Can a preoperative CA 125 level be a criterion for full pelvic lymphadenectomy in surgical staging of endometrial cancer?

OBJECTIVE: The aim of the present study was to evaluate whether a preoperative serum level of CA 125 in patients with endometrial cancer can provide additional information in determining the extent of lymphadenectomy required in the surgical staging and which cutoff value is optimal in this respect. METHODS: CA 125 was measured in 124 patients diagnosed with endometrial carcinoma who underwent surgery at our institution between January 1995 and May 2000. Statistic analysis was performed using the Mann-Whitney U test and Kruskal-Wallis test to evaluate the association of preoperative CA 125 levels with various factors. The chi(2)/Fisher's exact test and a logistic regression model were employed to examine the effects of clinicopathological factors on serum CA 125 levels. Furthermore, a receiver operating characteristic curve was used to determine which cutoff value of the preoperative CA 125 was the optimal one. RESULTS: Univariate analyses showed that elevated CA 125 levels were significantly correlated with an advanced stage, larger tumor size, increasing depth of the myometrial invasion, cervical invasion, positive cytology, and lymph node metastases (P < 0.05). Multivariate analyses using a logistic regression model showed lymph node metastases had the most significant effect on the elevation of CA 125 levels. The ROC curve determined that the best cutoff value was 40 U/ml; the sensitivity and specificity for screening lymph node metastases were found to be 77.8 and 81.0%, respectively. CONCLUSION: Our data provide evidence indicating that a preoperative CA 125 level greater than 40 U/ml can be considered a criterion for full pelvic lymphadenectomy in the surgical staging of endometrial cancer.     

Is selective lymphadenectomy more cost-effective than routine lymphadenectomy in patients with endometrial cancer?

ObjectiveThe objective of this study is to determine the cost-effectiveness of two strategies in women undergoing surgery for newly diagnosed endometrial cancer.MethodsA decision analysis model compared two surgical strategies: 1) routine lymphadenectomy independent of intraoperative risk factors or 2) selective lymphadenectomy for women with high or intermediate risk tumors based on intraoperative assessment including tumor grade, depth of invasion, and tumor size. Published data were used to estimate the outcomes of stage, adjuvant therapy, and recurrence. Costs of surgery, radiation, and chemotherapy were estimated using Medicare Current Procedural Technology codes and Physician Fee Schedule. Cost-effectiveness ratios were estimated for each strategy. Sensitivity analyses were performed including an estimate for lymphedema for patients that underwent a lymphadenectomy.ResultsFor 40,000 women diagnosed annually with endometrial cancer in the United States, the annual cost of selective lymphadenectomy is $1.14 billion compared to $1.02 billion for routine lymphadenectomy. The selective lymphadenectomy strategy cost an additional $123.3 million. Five-year progression-free survival was 85.9% in the routine strategy compared to 79.3% in the selective strategy. Treatment cost $6349 more per survivor in the selective strategy compared to routine strategy ($36,078 vs. $29,729). These results held up under a variety of sensitivity analyses including costs due to lymphedema which were higher in the routine lymphadenectomy strategy compared to the selective lymphadenectomy strategy ($10 million vs. $7.75 million).ConclusionsA strategy of selective lymphadenectomy based on intraoperative risk factors for patients with endometrial cancer was less cost-effective than routine lymphadenectomy even when the impact of lymphedema was considered.     

Could endometrial cytology be helpful in detecting endometrial malignancies?

This short communication assesses the concordance indexes between hysteroscopic biopsies and endometrial cytology for each endometrial pattern found in a sample of 37 women. Patients underwent endometrial cytology under sonographic guidance. The specimens were obtained with an endocervical brush and were fixed on slides (no liquid-based methods). After endometrial cytology, hysteroscopy with biopsy was performed. The best concordance index was found for endometrial malignancies, suggesting that endometrial cytology is able to detect cancers but not other endometrial diseases, as compared with endometrial hysteroscopic biopsies. Therefore, the overall concordance index suggests a fair concordance between histological and cytological findings. This leads us to conclude that usual endometrial cytology should not be recommended to screen endometrial diseases, but it may be used as an alternative diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted, because it allows malignancies to be detected as well as hysteroscopic-guided biopsies.     

Is aortic lymphadenectomy necessary in the management of endometrial carcinoma?

OBJECTIVE: To evaluate the role of aortic lymphadenectomy in the management of endometrial carcinoma. METHODS: Clinical notes of 163 patients with endometrial carcinoma were reviewed. All patients had peritoneal cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy with or without aortic lymphadenectomy. RESULTS: Seventy-five (46.0%) patients had pelvic lymphadenectomy alone whereas 88 (54.0%) had both pelvic and aortic lymphadenectomy. Thirty-five (21.5%) patients had nodal metastases with positive pelvic and aortic nodes in 26 (16.0%) and 24 (27.3%) patients, respectively. Isolated aortic metastases were found in 17 cases (19.3%). Among 35 patients with nodal metastases, recurrence developed in 15 (42.9%) patients and all except one died within five to 50 months. The remaining patients had a median disease-free period of 55 months (13-93 months). The recurrence rate was higher (63.6%) among patients with upper aortic lymph node metastases, and all those who recurred died of disease within seven to 28 months. CONCLUSIONS: Our data suggest that aortic lymphadenectomy provides both diagnostic and therapeutic value in the management of endometrial carcinoma with high metastatic risk. After surgical removal and adjuvant radiotherapy, patients with nodal metastases achieved a better survival chance.     

Multiple gestations in assisted reproductive technology: Can they be avoided with blastocyst transfers?

OBJECTIVE: Blastocysts are advanced-stage embryos with high implantation potential; theoretically, limited numbers of blastocysts can be used for embryo transfer to achieve good pregnancy rates with low multiple pregnancy rates. Clinical outcomes of a newly implemented blastocyst transfer program were evaluated. STUDY DESIGN: This study is a retrospective analysis of 553 blastocyst transfer cycles performed by a university-based in vitro fertilization program; risk factors associated with multiple gestations were analyzed. RESULTS: An average of 2.2 embryos were used for embryo transfer. The overall clinical pregnancy rate per embryo transfer was 45.1%; multiple gestation, twin, and triplet rates were 40.9%, 36.5%, and 4.3%, respectively. Multiple gestations increased significantly (1) when embryo transfer was done on day 5, (2) when > or =2 blastocysts were present on day 5, and (3) when maternal age was < or =30 years. CONCLUSION: In spite of a conservative approach to the number of blastocysts used for embryo transfer, the overall multiple pregnancy rate was high, and triplet pregnancies did occur.     

Surgical staging for endometrial cancer in the elderly - is there a role for lymphadenectomy?

Objectives

We sought to evaluate the effect of systematic lymphadenectomy (LND) on endometrial cancer-specific survival in an elderly population.

Methods

Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2006. Women who underwent primary hysterectomy for non-serous, non-clear cell endometrial carcinoma were included. Women were stratified by age (< 70, 70-79, and ≥ 80) and disease-specific survival (DSS) was analyzed via the Kaplan-Meier method and stratified by postoperative grade. Cohorts were compared using the log-rank test. In a simulated population, the disease-specific survival of women with pre-operative grade 1 endometrial carcinoma was calculated using a weighted average survival accounting for those upgraded at final pathology.

Results

Endometrial cancer was identified in 5759 women ≥ 80 years old. Disease specific survival at 5 years for the LND and no LND groups was 93.4% and 94.5% (p = 0.36) for grade 1, 84.4% and 85% (p = 0.97) for grade 2, and 65.9% and 60.9% (p = 0.002) for grade 3. In the simulated pre-operative grade 1 group, 5 year disease-specific survival (DSS) was 91% in the LND group and 92% in the no LND group.

Conclusion

In women older than 80, systematic lymphadenectomy is associated with improved DSS for high grade, but similar DSS for low grade endometrial cancer, consistent with what is seen with younger women. As there is no clear survival benefit to lymphadenectomy in elderly women presenting with low grade disease, the surgeon should carefully weigh the surgical risks and benefits in this patient population, which may be at higher risk for morbidity.     

Is older age a poor prognostic factor in stage I and II endometrioid endometrial adenocarcinoma?

Objective

Prior studies have shown that age ≥ 70 years is associated with more aggressive non-endometrioid histology and worse survival in endometrial cancer. The purpose of this study is to assess if age is an independent poor prognostic factor in endometrioid histologies.

Methods

Under an IRB-approved protocol, we identified patients with surgical stage I to II endometrioid endometrial adenocarcinoma from 1995 to 2008 at two institutions. Patients were divided into two groups based on age at diagnosis: Group A (age 50-69 years) and Group B (age ≥ 70 years). All patients underwent hysterectomy, bilateral salpingoophorectomy, +/−pelvic/aortic lymphadenectomy and adjuvant therapy. Prognostic factors were evaluated by univariate and multivariate analyses.

Results

We identified 338 patients with stage IA to IIB endometrioid endometrial adenocarcinoma. The median age in Group A was 59 years (range 50-69) and Group B was 75 years (range 70-92). Patients in Group B were more likely to have hypertension (51% vs. 68%, p = 0.006) and coronary artery disease (9% vs. 18%, p = 0.03). There were no differences in progression-free or disease-specific survival, however, Group B had a worse overall survival (OS) (50.1 vs. 62.6 months, p = 0.03). On univariate analysis, age (p = 0.04), grade (p = 0.006), and coronary artery disease (p = 0.01) were associated with worse OS. After adjusting for grade and coronary artery disease, age was no longer a significant variable for OS (p = 0.17).

Conclusions

After adjusting for other poor prognostic factors, age ≥ 70 years alone may not be a significant variable affecting overall survival in patients with early stage endometrioid endometrial adenocarcinoma.     

What is the role of lymphadenectomy in surgical management of patients with endometrial carcinoma?

The role of lymphadenectomy in the management of endometrial carcinoma remains controversial in gynecologic oncology. Comprehensive pelvic and paraaortic lymphadenectomy should be performed in patients with intermediate- and high-risk endometrial cancer.     

Can breast cancer be chemoprevented in 2003?

Breast cancer is certainly not preventable at the same degree as lung cancer is by avoiding cigarette smoking or bladder cancer by avoiding exposure to some specific professional carcinogens. Despite the increased availability of screening mammography and the use of adjuvant chemotherapy, breast cancer remains a major cause of morbidity and mortality in women. Chemoprevention could be one of the possible weapons to decrease the morbidity and the mortality due to breast cancer. Experimental, epidemiological and clinical data suggest that one can prevent occurrence of breast cancer. The results of five trials including more than 25,000 patients comparing the effectiveness of tamoxifen with a placebo were published. The results of these trials, at first sight, do not agree. Only in the USA, the results of the five trials have led to licence tamoxifen for chemoprevention of breast cancer. But the Food and Drug Administration stresses the fact that the noxious side effects are too numerous for this molecule to be prescribed with all the patients. It must be reserved for the women presenting an increased risk. The means of identifying the women at increased risk are not yet perfect.     

The racial disparity in outcomes in endometrial cancer: could this be explained on a molecular level?

OBJECTIVE: The racial disparities among patients with endometrial carcinoma have been previously reported. The objective of this study is to analyze and compare the molecular profiles in endometrial cancer in Caucasian and African American patients using a number of known molecular markers. MATERIALS AND METHODS: 147 patients diagnosed with endometrial cancer between 1995 and 2001 were included in the study. Patients' demographics, clinical and pathological data were reviewed. Immunohistochemical staining for p53, VEGF, Ki-67 and HIF-1alpha was performed on tissue micro array sections. Tumors' expression of p53, VEGF, Ki-67, and HIF-1alpha was compared based on ethnicity and tumor type (Type I = endometrioid carcinomas and Type II = non-endometrioid carcinomas). Spearman's correlation and Fisher's Exact Tests were used for statistical analysis and Kaplan-Meier, log-rank and Cox regression were used for survival analysis. RESULTS: 97 patients were Caucasian and 50 patients were African American. The mean age was 62 (33-91) years for Caucasian patients and 63.5 (24-89) years for the African American patients. African American patients had more Type II carcinoma than Caucasian patients (P = 0.055). High p53 expression was statistically significant among the African American patients (49% vs. 30%, P = 0.035) versus Caucasian patients. There was no significant difference demonstrated when comparing the VEGF, Ki-67, and HIF-1alpha expression between the racial groups. Survival analysis showed a trend toward a shorter survival in the African American patients compared to the Caucasian patients; median survival 62 versus 77 months (P = 0.061). On the other hand, we did not find a significant difference in survival by ethnicity when we adjusted for tumor histology. CONCLUSION: While African American patients with endometrial cancer seem to show a trend toward a shorter survival, this seems to be mainly due to the fact that they have a higher proportion of Type II tumors. The molecular profiles for p53, Ki-67, VEGF and HIF-1alpha expression of histologically matched tumors were similar between the two ethnic groups.     

Is endometrial apoptosis evidence of endometrial aging in unexplained infertility? a preliminary report

OBJECTIVE: To investigate spontaneous endometrial apoptosis in women with unexplained infertility and to find out whether there is a possible relationship between endometrial apoptosis, age, and hormonal parameters. STUDY DESIGN: This study was designed as a prospective, case-controlled study in a University Hospital setting. A total of 34 endometrial biopsies were performed from 17 women with unexplained infertility and 17 fertile controls, who were admitted for tubal ligation. Endometrium was sampled on the seventh post-ovulatory day. On the same day of endometrial sampling, serum levels of FSH, LH, PRL, TSH, E2, progesterone, 17alpha-hydroxyprogesterone, testosterone and DHEA-S were determined. Endometrial glandular and stromal apoptosis were investigated by DNA nick end labeling (TUNEL) method on each sample. Endometrial apoptotic index was calculated and correlated with age and hormonal parameters. RESULTS: There was no difference in either endometrial glandular apoptotic index (AI) or stromal AI between the groups. However, the mean glandular AI was significantly higher than the mean stromal AI (p = 0.0001). There was a strong correlation between endometrial AI and age (r = 0.91, p = 0.02). Serum T levels were significantly found to be decreased in the unexplained infertility group (p = 0.0001). In addition, serum TSH levels were positively correlated with AI in the glandular endometrium in women with unexplained infertility (r = 0.611, p = 0.009). CONCLUSION: Endometrial apoptosis increases with age. Serum levels of testosterone were lower in unexplained infertility. The effect of serum TSH levels on apoptosis in the glandular epithelium of the endometrium needs further studies.