Ovarian Cancer In Denmark Research Articles

Survival in Elderly Ovarian Cancer Remains Challenging in the Nordic Countries.

Despite treatment having improved through intensive surgical procedures and chemotherapy-and more recently, targeted therapies-ovarian cancer is the most fatal female cancer. As such, we wanted to analyze age-specific survival trends for ovarian cancer in Denmark, Finland, Norway and Sweden over the past 50 years, with a special aim of comparing survival development between the age groups. We modelled survival data from the NORDCAN database for 1-, 5- and conditional 5/1-year relative (between years 1 and 5) survival for ovarian cancer from 1972 to 2021. Young patients had a 70% 5-year survival while the survival was only 30% for the oldest patients. Conditional survival showed that survival between years 1 and 5 did not improve for patients older than 60 years throughout the 50-year period, during which time the gaps between the youngest and the oldest patients widened. Improvement in 1-year survival was so large that it masked the modest development between years 1 and 5, resulting in a widening age disparity in 5-year survival. The current treatment practices, which appear increasingly effective for younger patients, have not helped remedy the large age differences in ovarian cancer survival. Early detection methods and therapeutic innovations are urgently needed, and aged patients need a special focus.

P-783 Fertility treatment and risk of ovarian cancer in a large nationwide cohort of 151,821 infertile Danish women

Abstract Study question Do use of fertility drugs increase the risk of ovarian cancer among infertile women Summary answer Use certain types of fertility drugs may modify the risk of ovarian cancer among infertile women, primarily for serous ovarian tumors and among parous women. What is known already Even though most previous studies on the association between fertility treatment and ovarian cancer have not been able to show a convincing association, some studies have found an increased risk of this malignancy among women undergoing fertility treatment. However, many of the previous studies have had methodological limitations including selection bias and potential confounding due to missing information of important factors, such as parity status and hormonal contraceptive use, small sample size as well as short- and incomplete follow-up time. Furthermore, only few studies have assessed the association between fertility treatment and ovarian cancer according to histological type. Study design, size, duration This retrospective register-based cohort study included virtually all 20-45 year old infertile women in Denmark between 1971 and 2017 as identified in the Danish Infertility Cohort. All women were followed from entry in the cohort (i.e. the date of first infertility diagnosis) to occurrence of ovarian cancer, any other cancer (except non-melanoma skin cancer), death, emigration, bilateral oophorectomy or end of follow-up (December 31, 2017), whichever occurred first. The median follow-up length was 10.3 years Participants/materials, setting, methods In total, 332 women were diagnosed with ovarian cancer during the follow-up period. Information on the use of specific fertility drugs (clomiphene citrate, gonadotropins, hCGs, GnRH receptor modulators and progesterone), ovarian cancer, covariates and vital status was obtained from the Danish Infertility Cohort and various Danish national registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% CIs for ovarian cancer overall and for serous ovarian tumors. Main results and the role of chance After adjustment for attained age (as the underlying time scale), calendar year of study entry, highest obtained level of education, maternal age at first childbirth, number of childbirths, hormonal contraceptive use as well as mutual adjustment for treatment with any other specific fertility drugs, ever use of hCG (HR 0.62, 95% CI 0.44-0.89) and GnRH receptor modulators (HR 0.63, 95% CI 0.40-1.00) were associated with a decreased risk of overall ovarian cancer. In contrast, ever use of gonadotropins (HR 1.43; 95% CI 0.91-2.24) and especially progesterone (HR 1.81; 95% CI 1.18-2.78) increased the risk of overall ovarian cancer. No marked association was observed for clomiphene citrate (HR 1.07, 95% CI 0.80-1.44)). The rates for serous ovarian cancer generally resembled those observed for overall ovarian cancer; however only the association for progesterone reached statistical significance (HR 2.89; 95% CI 1.67-4.99). The observed associations existed mainly among parous women and did not vary with time since first use of the fertility drug in question and no statistically significant associations were observed with cumulative dose of the specific fertility drugs. Limitations, reasons for caution The median age at the end of follow-up was only 42.5 years, which is markedly lower than the usual peak age for ovarian cancer in Denmark (mid 60s). Hence, we were not able to capture the true, potential long-term association between use of fertility drugs and ovarian cancer. Wider implications of the findings Use of certain specific types of fertility drugs in fertility treatment may modify the risk of ovarian cancer among subgroups of women. However, although this study is by far the largest to date, additional large epidemiological studies with longer follow-up time are needed to further clarify the observed associations. Trial registration number Not applicable.

Non-epithelial ovarian cancer in Denmark – Incidence and survival over nearly 40 years

ObjectiveTo examine trends in incidence and survival of non-epithelial ovarian cancer in Denmark over nearly 40 years, using nationwide, population-based cancer registry data. MethodsFrom 1978 to 2016, we identified the non-epithelial ovarian cancer cases among all ovarian malignancies in the Danish Cancer Registry. Age-specific incidence rates, age-standardized incidence rates, and average annual percentage change (AAPC) were estimated with 95% confidence intervals (CIs). Overall and 5-year relative survival analyses were conducted and supplemented with Cox regression to explore the effect of different characteristics on overall mortality. ResultsA total of 720 non-epithelial ovarian cancers were identified, corresponding to 3.4% of all ovarian malignancies. The majority of non-epithelial ovarian cancers were germ cell tumors (49.9%) and sex cord-stromal tumors (38.6%). The age-standardized incidence rate of germ cell tumors was stable over the study period, ranging between 0.33 and 0.39 per 100,000 woman-years. In contrast, the age-standardized incidence rate of sex cord-stromal tumors declined from 0.30 (1978–1987) to 0.09 (2008–2016) per 100,000 woman-years (AAPC = −5.15%; 95% CI: −7.29, −2.96). The 5-year relative survival of germ cell tumors and sex cord-stromal tumors was 94% and 79%, respectively, in the most recent period (2008–2011). Cox regression showed that overall mortality was associated with calendar year, age, and stage. ConclusionsThe incidence of germ cell tumors was stable over calendar time, whereas the incidence of sex cord-stromal tumors decreased significantly. Non-epithelial ovarian cancer overall mortality has decreased during the study period and this could not be explained by taking stage and age at diagnosis into account.

Risk factors for early death among ovarian cancer patients: a nationwide cohort study.

ObjectiveTo characterize ovarian cancer patients who die within 6 months of diagnosis and to identify prognostic factors for these early deaths.MethodsA nationwide cohort study covering ovarian cancer in Denmark in 2005–2016. Tumor and patient characteristics including comorbidity and socioeconomic factors were obtained from the comprehensive Danish national registers.ResultsA total of 5,570 patients were included in the study. Three months after ovarian cancer diagnosis 456 (8.2%) had died and 664 (11.9%) died within 6 months of diagnosis. Adjusted for age and comorbidity, patients who died early were admitted to hospital significantly more often in a 6-month period before the diagnosis (odds ratio [OR]=1.61 [1.29–2.00], and OR=1.47 [1.21–1.78]), for patients who died within 3 and 6 months respectively). Low educational level (OR=2.11), low income (OR=2.50) and singlehood (OR=1.90) were factors significantly associated with higher risk of early death. The discriminative ability of risk factors in identifying early death was assessed by cross-validated area under the receiver operating characteristic curve (AUC). The AUC was found to be 0.91 (0.88–0.93) and 0.90 (0.87–0.92) for death within 3 and 6 months, respectively.ConclusionsDespite several admissions to hospital, the ovarian cancer diagnosis is delayed for a subgroup of patients, who end up dying early, probably due to physical deterioration in the ineffective waiting time. Up to 90% of high-risk patients might be identified significantly earlier to improve the prognosis. The admittance of the patients having risk symptoms should include fast track investigation for ovarian cancer.

The influence of polypharmacy, potentially inappropriate medications, and drug interactions on treatment completion and prognosis in older patients with ovarian cancer

BackgroundOlder patients with cancer are at increased risk of exposure to polypharmacy (PP), potential drug interactions (PDIs), and Potentially inappropriate Medications (PIMs). Objectives of this study were to describe PP, PIMs, and PDIs, and to analyse the associations with completion of 1st line chemotherapy and prognosis in ovarian cancer (OC) patients. MethodsRegistry-based study including a 10-year national cohort of patients diagnosed with epithelial OC in Denmark. Descriptive statistics, multivariate logistic regression analyses, Kaplan-Meier, and Cox regression analyses were performed to analyse the data. ResultsA total of 3795 patients were included and described. Further analyses were performed on 2219 patients registered with a date of surgery and combination chemotherapy with platinum and a taxane or platinum monotherapy. Exposure to ≥2 PDIs was associated with not completing chemotherapy, odds ratio (OR) 2.27 (1.18–4.37). Major and extensive PP were associated with increased mortality at 0–6 months after diagnosis, HR 3.15(1.59–6.22) and 5.43(2.34–12.6), respectively. PIMs were associated with increased mortality from six months after diagnosis. At 6–12 months: hazard ratio (HR) 1.50(1.06–2.11) and 2.38(1.25–4.50) with 1–2 and ≥ 3 PIMs, respectively. At 12 months: HR 2.08(1.31–3.29) with ≥3 PIMs. Age was not associated with treatment completion. ConclusionsDrug use influences treatment completion and prognosis in OC patients. A thorough review of patients' medications aiming to minimize the number of PIMs and PDIs might improve the course of these patients' disease.

Healthcare utilisation in general practice and hospitals in the year preceding a diagnosis of cancer recurrence or second primary cancer: a population-based register study

BackgroundThe organisation of cancer follow-up is under scrutiny in many countries, and general practice is suggested to become more involved. A central focus is timely detection of recurring previous cancer and new second primary cancer. More knowledge on the patient pathway before cancer recurrence and second primary cancer is warranted to ensure the best possible organisation of follow-up. We aimed to describe the healthcare utilisation in the year preceding a diagnosis of cancer recurrence or second primary cancer.MethodsThis nationwide register study comprises patients diagnosed with bladder, breast, colorectal, endometrial, lung, malignant melanoma and ovarian cancer in Denmark in 2008–2016. The frequency of healthcare contacts during the 12 months preceding a cancer recurrence or second primary cancer was estimated and compared to the frequency of cancer survivors in cancer remission. The main analyses were stratified on sex and healthcare setting. Furthermore, two sub-analyses were stratified on 1) sex, healthcare setting and age group and on 2) sex, healthcare setting and comorbidity status.ResultsThe study population consisted of 7832 patients with recurrence and 2703 patients with second primary cancer. On average, the patients were in contact with general practice one time per month in the 12th month preceding a new cancer diagnosis (recurrence or second primary cancer). Increasing contact rates were seen from 7 months before diagnosis in general practice and from 12 months before diagnosis in hospitals. This pattern was more pronounced in patients with cancer recurrence, younger patients and patients with no comorbidity. For instance, the contact rate ratios for hospital contacts in non-comorbid women with recurrence demonstrated 30% more contacts in the 12th month before recurrence and 127% more contacts in the 2nd month before recurrence.ConclusionsThe results show that cancer survivors are already seen in general practice on a regular basis. The increasing contact rates before a diagnosis of cancer recurrence or second primary cancer indicate that a window of opportunity exists for more timely diagnosis; this is seen in both general practice and in hospitals. Thus, cancer survivors may benefit from improvements in the organisation of cancer follow-up.

Tissue immune response in epithelial ovarian carcinoma.

2625 Background: Epithelial ovarian cancer (EOC) is a highly malignant disease with a fatal outcome for most patients. During recent years immunological mechanisms have proven important in relation to the treatment and prognosis of cancer, but within EOC the knowledge is still sparse. Understanding the importance of immune markers to the prognosis of ovarian cancer is essential for the future treatment of EOC. The aim of the present study was to investigate the prognostic impact of intratumoral PDL-1 expression, T cells, neutrophil granulocytes (NG) and Natural Killer (NK) cells in a population based cohort. Methods: All patients diagnosed with ovarian cancer in Denmark in 2005 were included in the study. Immunohistochemical staining was performed on tumor tissue from 412 patients. Antibodies for PD-L1, T cells (CD8), NG (CD66b), and NK cells (CD57) were used. Cell densities were analyzed using a digital image analysis method. The primary endpoint was overall survival (OS). Results: In high grade serous carcinoma (HGSC) the median OS in patients with a high level of tumor infiltrating T cells was 37 vs 25 months in patients with a low level(p = 0.0008). Multivariate analysis showed a hazard ratio (HR) of 0.72 (p = 0.020). The median OS in patients with a high level of tumor infiltrating NK cells was 45 vs 29 months in patients with a low level (p = 0.0310). Multivariate analysis showed a HR of 0.67 (p = 0.041). PD-L1 and NG had no statistically significant impact on OS. Only T cells showed prognostic significance across histological subtypes with a HR of 0.72 (p = 0.007) in favor of a high density of T cells. Conclusions: The present population based study demonstrated prognostic importance of tumor infiltrating T cells and NK cells in HGSC. Neither PD-L1 nor NG held prognostic significance.

Use of prescription drugs among women diagnosed with epithelial ovarian cancer in Denmark.

Epithelial ovarian cancer patients often suffer from chronic diseases requiring drug treatment. We assessed temporal patterns of drug use among women with ovarian cancer. We identified all postmenopausal women with epithelial ovarian cancer in Denmark 2005-2012 and a comparison cohort of age-matched women without cancer. We calculated rates of new drug treatment and total drug use and examined use of new and prevalent drugs before and after diagnosis. Analyses were stratified by histological type and stage of epithelial ovarian cancer. We identified 2742 patients. The rate of new drug treatment increased from 3 to 5months before diagnosis and peaked in the first month after diagnosis at 99 new types of drug therapy per 100 individuals (mainly antiemetics, proton-pump inhibitors, hypnotics, and opioids). Although declining, the rate of new drug use remained substantially higher among epithelial ovarian cancer patients than among controls throughout the 3-year postdiagnosis follow-up period. The number of prevalent drugs increased slightly from a median of 4 drugs (interquartile range 2-7) before diagnosis to 5 drugs (interquartile range 2-8) shortly after the diagnosis. The use of preventive drugs decreased only slightly after diagnosis. In stratified analyses, we found limited variation according to histological type, whereas patterns were slightly more pronounced among women with nonlocalized disease compared with localized disease. Drug use among postmenopausal women with epithelial ovarian cancer was substantial and varied considerably in relation to the time of cancer diagnosis, although only limited changes were seen in the use of preventive medicines.

Preterm delivery is associated with an increased risk of epithelial ovarian cancer among parous women.

Epithelial ovarian cancer is a fatal disease of largely unknown etiology. Higher parity is associated with reduced risk of ovarian cancer. However, among parous women, the impact of pregnancy-related factors on risk is not well understood. This population-based case-control study included all parous women with epithelial ovarian cancer in Denmark, Finland, Norway and Sweden during 1967-2013 (n = 10,957) and up to 10 matched controls (n = 107,864). We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for pregnancy-related factors and ovarian cancer risk by histological subtype. Preterm delivery was associated with an increased risk [pregnancy length (last pregnancy) ≤30 vs. 39-41 weeks, OR 1.33 (95% CI 1.06-1.67), adjusted for number of births]; the OR increased as pregnancy length decreased (p for trend < 0.001). Older age at first and last birth was associated with a decreased risk [first birth: 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.70-0.83); last birth 30-39 vs. <25 years: adjusted OR 0.76 (95% CI 0.71-0.82)]. Increasing number of births was protective [≥4 births vs. 1; OR 0.63 (95% CI 0.59-0.68)] for all subtypes, most pronounced for clear-cell tumors [OR 0.30, (95% CI 0.21-0.44), pheterogeneity < 0.001]. No associations were observed for multiple pregnancies, preeclampsia or offspring size. In conclusion, in addition to high parity, full-term pregnancies and pregnancies at older ages were associated with decreased risk of ovarian cancer. Our findings favor the cell clearance hypothesis, i.e. a recent pregnancy provides protection by clearing of precancerous cells from the epithelium of the ovary/fallopian tubes, mediated by placental or ovarian hormones.

Low-dose aspirin use and the risk of ovarian cancer in Denmark

A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low-dose aspirin and the risk of ovarian cancer. We identified all patients in the Danish Cancer Registry aged 30-84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000-2011. Each patient was sex- and age-matched to 15 population controls using risk-set sampling. Prescription use, comorbidity, reproductive history, and demographic characteristics data were obtained from nationwide registries. The use of low-dose (75-150 mg) aspirin was defined according to the dose as well as the duration and consistency of use. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. For 4103 ovarian cancer cases and 58 706 population controls, the adjusted OR for epithelial ovarian cancer associated with ever use (≥2 prescriptions) of low-dose aspirin was 0.94 (95% CI 0.85-1.05). ORs for epithelial ovarian cancer were lower with the use of 150 mg aspirin tablets (OR = 0.82; 95% CI 0.68-0.99) and with long-term use (≥5 years) of low-dose aspirin (OR = 0.77; 95% CI 0.55-1.08). Continuous long-term use of low-dose aspirin, defined as close consecutive prescriptions, was associated with a further reduction in OR (0.56; 95% CI 0.32-0.97). For histological types of epithelial ovarian cancer, the strongest inverse associations with low-dose aspirin use were seen for mucinous and endometrioid tumours. This nationwide case-control study indicates that low-dose aspirin use may be associated with a reduced risk of epithelial ovarian cancer.

Survival of ovarian cancer patients in Denmark: Excess mortality risk analysis of five‐year relative survival in the period 1978–2002

To explore the variation in ovarian cancer survival in Denmark in the period 1978-2002 in relation to time since diagnosis, age at diagnosis, period of diagnosis, stage and histology. Register-based cohort study. Denmark in the period 1978-2002. Using the nationwide Danish Cancer Registry, we included a total of 13,035 women diagnosed with invasive ovarian cancer in Denmark in the period 1978-2002. Excess mortality risk analyses of five-year relative survival of ovarian cancer patients diagnosed in the period 1978-2002 with follow-up through 2006 were made based on data from the NORDCAN database. Five-year relative survival, excess mortality rate (ER) and relative excess mortality risk (RER) after an ovarian cancer diagnosis. The relative survival of Danish ovarian cancer patients slightly increased in the period 1978-2002. The ERs were highest in the first year following diagnosis, in particular in the first three months, and among older patients, even for localized and regional tumors. The pattern remained the same when stratified by histological subgroup. Older age at diagnosis, earlier period of diagnosis, more advanced stage at diagnosis and being diagnosed with undifferentiated carcinoma predicted poorer survival among Danish ovarian cancer patients diagnosed in the period 1978-2002. The survival of Danish ovarian cancer patients has slightly increased from 1978 through 2002. Despite this, the mortality rate of ovarian cancer in Denmark is still higher than in the other Nordic countries. Explanations for these differences are still to be identified.

Organisation and quality of primary surgical intervention for ovarian cancer in Denmark

The positive effect on survival of maximal primary cytoreductive surgery for ovarian cancer is well established, and the highest rates of optimal cytoreduction are achieved by gynecological oncologists. Danish women have not only one of the highest incidences of ovarian cancer, but also the highest mortality rate. From 1981 to 1989, the overall Danish optimal debulking rate was 25% in patients with stage III and IV tumors. The primary aim of the present study was, therefore, to evaluate the organisation and quality of current primary surgical intervention for ovarian cancer in Denmark. All women diagnosed with epithelial ovarian carcinoma (DC56) were identified through the Danish National Patient Registry during the study period from 1 July 2002 to 31 December 2003, and surgical notes and histopathology were evaluated by a board of 7 gynecological-oncologists, focusing on maximal cytoreduction. For stage III, the nationwide optimal debulking rate was 39%, significantly higher in the major hospitals (49%) versus other hospitals (29%) (p<0.005). In 19% of cases, there was insufficient information to evaluate debulking from the surgical notes, significantly less at the major hospitals versus other hospitals (12 versus 25%, p<0.001). In Denmark, the quality of the primary surgical intervention for ovarian cancer is not optimal. In order to enhance survival, compliance with international guidelines and improved registration of the surgical procedures in clinical databases are mandatory.

Moving towards a new year

Moving towards a new year

Trends in the incidence and mortality of ovarian cancer in Denmark 1978–2002. Comparison with other Nordic countries

The Nordic countries are well-known high-incidence areas of ovarian cancer, but even within the Nordic countries, differences exist. Focus in this descriptive epidemiological study is to assess developments in incidence and mortality of ovarian cancer in Denmark 1978-2002 and to make a comparison with the development in the other Nordic countries. The results are based on data from the nationwide Danish Cancer Registry as well as the other Nordic Cancer Registries. A total of 14,325 cases of ovarian cancer were registered from 1978 to 2002 in Denmark. In this period, the age-standardized incidence decreased slightly from 14.3 (1978-1982) to 13.3 per 100,000 woman-years (1998-2002). The histology-specific time trends showed a tendency towards more specified histological diagnoses. Iceland had the highest age-adjusted ovarian cancer incidence in the Nordic countries, whereas Denmark had the highest mortality rate. In the entire period, the Danish mortality rate declined from 10.8 (1978-1982) to 9.0 per 100,000 woman-years (1998-1999). Only 19% of ovarian cancers in Denmark from 1978 to 2002 were localized at the time of diagnosis, while 30% had distant metastases. Older women were more likely to have advanced disease at diagnosis. The Danish distribution of stage at diagnosis seems less favorable compared to results from other countries. The Danish incidence of ovarian cancer seemed to decrease slightly from 1978 to 2002. Even though the mortality rate of ovarian cancer also declined, Denmark had the highest mortality rate of ovarian cancer in the world. Part of it may be explained by a less-favorable distribution of stage at diagnosis.

The results of treatment of epithelial ovarian cancer after centralisation of primary surgery. Results from North Jutland, Denmark

Objective. The study was performed to evaluate the results of treatment of ovarian carcinoma after the introduction of centralised primary surgery in the County of North Jutland, Denmark. Method. Prospective study of consecutive cases of ovarian cancer undergoing primary surgical treatment at the Gynecologic Oncologic Center after the introduction of centralised primary surgery. Results of treatment recorded up to the date of last examination or death. Results. From 1999 to 2002, 107 patients with primary epithelial ovarian cancer underwent primary surgery at the Gynecologic Oncologic Center, Aalborg. This corresponds to 95.5% of patients with invasive carcinoma in the County of North Jutland. All patients with Stage I to Stage IIIB disease had a complete, macroscopically radical cytoreduction performed. In patients with Stage III and IV invasive tumors, the optimal debulking rate was 79.5%, and, in Stage IIIC and IV, the optimal debulking rate was 78.2%. Intra-operative and post-operative complications were generally few. Post-operative death, defined as death within 30 days after surgery, was observed in 4 cases (3.7%). After primary surgery, platinum-based chemotherapy was given in most cases. For Stage I to IV invasive cancer, the median survival was 46 months. In patients with Stage IIIC and IV disease, the median survival was 32 months. In optimally debulked Stage IIIC and IV disease, the median survival was 41 months. Conclusions. The results indicate a survival benefit after introduction of centralised primary surgery. Compared to existing national and regional data on survival in ovarian cancer, the results indicate an increase in median survival for all stages of approximately 15 months. Centralisation of primary surgery to centres with the necessary expertise may be the most significant way to increase survival in ovarian cancer in Denmark.

Trends in the incidence and mortality of ovarian cancer in Denmark 1978-2002. Comparison with other Nordic countries

Trends in the incidence and mortality of ovarian cancer in Denmark 1978-2002. Comparison with other Nordic countries

The significance of differences in prognostic value of quantitative pathologic features in FIGO stage III and IV serous adenocarcinoma of the ovary between a group of Danish patients and other groups.

Previous studies have shown DNA cytometric, morphometric and stereologic features to be strong prognosticators in advanced ovarian cancer. However, in one Danish study a new stereologic parameter, the volume-weighted mean nuclear volume ( nuv), was not of prognostic significance. In that study, sampling was performed in the whole tumor section, contrary to that in other studies where measurements were performed in the worst differentiated area (the measurement area). The aim of the present investigation was, therefore, to confirm or reject the hypothesis that random estimates of nuclear {ovbar|nu}v over the whole tumor, rather than in the measurement area, are the cause for the lack of prognostic value in the Danish patients. Additionally, the mitotic activity index (MAI), volume percentage of epithelium (VPE), mean nuclear area (MNA) and standard deviation of the nuclear area (SDNA), which have proved to be of strong prognostic significance in advanced ovarian cancer, were assessed in the measurement area. The MAI, VPE, MNA, SDNA and nuclear {ovbar|nu}v were well reproducible, but prognostically not significant. This study thus excludes differences in microscopic sampling as an explanation for the contrasting findings in the Danish study and other ones. Possible remaining explanations are: (i) differences in sampling at the macroscopic level; (ii) fixation differences; (iii) patient selection bias; and (iv) geographic differences in the degree of malignancy of advanced ovarian cancer in Denmark and the Netherlands. As to the latter, in comparison with two Dutch studies the Danish ovarian cancers in this series had residual disease <2 cm (33% vs 50%) less often, were less often well differentiated (4% vs 19%), and less often had favorable morphometric characteristics (6% vs 15%). Further studies are required to analyze whether other Danish patient groups with advanced ovarian cancers differ from the Dutch.