Sara Pregnolato

The Relationship Between the Vaginal Microbiota and the Ovarian Cancer Microenvironment: A Journey from Ideas to Insights

Background: The tumor microenvironment offers a new perspective in gynecologic oncology. In ovarian cancer, numerous preclinical studies, especially organoid models, have highlighted cellular, immune, and biochemical mechanisms. Beyond these sophisticated findings, more practical aspects require attention, such as the role of vaginal microbiota, which represents an interplay between external agents and internal genitalia, and its potential profiling role in early detection beyond the promise of microbiota-targeted therapies. Objectives: This review aims to assess whether such a correlation is speculative or scientifically grounded. Methods: A focused literature search was conducted on vaginal microbiota and its correlation with ovarian cancer to define the current state of knowledge. Results: Mixed outcomes have been reported, yet there is a rational and scientific basis supporting further investigation. Clinical approaches increasingly consider vaginal microbiota as relevant. However, we have to say that most available evidence is still preliminary and largely preclinical to set realistic expectations for readers. Although additional studies are needed, emerging insights highlight its importance and practical implications. We present a diagnostic–therapeutic management flowchart summarizing current evidence). Discussion: Most links between the vaginal microbiota and ovarian cancer are correlational rather than causal. The idea that microbes ascend from the vagina to the ovaries is proposed but still definitely not demonstrated. Confounding factors like age, hormones, and BRCA status complicate interpretation, and ovarian cancer itself could secondarily alter the microbiota. Mechanistic studies and longitudinal data are still needed to clarify whether dysbiosis contributes to carcinogenesis or is merely a consequence. As gynecologists, we summarize key aspects and emphasize to colleagues the importance of incorporating these findings into daily clinical practice. Vaginal dysbiosis should be considered not only a local imbalance but also a potential strategy for primary cancer prevention. Conclusions: Future research on the tumor microenvironment and vaginal microbiota will expand scientific knowledge and guide innovative preventive and therapeutic strategies.

Survival and perioperative outcomes of pelvic exenteration in primary advanced and recurrent endometrial carcinoma: A systematic review and meta-analysis

To assess survival and perioperative complications and mortality of pelvic exenteration (PE) in recurrent and advanced endometrial carcinoma (EC) patients. A systematic review and a meta-analysis was performed searching 7 electronic databases from their inception to May 2024 for all peer-reviewed studies that reported as a study outcome at least the 5 years-overall survival (OS) of PE in recurrent and/or advanced EC patients. Our outcomes were 5 year-OS from PE as primary outcome, and all extractable outcomes about PE survival [overall OS, 5 year- and overall disease specific survival (DSS), 5 year- and overall progression free survival (PFS)] and perioperative mortality and complications. Rates of survival outcomes and perioperative mortality and complications were calculated as individual and pooled estimates, with 95 % confidence intervals (CI). Subgroup analyses were planned for all study outcomes based on recurrent or advanced EC, separately. 6 studies with 166 patients were included. In women underwent PE for advanced or recurrent EC, pooled rate was: 41.7 % (95 % CI: 25.6-57.8 %) for 5 year-OS; 30.4 % (95 % CI: 14.9-45.8 %) for 5 year-DSS; 26.6 % (95 % CI: 10.6-42.5 %) for overall DSS; 51.8 % (95 % CI: 25.6-78.0 %) for 5 year-PFS; 9.7 % (95 % CI: 5.7-16.1 %) for perioperative mortality; 56.1 % (95 % CI: 32.3-76.4 %) for perioperative complications. Subgroup analyses were suitable exclusively in the "recurrent EC" subgroup and showed even worsened outcomes. In women with advanced or recurrent EC, PE shows not encouraging survival outcomes, with relatively high rates of perioperative mortality and complications. These outcomes further worsened in the subgroup of only recurrent EC. However, they should be confirmed by more updated studies.

Application of novel algorithm on a retrospective series to implement the molecular classification for endometrial cancer

The study aimed to validate the Betella algorithm, focusing on molecular analyses exclusively for endometrial cancer patients, where molecular classification alters risk assessment based on ESGO/ESTRO/ESP 2020 guidelines. Conducted between March 2021 and March 2023, the retrospective research involved endometrial cancer patients undergoing surgery and comprehensive molecular analyses. These included p53 and mismatch repair proteins immunohistochemistry, as well as DNA sequencing for POLE exonuclease domain. We applied the Betella algorithm to our population and evaluated the proportion of patients in which the molecular analysis changed the risk class attribution. Out of 102 patients, 97 % obtained complete molecular analyses. The cohort exhibited varying molecular classifications: 10.1 % as POLE ultra-mutated, 30.3 % as mismatch repair deficient, 11.1 % as p53 abnormal, and 48.5 % as non-specified molecular classification. Multiple classifiers were present in 3 % of cases. Integrating molecular classification into risk group calculation led to risk group migration in 11.1 % of patients: 7 moved to lower risk classes due to POLE mutations, while 4 shifted to higher risk due to p53 alterations. Applying the Betella algorithm, we can spare the POLE sequencing in 65 cases (65.7 %) and p53 immunochemistry in 17 cases (17.2 %). In conclusion, we externally validated the Betella algorithm in our population. The application of this new proposed algorithm enables assignment of the proper risk class and, consequently, the appropriate indication for adjuvant treatment, allowing for the rationalization of the resources that can be allocated otherwise, not only for the benefit of settings with low resources, but of all settings in general.