rate ratios (EMR), and 95% confidence intervals (95% CI) were calculated. Results: The presence of LVSI presented the strongest association with lymph node metastases (RR = 5.46, CI 3.69-8.07, p amp;lt; .001) followed by deep myometrial invasion (RR = 1.64, CI 1.13-2.37). In the multivariable survival analyses, LVSI (EMR = 7.69, CI 2.03-29.10,) and non-diploidy (EMR = 3.23, CI 1.25-8.41) were associated with decreased relative survival. In sub-analyses including only patients with complete para-aortic and pelvic lymphadenectomy and negative lymph nodes (n = 404), only LVSI (HR = 2.50, CI 1.05-5.98) was associated with a worsened overall survival. Conclusion: This large nationwide study identified LVSI as the strongest independent risk factor for lymph node metastases and decreased survival in patients with endometrioid adenocarcinomas. Moreover, decreased overall survival was also seen in patients with LVSI-positive tumors and negative lymph nodes, indicating that hematogenous dissemination might also be important.Funding Agencies|Swedish Cancer Society</p