Recently, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer (EC) critically integrating new pathological and molecular features was published. The present study evaluated the clinical impact of the new 2023 FIGO staging system by comparing it to the previous 2009 system. This is an international, pooled retrospective study of 519 EC patients who underwent primary treatment (and molecular characterisation) at three European Society of Gynaecological Oncology (ESGO) accredited centres in Austria/Italy. Patients were categorised according to the 2009 and the 2023 FIGO staging systems. Stage shifts were analysed and (sub)stage specific 5-year progression-free (PFS) and overall survival (OS) rates were calculated and compared. Different statistical tests were applied to evaluate the prognostic precision of the two FIGO staging systems and to compare them to each other. (Sub)stage shifts occurred in 143/519 (27.6%) patients: 123 upshifts (23.7%) and 20 (3.9%) downshifts. 2023 FIGO staging system identified a stage I cohort with a notably higher 5-year PFS rate compared to 2009 (93.0% versus 87.4%, respectively). For stage II disease, the 5-year PFS rate was similar in the 2023 and the 2009 FIGO staging systems (70.2% versus 71.2%, respectively). The two new molecularly defined 2023 FIGO substages IAm_POLEmut and IICm_p53abn displayed distinct, particularly favourable and adverse oncologic outcomes within early stage disease, respectively. A remarkably lower 5-year PFS rate for stage III patients was revealed in the 2023 FIGO staging system compared to 2009 (44.4% versus 54.1%, respectively). All applied statistical tests confirmed a more accurate prediction of PFS and OS by the 2023 FIGO staging system compared to 2009. The new 2023 FIGO stating system led to a substantial stage shift in about one quarter of patients leading to a higher prognostic precision. In early stage disease, the new substages added further prognostic granularity and identified treatment relevant subgroups.

Purpose: The aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria. Methods: Data of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019. Results: Our results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p = 0.047). Conclusion: Both lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.

Introduction: Persistent tumor after combined chemoradiation for locally advanced cervical cancer is an established prognostic factor. Detection may include magnetic resonance imaging, positron emission tomography (PET) combined with CT scan, ultrasound, or biopsies; however, no agreement about the best method and time point has been reached. In our institution, a standardized biopsy protocol of at least four punch biopsies is routinely performed at the last brachytherapy with re‐biopsies 6 weeks later in cases not showing histologic complete response (hCR). This study aims to assess the prognostic relevance of these biopsies, especially with respect to the time point of hCR. Material and Methods: This investigation was a retrospective single‐center observational cohort study that included all patients treated for locally advanced or node‐positive cervical cancer with combined chemoradiation at the University Hospital Innsbruck between 2008 and 2023. Patients with a hCR at the end of radiotherapy were classified as primary negative and otherwise as primary positive. Primary positive patients that achieved complete response at a control biopsy 6 weeks later were classified as secondary negative, and the remaining patients with residual tumor as secondary positive. Progression‐free survival (PFS) and overall survival (OS) were compared between all these groups. Results: We included 184 patients in this study, from which 46 (25%) were classified as primary positive. These patients experienced a significantly worse PFS compared to primary negative patients ( p = 0.008, HR = 2.03, 95% CI [1.20, 3.45]). The difference in PFS was also evidenced when comparing primary negative patients to those who had a hCR 6 weeks after radiotherapy (secondary negative) ( p = 0.018, HR = 2.00, 95% CI [1.13, 3.56]). However, in primary positive patients, OS was not significantly reduced ( p = 0.29, HR = 1.45, 95% CI [0.73, 2.86]). Conclusions: Early response evaluation using punch biopsies at the time of the last brachytherapy can identify patients with residual tumor, which exhibit a statistically significant and clinically meaningful risk of disease progression. This risk was not reversed even in the case of a delayed hCR 6 weeks after completion of chemoradiation.

• Complete molecular classification leads to downstaging and therapy de-escalation in a high-risk uterine carcinosarcoma. • The tumor mutational burden in the mesenchymal component of this cancer is 60% higher than in the epithelial component. • Shared POLE mutations in both constituents of this biphasic tumor prove clonal origin and support conversion theory.

Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across three TP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC. Methods: RNA-sequencing and clinical data of 603 patients from The Cancer Genome Atlas were analyzed. DC subset abundance was assessed for cDC progenitor, conventional DC type 1 (cDC1), conventional DC type 2 (cDC2), plasmacytoid DC (pDC), and mature DC by marker gene signatures. Differences in DC scores across tumors were analyzed using Kruskal–Wallis. Survival analyses were performed using Kaplan–Meier and Cox regression. Spearman’s correlation was used to determine associations between parameters. Results: HGSOC showed the lowest pDC abundance, yet high pDC scores were independently associated with shorter PFS (HR = 1.55, 95% CI: 1.05–2.27; p = 0.027), representing the only DC-subset-related prognostic signal observed across tumor types. pDCs correlated positively with neutrophils and negatively with monocytes, and pDCs, cDC2s, and cDC progenitors correlated inversely with TMB. No consistent link was found between pDC and TP53 mutation classes. However, tumors harboring specific TP53 mutations within established hotspot regions exhibited significantly lower pDC levels (p = 0.015). Conclusions: Our findings reveal distinct DC infiltration patterns and highlight the immunological vulnerability of TP53-mutated HGSOC. pDCs appear to exert a tumor-promoting, immune-evasive role, suggesting that DC function depends on their programming and tumor context. Selective targeting of DC subsets may offer novel therapeutic opportunities in TP53-mutated, low-TMB cancers.

Definitive radiochemotherapy with external beam radiotherapy and brachytherapy is standard for locally advanced cervical cancer (LACC). Advanced techniques