Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Sertoli-Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort.

INTRODUCTION: Sertoli-Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli-Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants. METHODS: In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli-Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan-Meier analysis followed by a log rank test for differences between variables RESULTS: 41 women with Sertoli-Leydig cell tumors were identified. Median age was 41 years (range 6-79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I-II) and 0% in advanced tumor stages (stages III-IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli-Leydig cell tumor. CONCLUSION: The prognosis for women with Sertoli-Leydig cell tumors with localized disease is excellent. Women with advanced stages (III-IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli-Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.

Real-life data on treatment and outcomes in advanced ovarian cancer: An observational, multinational cohort study (RESPONSE trial).

BACKGROUND: This study aimed to describe the treatment strategies and outcomes for women with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer (OC). METHODS: This observational study collected real-world medical record data from eight Western countries on the diagnostic workup, clinical outcomes, and treatment of adult women with newly diagnosed advanced (Stage III-IV) high-grade serous or endometrioid OC. Patients were selected backward in time from April 1, 2018 (the index date), with a target of 120 patients set per country, followed for ≥20 months. RESULTS: Of the 1119 women included, 66.9% had Stage III disease, 11.7% had a deleterious BRCA mutation, and 26.6% received bevacizumab; 40.8% and 39.3% underwent primary debulking surgery (PDS) and interval debulking surgery (IDS), respectively. Of the patients who underwent PDS, 55.5% had no visible residual disease (VRD); 63.9% of the IDS patients had no VRD. According to physician-assessed responses (at the first assessment after diagnosis and treatment), 53.2% of the total population had a complete response and 25.7% had a partial response to first-line chemotherapy after surgery. After ≥20 months of follow-up, 32.9% of the patients were disease-free, 46.4% had progressive disease, and 20.6% had died. Bevacizumab use had a significant positive effect on overall survival (hazard ratio [HR], 0.62; 95% CI, 0.42-0.91; p = .01). A deleterious BRCA status had a significant positive effect on progression-free survival (HR, 0.60; 95% CI, 0.41-0.84; p < .01). CONCLUSIONS: Women with advanced high-grade serous or endometrioid OC have a poor prognosis. Bevacizumab use and a deleterious BRCA status were found to improve survival in this real-world population. LAY SUMMARY: Patients with advanced (Stage III or IV) ovarian cancer (OC) have a poor prognosis. The standard treatment options of surgery and chemotherapy extend life beyond diagnosis for 5 years or more in only approximately 45% of patients. This study was aimed at describing the standard of care in eight Western countries and estimating how many patients who are diagnosed with high-grade serous or endometrioid OC could potentially be eligible for first-line poly(adenosine diphosphate ribose) polymerase inhibitor (PARPi) maintenance therapy. The results highlight the poor prognosis for these patients and suggest that a significant proportion (79%) would potentially be eligible for first-line PARPi maintenance treatment.

Preoperative predictors of inguinal lymph node metastases in vulvar cancer - A nationwide study.

BACKGROUND: A combination of tumour size, differentiation grade and location may identify a group of vulvar squamous cell cancer (VSCC) patients with a very low risk of inguinal lymph node metastasis. We aim to examine these findings in a large national cohort of VSCC patients. MATERIALS AND METHODS: Population based prospective data on VSCC patients treated with vulvectomy and primary groin surgery was obtained from the Danish Gynaecological Cancer Database. Univariate chi-square and multivariate logistic regression analysis were used. Statistical tests were 2-sided. P-values of <0.05 were considered statistically significant. RESULTS: In all, 388 VSCC patients were identified. Of these 264 (63.3%) were node negative and 121 (36.7%) node positive. Increasing tumour size (diameter ≤ 2 cm vs. > 2 to 4 cm), grade (1 vs. 2-3) and location of tumour to clitoris were all associated with a significantly increased risk of inguinal lymph node metastasis OR 2.81(95% CI 1.52-5.20), OR 3.19 (95% CI 1.77-5.74) and OR 2.74 (95% CI 1.56-5.20), respectively. Previous vulvar disease was not associated with lymph node metastasis. No lymph node metastasis was demonstrated in patients with grade 1 tumours, tumour size less than 2 cm and located outside the clitoris area (n = 51). CONCLUSIONS: VSCC patients with grade 1 tumours, ≤ 2 cm and without clitoral involvement have a very low risk of inguinal lymph node metastasis. These patients may be spared inguinal lymph node staging to decrease operating time and peri- and postoperative morbidity in the future. However, studies validating our findings are needed.

Assessment of recurrence rate and risk factors of relapse in stage in IA vulvar carcinoma.

OBJECTIVE: To evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. MATERIAL AND METHODS: Population-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011-2017. A central pathology review was performed on tumors from women with recurrent disease. RESULTS: 62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6). Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. CONCLUSION: Pathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC. Resection margins <8 mm and tumor size were associated with relapse of the disease.

Incidence, treatment, and survival trends in older versus younger women with epithelial ovarian cancer from 2005 to 2018: A nationwide Danish study.

OBJECTIVE: To examine clinical trends in Denmark for younger and older epithelial ovarian cancer (EOC) patients, focusing on incidence, treatment, and survival changes. METHODS: We included a nationwide cohort diagnosed with EOC from 2005 to 2018. We described age-standardized incidence, surgical patterns, residual disease trends, and cancer-specific survival stratified by age (<70 and ≥ 70 years), stage, and period (2005-09, 2010-13, 2014-18). RESULTS: We included 7522 patients. The incidence decreased from 16.3 (2005) to 11.4 (2018) per 100,000 woman-years, driven by the younger cohort. While the proportion of patients with stage IIIC-IV disease undergoing primary debulking surgery (PDS) decreased, the proportion of patients having interval debulking surgery (IDS) and no debulking surgery increased significantly. In 2014-18, 36% and 24% had PDS for younger and older patients, respectively, compared to 72% and 62% in 2005-09. In both age cohorts, the proportion of patients debulked to no residual disease increased significantly among patients with stage IIIC-IV and in the total cohort. Two-year cancer-specific survival increased from 75% (2005-09) to 84% (2014-18) for younger patients and from 53% to 66% for older patients. After adjusting for potential confounders, age ≥ 70 was associated with a 1.4-fold increased risk of cancer-specific death (95% confidence interval: 1.2,1.5). CONCLUSIONS: The proportion of patients with advanced EOC not undergoing PDS or IDS increased significantly. During the same period, patients debulked to no residual disease, and cancer-specific survival increased. However, a survival gap in favor of the younger patients remains after adjusting for potential confounders.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer.

INTRODUCTION: It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer. MATERIAL AND METHODS: We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses. RESULTS: In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS. CONCLUSIONS: Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Toward PET/MRI as one-stop shop for radiotherapy planning in cervical cancer patients.

BACKGROUND: Radiotherapy (RT) planning for cervical cancer patients entails the acquisition of both Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Further, molecular imaging by Positron Emission Tomography (PET) could contribute to target volume delineation as well as treatment response monitoring. The objective of this study was to investigate the feasibility of a PET/MRI-only RT planning workflow of patients with cervical cancer. This includes attenuation correction (AC) of MRI hardware and dedicated positioning equipment as well as evaluating MRI-derived synthetic CT (sCT) of the pelvic region for positioning verification and dose calculation to enable a PET/MRI-only setup. MATERIAL AND METHODS: 16 patients underwent PET/MRI using a dedicated RT setup after the routine CT (or PET/CT), including eight pilot patients and eight cervical cancer patients who were subsequently referred for RT. Data from 18 patients with gynecological cancer were added for training a deep convolutional neural network to generate sCT from Dixon MRI. The mean absolute difference between the dose distributions calculated on sCT and a reference CT was measured in the RT target volume and organs at risk. PET AC by sCT and a reference CT were compared in the tumor volume. RESULTS: All patients completed the examination. sCT was inferred for each patient in less than 5 s. The dosimetric analysis of the sCT-based dose planning showed a mean absolute error (MAE) of 0.17 ± 0.12 Gy inside the planning target volumes (PTV). PET images reconstructed with sCT and CT had no significant difference in quantification for all patients. CONCLUSIONS: These results suggest that multiparametric PET/MRI can be successfully integrated as a one-stop-shop in the RT workflow of patients with cervical cancer.

Recurrence and survival rates in node negative patients after sentinel node biopsy for early-stage vulva cancer - A nationwide study.

OBJECTIVE: The sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients. METHODS: Nationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included. RESULTS: The SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1-83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%. CONCLUSIONS: This is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.

Exploring international differences in ovarian cancer treatment: a comparison of clinical practice guidelines and patterns of care.

INTRODUCTION: The International Cancer Benchmarking Partnership demonstrated international differences in ovarian cancer survival, particularly for women aged 65-74 with advanced disease. These findings suggest differences in treatment could be contributing to survival disparities. OBJECTIVE: To compare clinical practice guidelines and patterns of care across seven high-income countries. METHODS: A comparison of guidelines was performed and validated by a clinical working group. To explore clinical practice, a patterns of care survey was developed. A questionnaire regarding management and potential health system-related barriers to providing treatment was emailed to gynecological specialists. Guideline and survey results were crudely compared with 3-year survival by 'distant' stage using Spearman's rho. RESULTS: Twenty-seven guidelines were compared, and 119 clinicians completed the survey. Guideline-related measures varied between countries but did not correlate with survival internationally. Guidelines were consistent for surgical recommendations of either primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery with the aim of complete cytoreduction. Reported patterns of surgical care varied internationally, including for rates of primary versus interval debulking, extensive/'ultra-radical' surgery, and perceived barriers to optimal cytoreduction. Comparison showed that willingness to undertake extensive surgery correlated with survival across countries (rs=0.94, p=0.017). For systemic/radiation therapies, guideline differences were more pronounced, particularly for bevacizumab and PARP (poly (ADP-ribose) polymerase) inhibitors. Reported health system-related barriers also varied internationally and included a lack of adequate hospital staffing and treatment monitoring via local and national audits. DISCUSSION: Findings suggest international variations in ovarian cancer treatment. Characteristics relating to countries with higher stage-specific survival included higher reported rates of primary surgery; willingness to undertake extensive/ultra-radical procedures; greater access to high-cost drugs; and auditing.

Impact of residual disease on overall survival in women with Federation of Gynecology and Obstetrics stage IIIB-IIIC vs stage IV epithelial ovarian cancer after primary surgery.

INTRODUCTION: The objective of this study was to determine the impact of intra-abdominal residual disease size, type (carcinomatosis, tumor mass or both), and location (upper/lower abdominal/both) on overall survival in women with Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IIIC vs stage IV epithelial ovarian cancer who underwent primary debulking surgery. MATERIAL AND METHODS: Altogether 2092 women diagnosed with advanced epithelial ovarian cancer undergoing primary debulking surgery in Denmark during 2005-2016 were identified in the Danish Gynecological Cancer Database. The impact of residual disease size, type, and location were evaluated using univariate and multivariate analyses. RESULTS: Complete cytoreduction (residual disease = 0) was achieved in 47.3% and 38.4% of women with stage IIIB-IIIC and IV epithelial ovarian cancer, respectively. A benefit in overall survival was observed in women with residual disease = 0 compared with women with residual disease, and among women with residual disease ≤1 cm compared with residual disease >2 cm in both stages IIIB-IIIC and stage IV in multivariate analyses. Multivariate analyses showed an inferior overall survival for women with both residual carcinomatosis and residual tumor mass compared with those with residual tumor mass or residual carcinomatosis only for stage IIIB-IIIC and IV, and an inferior overall survival for women with residual disease located in both the upper and lower abdomen compared with residual disease in the upper abdomen only in stages IIIB-IIIC. CONCLUSIONS: Our results confirm the positive prognostic impact of both complete cytoreduction and residual disease ≤1 cm in stages IIIB-IIIC as well as stage IV epithelial ovarian cancer. Women with stage IV do benefit from cytoreductive surgery and should be considered for primary debulking surgery, if residual disease = 0 can initially be expected.

Assessing Patient-reported Quality of Life Outcomes in Vulva Cancer Patients: A Systematic Literature Review.

OBJECTIVES: Vulva cancer (VC) treatment carries a high risk of severe late effects that may have a negative impact on quality of life (QoL). Patient-reported outcome measures (PROMs) are increasingly used when evaluating disease- and treatment-specific effects. However, the adequacy of measures used to assess sequelae and QoL in VC remains unclear. The aims of the present study were to evaluate disease- and treatment-related effects as measured by PROMs in VC patients and to identify available VC-specific PROMs. METHODS/MATERIALS: A systematic literature search from 1990 to 2016 was performed. The inclusion criterion was report of disease- and treatment-related effects in VC patients using PROMs in the assessment. Methodological and reporting quality was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. This systematic review was performed as part of phase 1 of the development of a European Organisation for Research and Treatment of Cancer QoL questionnaire for VC patients. RESULTS: The search revealed 2299 relevant hits, with 11 articles extracted including a total of 535 women with VC; no randomized controlled trials were identified. The selected studies exhibited great heterogeneity in terms of PROMs use. Twenty-one different instruments assessed QoL. Most of the questionnaires were generic. Different issues (sexuality, lymphedema, body image, urinary and bowel function, vulva-specific symptoms) were reported as potentially important, but the results were not systematically collected. Only one VC-specific questionnaire was identified but did not allow for assessment and reporting on a scale level. CONCLUSIONS: Vulva cancer treatment is associated with considerable morbidity deteriorating QoL. To date, there is no validated PROM available that provides adequate coverage of VC-related issues. The study confirms the need for a VC-specific QoL instrument with sensitive scales that allows for broad cross-cultural application for use in clinical trials.

Demographic, Clinical, and Prognostic Factors of Ovarian Clear Cell Adenocarcinomas According to Endometriosis Status.

OBJECTIVES: Women with endometriosis carry an increased risk for ovarian clear cell adenocarcinomas (CCCs). Clear cell adenocarcinoma may develop from endometriosis lesions. Few studies have compared clinical and prognostic factors and overall survival in patients diagnosed as having CCC according to endometriosis status. METHODS: Population-based prospectively collected data on CCC with coexisting pelvic (including ovarian; n = 80) and ovarian (n = 46) endometriosis or without endometriosis (n = 95) were obtained through the Danish Gynecological Cancer Database. χ Test, independent-samples t test, logistic regression, Kaplan-Meier test, and Cox regression were used. Statistical tests were 2 sided. P values less than 0.05 were considered statistically significant. RESULTS: Patients with CCC and pelvic or ovarian endometriosis were significantly younger than CCC patients without endometriosis, and a higher proportion of them were nulliparous (28% and 31% vs 17% (P = 0.07 and P = 0.09). Accordingly, a significantly higher proportion of women without endometriosis had given birth to more than 1 child. Interestingly, a significantly higher proportion of patients with ovarian endometriosis had pure CCCs (97.8% vs 82.1%; P = 0.001) as compared with patients without endometriosis. Overall survival was poorer among CCC patients with concomitant ovarian endometriosis (hazard ratio, 2.56 [95% confidence interval, 1.29-5.02], in the multivariate analysis. CONCLUSIONS: Age at CCC diagnosis and parity as well as histology differ between CCC patients with and without concomitant endometriosis. Furthermore, CCC patients with concomitant ovarian endometriosis have a poorer prognosis compared with endometriosis-negative CCC patients. These differences warrant further research to determine whether CCCs with and without concomitant endometriosis develop through distinct pathogenic pathways.

Classification of Ovarian Cancer Surgery Facilitates Treatment Decisions in a Gynecological Multidisciplinary Team.

OBJECTIVE: Proper planning of intervention and care of ovarian cancer surgery is of outmost importance and involves a wide range of personnel at the departments involved. The aim of this study is to evaluate the introduction of an ovarian surgery classification (COVA) system for facilitating multidisciplinary team (MDT) decisions. MATERIALS AND METHODS: Four hundred eighteen women diagnosed with ovarian cancers (n = 351) or borderline tumors (n = 66) were selected for primary debulking surgery from January 2008 to July 2013. At an MDT meeting, women were allocated into 3 groups named "pre-COVA" 1 to 3 classifying the expected extent of the primary surgery and need for postoperative care. On the basis of the operative procedures performed, women were allocated into 1 of the 3 corresponding COVA 1 to 3 groups. The outcome measure was the predictive value of the pre-COVA score compared with the actual COVA performed. RESULTS: The MDT meeting allocated 213 women (51%) to pre-COVA 1, 136 (33%) to pre-COVA 2, and 52 (12%) to pre-COVA 3. At the end of surgery, 168 (40%) were classified as COVA 1, 158 (38%) were classified as COVA 2, and 28 (7%) were classified as COVA 3. Traced individually, 212 (51%) patients were correctly preclassified at the MDT meeting and distributed into 110 (52%) COVA 1, 71 (52%) COVA 2, and 17 (32%) COVA 3. Analyzing the subgroup of patients with cancer, 164 (47%) were correctly preclassified. Regarding the International Federation of Gynecology and Obstetrics (FIGO) stages, the pre-COVA classification predicted the actual COVA group in 79 (49%) FIGO stages I to IIIB and in 85 (45%) FIGO stages IIIC to IV. CONCLUSIONS: The COVA classification system is a simple and useful tool in the MDT setting where specialists make treatment decisions based on advanced technology. The use of pre-COVA classification facilitates well-organized patient care-relevant procedures to be undertaken. Pre-COVA accurately predicts the final COVA in 51% classified women.

Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review.

INTRODUCTION: The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle-Ottawa Scale. RESULTS: Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre- or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), premenopausal status at endometriosis diagnosis, solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer. CONCLUSIONS: A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, postmenopausal status at endometriosis diagnosis, larger size of endometrioma (>9 cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made.

A novel index for preoperative, non-invasive prediction of macro-radical primary surgery in patients with stage IIIC-IV ovarian cancer-a part of the Danish prospective pelvic mass study.

The purpose of this study was to develop a novel index for preoperative, non-invasive prediction of complete primary cytoreduction in patients with FIGO stage IIIC-IV epithelial ovarian cancer. Prospectively collected clinical data was registered in the Danish Gynecologic Cancer Database. Blood samples were collected within 14 days of surgery and stored by the Danish CancerBiobank. Serum human epididymis protein 4 (HE4), serum cancer antigen 125 (CA125), age, performance status, and presence/absence of ascites at ultrasonography were evaluated individually and combined to predict complete tumor removal. One hundred fifty patients with advanced epithelial ovarian cancer were treated with primary debulking surgery (PDS). Complete PDS was achieved in 41 cases (27 %). The receiver operating characteristic curves demonstrated an area under the curve of 0.785 for HE4, 0.678 for CA125, and 0.688 for age. The multivariate model (Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index), consisting of HE4, age, and performance status, demonstrated an AUC of 0.853. According to the Danish indicator level, macro-radical PDS should be achieved in 60 % of patients admitted to primary surgery (positive predictive value of 60 %), resulting in a negative predictive value of 87.5 %, sensitivity of 68.3 %, specificity of 83.5 %, and cutoff of 0.63 for the CONATS index. Non-invasive prediction of complete PDS is possible with the CONATS index. The CONATS index is meant as a supplement to the standard preoperative evaluation of each patient. Evaluation of the CONATS index combined with radiological and/or laparoscopic findings may improve the assessment of the optimal treatment strategy in patients with advanced epithelial ovarian cancer.

Demographic Clinical and Prognostic Factors of Primary Ovarian Adenocarcinomas of Serous and Clear Cell Histology-A Comparative Study.

OBJECTIVE: To compare clinical demographic and prognostic factors as well as overall survival in a nationwide cohort of patients diagnosed with ovarian clear cell carcinoma (oCCC) and high grade ovarian serous adenocarcinoma (oSAC) during 2005 to 2013. MATERIALS AND METHODS: Population-based prospectively collected data on oCCC (n = 179) and oSAC (n = 2363) cases were obtained from the Danish Gynecological Cancer Database. χ, Fischer or Wilcoxon-Mann-Whitney, multivariate logistic regression, univariate Kaplan-Meier, and multivariate Cox regression tests were used. Statistical tests were 2-sided. P values less than 0.05 were considered statistically significant. RESULTS: The oCCC cases were significantly younger than oSAC cases. An inverse association between ever smoking and oCCC as compared to oSAC was observed and a significantly higher proportion of oCCC was found to be nulliparous (odds ratio, 0.62; 95% confidence interval, 0.37-0.92).Although more oSAC than oCCC cases diagnosed in stage III or IV were referred to neoadjuvant chemotherapy, a higher proportion of oCCC achieved complete cytoreduction at primary debulking surgery and/or had lymphadenectomy performed; overall survival were poorer among oCCC than oSAC cases in analyses restricted to stages III and IV (odds ratio, 1.87; 95% confidence interval, 1.35-2.61), whereas no difference between early stage oCCC and oSAC was observed. CONCLUSIONS: The study confirms that demographic features and risk factors differ between oCCC and oSAC cases. Furthermore, our findings confirm that advanced stages of oCCC have a poorer prognosis compared with oSAC probably because of the resistance toward adjuvant chemotherapy. The observed differences highlight the need for subtype-specific research and individualized treatment within ovarian cancer.

Serous ovarian, fallopian tube and primary peritoneal cancers: a common disease or separate entities - a systematic review.

OBJECTIVE: The aim of this systematic review is to analyze data on risk factors, epidemiology, clinicopathology and molecular biology from studies comparing primary peritoneal cancer, fallopian tube cancer and ovarian cancer of serous histology, in order to achieve a greater understanding of whether or not these disorders should be considered as separate entities. METHODS: A systematic literature search was conducted in PubMed and MEDLINE. Case-control studies comparing primary serous peritoneal or fallopian tube carcinomas with primary serous ovarian carcinomas or a control group were included. RESULTS: Twenty-eight studies were found eligible. Primary peritoneal cancer patients were older, had higher parity, were more often obese and had poorer survival compared to ovarian cancer patients. Differences in protein expression patterns of Her2/neu, estrogen and progestin receptors and frequency of loss of heterozygosity differed between primary peritoneal cancer and primary ovarian cancer patients. No major differences were found between primary fallopian tube cancer and primary ovarian cancer. The proportion of serous tubal intraepithelial carcinomas (STIC) was lower in primary peritoneal cancer and primary ovarian cancer compared to primary fallopian tube cancer. CONCLUSION: Except from differences in the proportion of STIC only few differences between primary fallopian tube cancer and primary ovarian cancer have been found. In contrast, observed differences in risk factor profile, clinicopathologic and prognostic factors, as well as in the molecular patterns, indicate that peritoneal cancer and ovarian cancer may be linked to different carcinogenic pathways.