Incidence of omental metastasis in uterine serous carcinoma: a systematic review and meta-analysis.

OBJECTIVES: Previous studies examining the incidence of omental metastasis in uterine serous carcinoma generally suffered from small sample size, retrospective observational design, and single-center setting. So far, there was no systematic review and meta-analysis available on this topic, we conducted this study to quantitatively synthesize the data relating to this topic. DESIGN: systematic review and meta-analysis. MATERIAL AND METHODS: PubMed, Embase, and Web of Science were searched up until August 15, 2020. Two reviewers independently performed study selection, data extraction, and quality assessment. I2 was employed to assess the heterogeneity among the included studies. Effect sizes along with 95% confidence intervals were calculated to analyze outcomes of interest. Funnel plots and the Egger test were used to detect the risk of publication bias. OUTCOME MEASURES: incidence of omental metastasis in uterine serous carcinoma. RESULTS: A total of 16 studies involving 1012 women with uterine serous carcinoma were included in this study. All the included studies were at low risk of bias, and the heterogeneity among them was low. The pooled incidence of overall omental metastasis, occult omental metastasis, and gross omental metastasis in uterine serous carcinoma were 18% (95% CI, 0.15-0.20), 6% (95% CI, 0.04-0.08), and 10% (95% CI, 0.08-0.13), respectively. CONCLUSIONS: Uterine serous carcinoma has a high tendency of omental metastasis. The main form of omentum involvement is gross metastasis. However, occult metastasis in the normal-looking omentum is also worthy of note.

Improved long-term survival of corpus cancer in Japan: A 40-year population-based analysis.

The incidence of uterine corpus cancer has been increasing globally due to increase in obesity. However, a detailed analysis of long-term epidemiological trends of corpus cancer in Japan, where obesity is relatively minimal, has not been conducted. In this retrospective, population-based study using the Osaka Cancer Registry, we analyzed 15 255 cases of corpus neoplasia registered between 1977 and 2016. We determined the age-standardized incidence, mortality, relative survival and conditional survival rates, and the treatment trends for corpus cancer over the last 40 years in Japan. The age-standardized incidence rate of corpus neoplasia increased sharply in 2000-2011 (APC = 9.9, 95% CI: 8.4-11.3), whereas the mortality rate trended to a much more modest increase (APC = 3.3, 95% CI: 2.7-3.8). Compared to 1977-2000, 10-year survival rates for post-2000 cases of localized and regional corpus cancers significantly improved (from 87.7% [95% CI: 85.8-89.4] to 94.2% [95% CI: 92.7-95.7] and from 47.5% [95% CI: 43.3-51.6] to 64.4% [95% CI: 61.0-67.6], respectively). This was largely associated with the significant increase in the percentage of localized and regional patients who received chemotherapy instead of radiation as an adjuvant therapy combined to surgery (P < .001 for both). We found that each histological type (endometrioid carcinoma, serous carcinoma, clear cell carcinoma and carcinosarcoma) has different characteristics of trend of age-standardized incidence rate, relative survival and distribution of extent of disease. In endometrioid carcinoma, the age-standardized incidence rate increased consistently after 1990, but the rate of increase was decreasing after 1997.

Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC).

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

The blood transcriptome prior to ovarian cancer diagnosis: A case-control study in the NOWAC postgenome cohort.

Epithelial ovarian cancer (EOC) has a 5-year relative survival of 50%, partly because markers of early-stage disease are not available in current clinical diagnostics. The aim of the present study was to investigate whether EOC is associated with transcriptional profiles in blood collected up to 7 years before diagnosis. For this, we used RNA-stabilized whole blood, which contains circulating immune cells, from a sample of EOC cases from the population-based Norwegian Women and Cancer (NOWAC) postgenome cohort. We explored case-control differences in gene expression in all EOC (66 case-control pairs), as well as associations between gene expression and metastatic EOC (56 pairs), serous EOC (45 pairs, 44 of which were metastatic), and interval from blood sample collection to diagnosis (≤3 or >3 years; 34 and 31 pairs, respectively). Lastly, we assessed differential expression of genes associated with EOC in published functional genomics studies that used blood samples collected from newly diagnosed women. After adjustment for multiple testing, this nested case-control study revealed no significant case-control differences in gene expression in all EOC (false discovery rate q>0.96). With the exception of a few probes, the log2 fold change values obtained in gene-wise linear models were below ±0.2. P-values were lowest in analyses of metastatic EOC (80% of which were serous EOC). No common transcriptional profile was indicated by interval to diagnosis; when comparing the 100 genes with the lowest p-values in gene-wise tests in samples collected ≤3 and >3 years before EOC diagnosis, no overlap in these genes was observed. Among 86 genes linked to ovarian cancer in previous publications, our data contained expression values for 42, and of these, tests of LIME1, GPR162, STAB1, and SKAP1, resulted in unadjusted p<0.05. Although limited by sample size, our findings indicated less variation in blood gene expression between women with similar tumor characteristics.

Serous endometrial intraepithelial carcinoma: A clinico-pathological study of 48 cases and its association with endometrial polyps - A tertiary care oncology centre experience.

BACKGROUND: Endometrial serous carcinoma (ESC) is an aggressive neoplasm wherein the recent studies have shown that it arises from its putative precursor namely the serous endometrial intraepithelial carcinoma (SEIC). SEIC usually arises in inactive/ atrophic endometrium but surprisingly is frequently associated endometrial polyps (EPs). The aim of this study was to assess the incidence of SEIC with or without invasion, its clinical behaviour and association with endometrial polyp. MATERIALS AND METHODS: After Institutional review board approval, a total of 205 samples (belonging to 120 patients); diagnosed as ESC from January 2009 to December 2015 were retrieved and reviewed for presence of in situ carcinoma and also for associated endometrial polyp. RESULTS: The mean age at diagnosis was 62.40 years with postmenopausal bleeding being the most common presenting symptom. The incidence of SEIC with or without invasive tumor was 40% (48/120). Of these 48 cases; 25 cases were associated with in-situ carcinoma arising in the EPs which amounted to 52% of the total cases. The overall three year survival and disease free survival in SEIC with or without invasion were 1.9% and 0.25%, indicating the aggressive nature of the disease. CONCLUSION: SEIC is a difficult histopathological diagnosis and one should carefully look for these lesion, especially in the EPs which are frequently associated with them. Extensive sampling of the EP will be helpful to pick up in-situ carcinoma arising in EP. SEIC is an aggressive disease on its own with a propensity to develop distant metastasis even in the absence of myometrial invasion and hence should be treated with optimum surgical staging and if indicated aggressive adjuvant treatment protocols.

Identification of Novel Fusion Transcripts in High Grade Serous Ovarian Cancer.

Fusion genes are structural chromosomal rearrangements resulting in the exchange of DNA sequences between genes. This results in the formation of a new combined gene. They have been implicated in carcinogenesis in a number of different cancers, though they have been understudied in high grade serous ovarian cancer. This study used high throughput tools to compare the transcriptome of high grade serous ovarian cancer and normal fallopian tubes in the interest of identifying unique fusion transcripts within each group. Indeed, we found that there were significantly more fusion transcripts in the cancer samples relative to the normal fallopian tubes. Following this, the role of fusion transcripts in chemo-response and overall survival was investigated. This led to the identification of fusion transcripts significantly associated with overall survival. Validation was performed with different analytical platforms and different algorithms to find fusion transcripts.

Incidence and survival of epithelial ovarian, fallopian tube, peritoneal, and undesignated abdominal/pelvic cancers in Sweden 1960-2014: A population-based cohort study.

BACKGROUND: Despite improved surgical and oncological treatment, ovarian cancer continues to be the most lethal of the gynecologic malignancies. We aimed to analyze survival trends in epithelial ovarian cancer with regard to age, tumor site, and morphology in Sweden 1960 to 2014. METHODS: A nationwide population-based study was conducted using data from the Swedish Cancer Registry on 46,350 women aged 18 or older with a diagnosis of epithelial ovarian, fallopian tube, peritoneal, or undesignated abdominal/pelvic cancer 1960 to 2014. Analyses of age-standardized incidence and relative survival (RS) were performed and time trends modelled according to age, tumor site, and morphology. RESULTS: Overall incidence of ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers declined since 1980. Median age at diagnosis increased. Serous carcinoma increased in incidence. RS at 1, 2 and 5 years from diagnosis improved since 1960, although not for the youngest and the oldest patients. Ten-year RS did not improve. The best RS was found for fallopian tube cancer and the worst RS for undesignated abdominal/pelvic cancer. Among the morphologic subgroups, endometrioid carcinoma had the best RS. CONCLUSIONS: Survival in epithelial ovarian, tubal, peritoneal, and undesignated abdominal/pelvic cancers in Sweden has improved over the last six decades. Advances in epithelial ovarian cancer treatment have extended life for the first 5 years from diagnosis but 10-year survival remains poor.

The Prevalence, Associated Factors for Lung Metastases Development and Prognosis in Ovarian Serous Cancer Based on SEER Database.

Ovarian carcinoma (OC) is one of the 3 most common gynecological malignancies, and the prognosis of patients with lung metastasis was the worst. SEER documented OC patients, diagnosed between 2010 and 2016, were included in the study. Univariable and multivariable logistic regression analyses were performed to identify associated factors for lung metastases (LM) development. Kaplan-Meier analysis was used to estimate the overall survival for OC patients with LM. A total of 10146 eligible serous ovarian cancer (SOC) patients were included, the prevalence of LM was 3.77% (N = 378). Patients with T4 stage (χ2 = 128.515; P = 0.000), N1 stage (χ2 = 49.536; P = 0.000), right laterality (χ2 = 18.756; P = 0.000) (compared with left side), undifferentiated grade (χ2 = 36.174; P = 0.000), bone metastasis (χ2 = 183.529); P = 0.000), brain metastasis (χ2 = 117.539; P = 0.000), liver metastasis (χ2 = 442.472; P = 0.000) had a larger probability of LM than other groups. Results showed that T3/N1 stage, bone metastases, liver metastases, chemotherapy, surgery were positively correlated with LM. Multivariable cox analysis showed that age, bone metastasis, no chemotherapy, no surgery were independent risk factors in SOC-LM patients. This study provided new research insights on the prevalent LM in patients with SOC. The factors associated with LM development and prognosis can be potentially used for LM early screening and professional care.

Recurrent BRCA1 Mutation, but no BRCA2 Mutation, in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing.

BACKGROUND: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. METHODS: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. RESULTS: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. CONCLUSION: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
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Expression of palladin is associated with disease progression in metastatic high-grade serous carcinoma.

OBJECTIVE: To analyse the expression and clinical role of the actin-associated molecule palladin in serous effusions. METHODS: PALLD mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction in 83 high-grade serous carcinoma (HGSC) effusions. Fifteen malignant mesothelioma (MM) effusions and 18 surgical HGSC specimens from the ovary were studied for comparative purposes. Palladin protein expression by immunohistochemistry was analysed in another series consisting of 261 HGSC effusions. RESULTS: PALLD mRNA was significantly overexpressed in HGSC compared to MM effusions (P < .001). Palladin expression by immunohistochemistry was found in HGSC cells in 106/261 (41%) effusions, most commonly focally (<5% of cells). PALLD expression was additionally higher in ovarian HGSC specimens compared to HGSC effusions (P < .001). However, immunohistochemistry showed only stromal expression of this protein in surgical specimens. PALLD mRNA expression in HGSC effusions was unrelated to clinicopathological parameters, chemotherapy response or survival. Palladin protein expression was higher in post-chemotherapy, mainly disease recurrence, specimens compared to chemo-naïve effusions tapped at diagnosis (P = .018), although it was unrelated to other clinicopathological parameters or survival. CONCLUSION: PALLD mRNA is overexpressed in HGSC compared to MM effusions, and its protein product is overexpressed in post-chemotherapy compared to pre-chemotherapy HGSC effusions, suggesting upregulation along tumour progression. The presence of this molecule in HGSC effusions, at the mRNA or the protein level, is unrelated to disease outcome.

Malignant peritoneal cytology and increased mortality risk in stage I non-endometrioid endometrial cancer.

OBJECTIVE: To examine the survival of women with stage I non-endometrioid endometrial cancer with malignant peritoneal cytology. METHODS: A retrospective observational cohort study was conducted to examine the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I serous, clear cell, carcinosarcoma, undifferentiated, and mixed endometrial cancer with known peritoneal cytology results at hysterectomy were examined (N = 4506). Propensity score inverse probability of treatment weighting was used to balance the measured covariates, and survival outcomes were assessed according to peritoneal cytology results. RESULTS: Malignant peritoneal cytology was reported in 401 (8.9%) women. In multivariable analysis, older age, serous histology, and large tumors were associated with an increased likelihood of malignant peritoneal cytology (all, P < 0.05). In a propensity score weighted model, malignant peritoneal cytology was associated with a nearly two-fold increase in all-cause mortality risk compared to negative peritoneal cytology (5-year rates, 63.4% versus 80.2%, hazard ratio 2.18, 95% confidence interval 1.78-2.66). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in old and young age groups, serous, clear cell, carcinosarcoma, and mixed histology groups, stage T1a disease, and staged and unstaged cases, but not for stage T1b disease. Difference in 5-year overall survival rates between the malignant and negative peritoneal cytology groups was particularly large among those with clear cell histology (24.0%), stage T1a disease (19.4%), aged >78 years (18.2%), and serous tumors (17.6%). CONCLUSION: Malignant peritoneal cytology can be prevalent in stage I non-endometrioid endometrial cancer. Our study suggests that malignant peritoneal cytology is a prognostic factor for decreased survival in stage I non-endometrioid endometrial cancer.

BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: A cohort study.

BACKGROUND: An association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit. Data from a large, prospective cohort will be informative. METHODS: Data on UK BRCA pathogenic variant carriers were interrogated for endometrial cancer diagnoses. Standardised incidence ratios (SIRs) were calculated in four distinct cohorts using national endometrial cancer rates; either from 1/1/1980 or age 20, prospectively from date of personal pathogenic variant report, date of family pathogenic variant report or date of risk-reducing salpingo-oophorectomy. Somatic BRCA sequencing of 15 serous endometrial cancers was performed to detect pathogenic variants. RESULTS: Fourteen cases of endometrial cancer were identified in 2609 women (1350 BRCA1 and 1259 BRCA2), of which two were prospectively diagnosed. No significant increase in either overall or serous-like endometrial cancer risk was identified in any of the cohorts examined (SIR = 1.70, 95% confidence interval = 0.74-3.33; no cases of serous endometrial cancer diagnosed). Results were unaffected by the BRCA gene affected, previous breast cancer or tamoxifen use. No BRCA pathogenic variants were detected in any of the serous endometrial cancers tested. CONCLUSIONS: Women with a BRCA pathogenic variant do not appear to have a significant increased risk of all-type or serous-like endometrial cancer compared with the general population. These data provide some reassurance that hysterectomy is unlikely to be of significant benefit if performed solely as a preventive measure.

The prevalence of occult ovarian cancer in the series of 155 consequently operated high risk asymptomatic patients - Slovenian population based study.

Background We assessed the prevalence, localization, type and outcome of occult cancer at risk-reducing salpingo-oophorectomy or salpingectomy (RRSO) in asymptomatic carriers of pathogenic or likely pathogenic BRCA1/2 variants and high-risk BRCA1/2 negative women. Patients and methods A retrospective analysis of all consecutive gynaecologic preventive surgeries from January 2009 to December 2015 was performed. Participants underwent genetic counselling and BRCA1/2 testing before the procedure. Data on clinical parameters, adjuvant treatment and follow-up were collected and analysed. Results One hundred and fifty-five RRSO were performed in 110 BRCA1, 35 BRCA2 carriers of pathogenic or likely pathogenic variants and 10 high-risk BRCA1/2 negative women, at the mean age of 48.3 years. Nine occult cancers (9/155, 5.8%) were identified; eight in BRCA1 positive women and one in high-risk BRCA1/2 negative woman. We identified four non-invasive serous intraepithelial tubal carcinomas (3 in BRCA1 carriers and 1 in a high-risk BRCA1/2 negative woman) and five invasive tubo-ovarian high grade serous cancers (all detected in BRCA1 carriers). Only one out of nine patients (11.1%) with occult cancer had a slightly elevated CA-125 value preoperatively. Conclusions A 5.8% prevalence of occult invasive and noninvasive tubo-ovarian serous cancer after RRSO was found in high risk asymptomatic and screen negative women. We conclude that RRSO should be performed in BRCA1/2 carriers and in high-risk BRCA1/2 negative women. Age of preventive gynaecologic surgery should be carefully planned, taking into account the completion of childbearing age and type of mutation. The results favour the tubal hypothesis of tubal origin of high grade serous ovarian and peritoneal cancer. Cytology result of peritoneal cavity washing was important for the decision making process in determining treatment. Cytology examination should be performed in all cases of RRSO. CA-125 assay did not prove to be an effective screening tool for early cancer detection in our patients.

Multifocal/diffuse pancreatic serous cystic neoplasms: Systematic review with a new case.

BACKGROUND/OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are common, among which 13%-23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. OBJECTIVE: This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. METHODS: A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. RESULTS: A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. CONCLUSION: Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.

A modern assessment of the surgical pathologic spread and nodal dissemination of endometrial cancer.

OBJECTIVE: To examine the risk of nodal metastases in a contemporary cohort of women based on pathologic risk factors including histology, depth of invasion, tumor grade, and lymphovascular space invasion. METHODS: Women with endometrial cancer who underwent hysterectomy from 2004 to 2016 who were registered in the National Cancer Database were analyzed. Patients were stratified by T stage: T1A (<50% myometrial invasion), T1B (>50% myometrial invasion) and T2 (cervical involvement). Lymph node metastases were assessed in relation to tumor T stage and grade, and further stratified by lymphovascular space invasion. RESULTS: We identified 161,960 patients. The rate of nodal metastases within the endometrioid histology cohort was 2.2% for T1A cancers, 12.8% for T1B cancers and 19.9% for T2 cancers. For stage TIA cancers, the percent of patients with positive nodes increased from 1.1% for grade 1 cancers, to 2.9% for grade 2 cancers to 4.8% for grade 3 cancers. The corresponding rates of nodal metastases for stage T1B cancers were 8.6%, 13.7%, and 16.9%, respectively. For T1A cancers without lymphovascular space invasion, nodal metastases ranged from 0.6% in those with grade 1 cancers to 3.0% for grade 3 cancers. The corresponding risk of nodal disease ranged from 11.8% to 13.9% for T1A cancers with lymphovascular space invasion. CONCLUSIONS: There was a sequential increase in the risk of lymph node metastases based on depth of uterine invasion, tumor grade, and the presence of lymphovascular space invasion. The overall rate of nodal metastasis is lower than reported in the original GOG 33.

Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study.

OBJECTIVE: To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. METHODS: We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. RESULTS: In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). CONCLUSION: Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.

Association between pelvic inflammatory disease, infertility, ectopic pregnancy and the development of ovarian serous borderline tumor, mucinous borderline tumor and low-grade serous carcinoma.

OBJECTIVE: Risk factors for ovarian borderline tumors and low-grade serous carcinoma (LGSC) are poorly understood. The aim of this study was to examine the association between infertility, pelvic inflammatory disease (PID), endometriosis, ectopic pregnancy, hysterectomy, tubal ligation and parity and the risk of serous borderline tumor (SBT), mucinous borderline tumor (MBT) and LGSC. METHODS: This was a population-based cohort study using linked administrative and hospital data. Participants were 441,382 women born between 1945 and 1975 who had been admitted to hospital in Western Australia between 1 January 1980 and 30 June 2014. We used Cox regression to estimate hazard ratios (HRs). RESULTS: We observed an increased rate of SBT associated with infertility, PID and ectopic pregnancy (HRs and 95% CIs were, respectively, 1.98 (1.20-3.26); 1.95 (1.22-3.10) and 2.44 (1.20-4.96)). We did not detect an association between any of the factors under study and the rate of MBT. A diagnosis of PID was associated with an increased rate of LGSC (HR 2.90, 95% CI 1.21-6.94). CONCLUSIONS: The association with PID supports the hypothesis that inflammatory processes within the upper gynaecological tract and/or peritoneum may predispose to the development of SBT and LGSC.

Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study.

Population-based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow-up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 women with a BOT (2,058 serous BOTs and 2,223 mucinous BOTs) in Denmark during 1978-2012. We computed standardized incidence ratios (SIRs) to compare the incidence of ovarian cancer among women with BOTs compared to general population rates. We found that a serous BOT was especially and strongly associated with subsequent serous ovarian cancer (SIR = 9.2; 95% CI: 6.8-12.2), and that a mucinous BOT was strongly related to mucinous ovarian cancer (SIR = 18.6; 95% CI: 10.8-29.8). The SIRs remained elevated ≥10 years after a serous BOT and up to 5-9 years after a mucinous BOT. The increased incidence of serous ovarian cancer in women with a serous BOT was mostly pronounced in women <50 years at the serous BOT diagnosis. In conclusion, women with a serous BOT experience long-term increased incidence of serous ovarian cancer, and women with a mucinous BOT have long-term elevated incidence of mucinous ovarian cancer compared to the general population. This is the first population-based study to show compelling evidence of the histo-specific increased risk of ovarian cancer following specific types of BOTs. Thus, these results are supportive of the hypothesis that BOTs may be precursor lesions to carcinomas of the corresponding histologic type.

Risk of epithelial ovarian cancer among women with benign ovarian tumors: a follow-up study.

PURPOSE: The importance of benign ovarian tumors as precursors or risk markers for ovarian cancer is not fully understood. Studies on the association between benign ovarian tumors and ovarian cancer have provided inconclusive results. We examined the overall and histological type-specific risk of ovarian cancer among 158,221 Danish women diagnosed with a benign ovarian tumor during 1978-2016. METHODS: The study cohort was linked to the Danish Cancer Register to identify all cases of epithelial ovarian cancer, and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. RESULTS: After excluding the first year of follow-up, women with benign ovarian tumors did not have an increased risk for overall epithelial ovarian cancer (SIR 1.02; 95% CI 0.93-1.11), as compared with women in the general population. However, we found an increased risk for mucinous ovarian cancer (SIR 2.06; 95% CI 1.67-2.52); both solid and cystic benign ovarian tumors were associated with an increased risk. The risk for mucinous ovarian cancer was increased irrespective of the age at benign ovarian tumors diagnosis and persisted for up to 20 years after the benign ovarian tumor diagnosis. No clear associations for other histological types of ovarian cancer were observed, except for an increased risk for serous ovarian cancer among women diagnosed with benign ovarian tumors at an young age. CONCLUSIONS: Benign ovarian tumors may be associated with long-term increased risk for mucinous ovarian cancer.

Low-grade serous ovarian carcinoma: A comprehensive literature review.

BACKGROUND: Low-grade serous ovarian carcinoma (LGSOC) is a unique entity with clinical and molecular characteristics distinct from high-grade serous ovarian carcinoma (HGSOC). To date the majority of research has focused on the more common HGSOC, with treatment recommendations often extrapolated to LGSOC. Women with LGSOC are typically diagnosed younger and have indolent and relatively chemoresistant disease. Recently there have been major research advances in LGSOC. AIMS: This systematic review describes the epidemiological, clinical and molecular characteristics of LGSOC, with advances in research and novel treatment options also discussed. MATERIALS AND METHODS: A 10-year comprehensive systematic review of peer-reviewed literature was conducted, with a total of 132 abstracts read, 89 articles reviewed and 49 included in this review. RESULTS: This review highlights the clinical and molecular features of LGSOC, current and traditional treatment options and areas of current research into targeted agents. CONCLUSIONS: Our growing knowledge about LGSOC as a distinct clinical and molecular entity from HGSOC has led to the investigation of more targeted and tailored therapies as their clinical course, optimal management and therapeutic targets differ. There is a need for ongoing collaborative research to provide better treatment options for these patients.