Rahul A.K. Samlal

The prognosis of cervical cancer associated with pregnancy: A matched cohort study

Objective To assess the effect of pregnancy on the prognosis of cervical cancer and the morbidity of standard treatment. Methods We analyzed 44 women with cervical carcinoma associated with pregnancy, who were matched with 44 controls. Matching criteria were age, stage of disease (according to the International Federation of Gynecology and Obstetrics classification), tumor type, treatment modality, and period of treatment. Results In 23 cases, cervical cancer was diagnosed during pregnancy and in the other 21 cases, within 6 months after delivery. Thirty-nine women had early-stage disease (eight IA, 25 IB, and six IIA), and five had advanced stages (four IIB and one IIIB). The overall 5-year survival rate was 80% among subjects and 82% among controls, whereas the relative risk (RR) of dying within 5 years was 1.12 (95% confidence interval [CI] 0.48–2.65). With regard to the 5-year survival rate (85% for both subjects and controls, the RR of dying was 1.00 [95% CI 0.35–2.83]); no differences were found between subjects and controls for early-stage cervical carcinoma. The size of the group with advanced-stage cervical carcinoma was too small to allow any statistical analysis. No statistically significant differences in survival were observed between cases diagnosed during pregnancy and cases diagnosed after delivery. In addition, the mode of delivery had no effect on survival. Early complications within 6 weeks after treatment were seen 33 times in 25 subjects and 29 times in 23 controls. No differences were observed in the prevalence and type of early complications in subjects versus controls. Late complications after 6 weeks of treatment were seen nine times in nine subjects and 11 times in ten controls. No significant differences were observed in the prevalence and type of late complications in subjects versus controls. Conclusion The prognosis of early-stage cervical cancer is similar in pregnant and nonpregnant patients when standard treatment is given. Because of the limited number of patients, no conclusions can be drawn about advanced-stage cervical cancer. The goal should be standard oncologic treatment, which does not lead to morbidity in pregant patient.

Evaluation of the risk of malignancy index in daily clinical management of adnexal masses

OBJECTIVE To verify the effectiveness of the Risk of Malignancy Index in the discrimination between non-invasive (benign and borderline) lesions and invasive malignant adnexal masses in daily clinical practice. METHODS This prospective observational study was conducted in a multicentre cooperation of 11 hospitals. A total of 548 women with adnexal masses were included. Ultrasound characteristics, menopausal status and serum CA 125 level were registered preoperatively, and combined into the RMI afterwards. Final diagnosis was based on routine histopathologic examination. The decision to have patients operated by or with a gynecologic oncologist was based on the clinical impression of the gynecologist in the local hospital, based on physical examination, testing of serum samples, and ultrasound examination. This was compared with the hypothetical situation in which the RMI would have been applied as method of selection. RESULTS An RMI of 200 achieved a sensitivity of 81% and specificity of 85% in the detection of ovarian cancer. Positive and negative predictive values were 48% and 96% respectively. In current practice, 64% of ovarian cancer patients were operated by a gynecologic oncologist. This percentage would have increased to 80% if the RMI with a cutoff value of 200 would have been used as method of selection. CONCLUSIONS In our study population, introduction of the RMI would improve the management of adnexal masses, with a higher percentage of ovarian cancer patients that are operated by a gynecologic oncologist. At the same time, referral of patients with non-invasive (benign and borderline) lesions would be reduced.

External validation of the adapted Risk of Malignancy Index incorporating tumor size in the preoperative evaluation of adnexal masses

OBJECTIVE The Risk of Malignancy Index (RMI) is a simple scoring system to standardize and improve the preoperative evaluation of adnexal masses. Since 1990, three versions of the RMI have been validated in different clinical studies. Recently, a fourth version of the RMI (RMI-4) was introduced that includes tumor size as an additional parameter. The aim of this study was to validate the ability of RMI-4 to discriminate between non-invasive lesions and invasive malignant adnexal masses, and to compare its performance with RMI-3. STUDY DESIGN Women scheduled for surgery for an adnexal mass between 2005 and 2009 in 11 hospitals were included. Ultrasonographic characteristics, menopausal status and serum CA 125 level were registered preoperatively, and combined into the RMI. The performances of RMI-3 and RMI-4 were assessed and statistically tested for differences. RESULTS A total of 643 patients were included: 469 benign, 73 borderline and 101 malignant tumors. The RMI-3 had a sensitivity of 76%, specificity of 82%, positive and negative predictive values (PPV and NPV) of 45% and 95%, and an accuracy of 81%. The RMI-4 had a sensitivity of 74%, specificity of 79%, PPV of 40%, NPV of 94%, and an accuracy of 78%. The accuracy of RMI-3 was significantly higher than the accuracy of RMI-4 (p=.001). Both models had an area under the curve of 0.86. CONCLUSION Both RMI-3 and RMI-4 were able to discriminate between non-invasive lesions and invasive malignant adnexal masses, with similar performances. Including tumor size in the RMI does not improve its performance.

Efficacy of a Regional Network for Ovarian Cancer Care

OBJECTIVE: To study the influence of a regional collaboration in epithelial ovarian cancer care on staging procedures, debulking results, and survival. METHODS: In an effort to optimize epithelial ovarian cancer treatment, a regional collaboration was introduced in the Netherlands in 2000. Gynecologic oncologists from the university center conducted surgery in community hospitals when ovarian cancer was considered based on the risk of malignancy index or clinical suspicion. The National Cancer Registry registered 1,554 patients with epithelial ovarian cancer diagnosed in 11 participating Dutch hospitals between 1996 and 2010. Surgical procedures were compared during three periods (1996–1999, 2000–2004, and 2005–2009). Log-rank tests compared Kaplan-Meier survival curves of progression-free and overall survival before (1996–2000) and during the start of the collaboration (2001–2005). RESULTS: Staging was adequate for 139 patients (23.0%) before collaboration, and this proportion increased during the study periods to 32.1% and 62.1% (P<.01), when gynecologic oncologists more often staged cancer in patients (36.7% compared with 54.7% and 80.6%; P<.01). For 1,197 patients with advanced stage disease (stage IIb or greater), the proportion of debulking procedures with an optimal (residual volume less than1 cm) as well as a complete result (no residuals) increased during the 14-year study period from 57.4% to 76.5% (P<.01) and from 24.1% to 43.4% (P<.01), respectively. Survival rates were similar before and during the start of the collaboration. In multivariable analysis, the treatment variables completeness of debulking, chemotherapy, and gynecologic oncologist attendance were independent prognostic factors for overall survival, as were age, stage, and tumor grade. CONCLUSIONS: After regional collaboration, gynecologic oncologists attended more surgeries and surgical outcomes improved, but progress in survival could not be demonstrated. Regional collaboration improved care for ovarian cancer patients. LEVEL OF EVIDENCE: II

Do mucin-secreting squamous cell carcinomas of the uterine cervix metastasize more frequently to pelvic lymph nodes : A case-control study

SummaryTwenty-nine patients with stage IB/IIA squamous cell carcinoma of the uterine cervix who had positive pelvic nodes were matched with 29 cases of node-negative squamous cell carcinoma by depth of invasion and lymphovascular space invasion. By multivariate analysis, these criteria independently predicted pelvic node metastases. Intracellular mucin, demonstrated by alcian-blue staining at pH 2.5, was noted in 21 of the 58 patients (36%). The frequency of mucin-positive tumors was not significantly different between the patients and their controls (38 versus 34%, p = 0.78), nor was the degree of positivity. These results suggest that, although a substantial proportion of squamous cell carcinomas exhibit mucin secretion, patients with these tumors are not at increased risk for pelvic node metastases. We therefore do not recommend routine mucin staining in cervical squamous cell carcinomas.

Preoperative CA-125 predicts extra-uterine disease and survival in uterine papillary serous carcinoma patients

Objective We determined the clinical utility of preoperative serum CA-125 as predictor of extra-uterine disease and as prognosticator for survival in patients with uterine papillary serous carcinoma (UPSC). Methods Patients diagnosed with UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement were included. A receiver operator characteristic (ROC) curve was used to quantify marker performance. Overall and progression free survival were analyzed using the Kaplan-Meier method. Regression analyses were used to investigate the association of preoperative CA-125 levels and other clinicopathological variables with the presence of extra-uterine disease and the effects on survival. Results Sixty-six patients met the study criteria. Using ROC, the CA-125 concentration of 45 U/mL as cutoff level provided the best sensitivity (75%) and specificity (74%) for extra-uterine disease, with a positive predictive value of 86%. Survival was significantly longer in patients with preoperative CA-125 =45 U/mL (p<0.001). Only preoperative CA-125 >45 U/mL remained significantly associated with extra-uterine disease (OR=6.30, 95% CI 1.93–20.62). Furthermore, advanced FIGO stage (HR=4.53, 95% CI 1.50–13.62) and preoperative CA-125 >45 U/mL (HR=3.12, 95% CI 1.13–8.73) were associated with decreased survival. Conclusion Preoperative elevated serum CA-125 is an independent predictor for the presence of extra-uterine disease and an independent risk factor for survival in UPSC patients.

Factors influencing the use of frozen section analysis in adnexal masses

OBJECTIVE: To determine the factors that influence the use of frozen section analysis in adnexal masses and the factors that predict malignancy. METHODS: The study participants were women scheduled for adnexal mass surgery in 11 hospitals between 2005 and 2009. Factors that potentially influenced the use of frozen section analysis and potentially predicted malignancy were studied, such as menopausal status, CA 125 level, ultrasound characteristics, presence of adhesions, and tumor size. We used univariable and multivariable analyses to assess the factors. RESULTS: A total of 670 patients were included in the study. The frozen section analyses for 323 patients (48%) showed 206 benign, 55 borderline, and 62 malignant adnexal masses. The CA 125 level, locularity of the tumor, and presence of solid areas predicted both the use of frozen section analysis and the presence of malignancy. The presence of adhesions predicted malignancy, but not the use of frozen section analysis. Menopausal status and tumor size predicted the use of frozen section analysis, but not malignancy. CONCLUSION: Menopausal status and tumor size are associated with more use of frozen section analysis, but they have not been identified as factors associated with malignancy. Frozen section analysis is useful when the CA 125 levels are greater than 35 units/mL and when there are multilocular tumors, solid areas on ultrasonography, and adhesions revealed during surgery. LEVEL OF EVIDENCE: III

Use of risk of malignancy index to indicate frozen section analysis in the surgical care of women with ovarian tumors

To evaluate the importance of the risk of malignancy index (RMI) in the decision to perform frozen section analysis among women with ovarian tumors.

1170 The prognosis of cervical cancer associated with pregnancy

To evaluate the influence of pregnancy on the course and survival of cervical cancer (CC) we performed a matched cohort study. 44 patients with gestational CC and treated with standard oncological therapy were matched to 44 contemporary controls. Matching criteria were age, FIGO stage, tumor type, treatment modality. Results In 23 cases CC was diagnosed during pregnancy, in 21 cases within 6 months after delivery. 39 patients had an early stage of CC (8 IA, 25 IB, 6 IIA) and 5 had an advanced stage (4 IIB, 1 IIIB). For early stages the 5 year survival rate was 84.6% for both cases and controls (RR 1.00, CI 0.35–2.83). The size of the group with advanced carcinoma was too small to allow any statistical analysis. The moment at which the diagnosis was made (trimester of pregnancy or post-partum period) and mode of delivery (abdominally vs. vaginally) had no impact on survival. No differences were observed in the prevalence and type of early and late complications of standard oncological therapy (surgery and/or radiotherapy). Conclusion The prognosis of early stage CC is similar in gestational and non-gestational patients, provided standard oncological therapy is given. Due to the limited number of patients no conclusions can be drawn about advanced stage of CC. Standard therapy does not lead to increased morbidity in gestational patients and should be aimed for.