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Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment

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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 38428

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Dr. Edward J. Pavlik

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Director of Ovarian Screening Research in Gynecologic Oncology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA
Interests: ovarian cancer; cancer screening; tumor imaging
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Special Issue Information

Dear Colleagues,

Ovarian cancer is deadly, claiming more women than all other gynecological malignancies combined. However, when detected at an early stage, ovarian cancer is highly curable. Consequently, screening efforts are likely to be the best way to detect early stage disease. The forthcoming Special Issue focuses on several key elements that are essential for an understanding of ovarian cancer, its characteristics, and risk factors that are relevant to screening for ovarian cancer. Invited topics are the following:

Risk factors for ovarian cancer
Markers and new genes associated with ovarian cancer
Ovarian cancer subtypes and their relatedness
Treatment related to high volume centers and National Comprehensive Cancer Network guidelines
Predictors of treatment responses
Treatment costs and effectiveness
Therapies and precision therapies for ovarian cancer
Vaccines and checkpoints in the immune therapy of ovarian cancer
Diagnostic tools: Strengths and limitations
International variations in ovarian cancer diagnosis and treatment
Determining ovarian cancer risk by tests for the general population
Mitigating risk of ovarian cancer surgically or medically
Screening trial design: Selection, make-up, execution, protocol driven aspects, age of participants, duration of screening, follow-up and events to be censored
Collateral affectors in screening: Perceptions of well-being and potential complications of treatment as confounders of compliance
Endpoints and efficacy: Early stage detection, disease specific survival, overall survival and avoidance of an ovarian cancer death as endpoints, with considerations of screen performance and cost
Interpretation of ovarian screening trials. Comparisons between screening trials conducted in the United States, the United Kingdom and Japan are informative regarding the current status of ovarian screening

Dr. Edward J. Pavlik
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

ovarian cancer
risk
treatment
detection
screening
trail design
treatment
collateral affectors
endpoints
costs
efficacy

Related Special Issues

Ovarian Cancer: Characteristics, Screening, Diagnosis and Treatment in Diagnostics (24 articles)
Ovarian Cancer Screening in Diagnostics (11 articles)

Published Papers (10 papers)

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Research

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11 pages, 632 KiB

Open AccessArticle

Comparison of HE4, CA125, ROMA and CPH-I for Preoperative Assessment of Adnexal Tumors

by Núria Carreras-Dieguez, Ariel Glickman, Meritxell Munmany, Georgina Casanovas, Núria Agustí, Berta Díaz-Feijoo, Adela Saco, Beatriz Sánchez, Lydia Gaba, Martina Aida Angeles, Jaume Pahisa, Esther Fernández-Galán, Aureli Torné and Pere Fusté

Diagnostics 2022, 12(1), 226; https://doi.org/10.3390/diagnostics12010226 - 17 Jan 2022

Cited by 14 | Viewed by 3021

Abstract

(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features). Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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13 pages, 1304 KiB

Open AccessArticle

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

by Justin W. Gorski, Charles S. Dietrich III, Caeli Davis, Lindsay Erol, Hayley Dietrich, Nicholas J. Per, Emily Lenk Ferrell, Anthony B. McDowell, McKayla J. Riggs, Megan L. Hutchcraft, Lauren A. Baldwin-Branch, Rachel W. Miller, Christopher P. DeSimone, Holly H. Gallion, Frederick R. Ueland, John R. van Nagell, Jr. and Edward J. Pavlik

Diagnostics 2022, 12(1), 144; https://doi.org/10.3390/diagnostics12010144 - 07 Jan 2022

Cited by 1 | Viewed by 9273

Abstract

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. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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9 pages, 2552 KiB

Open AccessArticle

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

by Edward J. Pavlik, Emily Brekke, Justin Gorski, Lauren Baldwin-Branch, Rachel Miller, Christopher P. DeSimone, Charles S. Dietrich, Holly S. Gallion, Frederick Rand Ueland and John R. van Nagell, Jr.

Diagnostics 2022, 12(1), 128; https://doi.org/10.3390/diagnostics12010128 - 06 Jan 2022

Cited by 5 | Viewed by 1478

Abstract

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. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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8 pages, 214 KiB

Open AccessArticle

Salvaging Detection of Early-Stage Ovarian Malignancies When CA125 Is Not Informative

by Charles J. Dunton, Megan L. Hutchcraft, Rowan G. Bullock, Lesley E. Northrop and Frederick R. Ueland

Diagnostics 2021, 11(8), 1440; https://doi.org/10.3390/diagnostics11081440 - 10 Aug 2021

Cited by 14 | Viewed by 2617

Abstract

Background: Ovarian cancer is the deadliest gynecologic cancer, with no recommended screening test to assist with early detection. Cancer antigen 125 (CA125) is a serum biomarker commonly used by clinicians to assess preoperative cancer risk, but it underperforms in premenopausal women, early-stage malignancies, and several histologic subtypes. OVA1 is a multivariate index assay that combines CA125 and four other serum proteins to assess the malignant risk of an adnexal mass. Objective: To evaluate the performance of OVA1 in a cohort of patients with low-risk serum CA125 values. Study Design: We analyzed patient data from previous collections (N = 2305, prevalence = 4.5%) where CA125 levels were at or below 67 units/milliliter (U/mL) for pre-menopausal women and 35 U/mL for post-menopausal women. We compare the performance of OVA1 to CA125 in classifying the risk of malignancy in this cohort, including sensitivity, specificity, positive and negative predictive values. Results: The overall sensitivity of OVA1 in patients with a low-risk serum CA125 was 59% with a false-positive rate of 30%. OVA1 detected over 50% of ovarian malignancies in premenopausal women despite a low-risk serum CA125. OVA1 also correctly identified 63% of early-stage cancers missed by CA125. The most common epithelial ovarian cancer subtypes in the study population were mucinous (25%) and serous (23%) carcinomas. Despite a low-risk CA125, OVA1 successfully detected 83% of serous, 58% of mucinous, and 50% of clear cell ovarian cancers. Conclusions: As a standalone test, CA125 misses a significant number of ovarian malignancies that can be detected by OVA1. This is particularly important for premenopausal women and early-stage cancers, which have a much better long-term survival than late-stage malignancies. Using OVA1 in the setting of a normal serum CA125 can help identify at-risk ovarian tumors for referral to a gynecologic oncologist, potentially improving overall survival. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

13 pages, 39673 KiB

Open AccessArticle

Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts

by Jason Vincent, Sonya E. L. Craig, Mette L. Johansen, Jyosthna Narla, Stefanie Avril, Analisa DiFeo and Susann M. Brady-Kalnay

Diagnostics 2021, 11(2), 181; https://doi.org/10.3390/diagnostics11020181 - 27 Jan 2021

Cited by 7 | Viewed by 2203

Abstract

Background: We developed a fluorophore-conjugated peptide agent, SBK4, that detects a tumor-specific proteolyzed form of the cell adhesion molecule, PTPmu, found in the tumor microenvironment. We previously demonstrated its tissue specific distribution in high-grade brain tumors. To extend those studies to other aggressive solid tumor types, we assessed the tissue distribution of PTPmu/SBK4 in a set of matched gynecologic cancer patient derived xenografts (PDXs) and primary patient tumors, as well as a limited cohort of tumors from gynecological cancer patients. PDXs isolated from the tissues of cancer patients have been shown to yield experimentally manipulatable models that replicate the clinical characteristics of individual patients’ tumors. In this study, gynecological cancer PDXs and patient biopsies were examined to determine if tumor-specific proteolyzed PTPmu was present. Methods: We used the peptide agent SBK4 conjugated to the fluorophore Texas Red (TR) to label tumor tissue microarrays (TMAs) containing patient and/or PDX samples from several high-grade gynecologic cancer types, and quantified the level of staining with Image J. In one TMA, we were able to directly compare the patient and the matched PDX tissue on the same slide. Results: While normal tissue had very little SBK4-TR staining, both primary tumor tissue and PDXs have higher labeling with SBK4-TR. Matched PDXs and patient samples from high-grade endometrial and ovarian cancers demonstrated higher levels of PTPmu by staining with SBK4 than normal tissue. Conclusion: In this sample set, all PDXs and high-grade ovarian cancer samples had increased labeling by SBK4-TR compared with the normal controls. Our results indicate that proteolyzed PTPmu and its novel peptide detection agent, SBK4, allow for the visualization of tumor-specific changes in cell adhesion molecules by tissue-based staining, providing a rationale for further development as an imaging agent in aggressive solid tumors, including gynecological cancers. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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15 pages, 1256 KiB

Open AccessArticle

Diagnostic Added-Value of Serum CA-125 on the IOTA Simple Rules and Derivation of Practical Combined Prediction Models (IOTA SR X CA-125)

by Phichayut Phinyo, Jayanton Patumanond, Panprapha Saenrungmuaeng, Watcharin Chirdchim, Tanyong Pipanmekaporn, Apichat Tantraworasin, Theera Tongsong and Charuwan Tantipalakorn

Diagnostics 2021, 11(2), 173; https://doi.org/10.3390/diagnostics11020173 - 26 Jan 2021

Cited by 10 | Viewed by 2309

Abstract

Background: This study aimed to evaluate the diagnostic added-value of serum CA-125 to the International Ovarian Tumor Analysis (IOTA) Simple Rules in order to facilitate differentiation between malignant and benign ovarian tumors before surgery. Methods: A secondary analysis of a cross-sectional cohort of women scheduled for surgery in Maharaj Nakorn Chiang Mai Hospital between April 2010 and March 2018 was carried out. Demographic and clinical data were prospectively collected. Histopathologic diagnosis was used as the reference standard. Logistic regression was used for development of the model. Evaluation of the diagnostic added-value was based on the increment of the area under the receiver operating characteristic curve (AuROC). Results: One hundred and forty-five women (30.3%) out of a total of 479 with adnexal masses had malignant ovarian tumors. The model that included information from the IOTA Simple Rules and serum CA-125 was significantly more superior to the model that used only information from the IOTA Simple Rules (AuROC 0.95 vs. 0.89, p < 0.001 for pre-menopause and AuROC 0.98 vs 0.83, p < 0.001 for post-menopause). Conclusions: The IOTA SR X CA-125 model showed high discriminative ability and is potentially useful as a decision tool for guiding patient referrals to oncologic specialists. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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Review

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35 pages, 810 KiB

Open AccessReview

Surgery in Advanced Ovary Cancer: Primary versus Interval Cytoreduction

by Mackenzie Cummings, Olivia Nicolais and Mark Shahin

Diagnostics 2022, 12(4), 988; https://doi.org/10.3390/diagnostics12040988 - 14 Apr 2022

Cited by 10 | Viewed by 3638

Abstract

Primary debulking surgery (PDS) has remained the only treatment of ovarian cancer with survival advantage since its development in the 1970s. However, survival advantage is only observed in patients who are optimally resected. Neoadjuvant chemotherapy (NACT) has emerged as an alternative for patients in whom optimal resection is unlikely and/or patients with comorbidities at high risk for perioperative complications. The purpose of this review is to summarize the evidence to date for PDS and NACT in the treatment of stage III/IV ovarian carcinoma. We systematically searched the PubMed database for relevant articles. Prior to 2010, NACT was reserved for non-surgical candidates. After publication of EORTC 55971, the first randomized trial demonstrating non-inferiority of NACT followed by interval debulking surgery, NACT was considered in a wider breadth of patients. Since EORTC 55971, 3 randomized trials—CHORUS, JCOG0602, and SCORPION—have studied NACT versus PDS. While CHORUS supported EORTC 55971, JCOG0602 failed to demonstrate non-inferiority and SCORPION failed to demonstrate superiority of NACT. Despite conflicting data, a subset of patients would benefit from NACT while preserving survival including poor surgical candidates and inoperable disease. Further randomized trials are needed to assess the role of NACT. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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21 pages, 2096 KiB

Open AccessReview

Low-Grade Serous Carcinoma of the Ovary: The Current Status

by Abdulaziz Babaier, Hanan Mal, Waleed Alselwi and Prafull Ghatage

Diagnostics 2022, 12(2), 458; https://doi.org/10.3390/diagnostics12020458 - 10 Feb 2022

Cited by 14 | Viewed by 5654

Abstract

Low-grade serous carcinoma (LGSC) of the ovary is a rare histological subtype of epithelial ovarian carcinoma. It has distinct clinical behavior and a specific molecular profile. Compared with high-grade serous carcinoma, this tumor presents at a younger age, has an indolent course, and is associated with prolonged survival. LGSC can arise de novo or originate following a serous borderline tumor (SBT). Pathological differentiation between LGSC and other ovarian carcinoma histological subtypes is fundamental. Several factors might influence the overall outcome, such as the age at diagnosis, current smoking, elevated body mass index, mutational status, hormonal receptors’ expression, and Ki-67 proliferation index. Surgery is the main treatment option in LGSC, and efforts must be maximized to achieve a microscopic residual in metastatic disease. Despite being relatively chemo-resistant, adjuvant platinum-based chemotherapy remains the standard of care in LGSC. Hormonal maintenance therapy after adjuvant chemotherapy results in improved outcomes. Treatment options for disease recurrence include secondary cytoreductive surgery, chemotherapy, hormonal therapy, targeted therapy, and clinical trials. Advancements in genomic studies and targeted therapies are expected to change the treatment landscape in LGSC. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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Other

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13 pages, 305 KiB

Open AccessPerspective

Perspectives on Ovarian Cancer 1809 to 2022 and Beyond

by Frank G. Lawton and Edward J. Pavlik

Diagnostics 2022, 12(4), 791; https://doi.org/10.3390/diagnostics12040791 - 24 Mar 2022

Cited by 8 | Viewed by 3328

Abstract

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. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

15 pages, 6636 KiB

Open AccessCase Report

Ovarian Carcinosarcoma with Retroperitoneal Para-Aortic Lymph Node Dissemination Followed by an Unusual Postoperative Complication: A Case Report with a Brief Literature Review

by Stoyan Kostov, Yavor Kornovski, Yonka Ivanova, Deyan Dzhenkov, George Stoyanov, Stanislav Stoilov, Stanislav Slavchev, Ekaterina Trendafilova and Angel Yordanov

Diagnostics 2020, 10(12), 1073; https://doi.org/10.3390/diagnostics10121073 - 11 Dec 2020

Cited by 7 | Viewed by 2644

Abstract

Introduction. Ovarian carcinosarcoma (OCS), also known as malignant mixed Müllerian tumour (MMMT), is one of the rarest histological subtypes of ovarian cancer. It is an aggressive tumour with a dismal prognosis—the median survival of patients is less than two years. The rarity of the disease generates many controversies about histogenesis, prognostic factors and treatment of OCS. Histologically, OCS is composed of an epithelial and sarcomatous component. Case report. In the present case, a patient with bilateral ovarian cysts and bulky paraaortic lymph nodes is reported. Retroperitoneal paraaortic lymph node metastases were the only extrapelvic dissemination of OCS. The patient underwent comprehensive surgical staging procedures, including total abdominal hysterectomy and bilateral salpingo-oophorectomy, supracolic omentectomy and selective para-aortic lymphadenectomy. Histologically the ovarian carcinosarcoma was composed of an epithelial component (high-grade serous adenocarcinoma) and three sarcomatous components (homologous—endometrial stromal cell sarcoma, and heterologous—chondrosarcoma, rhabdomyosarcoma). Immunohistochemistry staining was performed. A postoperative complication (adhesion between the abdominal aorta and terminal ileum causing obstructive ileus) that has never been reported in the medical literature occurred. Conclusion. Carcinosarcomas are carcinomas with epithelial–mesenchymal transition and heterologous differentiation. Retroperitoneal pelvic and paraaortic lymph nodes should be carefully inspected in patients with ovarian tumours. Adhesions between the small bowels and abdominal aorta are possible complications after lymph node dissection in the paraaortic region. Full article

(This article belongs to the Special Issue Ovarian Cancer 3.0: Characteristics, Screening, Diagnosis and Treatment)

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