Trends in ovarian, fallopian tube, and primary peritoneal cancer incidence, mortality, and survival: A 15-year population-based analysis.

OBJECTIVE: To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin. METHODS: We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint 4.9.1.0 was used to characterize log-linear time trends. RESULTS: The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC -1.2%, p < 0.001), including that of high-grade (2006-2019: APC -1.2%, p < 0.05) and low-grade (2003-2019: APC -2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers. CONCLUSION: There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum.

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.

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.

Patterns and predictors of cancer-related fatigue in ovarian and endometrial cancers: 1-year longitudinal study.

BACKGROUND: Fatigue is a common and distressing symptom for patients with gynecologic cancers. Few studies have empirically examined whether it spontaneously resolves. This study was aimed at identifying longitudinal patterns of fatigue and predictors of clinically significant fatigue 1 year after treatment completion. METHODS: This was a prospective cohort study of women with newly diagnosed ovarian (n = 81) or endometrial cancer (n = 181) that did not progress or recur within 1 year of treatment completion. Symptoms of fatigue, depression, and anxiety were assessed after surgery and 6 and 12 months after treatment completion with the Fatigue Assessment Scale and the Hospital Anxiety and Depression Scale. Patients' fatigue scores over time were classified (scores of 22-50, clinically significant; scores of 10-21, not clinically significant). Logistic regression models were fit to examine associations between fatigue and patient characteristics. RESULTS: Among 262 participants, 48% reported clinically significant fatigue after surgery. One year later, 39% reported fatigue. There were 6 patterns over time: always low (37%), always high (25%), high then resolves (18%), new onset (10%), fluctuating (6%), and incidental (5%). Patients with fatigue after surgery were more likely to report fatigue at 12 months in comparison with others (odds ratio [OR], 6.08; 95% confidence interval [CI], 2.82-13.11; P < .001). Patients with depressive symptoms also had higher odds of fatigue (OR, 3.36; 95% CI, 1.08-10.65; P = .039), although only one-third of fatigued patients reported depressive symptoms. CONCLUSION: Nearly half of women with gynecologic cancers had clinically significant fatigue after surgery, whereas 44% and 39% had fatigue 6 months and 1 year later; this suggests that spontaneous regression of symptoms is relatively rare. Women who reported fatigue, depressive symptoms, or 2 or more medical comorbidities had higher odds of reporting fatigue 1 year later. Future studies should test scalable interventions to improve fatigue in women with gynecologic cancers.

Inherited mutations in fallopian tube, ovarian and primary peritoneal carcinoma: Changes in diagnoses and mutational frequency over 20 years.

OBJECTIVES: Women with fallopian tube carcinoma (FTC) are reported to have a higher frequency of inherited BRCA mutations than those with ovarian carcinoma (OC) or primary peritoneal carcinoma (PPC). We hypothesized that routine serial sectioning of fallopian tubes would increase the proportion of cases designated as FTC and change the frequency of inherited mutations between carcinoma types. METHODS: Eight hundred and sixty-seven women diagnosed from 1998 to 2018 were enrolled at diagnosis into an institutional tissue bank. Germline DNA, available from 700 women with FTC (N = 124), OC (N = 511) and PPC (N = 65), was assessed using targeted capture and massively parallel sequencing for mutations in ovarian carcinoma susceptibility genes. Cases were divided between those prior to routine serial sectioning (1998-2008) and after (2009-2019), and the frequency of FTC and inherited mutations was assessed. RESULTS: The proportion of carcinomas attributed as FTC after 2009 was 28% (128/465), significantly higher than before 2009 [5% (21/402), p < .0001, OR 6.9, 95% CI 4.3-11.2], with subsequent decreases in OC and PPC. In the sequenced group, overall inherited mutation frequency in FTC (24/124, 19%), OC (106/511, 21%, p = .42), and PPC (16/65, 25%, p = .25) were similar. Germline mutation rates in FTC were lower after 2009,16/107 cases (15%), compared to 8/17 cases (47.1%) before 2009 (p = .005, OR 0.20, 95% CI 0.06-0.64). CONCLUSIONS: The prevalence of inherited mutations is similar in FTC compared to OC or PPC when using modern pathological assignment. Complete serial sectioning of fallopian tubes has significantly increased the diagnosis of FTC, and subsequently decreased the frequency of inherited mutations within this group.

Oncologic outcomes in patients undergoing maximal or optimal cytoreductive surgery for Stage 3C serous ovarian, tubal or peritoneal carcinomas.

The aim of this study was to evaluate overall survival (OS) and disease-free survival (DFS) of patients with Stage 3C serous ovarian, tubal and peritoneal carcinomas. A retrospective analysis of 111 patients who underwent maximal or optimal cytoreductive surgery was performed. Patients were divided into three groups as ovarian cancer (n = 47), tubal cancer (n = 24) and peritoneal cancer (n = 40). Median follow-up was 30 months. There was no significant difference in DFS and OS among the groups. Complete cytoreduction was an independent prognostic factor for DFS in all groups (HR 2.3, 95% CI 1.14-4.93; p=.020). Positive peritoneal cytology (HR 2.2, 95% CI 1.02-4.78; p=.044), and retroperitoneal lymph node involvement (HR 2.3, 95% CI1.11-4.89; p=.025) were independent risk factors for decreased OS, and extended cytoreduction (HR 2.7, 95% CI 1.05-6.99; p=.039) were independent risk factors for increased OS. In conclusion, these malignancies should be considered a single entity during treatment.IMPACT STATEMENTWhat is already known on this subject? Epithelial ovarian cancer is the second most common gynaecological cancer in women worldwide. There are different histological types including ovarian, tubal and peritoneal carcinomas in which malignant cells form in the tissue covering the ovary or lining the fallopian tube of peritoneum. Recent data have supported the view that these malignancies should be considered a single entity and should be treated the same way.What the results of this study add? In the present study, we evaluated overall survival and disease-free survival of patients with Stage 3C ovarian, tubal and peritoneal cancer undergoing maximal or optimal cytoreductive surgery. We found similar oncologic outcomes in all patient groups. To the best of our knowledge, this is the first study to compare oncologic outcomes of these similar and often confused malignancies in the literature. We, therefore, believe that the present study provides additional information to the body of knowledge on this topic.What the implications are of these findings for clinical practice and/or further research? This study is important, as it indicates similar oncologic outcomes in patients undergoing maximal or optimal cytoreductive surgery for Stage 3C ovarian, tubal and peritoneal cancer. Based on these findings, clinicians should keep in mind that these malignancies should be considered a single clinical entity and be treated the same way. We believe that our study would pave the way for further studies regarding this subject.

Retrospective study of a 16 year cohort of BRCA1 and BRCA2 carriers presenting for RRSO: Prevalence of invasive and in-situ carcinoma, with follow-up.

OBJECTIVES: Carriers of BRCA1 and BRCA2 mutations are at increased risk of high grade serous carcinoma and are therefore offered risk-reducing salpingo-oophorectomy (RRSO) by 40-45 years. Most of these carcinomas are believed to arise in the fallopian tube from serous tubal intraepithelial carcinoma (STIC). We conducted a retrospective study on the prevalence of high grade serous carcinoma and STIC in BRCA1/2 carriers presenting for RRSO, and their follow-up. METHODS: Consecutive BRCA1/2 carriers presenting for an RRSO at Erasmus MC (2000-2016) were studied. SEE-FIM pathology protocol was followed from 2010 onwards. For the cases with carcinoma and/or STIC, the histology was reviewed and immunohistochemistry (p53 & MIB-1) was performed. Next Generation Targeted Sequencing (NGTS) for TP53 mutation was used to establish clonality in 2 cases. RESULTS: Of the 527 included patients, 68% were BRCA1, 31.6% were BRCA2, and 0.4% carried both mutations. The prevalence of high grade serous carcinoma was 2.3% (12/527); 59% of these were of tubal origin. High grade serous carcinoma was more common in patients operated on after the recommended age (p = 0.03). Isolated STIC was present in 0.8% (4/527). Two BRCA1 carriers with isolated STIC at RRSO developed peritoneal serous carcinoma >7 years later. Identical TP53 mutations in the peritoneal serous carcinoma and the preceding STIC established their clonal origin. CONCLUSIONS: High grade serous carcinoma is more common in BRCA1/2 carriers presenting for RRSO after the recommended age, and is more often of tubal origin. Longer follow up of patients with STIC at RRSO should be considered.

Development and validation of a risk-calculator for adverse perioperative outcomes for women with ovarian cancer.

BACKGROUND: Primary cytoreduction followed by platinum-based chemotherapy is the primary treatment for advanced ovarian cancer. However, neoadjuvant chemotherapy followed by interval debulking is an alternative option, particularly in those who may be poor surgical candidates. OBJECTIVE: The objective of this study was to determine factors associated with short-term, significant perioperative morbidity and mortality for women undergoing surgery for ovarian cancer and to create a nomogram to predict the risk of adverse perioperative outcomes. STUDY DESIGN: We used the National Surgical Quality Improvement Program database to identify women with ovarian, fallopian tube, or primary peritoneal cancer who underwent surgery from 2011 to 2015. Demographic factors, clinical characteristics, comorbidity, functional status, and the extent of surgery were used to predict the risk of severe perioperative complications or death using multivariable models. Multiple imputation methods were employed for missing data. A nomogram was developed based on the final model. The discrimination ability of the model was assessed with a calibration plot and discrimination concordance index. RESULTS: We identified a total of 7029 patients. Overall, 5.8% of patients experienced a Clavien-Dindo IV complication, 9.8% of patients were readmitted, 3.0% of patients required a reoperation, and 0.9% of patients died within 30 days. Among the baseline variables assessed, increasing age, emergent surgery, ascites, bleeding disorder, low albumin, higher American Society of Anesthesiology classification score, and a higher extended procedure score were associated with serious perioperative morbidity or mortality. Of these factors, performance of ≥3 cytoreductive procedures (adjusted odds ratio 4.53, 95% confidence interval 3.01-6.82), American Society of Anesthesiology classification score ≥ class 4 (adjusted odds ratio 2.89, 95% confidence interval 1.17-7.14), bleeding disorder (adjusted odds ratio 2.73, 95% confidence interval 1.82-4.10), and age ≥80 years (adjusted odds ratio 2.46, 95% confidence interval 1.66-3.63) were most strongly associated with risk of an event. The final nomogram included the above variables and had an internal discrimination concordance index of 0.71, with accurate predictions in an internal validation set, indicating a 71% correct identification of patients across all possible pairs. CONCLUSION: Women undergoing surgery for ovarian cancer are at significant risk for the occurrence of adverse perioperative outcomes. Using readily identifiable characteristics, this nomogram can predict adverse outcomes.

Second primary cancer after primary peritoneal, epithelial ovarian, and fallopian tubal cancer: a retrospective study.

BACKGROUND: In this retrospective study, data from patients listed in the Korea Central Cancer Registry during 1993-2014 were analysed, to investigate the incidence and survival of second primary cancers (SPCs) after a diagnosis of primary peritoneal, epithelial ovarian, and fallopian tubal (POFT) cancer. METHODS: The standardised incidence ratio (SIR) and survival outcomes of patients with SPCs among POFT cancer survivors were analysed. RESULTS: Among 20,738 POFT cancer survivors, 798 (3.84%) developed SPCs, at an average interval of 5.50 years. SPC risk in POFT survivors (SIR, 1.29) was higher compared to the general population. The most high-risk type of SPC was leukaemia (3.07) followed by the lung and bronchus (1.80), colon (1.58), rectum and rectosigmoid junction (1.42), thyroid (1.34), and breast (1.26). In women aged < 60 years, cancer of the breast (1.30), ascending colon (2.26), and transverse colon (4.07) as SPCs increased. Up to 10 years after POFT cancer treatment, leukaemia risk increased, especially in those < 60 years, with serous histology, and with distant stage, which required aggressive chemotherapy. The median overall survival time was 12.8 years and 14.3 years in women with POFT cancer and SPCs, respectively. Thyroid and breast cancers were favourable prognostic markers among SPCs. CONCLUSIONS: The overall SPC risk increases in POFT cancer survivors, especially in those < 60 years. The cancer risk of breast and the proximal colon increase based on hereditary predisposition, while leukaemia likely develops from aggressive treatment. The median overall survival is favourable in POFT cancer survivors with SPCs.

Trends in the incidence of serous fallopian tube, ovarian, and peritoneal cancer in the US.

OBJECTIVE: To identify the trends in incidence of serous fallopian tube, ovarian, and peritoneal epithelial cancers in the United States. METHODS: Data was obtained from United States Cancer Statistics (USCS) from 2001 to 2014. All incidences are per 100,000 women. Analyses were performed using SEER*Stat and Joinpoint regression programs. RESULTS: Of the 146,470 patients with serous cancers, 9381 (6.4%) were fallopian tube, 121,418 (82.9%) were ovarian, and 15,671 (10.7%) were primary peritoneal. The study period was divided from 2001 to 2005, 2006-2010, and 2011-2014, and there was an increase in fallopian tube incidence from 0.19 to 0.35 to 0.63, with a corresponding decrease in ovarian incidence from 5.31 to 5.08 to 4.86. There was no significant change in peritoneal cancers from 0.64 to 0.69 to 0.62. The age-specific peak incidence of fallopian tube cancer was younger at age 70-74, compared to ovarian and peritoneal cancer at age 75-79. Further, the incidence of serous fallopian tube cancer was highest in Whites at 0.42, compared to Blacks at 0.24, Hispanics at 0.27, and Asians at 0.28. CONCLUSION: From 2001 to 2014, the diagnosis of serous fallopian tube cancer increased fourfold with a corresponding decrease in ovarian cancer. The peak incidence of tubal cancer was 70-74years with an increased incidence in Whites.

Surgical Findings and Outcomes in Premenopausal Breast Cancer Patients Undergoing Oophorectomy: A Multicenter Review From the Society of Gynecologic Surgeons Fellows Pelvic Research Network.

STUDY OBJECTIVE: To describe the procedures performed, intra-abdominal findings, and surgical pathology in a cohort of women with premenopausal breast cancer who underwent oopherectomy. DESIGN: Multicenter retrospective chart review (Canadian Task Force classification II-3). SETTING: Nine US academic medical centers participating in the Fellows' Pelvic Research Network (FPRN). PATIENTS: One hundred twenty-seven women with premenopausal breast cancer undergoing oophorectomy between January 2013 and March 2016. INTERVENTION: Surgical castration. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 45.8 years. Fourteen patients (11%) carried a BRCA mutations, and 22 (17%) carried another germline or acquired mutation, including multiple variants of uncertain significance. There was wide variation in surgical approach. Sixty-five patients (51%) underwent pelvic washings, and 43 (35%) underwent concurrent hysterectomy. Other concomitant procedures included midurethral sling placement, appendectomy, and hysteroscopy. Three patients experienced complications (transfusion, wound cellulitis, and vaginal cuff dehiscence). Thirteen patients (10%) had ovarian pathology detected on analysis of the surgical specimen, including metastatic tumor, serous cystadenomas, endometriomas, and Brenner tumor. Eight patients (6%) had Fallopian tube pathology, including 3 serous tubal intraepithelial cancers. Among the 44 uterine specimens, 1 endometrial adenocarcinoma and 1 multifocal endometrial intraepithelial neoplasia were noted. Regarding the entire study population, the number of patients meeting our study criteria and seen by gynecologic surgeons in the FPRN for oophorectomy increased by nearly 400% from 2013 to 2015. CONCLUSION: Since publication of the Suppression of Ovarian Function Trial data, bilateral oophorectomy has been recommended for some women with premenopausal breast cancer to facilitate breast cancer treatment with aromatase inhibitors. These women may be at elevated risk for occult abdominal pathology compared with the general population. Gynecologic surgeons often perform castration oophorectomy in patients with breast cancer as an increasing number of oncologists are using aromatase inhibitors to treat premenopausal breast cancer. Our data suggest that other abdominal/pelvic cancers, precancerous conditions, and previously unrecognized metastatic disease are not uncommon findings in this patient population. Gynecologists serving this patient population may consider a careful abdominal survey, pelvic washings, endometrial sampling, and serial sectioning of fallopian tube specimens for a thorough evaluation.

Frequency of "incidental" serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: A six-year study.

Objective The purpose of this study was to determine the prevalence of incidentally discovered serous tubal intraepithelial carcinoma in women without a genetic risk for or history of high grade serous carcinoma (HGSC) in the gynecologic tract. METHODS: All pathology reports at our institution that included bilateral salpingectomies from January 2006-December 2011 were examined in women >50years old in which the entire tube or the distal one-third was examined histologically with the complete (proximal and distal fallopian tube) or modified (distal one third of the tube) SEE-FIM protocol. Cases were divided into: Group 1, a history of or known risk factors (BRCA1 or BRCA2 mutations) for HGSC and Group 2, those without these attributes for whom a STIC would be unexpected (incidental). Women undergoing unspecified "risk-reducing" procedures were included in Group 1. RESULTS: Of 4051 identified total, 2268 had complete examination of the distal fallopian tube and were age 50 or above. Of these, 1747 were in group 2. Two STICs were identified (0.1%), one associated with a grade 2 endometrial endometrioid adenocarcinoma and one with a low-grade ovarian serous carcinoma in the setting of a serous borderline tumor. CONCLUSIONS: Incidental STICs in women over age 50 are uncommon. However, the significance of lesser tubal atypias (0.3% in this study), risk of STIC in women with no epithelial pathology and the risk imposed by coexisting endometrioid neoplasia are unclear and require further study.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

STUDY OBJECTIVE: To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. DESIGN: A prospective study (Canadian Task Force classification II-1). SETTING: A gynecologic oncology referral center. PATIENTS: Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). INTERVENTIONS: Minimally invasive risk-reduction surgery. MEASUREMENTS AND MAIN RESULTS: Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). CONCLUSION: Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery.

Impact of levonorgestrel-releasing intrauterine system use on the cancer risk of the ovary and fallopian tube.

BACKGROUND: Levonorgestrel-releasing intrauterine system (LNG-IUS) is used for contraception and heavy menstrual bleeding. A long-term hormone therapy can modify the risk of gynecologic cancers. Little is known about the impact of LNG-IUS use on the risk for invasive and borderline ovarian tumor subtypes or for primary fallopian tube carcinoma. We examined the associations of LNG-IUS use with these tumors. MATERIAL AND METHODS: We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 years who had used LNG-IUS for menorrhagia in 1994-2007, and from the Finnish Cancer Registry ovarian cancers and primary fallopian tube carcinomas diagnosed before the age of 55 and by the end of 2013. RESULTS: A total of 77 invasive ovarian cancers and seven primary fallopian tube carcinoma cases were diagnosed in a cohort of 93 843 LNG-IUS users during the follow-up of 1 083 126 women-years. The LNG-IUS users had decreased risk for both invasive ovarian cancer [standardized incidence ratio (SIR) 0.59, 95% confidence interval (CI) 0.47-0.73] and for borderline ovarian tumors (SIR 0.76, 95% CI 0.57-0.99) as compared to the background population. The risk of primary fallopian tube carcinoma was not increased (SIR 1.22, 95% CI 0.49-2.50). Decreased risks for mucinous (SIR 0.49, 95% CI 0.24-0.87), endometrioid (SIR 0.55, 95% CI 0.28-0.98), and serous ovarian carcinomas (SIR 0.75, 95% CI 0.55-0.99) were seen in LNG-IUS users. CONCLUSIONS: LNG-IUS use associated with decreased risk for both invasive and borderline ovarian tumors. The incidence of primary fallopian tube carcinoma did not significantly differ between LNG-IUS users and the background population.

Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer: Population-Based Cohort Analysis of English National Cancer Registration Data.

OBJECTIVE: International studies show lower survival rates in the United Kingdom than other countries with comparable health care systems. We report on factors associated with excess mortality in the first year after diagnosis of primary invasive epithelial ovarian, tubal, and primary peritoneal cancer. METHODS: Routinely collected national data were used for patients diagnosed in England in 2008 to 2010. A multivariate Poisson model was used to model excess mortality in 3 periods covering the first year after diagnosis, adjusting for various factors including age at diagnosis, route to diagnosis, tumor stage, tumor morphology, and treatment received. RESULTS: Of 14,827 women diagnosed as having ovarian cancer, 5296 (36%) died in the first year, with 1673 deaths in the first month after diagnosis. Age older than 70 years, diagnosis after an emergency presentation or by an unknown route, and unspecified or unclassified epithelial morphologies were strongly and independently associated with excess mortality in the first year after diagnosis. Of the 2100 (14%) women who fulfilled all 3 criteria, 1553 (74%) did not receive any treatment and 1774 (85%) died in the first year after diagnosis. In contrast, only 193 (4%) of the 4414 women without any of these characteristics did not receive any treatment, and only 427 (9%) died in the first year after diagnosis. CONCLUSIONS: Although our results are based on data from England, they are likely to have implications for cancer care pathways worldwide because most of the identified factors are not specific to the UK health care system. Our results suggest the need to increase symptom awareness, promote timely general practitioner referral, and optimize diagnostic and early treatment pathways within secondary care to increase access to treatment for women with advanced-stage invasive epithelial ovarian, tubal, and primary peritoneal cancer. This process should be pursued alongside continued efforts to develop primary prevention and screening strategies.

Incidence and Characteristics of Unsuspected Neoplasia Discovered in High-Risk Women Undergoing Risk Reductive Bilateral Salpingooophorectomy.

OBJECTIVE: Risk reducing salpingooophorectomy is recommended to women with a BReast CAncer susceptibility gene (BRCA) 1 or 2 germline mutation to reduce the risk of ovarian cancer. The incidence of unsuspected neoplasia varies in the literature. The purpose of this study was to identify the rate of unsuspected neoplasia in a high-risk Australian population, discuss their management, and assess the clinical outcome. METHOD: This is a retrospective review of all women undergoing risk reductive salpingooophorectomy between January 2006 and December 2014. The medical, operative, and pathology results were reviewed. The specimens were assessed using the Sectioning and Extensively Examining the Fimbriated End protocol to the fallopian tube, and the ovary was also examined using 2 to 3 mm sectioning. RESULTS: During the study period, 138 patients underwent risk-reducing salpingooophorectomy for a known BRCA 1 or 2 germline mutation or a high-risk personal or family history of ovarian cancer. Five patients with neoplasia were identified, 2 with invasive tubal carcinoma and 3 with serous tubal intraepithelial carcinoma (STIC), giving an overall incidence of 3.62%. Invasive tubal carcinoma occurred in 1 woman with a BRCA 1 mutation and 1 woman with a BRCA 2 mutation. The incidence of carcinoma in women with either a BRCA 1 or 2 germline mutation was subsequently 2.78%. STIC occurred in 2 women with a BRCA 1 germline mutation and 1 woman carrying a BRCA 2 germline mutation. The incidence of STIC in women with either a BRCA 1 or 2 germline mutation was subsequently 4.17%. Of the patients with STIC, all 3 remain disease free at an average follow-up period of 79.33 months. CONCLUSIONS: In this retrospective review, we found the incidence of neoplasia within a high-risk Australian population undergoing risk-reducing bilateral salpingo-oophorectomy to be 3.62%. The incidence of STIC was 2.17%. During our follow-up period, all patients with STIC remained disease free.

Ovarian and tubal cancer in Denmark: an update on incidence and survival.

INTRODUCTION: The Nordic countries are areas with a high-incidence of ovarian cancer; however, differences between the countries exist. MATERIAL AND METHODS: We used the Danish Cancer Registry to identify 11 264 cases of ovarian cancer and 363 cases of tubal cancer during 1993-2013. We calculated age-standardized (world standard population) incidence rates for overall and subtype-specific ovarian cancer, and for tubal cancer. We compared age-standardized incidence rates, and 1- and 5-year age-standardized relative survival rates, respectively, for ovarian and tubal cancer combined in four Nordic countries using the NORDCAN database. RESULTS: The incidence rate of ovarian cancer overall in Denmark decreased statistically significantly by approximately 2.3% per year among women aged <70 years, whereas no change was seen among women aged 70+ years. In the <70-year age-group, the incidence of serous tumors was fairly steady, whereas that of other and unspecified epithelial tumors decreased significantly by 6.4% per year. The incidence of tubal cancer was quite stable. In Norway and Finland, the incidence rates of ovarian and tubal cancer combined decreased from 1993 to 2013 in women aged <70 years, whereas in Sweden the incidence rates decreased independently of age. The 1- and 5-year relative survival rates of ovarian and tubal cancer combined increased during the study period in all the Nordic countries. Denmark had the lowest survival; however, the survival rates approached those of the other countries in recent years. CONCLUSIONS: In Denmark, the positive development in ovarian cancer has continued during recent years with a lower incidence and an increased survival.

Patterns of First Recurrence in African American Patients with High Grade Epithelial Ovarian Carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians. METHODS: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022). CONCLUSION: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites.

Postmenopausal hormone therapy-also use of estradiol plus levonorgestrel-intrauterine system is associated with an increased risk of primary fallopian tube carcinoma.

Data on the possible impact of postmenopausal hormone therapy (HT) on the incidence of rare primary fallopian tube carcinoma (PFTC) are scarce. Therefore, we conducted a nationwide case-control study analyzing the association between the use of different HTs and PFTC. All women aged 50 years or older with an incident PFTC (n = 360) during 1995-2007 were identified from the Finnish Cancer Registry. For each case of PFTC, ten age- and place of residence-matched controls were selected from the Finnish National Population Register, which also provided information on parity. Data on HT purchases were received from the Prescription Register, and data on hysterectomies and sterilizations from the National Care Register. Controls with a salpingectomy before the PFTC diagnosis of the respective case were excluded. The PFTC risk in relation to different HTs was estimated with a conditional logistic regression model, adjusted for parity, age at last delivery, hysterectomy and sterilization. The use for five years or more of estradiol combined with levonorgestrel-releasing-intrauterine system (odds ratio 2.84, 95% confidence interval 1.10-7.38) and sequential estradiol-progestin therapy (EPT; 3.37; 2.23-5.08) were both linked with increases in the risk of PFTC, while the risk with use of estradiol-only therapy or continuous EPT was not statistically significantly increased. The OR for the use of tibolone for one year or more was 1.56 (0.55-4.41). The use of HT is related to an increased risk of PFTC, particularly when a progestin component is intrauterine or systemic progestin is given in sequential manner.

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition.

The role of endogenous androgens and sex hormone-binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64-0.97]). Moreover, associations differed for low-grade and high-grade carcinomas, with positive associations for low-grade and inverse associations for high-grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98-4.06]; high grade: ORlog2 = 0.75 [0.61-0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.