Can a lymphadenectomy be avoided in early-stage endometrial adenocarcinoma?

Purpose

Determination of early disease recurrence in patients with early-stage endometrial cancer operated laparoscopically without pelvic or paraaortic lymphadenectomy.

Methods

Retrospective chart review of all patients with endometrial carcinoma operated with laparoscopic-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy between 2004 and 2008.

Results

81 patients were eligible for data analysis. The operation time varied between 32 and 284 min. None of the patients suffered serious intraoperative complications. All patients had endometrial carcinoma of endometrioid type. As adjuvant therapy, patients received no further therapy (n = 30), radiation with brachytherapy with an afterloading technique alone (n = 36) or brachytherapy in combination with percutaneous radiation (n = 15). The observation period varied between 19 and 28 months (median 26 months). No patients were lost to follow-up. During the observation period, none of the patients had recurrence of disease or died.

Conclusions

Laparoscopic-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy without pelvic or paraaortic lymphadenectomy combined with stage-adapted postoperative irradiation is a safe and efficient treatment option for patients with early-stage endometrial cancer of the endometriod type regarding early disease recurrence.     

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.     

Can optimal primary cytoreduction be predicted in advanced stage epithelial ovarian cancer? Role of preoperative serum CA-125 level

The aim of this study was to determine the ability of preoperative serum CA-125 levels to predict optimal cytoreduction in patients with stage III epithelial ovarian cancer. A retrospective review was made of the records of 40 patients with FIGO stage III ovarian carcinoma who underwent primary cytoreductive surgery. A receiver operating characteristic (ROC) curve was used to determine the most useful CA-125 level in predicting optimal versus suboptimal tumour cytoreduction. Twenty-two (55%) patients were optimally cytoreduced (residual disease 500 U/ml. At this threshold, preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 72%, specificity of 73%, positive predictive value of 68%, and negative predictive value of 76%. In the management of patients with advanced epithelial ovarian carcinoma, preoperative serum CA-125 level may help to predict optimal primary cytoreduction and to identify candidates for alternative approaches other than traditional primary cytoreductive surgery, such as neoadjuvant chemotherapy.     

Can sentinel lymph node biopsy replace pelvic lymphadenectomy for early cervical cancer?

Objective

Evaluate recurrence-free survival (RFS) and short-term morbidity in patients with early cervical cancer who undergo bilateral pelvic lymphadenectomy (BPLND) versus bilateral sentinel lymph node biopsy only (BSLNB) at primary surgery.

Preoperative CA 125 in endometrial cancer: is it useful?

OBJECTIVE: We sought to determine the clinical utility of preoperative CA 125 measurement in determining the need for lymphadenectomy in patients with endometrial carcinoma.Study Design: A prospective nonrandomized study was performed over a 2-year period. Patients referred with the diagnosis of endometrial carcinoma had CA 125 levels determined before surgical staging. Operative findings were then correlated with preoperative CA 125 values. Standard statistical calculations were used to determine sensitivity, specificity, positive predictive value, and false-positive and false-negative rates. The Student t test was used to determine differences between mean values. RESULTS: Either a CA 125 level of >20 U/mL or a grade 3 tumor or both of these correctly predicted 87% of patients requiring surgical staging. In patients with a preoperative diagnosis of stage I, grade 1 or 2 tumors, a CA 125 level of >20 U/mL correctly identified 75% (9/12) of patients requiring lymphadenectomy compared with only 50% (6/12) identified when a CA 125 level of >35 U/mL was used. Two of 16 low-risk patients with preoperative grade 1 tumors and CA 125 levels of <20 U/mL had occult extrauterine disease at surgery. CONCLUSION: Measurement of preoperative CA 125 is a clinically useful test in endometrial cancer. CA 125 levels of >35 U/mL strongly predicted extrauterine disease but lacked sensitivity in identifying patients needing staging. Either a CA 125 level of >20 U/mL or a grade 3 tumor or both of these correctly identified 75% to 87% of patients requiring lymphadenectomy. Until more data are collected, abdominal hysterectomy should be the procedure of choice for patients with grade 1 tumors and CA 125 levels of <20 U/mL.     

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.     

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.     

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.     

What is the optimal minimally invasive surgical procedure for endometrial cancer staging in the obese and morbidly obese woman?

ObjectiveThirty-three percent of U.S. women are either obese or morbidly obese. This is associated with an increased risk of death from all causes and is also associated with an increased risk of endometrial carcinoma. We sought to compare minimally invasive surgical techniques for staging the obese and morbidly obese woman with endometrial cancer.Materials and methodsConsecutive robotic endometrial cancer staging procedures were collected from 2005–2007 and were compared to consecutive laparoscopic cases (2000–2004). Demographics including age, weight, body mass index (BMI), operative time, estimated blood loss, lymph node retrieval, hospital stay and complications were collected and compared.ResultsDuring the study period, there were 36 obese and 13 morbidly obese women who underwent surgery with the DaVinci® robotic system and 25 obese and 7 morbidly obese women who underwent traditional laparoscopy. For both the obese and morbidly obese patient, robotic surgery was associated with shorter operative time (p = 0.0004), less blood loss (p < 0.0001), increased lymph node retrieval (p = 0.004) and shorter hospital stay (p = 0.0119).ConclusionsRobotic surgery is a useful minimally invasive tool for the comprehensive surgical staging of the obese and morbidly obese woman with endometrial cancer. As this patient population is at increased risk of death from all causes, including post-operative complications, all efforts should be made to improve their outcomes and minimally invasive surgery provides a useful platform by which this can occur.     

Is there a benefit of pretreatment laparoscopic transperitoneal surgical staging in patients with advanced cervical cancer?

OBJECTIVE: At present, cervical cancer remains the only gynecologic tumor, which is staged by clinical examination according to FIGO. This is associated with a high percentage of over- and understaging of tumor extent. With the operative, especially laparoscopic staging, exact information about intraabdominal tumor spread, lymph node metastases, and involvement of adjacent organs is possible. However, the advantage of operative staging is still discussed controversially. The aim of this study is to describe the laparoscopic transperitoneal staging procedure in patients with cervical cancer and their oncologic outcome after primary chemoradiation. METHODS: From November 1994 to October 2003, 456 consecutive patients with histologically confirmed primary cervical cancer were admitted to the Department of Gynecology of the Friedrich-Schiller-University Jena, Germany. Out of these, 84 patients with locally advanced tumor (tumor size>or=4 cm) and/or lymph node involvement and/or tumor infiltration to bladder or rectum were selected by a standardized laparoscopic staging procedure for primary chemoradiation. Data of surgery, chemoradiation, and follow-up were analyzed retrospectively for these patients. RESULTS: The mean age of the patients was 54 years (26-80), and the mean body-mass-index was 24.8 (17.9-42.2). Preoperative clinical evaluation showed a stage distribution according to FIGO with stage IB1 in 15.5%, IB2 in 15.5%, IIA in 8.3%, IIB in 23.8%, IIIA in 8.3%, IIIB in 21.4%, IVA in 6%, and IVB in 1.2%. In 15 out of 84 (17.8%) patients, intraabdominal tumor spread was diagnosed by laparascopy. In 24 out of 84 (28.5%) patients, invasion of bladder and/or rectum was proven histologically after biopsy. In 60 out of 84 (71%) patients, lymph node metastases were confirmed histologically. In 2 out of 13 patients with FIGO-stage Ib1, skip metastases in infrarenal paraaortic lymph nodes were seen. Removal of more than 5 pelvic and/or more than 5 positive paraaortic lymph nodes was associated with significant improvement of overall survival. According to the histological findings following laparoscopic staging in 36 out of 84 (43%) patients, a higher tumor stage was diagnosed. If tumor involvement of lymph nodes is also included, an upstaging in 73/84 (87%) of patients has to be noted down. Downstaging was not necessary in any patient following laparoscopic evaluation. CONCLUSION: Only operative staging gives exact information about tumor extension in patients with locally advanced and/or nodal positive cervical cancer and allows individual treatment planning. This can be done successfully by a transperitoneal laparoscopic approach without serious adverse effects delaying chemoradiation. Debulking of tumor-involved lymph nodes significantly improves overall survival and should be performed prior to primary chemoradiation. Laparoscopic staging should be the basis for all treatment studies in order to group patients according to true tumor extent.     

Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?

Objective

To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.

Methods

We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan–Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer.

Results

A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83–1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75–4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63–5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age < 50 years (HR 1.48, 95% CI 1.15–1.91).

Conclusion

An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.     

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.     

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.     

Does postoperative radiotherapy provide any survival advantage over observation in stage IC endometrial cancer after comprehensive surgical staging?

ObjectiveTo compare postoperative radiotherapy and observation for survival and recurrence rates in stage IC endometrial carcinoma patients who underwent comprehensive surgical staging.Study designFifty-seven stage IC endometrial cancer patients who underwent surgical staging were included in this study. Twenty cases (35%) received postoperative radiotherapy and 37 (65%) were observed without additional therapy. The two groups were compared for survival and recurrence rates.ResultsMean follow-up times for the radiotherapy and observation groups were 52.05 and 38.71 months, respectively. Five-year disease-free survival rates for the radiotherapy and observation groups were 91% and 63%, respectively, and 5-year overall survival rates for the radiotherapy and observation groups were 90.0% and 80.8%, respectively. Both the disease-free and overall survival rates were similar between the two groups (p > 0.05). One (5%) of the 20 patients in the radiotherapy group, and four (10.8%) of the 37 patients in the observation group had recurrences and there was no statistical difference for the recurrence rates (p > 0.05). Disease grade had no prognostic significance in terms of survival after surgical staging.ConclusionsComprehensive surgical staging might minimize the unfavorable role of deep myometrial invasion and grade. After surgical staging, postoperative observation without radiotherapy may be an appropriate approach in stage IC, all grades, endometrial carcinoma.     

MRI,PET/CT and ultrasound in the preoperative staging of endometrial cancer — A multicenter prospective comparative study

ObjectivesThe aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC).Methods318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics.ResultsFor predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best.ConclusionsNone of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.