Tumor size,depth of invasion,and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis

Objectives

The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis.

Materials and methods

Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement.

Results

The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p < 0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p < 0.001).

Conclusions

In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis.     

MMR deficiency is common in high-grade endometrioid carcinomas and is associated with an unfavorable outcome

Objective

To assess the prevalence of MMR deficiency (dMMR) in contemporary reclassified high-grade endometrial carcinomas and correlate dMMR with molecular alterations and patient outcome.

Methods

In this study we evaluated the expression of MLH1, MSH2, PMS2 and MSH6 assessed by two different methods in a series of 102 high-grade endometrial carcinomas. The series was comprised of 64 high-grade endometrioid carcinomas (HGEC), 27 serous (ESC), and 11 clear cell (CCC) carcinomas. Absence of expression in any of the proteins was considered dMMR. dMMR was correlated with clinicopathological parameters using a Chi-square test. Univariate and multivariate survival analysis was performed using Kaplan–Meier and Cox regression analyses.

Results

The overall prevalence of dMMR was 28% (29/102) and was seen in 29/64 (45%) HGEC but not detected in any of the ESC and CCC. Within HGEC, dMMR was associated with loss of ARID1A (p = 0.0099), loss of PTEN (p = 0.044) and wild-type TP53 (p = 0.024) expression. dMMR was associated with increased risk for disease specific death by univariate analysis (p = 0.013) among stage III/IV HGEC but not in multivariate analysis (p = 0.12).

Conclusions

Among high-grade endometrial carcinomas, dMMR is restricted to HGEC and could be used as an adjunct diagnostic tool to refute a diagnosis of ESC. The association with dMMR in HGEC with ARID1A/PTEN alterations, TP53 wild type expression pattern and unfavorable outcome suggests that different oncogenetic pathways within HGEC are present.     

Quantifying the risk of recurrence and death in stage III (FIGO 2009) endometrial cancer

Objective

Advanced endometrial cancer patients comprise a heterogeneous group. This study assessed the association of clinicopathological factors with relapse and death from endometrial cancer.

Methods

Eligible patients were treated for stage III (FIGO 2009) endometrial adenocarcinoma, had peritoneal cytology performed, and had no gross residual disease post-operatively.

Results

Of 192 patients, 59% were ≥ 60 years old, 48% had ≥ 50% myometrial invasion, 71% lymphovascular invasion, 25% cervical stromal invasion, 37% adnexal involvement, and 23% positive peritoneal cytology. High-grade histology (serous, clear cell, undifferentiated, or grade 3 endometrioid) was present in 45%. Pelvic lymphadenectomy was performed in 93% and para-aortic lymphadenectomy in 73%. Adjuvant chemotherapy and/or radiation therapy was administered to 93%. At a median follow-up of 42 months, the 5-year rate of relapse was 37% and of death from endometrial cancer was 30%. On multivariate analysis, both outcomes were associated with high-grade histology, positive peritoneal cytology, and deep myometrial invasion (p ≤ 0.04). The cohort was divided into subgroups of patients with 0 (n = 46), 1 (n = 83), or ≥ 2 (n = 63) of these high-risk characteristics. The 5-year relapse rate for patients with 0 risk factors was 13%, 1 risk factor was 27%, and ≥ 2 risk factors was 62% (p < 0.001). The corresponding 5-year rates of death from endometrial cancer were 11%, 20%, and 56%, respectively (p < 0.001).

Conclusions

Stratification of stage III endometrial cancer according to high-grade histology, positive peritoneal cytology, and deep myometrial invasion is useful for prognostication and may grant insight into the optimal treatment for specific subgroups of patients.     

PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma

Objective

To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas.

Methods

We assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan–Meier and Cox regression analyses.

Results

PIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p = 0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p = 0.0029) but not endometrial serous (p = 0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p = 0.0058) and showed loss of ARID1A expression (p = 0.037).

Conclusions

PIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type.     

Peritoneal cytology: A risk factor of recurrence for non-endometrioid endometrial cancer

Objective

We compared the impact of positive peritoneal cytology on prognosis between patients with endometrioid and non-endometrioid endometrial carcinoma.

Methods

We retrospectively reviewed the medical records of 490 patients diagnosed with endometrial cancer between 2000 and 2012. These patients were divided into two groups: endometrioid and non-endometrioid histologies. We compared the patients' baseline characteristics, tumor recurrence patterns, and survival to determine the prognostic factors and how they differed between the two groups.

Results

Of the included patients, 448 had endometrioid histology and 42 had non-endometrioid histology. A total of 27 patients experienced tumor recurrence: 17 with endometrioid histology (4.0%) and 10 with non-endometrioid histology (23.8%). Compared to endometrioid type, non-endometrioid type exhibited higher rates of recurrence (p < 0.01). Recurrence sites of the non-endometrioid group were mainly peritoneal seeding (p < 0.01) and distant organ metastasis (p = 0.02). Risk factors for tumor recurrence included patient age, stage of disease, and adjuvant treatment for endometrioid type. On the other hand, in cases of non-endometrioid endometrial cancer, positive peritoneal cytology was an independent prognostic factor regardless of tumor stage (HR, 15.34; 95% CI, 3.55–66.25; p < 0.01). Among cases with non-endometrioid histology, median recurrence-free survival significantly differed between the negative peritoneal cytology group and the positive peritoneal cytology group (120 months versus 22 months, respectively; p < 0.01).

Conclusions

Positive peritoneal cytology is an independent prognostic factor for patients with non-endometrioid endometrial cancer.     

Metformin is associated with improved survival in endometrial cancer

Objective

Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes.

Methods

A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling.

Results

24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1–2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3–4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR.

Conclusion

Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.     

Association between tumor diameter and lymphovascular space invasion among women with early-stage endometrial cancer

Objective

To investigate the association between tumor diameter and intratumoral risk factors that might predict the need for full surgical staging among women with endometrial cancer (EC).

Methods

Data from patients with early-stage EC treated at the Istituto Nazionale dei Tumori, Milan, Italy, between January 2004 and December 2012 were retrospectively analyzed. Associations between tumor diameter and tumor grade, myometrial invasion, risk group, lymphovascular space invasion (LVSI), and lower uterine segment (LUS) involvement were assessed by bivariate and multivariate analysis.

Results

In total, 181 patients met the inclusion criteria. The tumor diameter was 2 cm or less in 110 women (60%). χ² analysis showed that tumor grading, myometrial invasion, risk group, and LVSI were significantly associated with tumor size (P < 0.001), whereas LUS involvement was marginally associated (P = 0.051). By multivariate analysis, LVSI and myometrial invasion had an independent association with tumor size greater than 2 cm (P < 0.018).

Conclusion

Tumor size greater than 2 cm was significantly and independently associated with LVSI and myometrial invasion among patients with early-stage EC. Given the difficulty of obtaining reliable LVSI data from frozen sections, tumor size might be used as a surrogate at the time of surgery to provide additional information to triage patients for full surgical staging.     

The importance of adjuvant chemotherapy and pelvic radiotherapy in high-risk early stage endometrial carcinoma

Objective

To determine the impact of a policy change in which women with high-risk early stage endometrioid endometrial cancer (EEC) received adjuvant chemoradiotherapy.

Methods

This is a population-based retrospective cohort study of British Columbia Cancer Registry patients diagnosed from 2008 to 2012 with high-risk early stage EEC, who received adjuvant chemoradiotherapy after primary surgery. High-risk early stage was defined as the presence of two or more high-risk uterine factors: grade 3 tumor, more than 50% myometrial invasion, and/or cervical stromal involvement. Adjuvant therapy consisted of 3 or 4 cycles of carboplatin and paclitaxel chemotherapy, followed by pelvic radiotherapy. Sites and rate of recurrence were compared to a historical cohort diagnosed from 2005 to 2008 in which none of the patients received adjuvant chemoradiotherapy. Five-year progression-free and overall survival rates were calculated.

Results

The study includes 55 patients. All patients except for 2 received at least 3 cycles of chemotherapy. All patients received pelvic radiotherapy except for 2 who received brachytherapy only. Median follow-up was 27 months (7–56 months). Four patients (7.3%) recurred, including three with distant recurrence only and one with both a pelvic and paraaortic nodal recurrence. The historical cohort had a 29.4% recurrence rate, and therefore the hazard ratio for recurrence was 0.27 (95% CI 0.02–4.11). Five-year progression-free and overall survival rates were 88.6% and 97.3%, respectively.

Conclusion

Patients with high-risk early stage endometrial carcinoma treated with adjuvant chemoradiotherapy have a low rate of recurrence compared to those not receiving such therapy.     

Preoperative anemia,leukocytosis and thrombocytosis identify aggressive endometrial carcinomas

Objectives

The objective of this study is to investigate preoperative hematological parameters for anemia, leukocytosis and thrombocytosis in relation to established prognostic factors and survival in endometrial cancer.

Methods

557 patients treated for endometrial carcinoma were prospectively included in a study focusing on the relationship between preoperative hemoglobin, leukocyte and platelet counts, and a panel of clinicopathological characteristics and outcome.

Results

Preoperative anemia was present in 15.8%, leukocytosis in 11.2% and thrombocytosis in 12.1%. Among patients with localized disease (FIGO stage I/II), 18.1% had anemia and/or thrombocytosis at diagnosis. Patients with advanced disease (high FIGO stage and lymph-node metastasis) had significantly lower hemoglobin count, higher leukocyte count and higher platelet count (all p < 0.008). Patients with anemia, leukocytosis and thrombocytosis had significantly shorter 5-year disease-specific survival of 61.3%, 66.0% and 61.0% respectively, compared to 87.7%, 86.3% and 87.3% for patients with normal counts (all p < 0.001). In multivariate Cox regression analysis, lower hemoglobin counts and higher platelet counts were independently associated with poor outcome adjusted for the standardly applied prognostic markers (p < 0.033).

Conclusion

Preoperative anemia, leukocytosis or thrombocytosis in women with endometrial carcinoma is associated with advanced disease and poor disease-specific survival.     

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Objective

Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.

Methods

Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I–IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.

Results

LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r = 0.31, p = 0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93–20.4, p = 0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p = 0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54–5.88, p = 0.001) and overall survival (HR 2.69, 95%CI 1.18–6.23, p = 0.021) while ER-expression did not remain as a significant variable in multivariate analysis.

Conclusion

Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.     

Minimally invasive surgery for endometrial cancer: Does operative start time impact surgical and oncologic outcomes?

Objective

Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer.

Methods

A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon.

Results

A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p = 0.57), number of prior surgeries (p = 0.28), medical comorbidities (p = 0.19), or surgical complexity of the case (p = 0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p = 0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p = 0.79), estimated blood loss (median 100 cc vs. 100 cc, p = 0.75), blood transfusion rates (7.4% vs. 8.2%, p = 0.85), and conversion to laparotomy (12.6% vs. 7.4%, p = 0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p = 0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p = 0.87), or postoperative infections (17.8% vs. 12.3%, p = 0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p = 0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p = 0.39), recurrence-free survival (p = 0.97), or overall survival (p = 0.94).

Conclusion

Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive endometrial cancer staging, despite longer length of hospital stay for surgeries beginning after noon.     

Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion

Objective

To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging.

Methods

All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with < 50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells.

Results

Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI < 50% were more likely to have positive SLNs on routine H&E (p < 0.005) or after ultrastaging (p = 0.01) compared to those without myoinvasion.

Conclusions

Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.     

Malignant ovarian germ cell tumor — Role of surgical staging and gonadal dysgenesis

Objective

To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor.

Methods

We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012.

Results

Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p = 0.048) and endodermal sinus tumor (p = 0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p = 0.029) and endodermal sinus tumor (p = 0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype.

Conclusions

Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype.     

Lymph node metastasis in endometrioid adenocarcinomas of the uterine corpus with occult cervical involvement

Objective

Surgical-pathologic studies have defined the risk of lymphatic metastasis in clinical stage I endometrial cancers. However, data on the risk of lymph node metastasis in endometrial cancers involving the uterine cervix are less robust. The aim of this study was to determine the risk of lymphatic metastasis in patients with endometrial cancers with occult tumor extension to the uterine cervix.

Methods

Our institutional tumor registry identified all patients with endometrioid endometrial cancers who underwent comprehensive surgical staging. Patients with gross involvement of the cervix and patients with extra-uterine disease were excluded. The risk of lymphatic metastasis associated with cervical involvement was analyzed in the context of known uterine risk factors for lymphatic metastasis such as age, depth of invasion, grade, and lymphovascular space invasion (LVSI).

Results

We identified 169 patients who met inclusion and exclusion criteria. Univariate analyses revealed that LVSI (p < 0.01), tumor grade (p < 0.01), depth of myometrial invasion (p < 0.01), tumor free distance (p < 0.01), tumor size (p = 0.02), and cervical involvement (p < 0.01) were associated with lymphatic metastasis while age at diagnosis (p = 0.85) was not. Multivariate analyses revealed that only LVSI (p < 0.01), tumor grade (p = 0.02), and depth of myometrial invasion (p = 0.03) were independently associated with lymphatic metastasis.

Conclusion

Cervical involvement is not an independent predictor of lymphatic metastasis in endometrial cancer. In an unstaged patient, decisions regarding adjuvant treatment or additional diagnostic procedures such as lymphadenectomy should be based on uterine factors.     

Impact of Age-Adjusted Charlson Comorbidity score on outcomes for patients with early-stage endometrial cancer

Objectives

To determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer.

Methods

After IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I–II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0–1 (n = 204), 2–3 (n = 293) and > 3 (n = 174). Kaplan–Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint.

Results

After a median follow-up of 85 months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0–1; 81.7%, 95.3%, and 89.8% for AAC 2–3: and 56%, 88.2%, and 84.9% for AAC > 3 (p < 0.0001, p = 0.005 and p = 0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not.

Conclusions

Comorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma.     

Reducing readmissions after robotic surgical management of endometrial cancer:A potential for improved quality care

Objective

To describe readmission patterns after robotic surgery for endometrial cancer and identify risk factors for readmission within 90 days of discharge.

Methods

Patients with endometrial cancer who underwent robotic surgical management at an academic institution from 2006 to 2010 were identified. Patient characteristics, intraoperative data, and postoperative complications were analyzed. Student's t-test and Fisher's exact test were used to compare patients readmitted within 90 days to those who were not.

Results

Three hundred ninety-five patients were included. Thirty (7.6%) were readmitted within 90 days of surgical discharge. Length of stay greater than one day (40.0% vs. 23.0%, p = 0.04) and postoperative complication (63.3% vs. 13.4%, p < 0.01) were associated with readmission. The median interval to readmission was 9.5 days and median duration of subsequent hospitalization was 2.5 days. Fever (31.3%) and workup for vaginal drainage (25.0%) were the most common reasons for readmission. Only 2 of the 10 patients readmitted with fever had culture-proven infection, and no patients readmitted for vaginal drainage had a confirmed urinary tract injury. Of the 30 patients readmitted, 5 required a second operation — 3 for vaginal cuff dehiscence and 2 for port site hernia.

Conclusions

Robotic surgery for endometrial cancer was associated with a 7.6% readmission rate. The most common reasons for readmission, fever and evaluation for urinary tract injury, were frequently not associated with severe illness. This supports additional education to consider raising the threshold for readmission by using more widespread outpatient evaluation for the potential complications of robotic endometrial cancer surgery.     

Prevalence of Human Papillomavirus in endometrial cancer: A systematic review and meta-analysis

Objective

HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.

Methods

We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue.

Results

We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2–16.2) with large between-study heterogeneity (I² = 88.2%, p < 0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p = 0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5–13.0) using general primers, 18.9% (95% CI: 8.6–32.1) using type-specific primers and 1.0% (95% CI: 0.0–3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68–3.00) indicating that the odds of HPV was not increased in cases versus controls.

Conclusions

HPV appears to have a limited or no role in the etiology of endometrial cancer.     

Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases

Objective

To assess prognostic factors associated with disease-related survival in endometrial stromal sarcoma (ESS) using the 2009 FIGO staging system.

Methods

From January 1990 to January 2012, 114 patients with ESS were identified at the Samsung and Asan Medical Center and data were retrospectively analyzed.

Results

Ten (8.7%) patients died of the disease and 33 (28.9%) patients relapsed. The 5- and 10-year overall survival (OS) rates for the entire cohort were 92.6% and 87.1%, respectively, and the 5- and 10-year recurrence-free survival (RFS) rates were 71.8% and 52.1%, respectively. The estimated median survival after recurrence for the 33 patients whose tumors relapsed was 133 months (95% CI, 7.7–258.4), and 5-year survival after recurrence was 68.9%. Stage I (P = 0.006), estrogen and/or progesterone receptor (ER/PR) positivity (P = 0.0027), and no nodal metastasis (P = 0.033) were associated with a good prognosis for OS in the univariate analysis. Ovarian preservation was revealed to be an independent predictor for poorer RFS (HR, 6.5; 95% CI, 1.23–34.19; P = 0.027). Positivity for ER/PR (HR, 0.05; 95% CI, 0.006–0.4; P = 0.006) and cytoreductive resection of recurrent lesions (HR, 0.14; 95% CI, 0.02–0.93; P = 0.042) were independent predictors of better survival after recurrence.

Conclusions

Stage, expression of ER/PR, and nodal metastasis are significantly associated with OS in ESS. Bilateral salpingo-oophorectomy (BSO) as the primary treatment and cytoreductive resection of recurrent lesions should be considered for improving survival of patients with ESS.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.     

Type II endometrial cancer in Hispanic women: Tumor characteristics,treatment and survival compared to non-Hispanic white women

Objectives

To compare survival of Hispanic white (HW) and non-Hispanic white (NHW) women with type II endometrial adenocarcinoma (EC).

Methods

Patients with serous, clear cell or grade 3 endometrioid EC were identified from the Surveillance, Epidemiology, and End Results (SEER) program 1988–2009 and were divided into HW and NHW. HW were subdivided into natives and immigrants.

Results

Of the 14,434 women, 13,012 (90.2%) were NHW and 1422 (9.8%) were HW. HW were younger than NHW (mean 63 vs. 68 years, p < 0.001). A higher proportion of HW presented with late stage disease than NHW (43.8% vs. 36.6%, p = 0.04). Performing lymphadenectomy was not different but HW were more likely to have positive lymph nodes than NHW (27.6% vs. 23.1%, p = 0.02). Further, HW were less likely to receive radiation than NHW (39.5% vs. 42.3%, p = 0.04). No difference in clinicopathologic characteristics was found between immigrant and native HW. In multivariate models adjusting for age, stage, histology, surgical treatment, extent of lymphadenectomy, and radiation therapy, no difference in overall survival (OS) (HR 1.06, 95% CI 0.97–1.16, p = 0.19) and cancer-specific survival (CSS) (HR 1.02, 95% CI 0.91–1.14, p = 0.75) was found between HW and NHW. Interestingly, immigrant HW had better OS (HR 0.74, 95% CI 0.62–0.89, p < 0.001) and CSS (HR 0.72, 95% CI 0.58–0.90, P = 0.003) than native HW.

Conclusions

Although they were more likely to present with advanced stage and positive nodal disease, no difference in outcome was noted between Hispanic and non-Hispanic whites with EC. Interestingly, immigrant HW had more favorable outcome compared to native HW.