Seok-Mo Kim

Preoperative Identification of a Low-Risk Group for Lymph Node Metastasis in Endometrial Cancer: A Korean Gynecologic Oncology Group Study

PURPOSEnThe aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery.nnnPATIENTS AND METHODSnThe medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions.nnnRESULTSnSerum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%.nnnCONCLUSIONnUsing serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.

Role of body mass index as a risk and prognostic factor of endometrioid uterine cancer in Korean women.

OBJECTIVEnWe aimed to evaluate the role of body mass index (BMI) as a risk and prognostic factor of endometrioid uterine cancer in Korean women.nnnMETHODSnThe records of 937 patients with endometrioid uterine cancer treated between 2000 and 2006 in Korea were reviewed. To determine the disease risk by BMI, four age-matched controls were recruited from healthy women (1-year age group).nnnRESULTSnThe obese (BMI > or =25 kg/m(2)) and overweight (23 kg/m(2)< or = BMI <25 kg/m(2)) women had an increased risk for endometrioid uterine cancer (OR=3.161, 95% CI=2.655-3.763 and OR=1.536, 95% CI=1.260-1.873, respectively) compared to the non-obese (BMI <23 kg/m(2)) women. That is, an increment of 1 kg/m(2) caused an 18% increase in the endometrioid uterine cancer risk (OR=1.181, 95% CI=1.155-1.207). However, there was no difference in overall survival according to the BMI-based subgroups (log-rank=0.366, p=0.8328). The crude Cox model showed that obesity was not associated with the patients overall survival when the obese and non-obese women were compared (crude HR=0.82, 95% CI=0.40-1.66). Furthermore, there was a significant trend toward a better prognosis at increased increments of BMI (p for trend<0.001), but this was not found in the multivariate analysis.nnnCONCLUSIONSnA high BMI was a significant risk factor for endometrioid uterine cancer in an Asian population. However, it was not associated with overall survival, in spite of the earlier tumor stage of the obese women.

Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study

OBJECTIVEnThe aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer.nnnMETHODSnUsing medical records of premenopausal women who received primary surgical treatment for stage I-II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups.nnnRESULTSnA total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P<0.001) and had an earlier year of diagnosis (P=0.014), a lower prevalence of lymphadenectomy (P<0.001), and a marginally significant association with lower tumor grade (P=0.052). The Kaplan-Meier curve and the log rank test showed no difference in either recurrence-free survival (P=0.742) or overall survival (P=0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29-1.81) or overall survival (HR, 1.33; 95% CI, 0.43-4.09).nnnCONCLUSIONSnOvarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries.

Human papillomavirus genotyping using HPV DNA chip analysis in Korean women.

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P< 0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P< 0.01) and increased with more advanced squamous cervical lesions (P< 0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81–87%), specificity 72% (70–74%), positive predictive value 47% (44–50%), and negative predictive value 94% (92–95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.

Evaluation of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer: A multi-center study

OBJECTIVEnTo evaluate the role of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer (EEC).nnnMETHODSnWe reviewed 413 patients with EEC from 6 tertiary medical centers between July 1996 and June 2008. All patients were divided into (1) 4 categories of preoperative serum CA-125 levels: <18 U/mL (n=203); 18-35 U/mL (n=114); 36-70 U/mL (n=53); >70 U/mL (n=43) or (2) 3 categories: low-risk (n=240); intermediate-risk (n=99); high-risk diseases (n=74).nnnRESULTSnReceiver operative curves showed the best cut-off values of 16.2-40.8 U/mL for predicting prognostic factors with 53.4-84.2% of sensitivity, 43.9-81.7% of specificity, 48.8-82.1% of positive predictive value (PPV), 48.5-83.8% of negative predictive value (NPV) and 48.6-83.0% of accuracy. Especially, adnexal involvement was predicted with the highest accuracy (83.0%) at >or=40.8 U/mL. The best cut-off values for preoperative selection of intermediate- to high-risk, and high-risk diseases were 17.3 U/mL and 21.9 U/mL (62.4% and 68.9% of sensitivity; 54.6% and 64.3% of specificity; 57.9% and 64.2% of PPV; 59.2% and 67.4% of NPV, 58.5% and 65.8% of accuracy). Furthermore, >70 U/mL of preoperative serum CA-125 levels was a prognostic factor for poor progression-free and overall survivals.nnnCONCLUSIONSnSerum CA-125 levels may not be useful for predicting most of prognostic factors, and may not contribute to preoperative selection of patients with intermediate- or high-risk disease who need adjuvant radiotherapy in EEC. However, serum CA-125 levels may be helpful in preoperative counseling for young patients who want ovarian preservation, and >70 U/mL could be considered as a risk factor for poor survival.

How low is low enough? Evaluation of various risk-assessment models for lymph node metastasis in endometrial cancer: a Korean multicenter study

Objective The aim of this study was to identify a standard for the evaluation of future models for prediction of lymph node metastasis in endometrial cancer through estimation of performance of well-known surgicopathological models. Methods Using the medical records of 947 patients with endometrial cancer who underwent surgical management with lymphadenectomy, we retrospectively assessed the predictive performances of nodal metastasis of currently available models. Results We evaluated three models included: 1) a model modified from the Gynecologic Oncology Group (GOG) pilot study; 2) one from the GOG-33 data; and 3) one from Mayo Clinic data. The three models showed similar negative predictive values ranging from 97.1% to 97.4%. Using Bayes theorem, this can be translated into 2% of negative post-test probability when 10% of prevalence of lymph node metastasis was assumed. In addition, although the negative predictive value was similar among these models, the proportion that was classified as low-risk was significantly different between the studies (56.4%, 44.8%, and 30.5%, respectively; p<0.001). Conclusion The current study suggests that a false negativity of 2% or less should be a goal for determining clinical usefulness of preoperative or intraoperative prediction models for low-risk of nodal metastasis.

Role of Systematic Lymphadenectomy and Adjuvant Radiation in Early-Stage Endometrioid Uterine Cancer

ObjectiveTo determine the roles of lymphadenectomy in endometrioid uterine cancer patients and adjuvant radiation in early-stage endometrioid uterine cancer patients who underwent systematic lymphadenectomy.MethodsA retrospective analysis of 758 patients surgically treated for early-stage endometrioid uterine cancer from 2000 to 2006 was conducted. The primary outcome was 5-year overall survival in relation to systematic lymphadenectomy with or without adjuvant radiation.ResultsOf the 758 patients, 547 (72.2%) underwent complete surgical staging, including systematic lymphadenectomy; adjuvant radiation was administered to 207 patients (27.3%). Within median follow-up of 35xa0months, systematic lymphadenectomy did not affect overall survival in early-stage patients (Pxa0=xa00.4480). In the high-risk, early-stage group, however, the 5-year survival rate of the systematic lymphadenectomy group showed better survival compared with the no systematic lymphadenectomy group (Pxa0=xa00.0095). Also, adjuvant radiation did not affect overall survival in early-stage patients (Pxa0=xa00.1170), even in the group of high-risk, early-stage patients (Pxa0=xa00.5680) who underwent systematic lymphadenectomy.ConclusionsSystematic lymphadenectomy provided a survival benefit in high-risk endometrioid uterine cancer patients. However, in patients who underwent systematic lymphadenectomy, adjuvant radiation was not beneficial, even in high-risk patients.To determine the roles of lymphadenectomy in endometrioid uterine cancer patients and adjuvant radiation in early-stage endometrioid uterine cancer patients who underwent systematic lymphadenectomy. A retrospective analysis of 758 patients surgically treated for early-stage endometrioid uterine cancer from 2000 to 2006 was conducted. The primary outcome was 5-year overall survival in relation to systematic lymphadenectomy with or without adjuvant radiation. Of the 758 patients, 547 (72.2%) underwent complete surgical staging, including systematic lymphadenectomy; adjuvant radiation was administered to 207 patients (27.3%). Within median follow-up of 35xa0months, systematic lymphadenectomy did not affect overall survival in early-stage patients (Pxa0=xa00.4480). In the high-risk, early-stage group, however, the 5-year survival rate of the systematic lymphadenectomy group showed better survival compared with the no systematic lymphadenectomy group (Pxa0=xa00.0095). Also, adjuvant radiation did not affect overall survival in early-stage patients (Pxa0=xa00.1170), even in the group of high-risk, early-stage patients (Pxa0=xa00.5680) who underwent systematic lymphadenectomy. Systematic lymphadenectomy provided a survival benefit in high-risk endometrioid uterine cancer patients. However, in patients who underwent systematic lymphadenectomy, adjuvant radiation was not beneficial, even in high-risk patients.

Efficacy of Para-Aortic Lymphadenectomy in Early-Stage Endometrioid Uterine Corpus Cancer

The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy. The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy. Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (pxa0=xa00.02) and lymphvascular space invasion (pxa0=xa00.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5–120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (pxa0=xa00.77), even in high-risk patients (pxa0=xa00.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR)xa0=xa07.38; 95% confidence interval (CI)xa0=xa01.86–29.23; pxa0=xa00.004). Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.PurposeThe objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy.MethodsThe authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy.ResultsAmong 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (pxa0=xa00.02) and lymphvascular space invasion (pxa0=xa00.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5–120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (pxa0=xa00.77), even in high-risk patients (pxa0=xa00.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR)xa0=xa07.38; 95% confidence interval (CI)xa0=xa01.86–29.23; pxa0=xa00.004).ConclusionsAlthough a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.

The comparison of clinicopathological characteristics in primary malignant mixed műllerian tumour with epithelial endometrial carcinoma.

Aims:u2002 We performed an age‐matched case–control study to compare the clinical and pathology outcomes between histologically diagnosed primary malignant mixed műllerian tumour (MMMT) of the uterus and endometrial carcinoma.

Comparison of radiation therapy alone and concurrent chemoradiation therapy in stage III cervical cancer: a multicenter retrospective study.

Objective. To evaluate whether concurrent chemoradiation therapy (CRT) improves overall survival as compared to radiation therapy (RT) alone in stage III cervical cancers. Design. A multicenter retrospective review. Setting. Nine tertiary medical centers in Korea. Population. A total of 277 patients treated for stage III cervical cancer without para‐aortic lymph node (PALN) metastasis based on clinical staging workup from 1996 to 2003. Methods. Medical and histopathological record review. Main outcome measures. Disease‐specific overall survival. Results. CRT and RT alone were performed in 172 and 105 patients, respectively. There was no significant difference in disease‐specific overall survival between the CRT and RT alone arms based on clinical staging workup, even though the CRT arm was characterized by younger age, more favorable performance status and lower pretreatment blood urea nitrogen level as compared to the RT alone arm. In the CRT arm, three patients succumbed to treatment‐related death. Conclusion. CRT does not improve the overall survival rate in stage III cervical cancer as compared to RT alone based on clinical staging workup for PALN status. Special care needs to be taken regarding optimal dose and duration of RT, use of brachytherapy, anemia control and accurate pretreatment staging workup to improve survival outcome in patients with stage III cervical cancer.