Variables Associated With Resolution and Persistence of Ovarian Cysts.

OBJECTIVE: To estimate surveillance intervals of incident ovarian cysts, and describe variables associated with cyst resolution times. METHODS: The UK-OCST (University of Kentucky Ovarian Cancer Screening Trial) was a prospective cohort that enrolled 47,762 individuals over 30 years, including 2,638 individuals with incident cysts. Cyst diameter and structure and patient age, body mass index, use of hormone therapy (HT), family history of ovarian cancer, and menopausal status were examined as variables associated with cyst resolution using t tests, χ 2 test, Kaplan Meier, and Cox multiple regression. RESULTS: Of 2,638 individuals with incident cysts, 1,667 experienced resolution (63.2%) within 1.2 years, and 971 experienced persistence (36.8%). Within 1 year, unilocular and septated cysts had similar resolution rates (35.4% and 36.7%, respectively, P >.05), but time to resolution was shorter for unilocular cysts compared with septated cysts (mean 1.89 years vs 2.58 years, respectively, P <.001). Both unilocular and septated cysts smaller than 3 cm resolved faster than cysts larger than 6 cm ( P <.001). Variables associated with percent resolution included being of younger age, premenopausal status (but not for synchronous bilateral cysts), and those reporting a family history of ovarian cancer ( P <.05). Variables associated with a faster cyst resolution rate included being older than age 70 years and not using hormone therapy. Body mass index and family history were not associated with cyst resolution time. CONCLUSION: Different surveillance times may be appropriate depending on cyst structure and size and patient age and HT use. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT04473833.

Perspectives on Ovarian Cancer 1809 to 2022 and Beyond.

Unlike many other malignancies, overall survival for women with epithelial ovarian cancer has improved only modestly over the last half-century. The perspectives presented here detail the views of a gynecologic oncologist looking back and the view of the academic editor looking forward. Surgical beginnings in 1809 are merged with genomics, surgical advances, and precision therapy at present and for the future. Presentations in this special issue focus on factors related to the diagnosis of ovarian cancer: (1) markers for the preoperative assessment of primary and metastatic ovarian tumors, (2) demonstrations of the presence of pelvic fluid in ultrasound studies of ovarian malignancies, (3) the effects of age, menopausal status, and body habitus on ovarian visualization, (4) the ability of OVA1 to detect ovarian cancers when Ca125 was not informative, (5) the detection of tumor-specific changes in cell adhesion molecules by tissue-based staining, (6) presentation of a high discrimination model for ovarian cancer using IOTA Simple Rules and CA125, (7) review of low-grade serous carcinoma of the ovary, and (8) a comprehensive case report on ovarian carcinosarcoma.

Subsequent Ultrasonographic Non-Visualization of the Ovaries Is Hastened in Women with Only One Ovary Visualized Initially.

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries when one or both ovaries are visualized on the first ultrasound exam. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams and 9703 women that had only one ovary visualized on their first exam were followed over 63,702 ultrasonography exams. All images were reviewed by a physician. While non-visualization of both ovaries increased with age in women selected on the basis of the visualization of only one ovary on their first ultrasound exam, one or both ovaries could be visualized in two out of every three women at 80 years of age and more than 50% of women over 80 years of age. At each age, more non-visualizations were associated with women that had only one ovary visualized on their first visit. Having only one ovary visualized on the first exam advanced non-visualizations by an average of ~10 years across all ages and by >20 years in women under 40 years of age. Conclusions: Having only one ovary visualized on an initial ultrasound exam considerably hastens complete non-visualization for this population; however, in these women, ovaries can still be visualized well past menopause, and body habitus is not limiting to TVS ovarian imaging, thus TVS should be considered capable of capturing an ovarian image in two out of every three women at 80 years of age.

Ultrasonographic Visualization of the Ovaries to Detect Ovarian Cancer According to Age, Menopausal Status and Body Type.

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams. All images were reviewed by a physician. While visualization of both ovaries decreased with age, one or both ovaries could be visualized in two of every three women over 80 years of age. Around 93% of pre-menopausal women and ~69% of post-menopausal women had both ovaries visualized. Both ovaries were visualized in ~72% of women weighing over 300 lbs. and in ~70% of women with a BMI over 40. Conclusions: Age had the greatest influence on the visualization of the ovaries. The ovaries can be visualized well past the menopause. Body habitus was not limiting to TVS ovarian imaging, and TVS should be considered capable of imaging one or both ovaries in two of every three women over 80 years of age. Thus, older and obese patients remain good candidates for TVS exams.

Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram.

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison group (TN screen; OR = 1) significantly differed from that of the FP cases (benign pathology; OR: 13.4; 95% confidence interval (CI): 9.1-19.8), the TP cases with a low malignant potential (LMP; OR: 28; 95% CI: 26.5-29.5), TP ovarian cancer cases (OR: 50.4; 95% CI: 27.2-93.2), and FN ovarian cancer cases (OR: 59.3; 95% CI: 19.7-178.1). The mean duration that pelvic fluid was present for women with TN screens was 2.2 ± 0.05 encounters, lasting 38.7 ± 1.3 months. In an asymptomatic screening population, free fluid identified in TVS exams was more associated with ovarian malignancy than in the control group or benign ovarian tumors. While pelvic free fluid may not solely discriminate malignancy from non-malignancy, it appears to be clinically relevant and warrants thoughtful consideration.

Disease-Specific Survival of Type I and Type II Epithelial Ovarian Cancers-Stage Challenges Categorical Assignments of Indolence & Aggressiveness.

Epithelial ovarian cancers (EOC) consist of several sub-types based on histology, clinical, molecular and epidemiological features that are termed "histo-types", which can be categorized into less aggressive Type I and more aggressive Type II malignancies. This investigation evaluated the disease-specific survival (DSS) of women with Type I and II EOC using histo-type, grade, and stage. A total of 200,658 EOC cases were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data. Kaplan-Meier survival analyses, one-factor ANOVA and Chi-square analyses were performed on 10-year DSS survivals. DSS strongly supported a 2-tiered classification (grade 1 vs. grade 2 & 3) for serous EOC. DSS of early stage serous EOC for grade 2 was significantly different from grade 3 indicating that a 2-tier classification for serous EOC applied only to late stage. DSS of Type I EOC was much better than Type II. However, DSS was 46-58% lower with late stage Type I than with early stage Type I indicating that Type I ovarian cancers should not be considered indolent. Early stage Type II EOC had much better DSS than late stage Type II stressing that stage has a large role in survival of both Type I and II EOC.

Assessing the Costs of Screening for Ovarian Cancer in the United States: An Evolving Analysis.

The primary objective of this study is to provide an updated analysis of the cost of screening for ovarian cancer in the United States. Here, we use updated information from the University of Kentucky Ovarian Cancer Screening Trial in conjunction with new modifying factors such as U.S. national estimates of the cost of care (Truven Health MarketScan Database), recently published estimates of earnings lost due to ovarian cancer death and estimates of federal income taxes paid on those earnings. In total, 326,998 screens were performed during the Kentucky trial from 1987 to 2019. At a cost of $56 per screen, we estimate that the total base cost to operate the program over the last 32 years is $18,311,888. When accounting for the surgical cost of 381 false-positive cases, the total cost of the screening program increases by $3,030,474. However, these costs are offset by the benefit of treating more early-stage ovarian cancer in the screened population, with a total cost advantage of $4,016,475 at our institution (Kentucky) or $1,525,050 ($725,700-$3,312,650) (U.S.) nationally. Additionally, program costs are offset by approximately $3,549,000 due to the potential earnings gained by the 26 women whose lives have been saved with screening. Furthermore, the cost of the program is offset by the federal tax dollars paid on the recovered earnings and amounts to $383,292. Ultimately, the net adjusted total cost of the Kentucky screening program is an estimated $13,393,595 at our institution or $15,885,020 ($13,978,068-$16,799,083) nationally. Thus, the adjusted cost per screen is an estimated $40.96 in Kentucky or $48.58 ($42.75-$51.37) nationally.

Psychological Response to a False Positive Ovarian Cancer Screening Test Result: Distinct Distress Trajectories and Their Associated Characteristics.

Routine screening for ovarian cancer (OC) can yield an abnormal result later deemed benign. Such false positive (FP) results have been shown to trigger distress, which generally resolves over time. However, women might differ in the trajectory of the distress experience. Women participating in a routine OC screening program (n = 373) who received an abnormal screening result completed a baseline assessment prior to a follow-up screening test to clarify the nature of their abnormal result. All women were subsequently informed that no malignancy was present, and follow-up assessments were completed one and four months post-baseline. Demographic, clinical, dispositional (optimism, monitoring), and social environmental (social constraint, social support) variables were assessed at baseline. OC-specific distress was assessed at all three assessments. Trajectory analyses identified three distress trajectories differing in the baseline level of distress. A high decreasing trajectory, representing about 25% of women, was characterized by high levels of distress at baseline with distress declining over time, but still elevated at four-month follow-up. In contrast, a no distress trajectory group, representing about 30% of women, was characterized by essentially no distress at any time point. Principal risk factors for membership in the high decreasing trajectory group included a family history of OC, lower dispositional optimism, and greater social constraint. These risk factors could be used to target resources efficiently towards managing women at risk for potentially clinically-significant distress after receipt of an FP OC screening test.

Clinical Factors Associated with Longer Hospital Stay Following Ovarian Cancer Surgery.

Background: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy and is treated with a combination of cytoreductive surgery and platinum-based chemotherapy. Extended length of stay (LOS) after surgery can affect patient morbidity, overall costs, and hospital resource utilization. The primary objective of this study was to identify factors contributing to prolonged LOS for women undergoing surgery for ovarian cancer. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried to identify women from 2012-2016 who underwent hysterectomy for ovarian, fallopian tube and peritoneal cancer. The primary outcome was LOS >50th percentile. Preoperative and intraoperative variables were examined to determine which were associated with prolonged LOS. Results: From 2012-2016, 1771 women underwent elective abdominal surgery for OC and were entered in the ACS-NSQIP database. The mean and median LOS was 4.6 and 4.0 days (IQR 0-38), respectively. On multivariate analysis, factors associated with prolonged LOS included: American Society of Anesthesiologists (ASA) Classification III (aOR 1.71, 95% CI 1.38-2.13) or IV (aOR 1.88, 95% CI 1.44-2.46), presence of ascites (aOR 1.88, 95% CI 1.44-2.46), older age (aOR 1.23, 95% CI 1.13-1.35), platelet count >400,000/mm3 (aOR 1.74, 95% CI 1.29-2.35), preoperative blood transfusion (aOR 11.00, 95% CI 1.28-94.77), disseminated cancer (aOR 1.28, 95% CI 1.03-1.60), increased length of operation (121-180 min, aOR 1.47, 95% CI 1.13-1.91; >180 min, aOR 2.78, 95% CI 2.13-3.64), and postoperative blood transfusion within 72 h of incision (aOR 2.04, 95% CI 1.59-2.62) (p < 0.05 for all). Conclusions: Longer length of hospital stay following surgery for OC is associated with many patient, disease, and treatment-related factors. The extent of surgery, as evidenced by perioperative blood transfusion and length of surgical procedure, is a factor that can potentially be modified to shorten LOS, improve patient outcomes, and reduce hospital costs.

Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening.

OBJECTIVE: To estimate the effect of ultrasound screening on stage at detection and long-term disease-specific survival of at-risk women with epithelial ovarian cancer. METHODS: Eligibility included all asymptomatic women 50 years of age or older and women 25 years of age or older with a documented family history of ovarian cancer. From 1987 to 2017, 46,101 women received annual ultrasound screening in a prospective cohort trial. Women with a persisting abnormal screen underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS: Seventy-one invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential were detected. No women with a low malignant potential tumor experienced recurrent disease. Stage distribution for screen-detected invasive epithelial ovarian cancers was stage I-30 (42%), stage II-15 (21%), stage III-26 (37%), and stage IV-0 (0%). Follow-up varied from 9.2 months to 27 years (mean 7.9 years). Disease-specific survival at 5, 10, and 20 years for women with invasive epithelial ovarian cancer detected by screening was 86±4%, 68±7%, and 65±7%, respectively, vs 45±2%, 31±2%, and 19±3%, respectively, for unscreened women with clinically detected ovarian cancer from the same geographic area who were treated at the same institution by the same treatment protocols (P<.001). Twenty-seven percent of screen-detected malignancies were type I and 73% were type II. The disease-specific survival of women with type I and type II screen-detected tumors was significantly higher than that of women with clinically detected type I and type II tumors and was related directly to earlier stage at detection. CONCLUSION: Annual ultrasound screening of at-risk asymptomatic women was associated with lower stage at detection and increased 5-, 10-, and 20-year disease-specific survival of women with both type I and type II epithelial ovarian cancer. CLINICAL TRIAL REGISTRATION: OnCore Clinical Trials Management System, NCI-2013-01954.

Demographic, clinical, dispositional, and social-environmental characteristics associated with psychological response to a false positive ovarian cancer screening test: a longitudinal study.

Cancer screening can facilitate early detection that improves survival, but also can identify an abnormal finding that is not malignant and deemed benign. While such false positive (FP) results can impact a variety of psychological outcomes, little is known about demographic, clinical, dispositional, and social-environmental characteristics associated with psychological outcomes after a FP result. Women participating in an ovarian cancer (OC) screening program and experiencing a FP screening test result (n = 375) completed assessments at baseline and 4-months. Results indicated greater social constraint and less education were linked to greater OC-specific distress at both assessments. Short-term predictors included less optimism and no previous abnormal test, while longer-term predictors were fewer previous screens and the interaction between OC family history and monitoring coping style. Younger age, less education, less optimism, greater social constraint, and family history of OC were associated with greater perceptions of OC risk. Brief interventions prior to screening may minimize the negative impact of a false positive result and not interfere with compliant participation in screening programs.

Ovarian Cancer Screening: Lessons about Effectiveness.

Ovarian cancer screening has been described in scientific reports [1-4], as well as in reviews and summaries[...].

Affective, cognitive and behavioral outcomes associated with a false positive ovarian cancer screening test result.

While participation in cancer screening can facilitate early detection and improved prognosis, all screening tests yield some proportion of abnormal test results which are later determined benign. These false positive (FP) results can negatively impact affective, cognitive, and behavioral outcomes. Women participating in an ovarian cancer (OC) screening program receiving an abnormal screening test result (n = 375) were matched with women receiving normal results (n = 375). Both groups completed a baseline and 1- and 4-month follow-up assessments. FP test results were clearly associated with increased cancer-specific distress and increased perceptions of OC risk with more limited evidence for increased perceived positive consequences of screening and increased intentions to participate in future OC screening. FP OC screening test results negatively impact both affective and cognitive outcomes which may serve to reduce motivation to participate in future routine screening. The development and testing of brief, timely interventions to minimize this negative impact is warranted.

Ten Important Considerations for Ovarian Cancer Screening.

The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most appropriate way to assign disease-specific death; (9) Deciding how to avoid biases caused by enrollments that attract participants with late-stage disease who are either symptomatic or disposed by factors that are genetic, environmental or social; and (10) Deciding whether the screening tool or a screening process is being tested. These considerations are presented in depth along with illustrations of how they impact the outcomes of ovarian cancer screening. The considerations presented provide alternative explanations of effects that have an important bearing on interpreting ovarian screening outcomes.

Ultrasound Monitoring of Extant Adnexal Masses in the Era of Type 1 and Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials.

Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in normal women that can define growth, stability or resolution and give some idea of the time frame over which changes occur. The present report examines these experiences and relates them to the current understanding of ovarian cancer ontology, presenting arguments related to the benefits of surveillance.

First International Consensus Report on Adnexal Masses: Management Recommendations.

The First International Consensus Conference on Adnexal Masses was convened to thoroughly examine the state of the science and to formulate recommendations for clinical assessment and management. The panel included representatives of societies in the fields of gynecology, gynecologic oncology, radiology, and pathology and clinicians from Europe, Canada, and the United States. In the United States, there are approximately 9.1 surgeries per malignancy compared to the European International Ovarian Tumor Analysis center trials, with only 2.3 (oncology centers) and 5.9 (other centers) reported surgeries per malignancy, suggesting that there is room to improve our preoperative assessments. The American College of Obstetricians and Gynecologists Practice Bulletin on "Management of Adnexal Masses," reaffirmed in 2015 (Obstet Gynecol 2007; 110:201-214), still states, "With the exception of simple cysts on a transvaginal ultrasound finding, most pelvic masses in postmenopausal women will require surgical intervention." The panel concluded that patients would benefit not only from a more conservative approach to many benign adnexal masses but also from optimization of physician referral patterns to a gynecologic oncologist in cases of suspected ovarian malignancies. A number of next-step options were offered to aid in management of cases with sonographically indeterminate adnexal masses. This process would provide an opportunity to improve risk stratification for indeterminate masses via the provision of alternatives, including but not limited to evidence-based risk-assessment algorithms and referral to an "expert sonologist" or to a gynecologic oncologist. The panel believed that these efforts to improve clinical management and preoperative triage patterns would ultimately improve patient care.