Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion

2020 ◽  
Vol 30 (11) ◽  
pp. 1738-1747
Author(s):  
Ji Son ◽  
Laura M Chambers ◽  
Caitlin Carr ◽  
Chad M Michener ◽  
Meng Yao ◽  
...  

BackgroundAdjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial.ObjectiveTo determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes.MethodsA multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis.Results405 patients were included with the median age of 67 years (range 27–92, IQR 59–73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively).ConclusionAdjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

2018 ◽  
Vol 28 (5) ◽  
pp. 890-894 ◽  
Author(s):  
Ellen Cusano ◽  
Victoria Myers ◽  
Rajiv Samant ◽  
Talia Sudai ◽  
Allison Keller ◽  
...  

ObjectiveLymphovascular space invasion (LVSI) has been defined as a significant adverse prognostic factor in early-stage endometrial cancer, primarily because of its high association with nodal metastases. This study aimed to determine if LVSI provides any prognostic significance in pathologic node-negative surgically staged (T1N0) endometrial cancer patients.Methods/MaterialsThis retrospective cohort study included all patients with pathologic stage T1N0 endometrial carcinoma treated at The Ottawa Hospital Cancer Centre from 1998 to 2007. Patient demographics, pathologic findings, treatment, and outcome data were collected. Univariate and multivariate cox regression modeling was used to assess significance and adjust for demographic and histopathologic covariates. Kaplan-Meier curves were used to estimate the 5-year overall and recurrence-free survival.ResultsOur study included 400 pathologic stage T1N0 patients who received an initial total hysterectomy and bilateral salpingo-oophorectomy with lymphadenectomy. The median age at diagnosis was 62 years, and the median follow-up was 66 months. Fifty-four patients (13.5%) had a positive LVSI status, and 346 (86.5%) had a negative LVSI status. The 5-year overall survival was 97.3% in patients without LVSI and 90.9% in those with LVSI (P < 0.001). The 5-year recurrence-free survival was 95.2% in patients without LVSI and 85.9% in those with LVSI (P = 0.006). Univariate analysis identified grade, stage, and LVSI as the covariates significantly associated with time to recurrence, and identified age, grade, stage, and LVSI to be significantly associated with overall survival. There were no significant covariates for recurrence-free survival by multivariate analysis, and only age and LVSI were significant for overall survival.ConclusionsLymphovascular space invasion is an overall poor prognostic factor in T1N0 endometrial cancer. After adjusting for other factors, LVSI remains an independent risk factor for worse overall survival. Therefore, estimation of overall survival in patients with early-stage, node-negative endometrial cancer should take into account LVSI status.


2005 ◽  
Vol 91 (3) ◽  
pp. 215-220 ◽  
Author(s):  
Daniela Smaniotto ◽  
Giuseppe D'Agostino ◽  
Stefano Luzi ◽  
Vincenzo Valentini ◽  
Gabriella Macchia ◽  
...  

Aims and background This prospective, phase II study aimed to test the efficacy of concurrent 5-fluorouracil, mitomycin C and radiation, with or without brachytherapy, on the clinical outcome of a series of recurrent endometrial cancer patients and to determine the prognostic impact of a subset of factors. Methods Thirty patients with locally recurrent, nonmetastatic endometrial cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continous infusion, days 1-4; 1 g/m2/day; mitomycin C, 10 mg/m2, bolus iv, day 1). Nineteen patients (63.3%) underwent endocavitary, low-dose brachytherapy boost (20-25 Gy); eight patients (26.7%) received external beam radiation boost (14-20 Gy). Results Eleven complete responses (36.7%), 11 partial responses (36.7%), 6 disease stabilizations (20.0%) and 2 progressions (6.6%) were observed. After a median follow-up of 27 months (range, 1-108), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 46.8%, 35.2% and 41.2%, respectively. Two patients (6.7%) experienced hematological grade 3 toxicity. Two patients (6.7%) had grade 3 intestinal toxicity. Severe late toxicity was infrequent, only 3 patients showing severe vaginal stenosis (10.0%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin <11 g/dL. With this device, it was clear that patients with a low score had a significantly better outcome (clinical remission: 77.2% of patients with a score <2 vs 25.0% of patients with a score ≥2, P = 0.009), better local control of the disease (50.2% vs. 0 at 3 years, P = 0.014,) and better overall survival (65.8% vs 0 at 3 years, P = 0.003). Conclusions Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful in identifying patients with the best chance of benefiting from the treatment.


2017 ◽  
Vol 27 (4) ◽  
pp. 730-737 ◽  
Author(s):  
Erin A. Bishop ◽  
James J. Java ◽  
Kathleen N. Moore ◽  
Joan L. Walker

ObjectivesElderly endometrial cancer patients have worse disease-specific survival than their younger counterparts, but the cause for this discrepancy is unknown. The goal of this analysis is to compare outcomes by age in a fully staged elderly endometrial cancer population.Methods/MaterialsThis is an analysis of patients on Gynecologic Oncology Group Study (GOG) LAP2, which included clinically early stage endometrial cancer patients randomized to laparotomy versus laparoscopy for surgical staging. Patients were divided into risk groups based on criteria defined by GOG protocol 99. Differences in outcomes and adjuvant therapy were assessed within these risk groups.ResultsLAP2 included 715 patients 70 years or older. With increasing age, worse tumor characteristics were seen. Older patients received similar rates of adjuvant therapy when stratified by stage. Patients 70 years or older had significantly worse progression-free survival and overall survival, and on multivariate analysis, older age and high-risk uterine factors were predictors of progression-free survival and overall survival, whereas stage and lymph node metastases were not. When patients were divided into GOG protocol 99 risk categories, most of those who met the high-intermediate risk criteria did so based on age above 70 years and grade 2 to 3 disease. These patients had low risk of recurrence (3.3%) compared with those who met the criteria by age above 70 years and all 3 uterine factors (20.9%).ConclusionsIn early stage endometrial cancer, patients 70 years or older who undergo similar surgical management and adjuvant therapy, age and tumor characteristics independently predict recurrence. Most patients older than 70 years meet the high-intermediate risk criteria for recurrence based on age and 1 other uterine risk factor, and our results suggest that these patients are at low risk for recurrence.


2013 ◽  
Vol 31 (31) ◽  
pp. 3951-3956 ◽  
Author(s):  
Mathias Onsrud ◽  
Milada Cvancarova ◽  
Taran P. Hellebust ◽  
Claes G. Tropé ◽  
Gunnar B. Kristensen ◽  
...  

Purpose This follow-up of a randomized study was conducted to assess the long-term effects of external beam radiation therapy (EBRT) in the adjuvant treatment of early-stage endometrial cancer. Patients and Methods Between 1968 and 1974, 568 patients with stage I endometrial cancer were included. After primary surgery, patients were randomly assigned to either vaginal radium brachytherapy followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses stratified by age groups. Results After median 20.5 years (range, 0 to 43.4 years) of follow-up, no statistically significant difference was revealed in overall survival (P = .186) between treatment groups. However, women younger than age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95% CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30 to 3.15). Conclusion We observed no survival benefit of external pelvic radiation in early-stage endometrial carcinoma. In women younger than age 60 years, pelvic radiation decreased survival and increased the risk of secondary cancer. Adjuvant EBRT should be used with caution, especially in women with a long life expectancy.


2020 ◽  
Vol 30 (5) ◽  
pp. 631-639 ◽  
Author(s):  
Ji Son ◽  
Caitlin Carr ◽  
Meng Yao ◽  
Milena Radeva ◽  
Anju Priyadarshini ◽  
...  

ObjectiveEndometrial cancer in pre-menopausal patients aged ≤40 years is rare and poses both diagnostic and management challenges. The goal of this study was to investigate the clinical and pathologic factors associated with endometrial cancer in this group and their impact on survival.MethodsPatients with endometrial cancer treated between January 2004 and August 2016 were retrospectively reviewed. Patients who underwent either primary surgical treatment or fertility-sparing therapy were included. Exclusion criteria were age >60 years and patients who received neoadjuvant chemotherapy or primary radiation. Age at diagnosis was used to classify patients into two groups: ≤40 and 41–60 years. Clinical and pathologic variables were compared between the groups. Progression-free survival and overall survival were estimated using Cox proportional hazards.ResultsA total of 551 patients were evaluated, of which 103 (18.7%) patients were ≤40 years and 448 (81.3%) were 41–60 years. Age ≤40 years was associated with higher body mass index (38.8 vs 35.8 kg/m2, p=0.008), non-invasive cancers (54.2% vs 32.6%, p<0.001), lower uterine segment involvement (27.2% vs 22.5%, p<0.001), and less lymphovascular space invasion (16.8% vs 29.1%, p=0.015). The rate of synchronous ovarian cancer was 9.2% vs 0.7% in age 41–60 years (p<0.001), and 19% of women with endometrial cancer aged ≤40 years underwent fertility-sparing therapy. Grade, stage, myometrial invasion, lymphovascular space invasion, and lymph node status were associated with survival, and fertility-sparing therapy adversely affected the recurrence rate of the age ≤40 years cohort. Among all patients aged ≤60 years, mismatch repair deficiency due to MLH1 methylation was associated with worse progression-free survival, 48.6% vs 83.3% (HR 1.98, 95% CI 1.06 to 3.17, p=0.032), and overall survival, 56.5% vs 90.0% (HR 2.58, 95% CI 1.13 to 5.90, p=0.025).ConclusionsPatients aged ≤40 years with endometrial cancer have more favorable prognostic factors and higher rates of synchronous tumors. Fertility-sparing therapy was associated with higher recurrence rates. The prognostic value of MLH1 methylation in this population warrants further investigation.


2018 ◽  
Vol 28 (7) ◽  
pp. 1285-1289
Author(s):  
Min Gao ◽  
Naiyi Zhang ◽  
Nan Song ◽  
Hong Zheng ◽  
Xin Yan ◽  
...  

ObjectiveThe aim of this study was to explore the role of chemotherapy as adjuvant treatment for early-stage endometrial cancer (EC) with high-intermediate-risk (HIR) factors.MethodsA prospective study of patients with early-stage EC with HIR factors for recurrence was performed between 2006 and 2014. A total of 96 patients were enrolled, and 50 patients received 3 cycles of platinum-based chemotherapy after surgery. Five-year disease-free survival and overall survival were evaluated.ResultsA total of 11 (11.5%) of the 96 patients had recurrence, with a median recurrent time of 15.4 months. Of these 11 patients with recurrence, 2 received adjuvant chemotherapy after surgery, whereas 9 did not receive any treatment. Patients without adjuvant chemotherapy exhibited a significantly higher recurrence rate than those with adjuvant chemotherapy (19.6% vs 4%; P = 0.024). Meanwhile, patients with adjuvant chemotherapy had significantly higher 5-year disease-free survival compared with the control group (92.1% vs 70.0%, P = 0.024).ConclusionsChemotherapy is feasible and safe as adjuvant treatment for early-stage EC with HIR factors. Three cycles of platinum-based chemotherapy are sufficient for reducing the risk of recurrence. Further, large sample randomized studies are needed to confirm these results.


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