Lower-Limb Lymphedema after Sentinel Lymph Node Biopsy in Cervical Cancer Patients.

BACKGROUND: To prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. METHODS: A prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. RESULTS: The cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. CONCLUSIONS: The replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed.

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial.

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Central Pathology Review in SENTIX, A Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2).

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review.

Late-week surgical treatment of endometrial cancer is associated with worse long-term outcome: Results from a prospective, multicenter study.

Surgery is the cornerstone in primary endometrial cancer treatment, and with curative intent it constitutes total hysterectomy and bilateral salpingo-oopherectomy. In addition, lymphadenectomy is performed in selected patients dependent on a preoperative risk assessment. Recent reports from the surgical approach to esophageal cancer reveal worse outcome when esophagectomy is performed later in the week. On this basis, we set out to explore weekday of surgery in relation to long-term outcome in 1302 endometrial cancer patients prospectively included in the MoMaTEC multicenter study. Day of surgery was dichotomized as early-week (Monday-Tuesday) or late-week (Wednesday-Friday), and evaluated as a discrete variable. Adjusted for patient age, Body Mass Index (BMI), FIGO stage, and histology, surgery performed later in the week was associated with 50.9% increased risk of all-cause death (p = 0.029). Among high-stage patients (FIGO stage III and IV), 5-year disease-specific survival proportions were 53.0% for early-week operated vs. 40.2% for late-week operated (p = 0.005 for difference). In multivariate survival analysis of high-stage patients, late-week surgery correlated with an increased risk of disease-specific death by 88.7% and all-cause death by 76.4% (p<0.017). Evaluating only patients who underwent lymphadenectomy, the adverse prognostic effect of being operated late-week remained for both disease-specific and all-cause death (HR 2.151 and HR 1.912, p = 0.004). Whether surgery was performed early- or late-week was not influenced by patient age, BMI, preoperative histology risk classification, FIGO stage or postoperative histology (all p>0.05). In conclusion, endometrial cancer surgery conducted late-week is associated with worse long-term outcome. Our findings are most evident among patients with higher FIGO stages, and patients who underwent more extensive surgical procedure (lymphadenectomy). With support from other studies, our results suggest that high-risk patients may benefit from surgery earlier in the week.

Expression of L1CAM in curettage or high L1CAM level in preoperative blood samples predicts lymph node metastases and poor outcome in endometrial cancer patients.

BACKGROUND: Several studies have identified L1 cell adhesion molecule (L1CAM) as a strong prognostic marker in endometrial cancer. To further underline the clinical usefulness of this biomarker, we investigated L1CAM as a predictive marker for lymph node metastases and its prognostic impact in curettage specimens and preoperative plasma samples. In addition, we aimed to validate the prognostic value of L1CAM in hysterectomy specimen. METHODS: Immunohistochemical staining of L1CAM was performed for 795 hysterectomy and 1134 curettage specimen from endometrial cancer patients. The L1CAM level in preoperative blood samples from 372 patients was determined using ELISA. RESULTS: Expression of L1CAM in curettage specimen was significantly correlated to L1CAM level in corresponding hysterectomy specimen (P<0.001). Both in curettage and preoperative plasma samples L1CAM upregulation was significantly associated with features of aggressive disease and poor outcome (P<0.001). The L1CAM was an independent predictor of lymph node metastases, after correction for curettage histology, both in curettage specimen (P=0.002) and plasma samples (P=0.048). In the hysterectomy samples L1CAM was significantly associated with poor outcome (P<0.001). CONCLUSIONS: We demonstrate that preoperative evaluation of L1CAM levels, both in curettage or plasma samples, predicts lymph node metastases and adds valuable information on patient prognosis.

Prevalence of human papillomavirus infection among women in rural Nepal.

INTRODUCTION: In this study we aimed to determine the overall and type-specific prevalence of cervical human papillomavirus (HPV) infection and risk factors for such infection among women in rural Nepal, and to investigate the distribution of HPV infection by cervical cytology. MATERIAL AND METHODS: The study was conducted among women aged ≥15 years in five rural villages within Kavre District in Nepal. Sociodemographic data and information on risk factors for cervical cancer were obtained through an interview, and a cervical specimen was collected for HPV DNA detection and typing using the Anyplex™ ll HPV28 Detection system, and for Papanicolaou test. RESULTS: Among the 1289 women in whom a valid HPV result was obtained the median age was 40 years (range 17-86 years). Overall, the HPV prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV-51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of high-risk types in women with and without abnormal cytology was 8.3 and 7.7%, respectively. HPV infection was associated with current smoking, formal education, and being married to a husband with at least one previous marriage. CONCLUSIONS: This is the first population-based study to report the prevalence of a broad range of HPV types among women from rural Nepal. These data are crucial for development of preventive strategies to reduce cervical cancer burden in the country.

Changes in Chromatin Structure in Curettage Specimens Identifies High-Risk Patients in Endometrial Cancer.

BACKGROUND: Most endometrial carcinoma patients are diagnosed at an early stage with a good prognosis. However, a relatively low fraction with lethal disease constitutes a substantial number of patients due to the high incidence rate. Preoperative identification of patients with high risk and low risk for poor outcome is necessary to tailor treatment. Nucleotyping refers to characterization of cell nuclei by image cytometry, including the assessment of chromatin structure by nuclear texture analysis. This method is a strong prognostic marker in many cancers but has not been evaluated in preoperative curettage specimens from endometrial carcinoma. METHODS: The prognostic impact of changes in chromatin structure quantified with Nucleotyping was evaluated in preoperative curettage specimens from 791 endometrial carcinoma patients prospectively included in the MoMaTEC multicenter trial. RESULTS: Nucleotyping was an independent prognostic marker of disease-specific survival in preoperative curettage specimens among patients with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I-II disease (HR=2.9; 95% CI, 1.2-6.5; P = 0.013) and significantly associated with age, FIGO stage, histologic type, histologic grade, myometrial infiltration, lymph node status, curettage histology type, and DNA ploidy. CONCLUSIONS: Nucleotyping in preoperative curettage specimens is an independent prognostic marker for disease-specific survival, with potential to supplement existing parameters for risk stratification to tailor treatment. IMPACT: This is the first study to evaluate the prognostic impact of Nucleotyping in curettage specimens from endometrial carcinoma and shows that this may be a clinically useful prognostic marker in endometrial cancer. External validation is warranted. Cancer Epidemiol Biomarkers Prev; 26(1); 61-67. ©2016 AACR.

Indocyanine green fluorescence imaging of lymph nodes during robotic-assisted laparoscopic operation for endometrial cancer. A prospective validation study using a sentinel lymph node surgical algorithm.

OBJECTIVE: A sentinel lymph node (SLN) strategy may have particular value in endometrial cancer (EC) because a therapeutic effect of lymphadenectomy per se is unproven. The aim was to evaluate indocyanine green (ICG) and near-infrared (NIR) fluorescence mapping using a surgical algorithm. METHODS: From November 2012 through December 2015, women with apparently early stage EC underwent robot-assisted laparoscopic hysterectomy including ICG fluorescence SLN mapping following the Memorial Sloane Kettering Cancer Center (MSKCC) surgical algorithm. RESULTS: Among 108 patients included, ≥1 SLNs was identified in 104 (96%), bilaterally in 84 (78%) and unilaterally in 20 patients (18%). Four patients failed SLN mapping. All SLN-positive patients had pelvic SLNs. Median number of nodes were 4.0 and 6.0 (p<0.001), when SLNs only and SLNs plus non-SLNs were removed, respectively. Lymph node metastases were detected in 17 patients (16%). One patient who failed SLN mapping had a non-SLN metastasis. The remaining 16 patients had metastases in SLNs, 12 in SLNs only and four in both SLNs and non-SLNs. Routine pathology detected 75% of patients with cancer positive SLNs while 25% were based on extended pathology. Lymph node metastases were found among 9% with low-, 11% with intermediate- and 32% with high-risk profiles, respectively. CONCLUSIONS: We have reproduced the high total and bilateral SLN mapping using cervical ICG injection and NIR fluorescence. Practical application of the MSKCC algorithm allowed high lymph node metastasis detection in combination with a low extent of lymph node removal.

Community-Based Health Education has Positive Influence on the Attitude to Cervical Cancer Screening among Women in Rural Nepal.

The main purpose of this study was to assess the knowledge of cervical cancer among women in rural Nepal and explore the feasibility and impact of a community-based awareness program on cervical cancer. Community-based educational meetings on cervical cancer and its prevention were conducted among women's groups in rural Nepal. Through a questionnaire, the women's baseline knowledge of risk factors, symptoms, and perceived risk of cervical cancer were identified. The willingness to participate in cervical cancer screening was compared before and after the educational meeting. The meetings were followed by a cervical cancer screening program. Among the 122 participants at the educational meeting, only 6 % had heard of cervical cancer. Their baseline knowledge of risk factors and symptoms was poor. The proportion of women willing to participate in cervical screening increased from 15.6 to 100 % after attending the educational meeting. All the study subjects participated in the screening program. Additionally, the study participants recruited a further 222 of their peers for screening. Poor knowledge of cervical cancer among women in rural Nepal highlights the urgency of public awareness programs for cervical cancer at a national level. A community-based awareness program can change women's attitude to cervical screening, and women's groups can play a major role in promoting participation in cervical cancer screening programs.

Hormone receptor loss in endometrial carcinoma curettage predicts lymph node metastasis and poor outcome in prospective multicentre trial.

BACKGROUND: Preoperative histologic examination of tumour tissue is essential when deciding if endometrial cancer surgery should include lymph node sampling. We wanted to investigate if biomarkers could improve prediction of lymph node metastasis and outcome. PATIENTS AND METHODS: Curettage specimens from 832 endometrial carcinoma patients prospectively recruited from 10 centres in the MoMaTEC trial (Molecular Markers in Treatment of Endometrial Cancer) were investigated for hormone receptor and p53 status. RESULTS: Eighteen per cent of tumours were double negative for oestrogen- and progesterone receptors (ER/PR loss), 24% overexpressed p53. Pathologic expression of all markers correlated with nodal metastases, high FIGO (Federation International of Gynecology and Obstetrics) stage, non-endometrioid histology, high grade and poor prognosis (all P<0.001). ER/PR loss independently predicted lymph node metastasis (odds ratios (OR) 2.0, 95% confidence interval (CI) 1.1-3.7) adjusted for preoperative curettage histology and predicted poor disease-specific survival adjusted for age, FIGO stage, histologic type, grade and myometrial infiltration (hazard ratio (HR) 2.3, 95% CI 1.4-3.9). For lymph node negative endometrioid tumours, ER/PR loss influenced survival independent of grade. CONCLUSION: Double negative hormone receptor status in endometrial cancer curettage independently predicts lymph node metastasis and poor prognosis in a prospective multicentre setting. Implementing hormone receptor status to improve risk-stratification for selecting patients unlikely to benefit from lymphadenectomy seems justified.

Ten years' experience with centralized surgery of ovarian cancer in one health region in Norway.

BACKGROUND: Better outcome of advanced ovarian cancer after centralized surgery has led to the recommendation for centralized surgery in a Norwegian health region. Whether the practice pattern has changed according to this recommendation has not been examined. OBJECTIVE: The objective of this study was to evaluate the referral practice and treatment of ovarian cancer in a Norwegian health region after the introduction of centralized surgery. METHODS: This was a retrospective, population-based study, including all women undergoing surgery for primary ovarian, tubal, and peritoneal cancer between 2000 and 2005, in Health Region IV of Norway. Clinical data and data regarding treatment and 5-year follow-up were analyzed. RESULTS: In total, 279 cases of ovarian, peritoneal, and tubal cancer were included. Eighty-four percent underwent primary surgery at the teaching hospital and 16% at the nonteaching hospitals. After an immediate rise in the number of cases undergoing primary surgery at the teaching hospital after the introduction of centralization in 1995, the percentage distribution between the teaching and nonteaching hospitals was stable during the study period. The women who underwent surgery at the nonteaching hospitals had a higher percentage of early-stage disease and were at higher risk of reoperation for comprehensive staging. CONCLUSIONS: Centralization of ovarian cancer surgery has been successfully accomplished in a health region in Norway. The referral practice of assumed advanced ovarian cancer cases shows satisfactory compliance with centralization at 10 years after the implementation of centralized surgery.

Circulating interleukin-8 and plasminogen activator inhibitor-1 are increased in women with ovarian carcinoma.

Elevated serum levels of several cytokines have been reported in ovarian cancer. We have previously found a diagnostic and prognostic value of hepatocyte growth factor (HGF). The aims of this study were to evaluate the diagnostic and prognostic value of multiple serum cytokines in women with ovarian tumors, and to examine possible associations between serum levels of cytokines and the previously analyzed HGF. Preoperative levels of multiple cytokines were quantified by serum-based immunoassays in 113 women with a pelvic mass: 57 carcinomas, 23 borderline tumors, and 33 benign ovarian tumors. The results were related to clinicopathological parameters. Univariate and multivariate analyses of five-year overall survival were performed. The women with ovarian carcinoma had significantly higher preoperative serum levels of cancer antigen 125 (CA 125), interleukin 8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1) than women with benign ovarian tumors. Serum IL-8 and PAI-1 levels were positively correlated to serum levels of HGF. In a multivariate analysis of five-year overall survival, IL-8 had a prognostic impact. Serum levels of IL-8 and PAI-1 were elevated in women with ovarian carcinoma compared to women with benign ovarian tumors, and positively correlated to serum HGF levels in women with ovarian tumors. IL-8 also seemed to have a prognostic impact.

SNP285C modulates oestrogen receptor/Sp1 binding to the MDM2 promoter and reduces the risk of endometrial but not prostatic cancer.

INTRODUCTION: The MDM2 promoter polymorphism (SNP309T > G) extends a binding site for the transcription factor Sp1 and has been linked to elevated cancer risk and/or young age at cancer diagnosis, especially in females. Recently, we reported an adjacent polymorphism (SNP285G > C). SNP285C antagonises the effect of SNP309G by reducing Sp1 binding and lowers the risk of breast and ovarian cancer. METHODS: We assessed the potential gender specificity in the effect of this polymorphism. We performed in silico predictions of transcription factor binding sites in the MDM2 promoter and analysed MDM2 SNP285 and SNP309 status in two independent cohorts of endometrial (n = 438 and 472) and 666 prostatic cancer patients, and compared to 3.140 healthy controls. RESULTS: We identified three oestrogen-receptor binding elements (EREs) within the MDM2 intronic promoter, one of which overlapping the Sp1 binding-site harbouring SNP285. The SNP285C/309G haplotype was associated with a reduced Odds Ratio (OR) for endometrial cancer (OR1: 0.55; Confidence Interval (CI) 0.32-0.97; OR2: 0.65; CI 0.40-1.08, especially for ER+ tumours; OR: 0.48; CI 0.28-0.87) but not for prostatic cancer among SNP309TG heterozygotes. SNP309G (SNP309TG or SNP309GG genotype) was associated with a moderately increased risk of endometrial cancer (OR: 1.17; CI 1.00-1.37) compared to SNP309TT homozygotes. Removing individuals harbouring the SNP309G-counteracting SNP285C polymorphism from the analysis strengthened this association (OR: 1.20; CI 1.02-1.41). CONCLUSION: The finding of an ERE overlapping with the Sp1-binding site affected by SNP285, taken together with the significant impact of SNP285 on the risk of breast, ovarian and now endometrial cancer but not prostatic cancer, suggests a gender specific effect of SNP285C on cancer risk.

The proliferation markers Ki-67/MIB-1, phosphohistone H3, and survivin may contribute in the identification of aggressive ovarian carcinomas.

The identification of new proliferation markers could have clinical implications in ovarian carcinoma by stratifying patients for treatment and follow-up. The aim of this study was to evaluate the diagnostic and prognostic value of the proliferation markers Ki-67/MIB-1, phosphorylated histone H3 (PHH3), and survivin in epithelial ovarian tumors. Ninety women with a pelvic mass who underwent surgery at the Department of Gynecological Oncology were included: 68 ovarian carcinomas, 11 borderline tumors, and 11 ovarian cystadenomas. We performed mitotic count and immunohistochemical analyses of Ki-67/MIB-1, PHH3, and survivin, related to clinicopathological parameters. Uni- and multivariate analyses of five-year overall survival were performed. We found statistically significant correlations between mitotic count, Ki-67/MIB-1, PHH3, and survivin. The expression of all proliferation markers was significantly higher in the carcinomas than in the borderline and benign tumors (p<0.05). There was, however an overlap of indices between the different malignancy groups. Women with advanced stage cancers (FIGO stage III and IV) had significantly higher tumor expression of all markers compared to patients with early stage cancers (FIGO stage I and II). Women with advanced disease and complete chemotherapy response had higher Ki67/MIB-1 expression than women without complete chemotherapy response. All markers had an impact on survival in the univariate analyses. In the multivariate analysis, however, only age and stage of disease reached statistical significance as prognostic factors. In conclusion, the proliferation markers Ki-67/MIB-1, PHH3, and survivin are positively correlated with each other and with tumor grade, and may contribute in the identification of aggressive ovarian carcinomas.

Increased circulating hepatocyte growth factor (HGF): a marker of epithelial ovarian cancer and an indicator of poor prognosis.

OBJECTIVE: Hepatocyte growth factor (HGF) has been described to be increased in different cancers. In the present study we wanted to investigate whether HGF in serum can distinguish between benign and malignant ovarian tumors, and whether serum HGF levels can predict the outcome in patients with ovarian carcinomas. METHODS: We included 123 consecutive patients appointed for laparotomy due to a pelvic mass. Preoperative levels of serum cancer antigen 125 (CA 125), HGF and HGF activator (HGFA) were quantified with immunological methods. We performed immunohistochemical analyses of HGFα, HGFß and the receptor c-Met. Five-year survival of patients with advanced disease (stage III and stage IV) was analyzed with the Kaplan-Meier method. RESULTS: Sixty patients had ovarian carcinomas, 23 borderline tumors, and 40 benign ovarian tumors. Patients with ovarian carcinomas had significantly higher preoperative HGF and CA 125 serum levels than patients with benign ovarian tumors, and borderline tumors. Patients with borderline tumors had significantly higher CA 125 values than benign cases. A combination of CA 125 and HGF increased the specificity in predicting carcinoma. We observed abundant HGFα, HGFß and c-Met expressions in all ovarian tumors. Patients with advanced disease and preoperative serum HGF values ≥2SD above reference value had a shorter disease-free survival than patients with advanced disease and serum HGF <2SD above reference value. CONCLUSIONS: HGF in serum is an indicator of ovarian carcinoma in women with a pelvic mass, and of a poor prognosis in advanced ovarian cancer.

Stathmin overexpression identifies high-risk patients and lymph node metastasis in endometrial cancer.

PURPOSE: Overexpression of the oncogen Stathmin has been linked to aggressive endometrial carcinoma and a potential for PI3Kinase inhibitors in this disease. We wanted to validate the prognostic value of Stathmin expression in a large prospective multicenter setting. As lymph node sampling is part of current surgical staging, we also aimed to test if Stathmin expression in endometrial curettage specimens could predict lymph node metastasis. EXPERIMENTAL DESIGN: A total of 1,076 endometrial cancer patients have been recruited from 10 centers to investigate the biological tumor marker Stathmin in relation to clinicopathologic variables, including lymph node status and survival. Stathmin immunohistochemical staining was carried out in 477 hysterectomy and 818 curettage specimens. RESULTS: Seventy-one percent of the patients (n = 763) were subjected to lymph node sampling, of which 12% had metastatic nodes (n = 94). Overexpression of Stathmin was detected in 37% (302 of 818) of the curettage and in 18% (84 of 477) of the hysterectomy specimens investigated. Stathmin overexpression in curettage and hysterectomy specimens were highly correlated and significantly associated with nonendometrioid histology, high grade, and aneuploidy. Stathmin analysis in preoperative curettage samples significantly correlated with, and was an independent predictor of, lymph node metastases. High Stathmin expression was associated with poor disease-specific survival (P ≤ 0.002) both in curettage and hysterectomy specimens. CONCLUSIONS: Stathmin immunohistochemical staining identifies endometrial carcinomas with lymph node metastases and poor survival. The value, as a predictive marker for response to PI3Kinase inhibition and as a tool to stratify patients for lymph node sampling in endometrial carcinomas, remains to be determined.

The effect of centralization of primary surgery on survival in ovarian cancer patients.

OBJECTIVE: To examine the effect of centralized surgery on overall survival in patients with ovarian cancer and, in particular, patients with advanced disease (stage III/IV). METHODS: In a historical prospective study design, patients referred from community hospitals to a teaching hospital for primary surgery during the 2-year period, 1995-1997, were included as cases. For each referred case, two controls, matched for International Federation of Gynecology and Obstetrics (FIGO) stage and age, were selected among patients who had had primary surgery at the referral hospitals (nonteaching) in the years, 1992-1995. Kaplan-Meier survival curves were computed and tested statistically by the log rank test. Cox proportional hazard model was applied for estimation of prognostic factors of survival. RESULTS: There was no difference in postoperative mortality for stage I/II patients by level of care (community hospitals versus teaching hospital). However, for advanced stage disease (III + IV), the controls had significantly shorter crude survival than patients who had been operated on at the teaching hospital (5-year survival: 4% versus 26%; median survival: 12 months versus 21 months) (P=.01). Multivariable analyses showed that completed chemotherapy and size of residual tumor after primary surgery were independent prognostic factors of survival. Patients optimally operated on at the teaching hospital had significantly lower risk of death compared with all other groups, independently of chemotherapy. This indicates that the extent of cytoreductive surgery and the overall management undertaken in the teaching hospital are significant predictors of improved survival. CONCLUSION: Centralization of primary ovarian cancer surgery in one health region in Norway has improved survival for patients with advanced disease. Patients with apparent advanced ovarian cancer should be referred to a subspecialty unit for primary surgery, and every effort should be made to attain as complete cytoreduction as possible.

Survival and prognostic factors in patients with ovarian cancer.

OBJECTIVE: To assess incidence during a 10-year study period and to identify and discuss clinical relevance for prognostic factors of survival within a cohort of Norwegian ovarian cancer patients. METHODS: Incidence and prognostic factors of survival within a population-based cohort of ovarian cancer patients from one health region in Norway were examined over the 10-year period 1987 through 1996. A total of 571 histologically verified cases of primary ovarian cancer originally registered either in the Cancer Registry of Norway or in the hospital's discharge registers were included in the study. Pearson chi(2) test was used in univariate analyses of cofactors by 5-year survival, and Kaplan-Meier survival curves were computed and tested statistically by the log rank test. A multivariable proportional hazard model (Cox) was applied to assess the prognostic significance of the different covariates. RESULTS: The incidence and crude 5-year survival remained stable over the 10-year study period. The standardized incidence rate for the time periods 1987-1991 and 1992-1996 was 11.9/100,000 and 12.5/100,000, respectively. The crude 5-year survival rate for the cohort was 39%, whereas median survival was 32 months. Cox multivariable regression analysis showed that the only independent significant prognostic factors were International Federation of Gynecology and Obstetrics stage (P <.001), size of residual tumor at the end of primary surgery (P <.001), and age at diagnosis (P <.01). Variables such as time period, histologic type and grade, treating hospital, comorbidity, or CA 125 were insignificant in predicting 5-year survival. CONCLUSION: The results underline the importance of improved surgical management of ovarian cancer, as residual tumor is the only prognostic factor achievable.

Completeness and accuracy of registration of ovarian cancer in the cancer registry of Norway.

Completeness of reporting and accuracy of the diagnosis of ovarian cancer from one health region in Norway to the Cancer Registry were examined. Data kept by the Cancer Registry were evaluated against discharge diagnosis data from all 8 hospitals in the health region during the period of 1987-1996. The assessment of the accuracy of the diagnosis recorded in the Cancer Registry was based on review of all medical records in the hospital setting and on slide review of all histologic diagnoses. The overall completeness of reporting ovarian cancer to the Cancer Registry was 99.6%. The organ specific completeness of registration of histologic verified ovarian cancer within the Cancer Registry was 95.3%; 0.9% was erroneously coded and 3.5% had their diagnosis changed to ovarian cancer at re-evaluation. Of all ovarian cancer cases registered at the Cancer Registry, 91% had a primary histologic diagnosis. Among 591 cases identified with a histologic diagnosis in the Cancer Registry, the accuracy of the diagnosis was estimated at 92%. Coding errors were found in 2% of these cases, while in 6% of the cases it was not possible to reproduce the original diagnosis of ovarian cancer at re-evaluation. In order to provide data of high quality for cancer surveillance a cancer registry needs several data providers, such as histopathologic laboratory reports and clinical reports. In addition, assessment of reported data through stringent quality assurance procedures within the registry are necessary for reaching a nearly 100% completeness of registration as found for ovarian cancer in the Cancer Registry of Norway.