Results of radical surgery in women with stage IB2/IIA2 cervical cancer.

INTRODUCTION: There is ongoing discussion about the primary treatment of women with bulky early-stage cervical cancer. Because of the high number of patients who need adjuvant (chemo)radiotherapy after initial surgical treatment, some state that primary (chemo)radiotherapy should be the treatment of choice to prevent morbidity. The aim of our study is to assess the results of radical surgery for women with bulky early-stage cervical cancer in terms of recurrence patterns and survival. MATERIALS AND METHODS: We conducted a retrospective cohort study. We included 129 women who underwent a radical hysterectomy with pelvic lymphadenectomy for stage IB2/IIA2 cervical cancer between 1984 and June 2010. Disease-specific survival was measured using a Kaplan-Meier method and univariate and multivariate regression analyses were performed to determine prognostic factors associated with survival. A literature search was performed to analyze our data in the context of findings from the literature. RESULTS: Five-year disease-specific survival was 84%. Fifty percent of the women received adjuvant treatment. The pelvic recurrence rate was 8%. With our multivariate analysis we found that histology, tumor diameter, and parametrial involvement were independently associated with disease-specific survival. Our literature search showed wide diversity in rates of adjuvant treatment after initial surgery as well as for survival and recurrence rates. CONCLUSIONS: In the context of current knowledge about survival and side effects of various treatments for bulky early-stage cervical cancer, radical surgery is a good treatment option in these patients. Depending on the type of surgery used, adjuvant radiotherapy can be minimized.

Prognostic model for survival in patients with early stage cervical cancer.

BACKGROUND: In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. METHODS: A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. RESULTS: The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). CONCLUSIONS: In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients.

Can we predict vesicovaginal or rectovaginal fistula formation in patients with stage IVA cervical cancer?

INTRODUCTION: Patients with cervical carcinoma that invade the bladder or rectum (International Federation of Obstetrics and Gynecology stage IVA) have a high risk to develop vesicovaginal and/or rectovaginal fistulae. If we could identify pretreatment factors that predict fistula formation, these patients could be offered less debilitating treatment. MATERIALS AND METHODS: Data were retrieved from the database of consecutive patients diagnosed with stage IVA cervical cancer from 1992 to 2008. Overall survival and fistula-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to study the association between pretreatment prognostic variables and fistula formation. RESULTS: Thirty patients with stage IVA cervical cancer were diagnosed. Extension to the bladder was present in 27 patients; three patients had only rectal involvement. Twenty-three patients (77%) had curative radiotherapy with or without chemotherapy and/or hyperthermia. Seven patients (23%) received only palliative therapy or no treatment at all. The 5-year overall survival in the curatively treated group was 42%. Five (22%) of these 23 patients developed one or more fistulae: 3 vesicovaginal, 1 rectovaginal, and 1 vesicovaginal and rectovaginal fistulae. The 5-year fistula-free survival of this group was 64%. No significant association was found between the prognostic variables and fistula formation. CONCLUSIONS: The risk to develop vesicovaginal and/or rectovaginal fistulae is high after curative radiotherapy with or without chemotherapy and/or hyperthermia in patients with stage IVA cervical cancer. We could not identify further pretreatment factors that might have predicted fistula formation.

Validation of existing prognostic models in patients with early-stage cervical cancer.

OBJECTIVE: Models that predict survival and recurrence in patients with early-stage cervical cancer are important tools in patient management. We validated 12 existing prognostic models in an independent population of patients with early-stage cervical cancer. MATERIALS AND METHODS: We searched the literature for prognostic models in patients with surgically treated early-stage cervical cancer. The prognostic performance of these models was assessed in a consecutive group of surgically treated patients with early-stage cervical cancer treated in our hospital between 1982 and 2004. The performance of the models was visually assessed with calibration plots, which display the relation between the predicted and observed survival. RESULTS: Twelve published prognostic models met the inclusion criteria. The models categorized the patients into two to four risk groups. Prognostic factors most frequently used in these models were depth of invasion, lymph node metastasis, vascu/vascular space involvement, and tumor size. The models were validated in 563 consecutive patients with early-stage cervical cancer. All of the models underestimated the recurrence-free survival or disease-specific survival in our patients. Only two models performed reasonably well in our population. The use of more than three prognostic categories in the models was not meaningful. CONCLUSION: In general, the models underestimated the survival. Only 2 of the 12 prognostic models for patients with early-stage cervical cancer were valid for the prediction of the recurrence-free or disease-specific survival in our patient population.

Gene expression in early stage cervical cancer.

OBJECTIVE: Pelvic lymph node metastases are the main prognostic factor for survival in early stage cervical cancer, yet accurate detection methods before surgery are lacking. In this study, we examined whether gene expression profiling can predict the presence of lymph node metastasis in early stage squamous cell cervical cancer before treatment. In addition, we examined gene expression in cervical cancer compared to normal cervical tissue. METHODS: Tumour samples of 35 patients with early stage cervical cancer who underwent radical hysterectomy and pelvic lymph node dissection, 16 with and 19 without lymph node metastasis, were analysed. Also five normal cervical tissues samples were analysed. We investigated differential expression and prediction of patient status for lymph node positive versus lymph node negative tumours and for healthy versus cancer tissue. Classifiers were built by using a multiple validation strategy, enabling the assessment of both classifier accuracy and variability. RESULTS: Five genes (BANF1, LARP7, SCAMP1, CUEDC1 and PEBP1) showed differential expression between tumour samples from patients with and without lymph node metastasis. Mean accuracy of class prediction is 64.5% with a 95% confidence interval (CI) of 40-90%. For healthy cervical tissue versus early stage cervical cancer, the mean accuracy of class prediction is 99.5% (95% CI of 90-100%). A subset of genes involved in cervical cancer was identified. CONCLUSION: No accurate class prediction for lymph node status in early stage cervical cancer was obtained. Replication studies are needed to determine the relevance of the differentially expressed genes according to lymph node status. Early stage cervical cancer can be perfectly differentiated from healthy cervical tissue by means of gene expression profiling.

Does diagnostic hysteroscopy in patients with stage I endometrial carcinoma cause positive peritoneal washings?

OBJECTIVES: Previous studies have shown that positive peritoneal washings may adversely affect cancer survival rates and that hysteroscopy is associated with a higher risk of positive washings in patients with endometrial carcinoma. Our aim was to assess if diagnostic hysteroscopy increases the risk of positive peritoneal washings in patients with endometrial cancer and affects the prognosis after surgery. STUDY DESIGN: Retrospective cohort study. The medical records of 50 consecutive patients with endometrial carcinoma, diagnosed with hysteroscopy and tissue sampling and treated by abdominal hysterectomy with bilateral salpingo-oophorectomy and peritoneal washings were reviewed. RESULTS: Of the 43 patients with endometrial carcinoma FIGO stage I, none had positive peritoneal washings (95%CI: 0-8.2%). The mean interval between hysteroscopy and surgery was 33.5 days. The 5-year disease-specific survival rate was 91.8%, the 5-year recurrence-free survival rate was 85.4%. CONCLUSIONS: Diagnostic hysteroscopy had no adverse effect on the incidence of positive peritoneal washings or on prognosis in stage I endometrial cancer patients.

The natural course of spontaneous miscarriage: analysis of signs and symptoms in 188 expectantly managed women.

BACKGROUND: Expectant management is an alternative for curettage in women with a miscarriage. AIM: To assess the pattern of vaginal bleeding and pain in expectantly managed women with a miscarriage, and to analyse the factors predictive of a relatively quick spontaneous loss of pregnancy. DESIGN OF STUDY: Part of a study comparing expectant management with surgical evacuation. SETTING: Two hospitals in Amsterdam. METHOD: In expectantly managed women with a miscarriage, the pattern of vaginal bleeding and pain and the probability of a spontaneous loss of pregnancy was analysed. RESULTS: Of the 188 expectantly managed women 95 (51%) experienced a spontaneous loss of their pregnancy. In women with bleeding at inclusion, 52% had a completed miscarriage loss, while of the women without bleeding but with a coincidentally diagnosed non-viable pregnancy during routine ultrasonographic examination, 46% had a completed miscarriage. In the multivariate analysis an increasing bleeding pattern at inclusion was predictive of a relatively quick spontaneous loss of pregnancy. The median daily levels of bleeding and pain were the most prominent during the first 8 days after the start of the bleeding and decreased thereafter. CONCLUSIONS: Expectant management is effective in 51% of unselected women with a miscarriage. An increasing bleeding pattern is predictive of a relatively quick spontaneous loss of pregnancy in first-trimester miscarriages. The graphical representation of our findings can be used to inform women about the natural course of miscarriages and a well-informed treatment choice.