Meletios-Athanasios Dimopoulos

Possible Prognostic Role of BMI Before Chemotherapy in the Outcomes of Women with Ovarian Cancer

Background/Objectives: Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need to identify modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, both prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conflicting data on the associations of body mass index (BMI) with progression-free survival (PFS) and overall survival (OS) in ovarian cancer patients necessitate further exploration. This study aims to investigate the prognostic role of BMI before chemotherapy in women with ovarian cancer, specifically focusing on PFS and OS. Methods: A retrospective analysis encompassed 1,136 patients diagnosed with ovarian carcinomas between 1995 and 2018. Patients were categorized based on BMI at presentation, and a comprehensive examination of clinicopathological, treatment, and survival data was conducted. Results: In the patient population, normal weight patients (BMI < 25 kg/m2) demonstrated a median PFS of 12.8 months (95% CI 11.7–13.9 months), while overweight/obese patients (BMI ≥ 25 kg/m2) exhibited a significantly longer median PFS of 14.9 months (95% CI 13.6–16.4 months, P = 0.006). No statistically significant difference was noted in median OS between the two BMI groups. Subgroup analysis for different histological subtypes revealed a statistically significant benefit for overweight and obese patients with serous and endometrioid histology (mPFS 12.9 months, 95% CI 11.7–14.0 vs. 15.6 months, 95% CI 13.9–17.3, P = 0.012 and 14.6 months 95% CI 13.7–15.5 vs. 25.6 months, 95% CI 9.5–41.7, P = 0.031, respectively). Additionally, BMI ≥ 25 kg/m2 demonstrated a significant advantage in advanced-stage disease. Conclusions: The study underscores the intricate association between BMI and ovarian cancer prognosis. While a statistically significant difference in progression-free survival was noted between normal weight and overweight/obese patients, with the latter group experiencing a survival benefit, no such difference was observed in overall survival.

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.

Molecular Profiling and Treatment Outcomes in Uterine Serous Carcinoma: Prognostic Role of Estrogen Receptor Expression

Background: Uterine serous carcinoma (USC) represents a rare but aggressive subtype of endometrial cancer, accounting for a disproportionate number of disease-related deaths. Although molecular classification has improved risk stratification, prognostic heterogeneity highlights the need for new prognostic markers. Methods: We retrospectively analyzed 83 patients with USC treated at our institution between 1 January 2015 and 31 December 2023. Clinicopathological characteristics, treatment strategies, molecular biomarkers accessed by immunohistology (TP53, ER, PR, HER2, and MMR status), and survival outcomes were collected. Patients were first staged by FIGO 2009 and retrospectively reclassified by FIGO 2023. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. Results: The majority of patients were presented with advanced disease (FIGO stage IIIC-IV). TP53 mutations were found in 88% of cases, HER2 amplification in 18%, and ER expression in 57.8%. ER-positive patients showed significantly improved DFS in the adjuvant setting compared with ER-negative patients, whereas no significant associations were observed for first-line PFS or OS in multivariable analyses. HER2 amplification was not associated with inferior survival in our cohort. The advanced stage remained an independent predictor of worse OS. Conclusions: USC is a biologically heterogeneous disease, and its treatment should be guided by its molecular profile. ER expression identifies a subset of patients with improved DFS, suggesting potential prognostic relevance in this high-risk histology.

Molecular Prognostic Factors in Uterine Serous Carcinomas: A Systematic Review

Uterine serous carcinomas are an aggressive minority of endometrial cancers. They are characterized by mutations in TP53 and extensive copy number alterations and are primarily classified in the copy number-high/p53abn molecular prognostic group, highlighting a unique molecular profile that is crucial for understanding their behavior and treatment responses. Clinical studies have shown that molecular categorization via biomarkers can facilitate proper treatment selection, and this is now widely used. In this context, the scope of this systematic review is to identify molecular characteristics with prognostic significance for these neoplasms to further inform on their treatment needs. We performed a comprehensive literature search of all articles written in English using the PubMed/Medline and Cochrane databases through February 2025. Our review led to the inclusion of 95 studies, from which we identified a total of 66 distinct molecular characteristics along with new cancer signatures that may impact prognosis. These findings have the potential to inform clinical practice by aiding in the development of tailored treatment strategies for patients with uterine serous carcinoma, ultimately improving outcomes in this challenging malignancy.

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.