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Adjuvant chemotherapy for patients with early-stage endometrioid ovarian cancer (stage I-IIA). a Considered no adjuvant chemotherapy only for patients with complete surgical staging.
Source publication
The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and...
Similar publications
The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based...
Citations
... FSS is usually defined as the conservation of the uterus and at least part of one ovary, including unilateral cystectomy and unilateral salpingo-oophorectomy. The European guidelines propose that FSS can be safely performed in patients with stage IA and IC1 low-grade ovarian cancer [7]. However, whether the effect of FSS on patients' survival and disease recurrence is consistent with that of RS remains controversial. ...
Background
The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS.
Methods
We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460).
Results
From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04).
Conclusions
This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer.
... Ovarian cancer is the leading cause of death among gynecological cancers in developed countries [1,2]. More than 90% of malignant ovarian tumors are of epithelial origin, and high-grade serous carcinoma (HGSC) is the most common and most lethal type [3]. Despite efforts, overall survival of patients with HGSC has not significantly changed in recent decades. ...
... Despite efforts, overall survival of patients with HGSC has not significantly changed in recent decades. There are still no validated predictive biomarkers for platinum resistance or resistance to targeted therapies or prognostic biomarkers in clinical practice that could help inform treatment decisions and enable more personalized treatment [3]. An individualized approach would require the identification of appropriate molecular targets in tumor tissue, but tissue biopsies are invasive and carry potential risk for patients. ...
... Platinum-resistant HGSC is still a fatal disease, so predictive biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought [3]. Tumor-derived EVs that contain tissue-specific signaling molecules (e.g., proteins, mRNA, and miRNA) and reflect the pathophysiological state of the cell of origin are such promising biomarkers [4,5]. ...
Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.
... Advanced-stage OC is managed with debulking surgery with the aim of optimal cytoreduction and platinum-based systemic therapy administered after surgery or in the neoadjuvant setting [2][3][4][5]. More recently, the use of the antiangiogenic agent bevacizumab and poly-ADP ribose polymerase (PARP) inhibitors as maintenance in the front line has been shown to improve patients' outcomes [6][7][8]. However, despite the initial chemosensitivity, many patients relapse and ultimately develop platinum resistance. ...
... Understanding the complex genomic background of OC could guide the use of targeted therapies, which will pave the way for the implementation of precision medicine. To date, the only molecular characteristics routinely used for decision-making are breast cancer gene 1 and 2 (BRCA1/2) mutations and homologous recombination (HR) deficiency, which have been demonstrated and validated as predictive biomarkers of response to platinum therapy and PARP inhibitors in the frontline setting [7][8][9][10]. Thus, there is an urgent need to identify disease-specific biomarkers, which could improve the detection rate of OC and be implemented in treatment algorithms. ...
... Nearly half of HGSOCs harbor defects in HR, which is a biomarker of platinum-based chemotherapies and PARP inhibitors sensitivity [73]. In the last decade, the introduction of PARP inhibitors has revolutionized the treatment landscape of OC in both first line and relapsed settings [7,8,74,75]. However, acquired mutations that confer resistance to PARP inhibitors have been reported in some patients after long-term exposure to treatment [76,77]. ...
Ovarian cancer (OC) is the most lethal gynecologic malignancy worldwide. Due to the lack of effective screening and early detection strategies, many patients with OC are diagnosed with advanced disease, where treatment is rarely curative. Moreover, OC is characterized by high intratumor heterogeneity, which represents a major barrier to the development of effective treatments. Conventional tumor biopsy and blood-based biomarkers, such as cancer antigen 125 (CA125), have different limitations. Liquid biopsy has recently emerged as an attractive and promising area of investigation in oncology, due to its minimally invasive, safe, comprehensive, and real-time dynamic nature. Preliminary evidence suggests a potential role of liquid biopsy to refine OC management, by improving screening, early diagnosis, assessment of response to treatment, detection, and profiling of drug resistance. The current knowledge and the potential clinical value of liquid biopsy in OC is discussed in this review to provide an overview of the clinical settings in which its use might support and improve diagnosis and treatment.
... The prevalence and histological patterns of ovarian cancer vary around the world, but because the disease typically manifests at an advanced stage, it is regarded as systemic in most cases. As a result, chemotherapy, which primarily consists of a combi-nation of platinum (carboplatin) and taxane (paclitaxel) chemotherapy, is the main treatment for ovarian cancer 3 . When combined with anti-VEGF (vascular endothelial growth factor) therapy, the use of PARP (poly-ADP ribose polymerase) inhibitors has significantly extended overall and recurrence-free survival in certain populations with known mutations in the BRCA 1 and BRCA 2 genes and those with homologous recombination deficiency 3 . ...
Background: Splenectomy is a very common procedure that is frequently necessary in cases requiring
... Patients with LGSOC may have more indolent onset of symptoms, but still most are diagnosed at advanced stages (FIGO II-IV). While professional societies recommend germline genetic testing for all patients with epithelial ovarian cancer, the likelihood of LGSOC being associated with a genetic predisposition is low, < 5% [6][7][8]. Somatic testing of LGSOC also reveals low rates of genetic mutation associated with homologous recombination deficiency [9,10]. Somatic MAPK pathway alteration has been associated with improved survival outcomes, in addition to older age, lower BMI, and lack of tobacco use [4•, 8, 11, 12]. ...
... Surgery is the preferred primary treatment strategy for LGSOC [6,7]. Surgical staging for patients with early-stage disease includes hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic Current Treatment Options in Oncology lymphadenectomy, peritoneal washings and biopsies [22]. ...
... Selumetinib demonstrated activity with ORR 15.4% and clinical benefit rate 81%. While the treatment regimen was reported to be well-tolerated, 25% of patients discontinued study treatment due to toxicity and grade 3-4 adverse events included cardiac (1), pain (1), pulmonary (1), gastrointestinal (13), dermatologic (9), and metabolic (7). Tumor tissue was available for testing for 34 patients, and BRAF (6%), KRAS (41%), other RAS (21%) mutations were observed. ...
Opinion Statement
Low grade serous carcinoma of the ovary has been delineated as a separate entity from its counterpart high grade serous carcinoma of the ovary. Molecular profiling has helped to further characterize this disease process and has led to new and exciting treatment options. Surgery has always been a cornerstone of management both in primary and recurrent disease settings. Chemotherapy has been a long-standing backbone of adjuvant treatment, but its efficacy continues to be questioned. Hormonal therapy for upfront and recurrent disease is an effective treatment option with a high response rate and minimal side effects. Newer therapies including MEK, CDK 4/6, and PI3KCA inhibitors have emerged as exciting options for recurrent disease. Ongoing clinical trials will hopefully lead to additional therapeutic opportunities based on novel biomarkers in this disease.
... In patients with BOT, uterine-sparing surgery may also be considered; despite the increased risk of disease recurrence, the risk of death due to BOT does not increase in such cases [10]. While most patients with BOTs are usually diagnosed at early stages, the prognosis is still favourable even if the diagnosis is delayed [11]. An additional option for preserving fertility in BOTs consists of harvesting and cryopreserving oocytes prior to cytoreductive intervention [12]. ...
... Although the prognosis in patients with BOTs is typically promising, the risk of recurrence needs to be considered. The overall recurrence rate for BOTs is approximately 30%, but it may increase to 50% in patients diagnosed at advanced clinical stages [11]. Prognostic factors for recurrent and/or progressive disease include BOT type, patient age, stage, presence of invasive implants, microinvasion in the primary tumuor, and micropapillary architecture [11]. ...
... The overall recurrence rate for BOTs is approximately 30%, but it may increase to 50% in patients diagnosed at advanced clinical stages [11]. Prognostic factors for recurrent and/or progressive disease include BOT type, patient age, stage, presence of invasive implants, microinvasion in the primary tumuor, and micropapillary architecture [11]. Notably, however, no single clinical or pathological feature, or a combination thereof, can be considered an accurate predictor of unfavourable outcomes. ...
Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.
... These biomarkers could be exploited for the selective delivery of bioactive payloads to the site of disease. Approximately 20% of EOC patients that currently do not respond to any standard therapy, may bene t from the development of such innovative treatment approaches (5); (6); (7). ...
Background
Ovarian cancer is a significant health concern, necessitating the identification of potential diagnostic markers and novel therapeutic targets. This study presents, to the best of our knowledge, the first comparative immunohistochemical analysis of five tumor markers, namely the extra-domains A and B of fibronectin, fibroblast activation protein, carcinoembryonic antigen, and MUC16 in human epithelial ovarian cancer tissue samples.
Methods
Formalin-fixed paraffin-embedded human ovarian tissue sections were stained using previously validated antibodies to assess the percentage and intensity of marker expressions.
Results
Our results indicate a similar stromal pattern of expression for fibroblast activation protein, extra-domains A, and extra-domains B, with extra-domains A exhibiting the most intense staining. MUC16 was abundantly expressed on tumor cells of high-grade serous carcinoma samples, while carcinoembryonic antigen was not detected in this indication. Subsequent staining revealed that carcinoembryonic antigen was highly expressed on mucinous ovarian cancer specimens. With respect to clinical features, MUC16 and extra-domains A were found to be highly expressed in the most challenging scenarios namely platinum-resistant (100% and 50% respectively) and BRCA WT (75% and 45% respectively) patients.
Conclusions
The findings of this study highlight that MUC16, extra-domains B, and extra-domains A are attractive targets for the treatment of serous ovarian carcinoma, while carcinoembryonic antigen could be exploited for mucinous ovarian cancer. Clinical investigations are warranted to validate the potential of antibody-based therapies targeting these antigens in the context of ovarian cancer.
... Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological cancer in developed countries. The high mortality rate in EOC is due to the fact that 75% of women present with advanced stage disease [1]. In these women, treatment consists of cytoreductive surgery, supplemented with (neo)adjuvant chemotherapy (NACT) [1,2]. ...
... The high mortality rate in EOC is due to the fact that 75% of women present with advanced stage disease [1]. In these women, treatment consists of cytoreductive surgery, supplemented with (neo)adjuvant chemotherapy (NACT) [1,2]. Complete cytoreduction is the most significant prognostic factor in advanced EOC patients [3], and whether NACT is administered is determined based on the patient's performance status and surgical resectability as estimated on preoperative computed tomography (CT) and laparoscopy, if applicable. ...
Purpose
To describe the pharmacokinetic properties of the [ ¹⁸ F]fluoro-polyethylene glycol(PEG)-folate radiotracer in PET/CT imaging of patients with advanced stage epithelial ovarian cancer (EOC).
Procedures
In five patients with advanced EOC (FIGO stage IIIB/IIIC, Fédération Internationale de Gynécologie et d’Obstétrique), a 90-min dynamic PET acquisition of the pelvis was performed directly after i.v. administration of 185 MBq [ ¹⁸ F]fluoro-PEG 6 -folate. Arterial blood samples collected at nineteen timepoints were used to determine the plasma input function. A static volume of interest (VOI) for included tumor lesions was drawn manually on the PET images. Modelling was performed using PMOD software. Three different models (a 1-tissue compartment model (1T2k) and two 2-tissue compartment models, irreversible (2T3k) and reversible (2T4k)) were compared in goodness of fit with the time activity curves by means of the Akaike information criterion.
Results
The pharmacokinetic analysis in the pelvic area has proven to be much more challenging than expected. Only four out of 22 tumor lesions in five patients were considered suitable to perform modelling on. The remaining tumor lesions were inapt due to either low tracer uptake, small size, proximity to other [ ¹⁸ F]fluoro-PEG 6 -folate -avid structures and/or displacement by abdominal organ motion in the dynamic scan. Data from the four analyzed tumor lesions suggest that the irreversible 2T3k may best describe the pharmacokinetics. All 22 lesions were immunohistochemically stained positive for the folate receptor alpha (FRα) after resection.
Conclusion
Performing pharmacokinetic analysis in the abdominal pelvic region is very challenging. This brief article describes the challenges and pitfalls in pharmacokinetic analysis of a tracer with high physiological accumulation in the intestines, in case of lesions of limited size in the abdominal pelvic area.
... There is no consensus about the standard adjuvant therapy for stage I LGSC. Routinely, observation is recommended for stage IA disease, whereas stage IB and IC has no universally recognized standardized approach, especially for patients with complete surgical staging (45,46). Chemotherapy with carboplatin alone for six cycles or carboplatin/paclitaxel for a minimum of three cycles or six cycles if FIGO stage IC, as well as endocrine therapy, are plausible options to be discussed individually with the patients (39). ...
By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.
... [4] Platinum-based chemotherapy has traditionally been the mainstay of treatment for ovarian cancer. [5] However, a subset of patients develops resistance to platinum-based therapies, presenting a formidable challenge in the management of the disease. [6] This platinum-resistant phenotype necessitates exploring alternative therapeutic strategies to improve outcomes for affected individuals. ...
Ovarian cancer, ranked as the second leading cause of gynecologic malignancy-related deaths globally, poses a formidable challenge despite advances in early detection and treatment modalities. This paper explores the efficacy and safety of mirvetuximab soravtansine, the first folate receptor alpha (FRα)-targeting antibody-drug conjugate, in platinum-resistant ovarian cancer expressing FRα. A review of 4 key studies involving 453 participants consistently demonstrates mirvetuximab soravtansine's clinically meaningful antitumor activity and favorable safety profile. Clinical implications emphasize mirvetuximab soravtansine's pivotal role in targeted therapy, especially for high FRα-expressing tumors, potentially reshaping platinum-resistant ovarian cancer management. The combination therapy approach introduces a novel dimension, suggesting enhanced therapeutic outcomes. Even in heavily pretreated patients, mirvetuximab soravtansine's favorable tolerability positions it as a viable option. The reliability of archival tissue for FRα assessment simplifies patient selection, streamlining accessibility to targeted therapies. However, identified gaps, including limited diversity in patient populations, sparse quality of life data, and the need for long-term safety information, indicate areas for future research. Exploration of additional biomarkers predicting mirvetuximab soravtansine responsiveness is essential for personalized treatment. Abbreviations: ADC = antibody-drug conjugate, FRα = folate receptor alpha, MIRV = mirvetuximab soravtansine, ORR = objective response rate.
