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. 2025 Jan;10(1):104090.
doi: 10.1016/j.esmoop.2024.104090. Epub 2024 Dec 19.

Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort

F Camarda  1 , L Mastrantoni  2 , C Parrillo  3 , A Minucci  4 , F Persiani  5 , D Giannarelli  6 , T Pasciuto  7 , F Giacomini  8 , E De Paolis  4 , M Manfredelli  8 , C Marchetti  9 , G F Zannoni  10 , A Fagotti  11 , G Scambia  9 , C Nero  12
Affiliations

Actionable mutations in early-stage ovarian cancer according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT): a descriptive analysis on a large prospective cohort

F Camarda et al. ESMO Open. 2025 Jan.

Abstract

Background: According to the European Society for Clinical Oncology (ESMO) guidelines, the therapeutic algorithm for early-stage epithelial ovarian carcinoma (EOC) is primarily based on grading and histotype. Adjuvant chemotherapy is usually recommended for high-grade tumors and for the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IC; however, overtreatment remains a concern. Conversely, patients truly at higher risk of recurrence currently lack access to additional therapeutic strategies.

Patients and methods: This study presents a descriptive analysis of early-stage EOC patients who were prospectively sequenced and stratified into high-, intermediate-, and low-risk groups based on clinicopathological features. Oncogenic alterations were identified using OncoKB and classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) Tier I-III. The prevalence of molecular findings was first reported for each risk subgroup, followed by an analysis on the cohort of patients who experienced relapse.

Results: A total of 180 patients with FIGO stage I-II EOC were enrolled between January 2022 and December 2023; 126 patients (70%) had at least one ESCAT Tier I-III alteration (including 51% high risk, 35% intermediate risk, and 14% low risk); among them, approximately one-quarter (26%, 95% confidence interval 19% to 35%) had an ESCAT Tier I alteration. BRCA1 and BRCA2 alterations were observed in about one-quarter of patients, with BRCA2 often co-altered with POLE mutations (55%, P = 2.1 × 10-4). Notably, almost all BRCA1 variants were found in high-risk patients. BRAF V600E mutation (ESCAT IC) was found in 2.4% of patients. PIK3CA variants were the most common Tier IIIA alterations found in 59% of patients. Among those who experienced recurrence, 60% had at least one ESCAT Tier I-III alteration, with PIK3CA mutations being the most frequent.

Conclusions: These findings highlight the potential for actionable alterations in most early-stage EOC patients and support the exploration of chemotherapy-free regimens for low- to intermediate-risk groups, as well as targeted maintenance therapy for high-risk individuals.

Keywords: ESCAT; actionable alterations; early-stage ovarian cancer; target therapy.

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Figures

Figure 1
Figure 1
STROBE diagram summarizing the early-stage EOC patients included in the study. EOC, epithelial ovarian cancer; FPG, Fondazione Policlinico Gemelli; HT, High-Throughput; TSO, TruSight Oncology 500.
Figure 2
Figure 2
Oncoplot of those patients with at least one alteration in a gene classified as level I-III according to ESCAT (n = 126). ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; MSI, microsatellite instability; TMB, tumor mutational burden; VAF, variant allele frequency.
Figure 3
Figure 3
Relapse-free survival (RFS) curves of the entire cohort (n = 180).
Figure 4
Figure 4
Oncoplot of those patients who recurred and had at least one alteration in a gene classified as level I-III according to ESCAT (n = 9). ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; MSI, microsatellite instability; TMB, tumor mutational burden; VAF, variant allele frequency.
See this image and copyright information in PMC

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