High-Grade Serous Ovarian Cancer during Pregnancy: From Diagnosis to Treatment.

BACKGROUND: Due to the rarity of ovarian cancer diagnosed during pregnancy, the literature on the treatment of subtypes of epithelial ovarian cancer in pregnancy is sparse. The aim of our review was to analyze cases of high-grade serous ovarian cancer in pregnancy. METHODS: The PubMed and Scopus databases were searched for relevant articles published in English between January 2000 and December 2023. The references of all the relevant reviews found were also checked to avoid omitting eligible studies. Information on the all retrieved cases was extracted and reviewed in detail. The most important detail was the subtype of high-grade serous ovarian cancer, which was referred to as serous adenocarcinoma (grade 2 or grade 3) in older cases. RESULTS: We found eleven cases with relevant details of high-grade serous ovarian cancer diagnosed in pregnancy. Despite the small number of cases we found, our study demonstrated the importance of an accurate initial vaginal ultrasound at the first examination in pregnancy and the safety of diagnostic surgery and chemotherapy in pregnancy. CONCLUSIONS: There have not been long-term follow-ups of patients' oncologic and obstetric outcomes. As patients should be comprehensively informed, more detailed case reports or series with longer follow-up periods are needed.

Metastasis of serous ovarian carcinoma to the breast: a case report and review of the literature.

BACKGROUND: Breast metastasis from primary ovarian cancer is rare, with an estimated frequency of 0.07%. More than 110 cases are reported in the literature of metastatic spread of ovarian cancer to the breast and axilla. This entity usually represents aggressive late disease characterized by multi-drug chemoresistance and a poor prognosis with a median survival time of 16 months. Currently no standardized treatment protocol exists for this condition. CASE PRESENTATION: We present a case of a 59-year-old Caucasian female with recurrent high-grade serous ovarian cancer who was diagnosed with symptomatic unilateral breast metastasis while on fourth line chemotherapy with weekly paclitaxel. She was treated with local radiation with 2300 cGy to the right breast with a complete response. She then had a subsequent recurrence in the ipsilateral breast 8 months after completion of post treatment imaging. She remains alive to date approximately 2 years after her initial diagnosis of breast metastasis on seventh line treatment. CONCLUSIONS: Breast metastasis from primary ovarian cancer is rare and represents advanced disease characterized by multi-drug chemoresistance and a poor prognosis. This case describes radiation therapy as a safe, effective treatment option to improve local control and quality of life in these patients, but with limited durability of response.

Low-grade serous ovarian cancer: expert consensus report on the state of the science.

Compared with high-grade serous carcinoma, low-grade serous carcinoma of the ovary or peritoneum is a less frequent epithelial ovarian cancer type that is poorly sensitive to chemotherapy and affects younger women, many of whom endure years of ineffective treatments and poor quality of life. The pathogenesis of this disease and its management remain incompletely understood. However, recent advances in the molecular characterization of the disease and identification of novel targeted therapies with activity in low-grade serous carcinoma offer the promise of improved outcomes. To update clinicians regarding recent scientific and clinical trial advancements and discuss unanswered questions related to low-grade serous carcinoma diagnosis and treatment, a panel of experts convened for a workshop in October 2022 to develop a consensus document addressing pathology, translational research, epidemiology and risk, clinical management, and ongoing research. In addition, the patient perspective was discussed. The recommendations developed by this expert panel-presented in this consensus document-will guide practitioners in all settings regarding the clinical management of women with low-grade serous carcinoma and discuss future opportunities to improve research and patient care.

Construction and validation of nomograms for predicting the prognosis of elderly patients with uterine serous carcinoma: a SEER-based study.

PURPOSE: To investigate the prognostic indicators, develop and verify nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in elderly patients with uterine serous carcinoma (USC). METHODS: Data of eligible USC patients aged ≥ 65 years from 2004 to 2015 in the Surveillance, Epidemiology and End Results (SEER) database were collected for retrospective analysis. X-tile software was used to assess the optimal cut-off values. Univariate and multivariate Cox regression analyses were performed to explore the prognostic factors. Nomograms were developed to predict the probability of 1-, 3- and 5-year OS and CSS. Concordance indexes (c-index), receiver operating characteristic analysis and calibration curves were used to evaluate the model. Decision curve analysis (DCA) was introduced to examine the clinical value of the models. RESULTS: Age, Federation International of Gynecology and Obstetrics stage, N stage, tumor size, number of lymph nodes resected, and adjuvant therapy were independent prognostic factors for OS and CSS. The C-indexes were 0.736 (OS), 0.754 (CSS) in the training set and 0.731 (OS), 0.759 (CSS) in the validation set. The area under the curve (AUCs) of OS and CSS for 1-, 3-, and 5-years all exceeded 0.75. The calibration plots for the probability of survival were in good agreement. As shown in DCA curves, the nomograms showed better discrimination power and higher net benefits than the 6th American Joint Committee on Cancer staging system. CONCLUSIONS: The nomograms constructed based on prognostic risk factors could individually predict the prognosis of elderly USC patients and provide a reference for clinical decision-making.

Serous endometrial intraepithelial carcinoma: a case report.

Serous endometrial intraepithelial carcinoma (SEIC) is a rare but highly aggressive form of uterine endometrial cancer. We report two cases of post-menopausal, 58-year-old patients with abundant vaginal bleeding and pelvic pain. The first patient had a history of surgical hysteroscopy in 2019 for an endocervical polyp. The second patient had a history of breast resection, axillary lymph node dissection, chemotherapy, radiation therapy, and tamoxifen therapy for breast carcinoma 6 years ago. An abdominal hysterectomy was performed in both patients. The pathological assessment showed serous endometrial intraepithelial carcinoma. Diagnosis of a serous proliferation of the uterus implies the exploration of other genital tract organs as well as distant locations in search of metastatic disease.

Monitoring Treatment Response, Early Recurrence, and Survival in Uterine Serous Carcinoma and Carcinosarcoma Patients Using Personalized Circulating Tumor DNA Biomarkers.

Uterine serous carcinoma (USC) and carcinosarcomas (CSs) are rare, highly aggressive variants of endometrial cancer. No reliable tumor biomarkers are currently available to guide response to treatment or detection of early recurrence in USC/CS patients. Circulating tumor DNA (ctDNA) identified using ultrasensitive technology such as droplet digital polymerase chain reaction (ddPCR) may represent a novel platform for the identification of occult disease. We explored the use of personalized ctDNA markers for monitoring USC and CS patients. Tumor and plasma samples from USC/CS patients were collected at the time of surgery and/or during the treatment course for assessment of tumor-specific somatic structural variants (SSVs) by a clinical-grade next-generation sequencing (NGS) platform (i.e., Foundation Medicine) and a droplet digital PCR instrument (Raindance, ddPCR). The level of ctDNA was quantified by droplet digital PCR in plasma samples and correlated to clinical findings, including CA-125 serum and/or computed tomography (CT) scanning results. The genomic-profiling-based assay identified mutated "driver" target genes for ctDNA analysis in all USC/CS patients. In multiple patients, longitudinal ctDNA testing was able to detect the presence of cancer cells before the recurrent tumor was clinically detectable by either CA-125 or CT scanning. Persistent undetectable levels of ctDNA following initial treatment were associated with prolonged progression-free and overall survival. In a USC patient, CA-125 and TP53 mutations but not PIK3CA mutations become undetectable in the plasma at the time of recurrence, suggesting that more than one customized probe should be used for monitoring ctDNA. Longitudinal ctDNA testing using tumor-informed assays may identify the presence of residual tumors, predict responses to treatment, and identify early recurrences in USC/CS patients. Recognition of disease persistence and/or recurrence through ctDNA surveillance may allow earlier treatment of recurrent disease and has the potential to change clinical practice in the management of USC and CS patients. CtDNA validation studies in USC/CS patients prospectively enrolled in treatment trials are warranted.

Genomic profiling in low grade serous ovarian cancer: Identification of novel markers for disease diagnosis and therapy.

OBJECTIVES: Low grade serous ovarian cancer (LGSOC) differs from high grade serous in terms of pathogenesis, molecular, genetic, and clinical features. Molecular studies have been hampered by small sample sizes, heterogenous histology, and lack of comprehensive testing. We sought to molecularly profile LGSOC in a homogenously tested, histologically confirmed cohort. METHODS: Using hot-spot and whole exome next generation sequencing (NGS), fusion gene analysis interrogating RNA, fragment analysis, in situ hybridization and/or immunohistochemistry, 179 specimens were evaluated by Caris Life Sciences (Phoenix, AZ). A second independent histologic review confirmed histology in 153 specimens. RESULTS: Most frequently mutated genes (5% or greater) were members of the mitogen-activated protein kinase (MAPK) pathway: KRAS (23.7%, n = 36), NRAS (11.2%, n = 19), NF1 (7.9%, n = 5), and BRAF (6.6%, n = 10). Class III mutations were seen in 3 of 10 BRAF mutations while 7 were Class I V600E. Overall, estrogen and progesterone receptor expression was 80.2% (n = 130) and 27.8% (n = 45), respectively. Of those that were hormone negative, nearly 50% contained KRAS or NF1 mutations. None were NRAS mutated. Markers of response to immunotherapy were low to absent. CONCLUSION: BRAF mutations were seen to be lower than those traditionally reported. With increased MAPK activation resulting in ligand independent activation of ERα, a role of combination therapy with hormonal and targeted therapy should be considered as 49.2% of hormone negative specimens were KRAS or NF1 mutated. Absence of immunotherapy biomarkers suggest limited benefit to immunotherapeutic agents.

Clinical Characteristics in the Prediction of Posttreatment Survival of Patients with Ovarian Cancer.

Objective: To determine the efficacy of clinical characteristics in the prediction of prognosis in patients with ovarian cancer. Methods: Clinical data were collected from 3 datasets from TCGA database, including 1680 cases of ovarian serous cystadenocarcinoma, and were analyzed. Patients with ovarian cancer admitted to our hospital in 2016 were retrieved and followed up for prognosis analysis. Results: From the datasets, for patients > 75 years old at the time of diagnosis, histologic grade and mutation count were good predictors for disease-free survival, while for patients > 50 years old at the time of diagnosis, histologic grade, race, fraction genome altered, and mutation count were good predictors for overall survival. In the patients (n = 38) retrieved from our hospital, the longest dimension of lesion (cm) and body weight at admission were good predictors for overall survival. Conclusions: Those clinical factors, together with the two predictive equations, could be used to comprehensively predict the long-term prognosis of patients with ovarian cancer.

Immuno-genomic characterisation of high-grade serous ovarian cancer reveals immune evasion mechanisms and identifies an immunological subtype with a favourable prognosis and improved therapeutic efficacy.

BACKGROUND: Immunotherapy has revolutionised the field of cancer therapy and immunology, but has demonstrated limited therapeutic efficacy in high-grade serous ovarian cancer (HGSOC). METHODS: Multi-omics data of 495 TCGA HGSOC tumours and RNA-seq data of 1708 HGSOC tumours were analyzed. Multivariate Cox regression analysis and meta-analyses were used to identify prognostic genes. The immune microenvironment was characterised using the ssGSEA methods for 28 immune cell types. Immunohistochemistry staining of tumour tissues of 14 patients was used to validate the key findings further. RESULTS: A total of 1142 genes were identified as favourable prognostic genes, which are prevailing in immune-related pathways and the infiltration of most immune subpopulations was observed to be associated with a favourable prognosis suggesting that tumour immunogenicity was the most prominent factor associated with improved clinical outcomes and response to chemotherapy of HGSOC. We identified multiple genomic and transcriptomic determinants of immunogenicity, including the copy loss of chromosome 4q and deficiencies of the homologous recombination pathway. Finally, an immunological subtype characterised by increased infiltration of activated CD8 T cells and decreased Tregs was associated with favourable prognosis and improved therapeutic efficacy. CONCLUSIONS: Our study characterised the immunogenomic landscape and refined the immunological classifications of HGSOC. This may improve the selection of patients with HGSOC who are suitable candidates for immunotherapy.

Comprehensive characterization of 11 prognostic alternative splicing events in ovarian cancer interacted with the immune microenvironment.

Alternative splicing (AS) events play a crucial role in the tumorigenesis and progression of cancer. Transcriptome data and Percent Spliced In (PSI) values of ovarian cancer patients were downloaded from TCGA database and TCGA SpliceSeq. Totally we identified 1472 AS events that were associated with survival of ovarian serous cystadenocarcinoma (OC) and exon skipping (ES) was the most important type. Univariate and multivariate Cox regression analysis were performed to identify survival-associated AS events and developed the prognostic model based on 11-AS events. The immune cells and different response to cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) blockers in low-risk and high-risk group of OC patients were analyzed. Ten kinds of immune cells were found up-regulated in low-risk group. Activated B cell, natural killer T cell, natural killer cell and regulatory T cell were associated with survival of OC. The patients in low-risk group had good response to CTLA-4 and PD-1 blockers treatment. Moreover, a regulatory network was established according to the correlation between AS events and splicing factors (SFs). The present study provided valuable insights into the underlying mechanisms of OC. AS events that were correlated with the immune system might be potential therapeutic targets.

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

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

What Has Changed in the Management of Uterine Serous Carcinomas? Two Decades of Experience.

Uterine serous carcinoma accounts for 3-10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients' median disease-free survival was 42.07 months (95% CI: 20.28-63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18-62.83), and it significantly favored the first decade's patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81-9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma's treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future.

Extracellular microRNA profiling for prognostic prediction in patients with high-grade serous ovarian carcinoma.

High-grade serous ovarian carcinoma is a leading cause of death in female patients worldwide. MicroRNAs (miRNAs) are stable noncoding RNAs in the peripheral blood that reflect a patient's condition, and therefore, they have received substantial attention as noninvasive biomarkers in various diseases. We previously reported the usefulness of serum miRNAs as diagnostic biomarkers. Here, we investigated the prognostic impact of the serum miRNA profile. We used the GSE106817 dataset, which included preoperative miRNA profiles of patients with ovarian malignancies. Excluding patients with other malignancy or insufficient prognostic information, we included 175 patients with high-grade serous ovarian carcinoma. All patients except four underwent surgery and received chemotherapy as initial treatment. The median follow-up period was 54.6 months (range, 3.5-144.1 months). Univariate Cox regression analysis revealed that higher levels of miR-187-5p and miR-6870-5p were associated with both poorer progression-free survival (PFS) and overall survival (OS), and miR-1908-5p, miR-6727-5p, and miR-6850-5p were poor prognostic indicators of PFS. The OS and PFS prognostic indices were then calculated using the expression values of three prognostic miRNAs. Multivariate Cox regression analysis showed that both indices were significantly independent poor prognostic factors (hazard ratio for OS and PFS, 2.343 [P = .015] and 2.357 [P = .005], respectively). In conclusion, circulating miRNA profiles can potentially provide information to predict the prognosis of patients with high-grade serous ovarian carcinoma. Therefore, there is a strong demand for early clinical application of circulating miRNAs as noninvasive biomarkers.

MicroRNA profiling in a case-control study of African American women with uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer associated with worse survival outcomes in African American (AA) patients. This study evaluated tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. METHODS: FFPE tumor tissue from hysterectomy specimens was identified for 29 AA cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age, stage and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens (54 tumors and 23 matched normal endometrium). MicroRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen. RESULTS: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, the three most upregulated miRNAs were miR-1, miR-21-5p and miR-223. Of these, increased miR-223 expression (>median) was associated with worse OS (p = 0.0496) in an independent dataset (TCGA dataset) comprising of 140 patients with USC (mixed or pure serous). After adjusting for age, ethnicity and BMI, upregulation of miR-223 remained risk factor for death (adjusted HR 2.87, 95% CI 1.00-8.27). CONCLUSIONS: MiRNA profiling did not identify biological differences between AA and Caucasian patients with USC. Upregulation of miR-223 may be a prognostic factor in USC.

Feature Selection is Critical for 2-Year Prognosis in Advanced Stage High Grade Serous Ovarian Cancer by Using Machine Learning.

INTRODUCTION: Accurate prediction of patient prognosis can be especially useful for the selection of best treatment protocols. Machine Learning can serve this purpose by making predictions based upon generalizable clinical patterns embedded within learning datasets. We designed a study to support the feature selection for the 2-year prognostic period and compared the performance of several Machine Learning prediction algorithms for accurate 2-year prognosis estimation in advanced-stage high grade serous ovarian cancer (HGSOC) patients. METHODS: The prognosis estimation was formulated as a binary classification problem. Dataset was split into training and test cohorts with repeated random sampling until there was no significant difference (p = 0.20) between the two cohorts. A ten-fold cross-validation was applied. Various state-of-the-art supervised classifiers were used. For feature selection, in addition to the exhaustive search for the best combination of features, we used the-chi square test of independence and the MRMR method. RESULTS: Two hundred nine patients were identified. The model's mean prediction accuracy reached 73%. We demonstrated that Support-Vector-Machine and Ensemble Subspace Discriminant algorithms outperformed Logistic Regression in accuracy indices. The probability of achieving a cancer-free state was maximised with a combination of primary cytoreduction, good performance status and maximal surgical effort (AUC 0.63). Standard chemotherapy, performance status, tumour load and residual disease were consistently predictive of the mid-term overall survival (AUC 0.63-0.66). The model recall and precision were greater than 80%. CONCLUSION: Machine Learning appears to be promising for accurate prognosis estimation. Appropriate feature selection is required when building an HGSOC model for 2-year prognosis prediction. We provide evidence as to what combination of prognosticators leads to the largest impact on the HGSOC 2-year prognosis.

Matched-pair Analysis for Survival Endpoints Between Women With Early-stage Uterine Carcinosarcoma and Uterine Serous Carcinoma.

OBJECTIVE: The objective of this study was to compare survival endpoints between women with uterine carcinosarcoma and those with uterine serous carcinoma utilizing matching analysis. METHODS: Patients with stages I to II who underwent hysterectomy at our institution were included in this analysis. Patients with carcinosarcoma were then matched to patients with serous carcinoma based on stage, and adjuvant management received (observation, radiation treatment alone, chemotherapy alone, or combined modality with radiotherapy and chemotherapy. Recurrence-free survival, disease-specific survival, and overall survival were calculated for the 2 groups. RESULTS: A total of 134 women were included (67 women with carcinosarcoma and 67 with serous carcinoma, matched 1:1). There was no statistically significant difference between the 2 groups regarding 5-year recurrence-free survival (59% vs. 62%), disease-specific survival (66% vs. 67%), or overall survival (53% vs. 57%), respectively. The only independent predictor of shorter recurrence-free survival for the entire cohort was the lack of adjuvant combined modality therapy, while lower uterine segment involvement was the only independent predictor for shorter disease-specific survival. Lack of lymph node dissection and lack of adjuvant combined modality therapy were independent predictors of shorter overall survival. DISCUSSION: When matched based on stage and adjuvant treatment, our study suggests that there is no statistically significant difference in survival endpoints between women with early-stage carcinosarcoma and serous carcinoma. Adjuvant combined modality treatment is an independent predictor of longer recurrence-free survival and overall survival.

Uterine serous carcinoma: key advances and novel treatment approaches.

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast-ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening.

High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management.

Uterine serous carcinoma.

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1, MYC, PPP2R1A, PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease.

Rare clinical manifestations of primary peritoneal serous carcinoma presenting as colorectal cancer: A report of two cases.

OBJECTIVE: To report two cases of for primary peritoneal serous carcinoma (PPSC) to present with gastrointestinal manifestations that mimic colorectal cancer. CASE REPORT: There were two patients with initial presentations of fatigue with iron deficiency anemia, and tenesmus with bloody stool. Tumors of the ascending colon and rectum were detected by colonofiberoscope, and pathologic reports of tumor biopsies revealed adenocarcinoma of suspected gynecologic origin. Both patients underwent optimal debulking surgery without macroscopic residual tumor, and then received adjuvant carboplatin and paclitaxel chemotherapy with bevacizumab. CONCLUSIONS: PPSC can clinically present like primary colorectal carcinoma. The differential diagnosis requires special staining of several markers for tumor tissues.