Recurrence and survival in endometrioid endometrial cancer - a population-based cohort study.

OBJECTIVE: The aim of this study was to investigate recurrences and survival in endometrioid endometrial cancer (EC) in a complete population-based cohort. METHODS: A regional population-based study including women with endometrioid EC, identified by the Swedish Quality Registry for Gynecological Cancer (SQRGC), where primary surgery was performed between 2010 and 2017. Patient characteristics and outcomes, including recurrences, were retrieved from the SQRGC and completed by records reviews. Overall (OS), net (NS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The Fine and Gray proportional subdistribution hazards' regression model was used for risk factors for recurrence. RESULTS: There were 1630 women included in the study, whereof 136 (8.3%) had a recurrence with a median time to recurrence of 22.5 months (range 3.2-59.3). One site of recurrence was diagnosed in 69.1%, while 27.2% being only vaginal. The total 5-year OS was 88.0%(95% CI:86.4-89.7) and the 5-year NS 98.6%(95% CI:96.5-100.7). If no recurrence occurred, the OS was 91.9%(95% CI:90.4-93.3) and NS 102.8%(95% CI:100.9-104.8). For only vaginal recurrence, 5-year OS was 77.0%(95% CI:64.0-92.6) compared to 36.1%(95% CI:27.5-47.3) for all other recurrences. The total 5-year DFS was 83.9%(95% CI:82.0-85.7). In the multivariable analysis, age, FIGO stage and primary treatment were found independent factors for recurrence with a HR of 1.29(95% CI:1.11-1.51;p = 0.001) for age, 2.78(95% CI:1.80-4.29;p < 0.001) for FIGO stage III and 1.84(95% CI:1.22-2.78;p 0.004) for adjuvant treatment. CONCLUSION: There is an overall low recurrence rate for endometrioid ECs with a minor portion being only vaginal, associated with a favorable survival in contrast to other recurrences with a poor prognosis. Age, FIGO stage III and adjuvant treatment were found independent prognostic factors for recurrence.

Increased survival in non-endometrioid endometrial cancer after introducing lymphadenectomy and tailoring radiotherapy - A population-based cohort study.

OBJECTIVE: To investigate recurrence and survival in non-endometrioid endometrial cancer in a population-based cohort and evaluate the implementation of the first national guidelines (NGEC) recommending pelvic and paraaortic lymphadenectomy for surgical staging and tailored adjuvant therapy. METHODS: A population-based cohort study that used the Swedish quality registry for gynaecological cancer for the identification of all women with early-stage non-endometrioid endometrial cancer between 2010 and 2017. Five-year overall (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to evaluate the effect of age, FIGO stage, primary treatment and lymph node dissection on DFS. RESULTS: There were 228 patients included in the study cohort and 67 (29%) patients had a recurrence within five years. In the recurrence cohort, the OS was 13.4% (95%CI:7.3-24.7) compared to 88.5% (95%CI:83.4-93.9) if no recurrence occurred (log-rank p < 0.001). The DFS for the complete cohort was 61.9% (95%CI:55.7-68.7). The OS before implementation of NGEC was 57.3% (95%CI:48.2-68.1) and the DFS was 52.1% (95%CI:43.0-63.1) compared to an OS of 72.0% (95%CI:64.2-80.7; log-rank p = 0.018) and a DFS of 70.1% (95%CI:62.4-78.7; log-rank p = 0.008) after implementing NGEC. Patients received adjuvant radiotherapy in 92.7% before and 42.4% after NGEC implementation (p < 0.001). In the multivariable regression analysis, age, FIGO stage and lymph node dissection were found to be significant prognostic factors, where having a lymph node dissection decreased the risk of recurrence or death with a HR of 0.58 (95%CI:0.33-1.00). CONCLUSION: In this population-based cohort of preoperative early-stage non-endometrioid EC, a significant improvement in survival was seen after NGEC implementation where lymph node staging for tailoring adjuvant therapy was introduced and less pelvic radiotherapy was given.

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.

Lymphadenectomy, obesity and open surgery are associated with surgical complications in endometrial cancer.

OBJECTIVE: To investigate surgical complications related to the staging procedure for endometrial cancer (EC) and to explore complication associations towards patient characteristics and survival. METHODS: A population-based cohort study of women diagnosed with EC where primary surgery was performed at a tertiary centre between 2012 and 2016. The Swedish Quality Registry for Gynecological Cancer was used for identification, medical records reviewed and surgical outcomes, including complications according to Clavien-Dindo (CD), and comorbidity (Charlson's index) registered. Uni- and multivariable logistic regression analyses were performed with complications as outcome and multivariable Cox regression analysis with overall survival (OS) as endpoint. RESULTS: In total 549 women were identified where 108 (19.7%) had CD grade II-V complications. In the multivariable regression analysis; surgical technique, BMI and lymph node dissection, but not comorbidity or age, were found to be risk factors for complications CD grade II-V, with OR of 0.32 (95%CI:0.18-0.56) for minimalinvasive surgery (MIS) compared to open, OR 2.18 (95%CI:1.37-3.49) for BMI ≥30 and OR 2.63 (95%CI:1.32-5.31) for pelvic and paraaortic lymphnode dissection. In Cox regression analysis, a significant lower OS was found within the first 1.5 years for the cohort of complications (CD II-V) compared to no complications. CONCLUSION: Surgical staging with lymphadenectomy was found a risk factor for complications together with high BMI in EC. Using MIS was significantly associated with less complications. Overall survival was found to be negatively affected within the first years after complications. Our results may be taken into consideration when performing updated treatment guidelines including surgical staging.

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 patient's 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 -LA 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 4.3% after one year. CONCLUSIONS: Although the incidence of LLL 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.

Robotic vs Open Surgery for Endometrial Cancer in Elderly Patients: Surgical Outcome, Survival, and Cost Analysis.

OBJECTIVE: This study aimed to compare robotic and open surgery in elderly women diagnosed as having endometrial cancer, in terms of costs, survival, surgical outcome, and operating time. METHODS: Women 70 years or older undergoing open and robotic surgery for endometrial cancers were included consecutively before and after the introduction of robotic surgery at a tertiary center. Costs were calculated using the case-costing system, cost per patient, including the first 30 postoperative days. Relative and overall survival outcomes were obtained from the Swedish National Cancer Registry and analyzed using the Kaplan-Meier method. Surgical outcomes including operating and anesthesia times, estimated blood loss, hospital stay, and intraoperative and postoperative complications were reviewed. RESULTS: In all, 137 and 141 women 70 years or older were identified to have undergone open and robotic surgery, respectively. The groups showed similar body mass index, comorbidities, and tumor characteristics. No statistically significant differences were seen in costs (robotic &OV0556;11,874 vs open &OV0556;11,521, P = 0.463) or 5-year survival outcomes (robotic 94% [95% confidence interval {CI}, 84-105] vs open 87% [95% CI, 78-98], P = 0.529). Robotic surgery was associated with significantly lower estimated blood loss (P < 0.001) and shorter hospital stay (P < 0.001) but longer anesthesia time (186 vs 174 minutes; P < 0.05) and operating theater time (205 vs 190 minutes; P < 0.05). There were no significant differences in intraoperative complications, but robotic surgery resulted in fewer postoperative Clavien-Dindo grade II complications. CONCLUSIONS: Elderly women can safely undergo robotic surgery for endometrial cancer and could be offered this technique to the same extent as younger patients. They may benefit from shorter hospital stay, decreased blood loss, and postoperative complications, without resulting in higher costs to the health care system or jeopardizing their survival.