Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study

Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 30 March 2026 V1 Latest version Share on Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study Authors : M. Teresa Dawid de Vera 0000-0002-5259-335X [email protected] , Iria Rey , Beatriz Montero , Marta Arnáez De La Cruz , Manel Montesinos-Albert , Pablo Padilla Iserte , Luis Matute , Ana Santaballa , Pilar Eroles , Santiago Domingo del Pozo , and VICTOR LAGO Authors Info & Affiliations https://doi.org/10.22541/au.177485619.93731704/v1 117 views 73 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objective: To evaluate the prognostic value of Chemotherapy Response Score (CRS) in relation to Homologous Recombination (HR) status and PARP inhibitor (PARPi) maintenance in advanced high-grade serous carcinoma (HGSC) Design: retrospective cohort study Setting: University Hospital La Fe, Valencia, Spain, June 1st 2009– January 31st 2025. Population or sample: 168 patients with FIGO stage III–IV HGSC treated with neoadjuvant chemotherapy and interval debulking surgery Methods: Patients were stratified by CRS (1/2 vs. 3), HR status, and maintenance therapy. Survival was analysed using Kaplan–Meier curves and multivariate Cox models. Main Outcome Measures: Progression-free survival and overall survival. Results: CRS3 (37.5%) was associated with higher complete cytoreduction rates (p<0.001). Overall, CRS3 patients showed longer median progression-free survival (24 months, 95% CI 18–32 vs. 16 months, 95% CI 15–20; p=0.008) and overall survival (62 months, 95% CI 46–NA vs. 39 months, 95% CI 32–47; p=0.003). In stratified analysis, the prognostic benefit of CRS3 was exclusively maintained among BRCA-wild-type/HR-proficient patients and those not receiving PARPi maintenance (p<0.01). In multivariate analysis, BRCA-mutated/HR-deficiency was the primary independent factor for progression-free survival (HR 0.49, 95% CI 0.28–0.88; p=0.016), while CRS3 was the only independent predictor for overall survival (HR 0.53, 95% CI 0.31–0.90; p=0.019). Conclusions: CRS3 is associated with improved surgical outcomes and survival. However, its independent prognostic value is primary maintained for overall survival, particularly in BRCA-wild-type/HR-proficient patients or those without PARPi maintenance, suggesting its utility should be interpreted alongside molecular profiling for refined risk stratification. TITLE: Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study Shortened running title: Prognostic Value of CRS in HR-proficient or iPARP-naïve HGSC Authors: M. Teresa Dawid de Vera, MD1,2*; Iria Rey, MD1,3; Beatriz Montero, MD2; Marta Arnáez, MD1,3; Manel Montesinos-Albert, MD1,3; Pablo Padilla-Iserte, MD, PhD1,3; Luis Matute, MD1,3; Ana Santaballa, MD, PhD1,4; Pilar Eroles, PhD5,6; Santiago Domingo del Pozo, MD, PhD3,7; Víctor Lago, MD, PhD3,8 Affiliations: 1. Gynecological Tumours, Breast and Hereditary Cancer Research Group, La Fe Health Research Institute (IIS La Fe), Avinguda de Fernando Abril Martorell, 106, 1.08, 46026, Valencia, Spain. 2. Department of Pathology, University Hospital La Fe, 46026, Valencia, Spain 3. Department of Gynecologic Oncology. Gynecologic Oncology Unit, University Hospital La Fe, 46026, Valencia, Spain 4. Department of Medical Oncology, University Hospital La Fe, 46026, Valencia, Spain 5. INCLIVA Biomedical Research Institute, Department of Physiology, University of Valencia, 46010, Valencia, Spain. 6. Center for Biomedical Network Research on Cancer (CIBERONC), Madrid, 28019, Spain. 7. Department of Surgery, University of Valencia, 46010, Valencia, Spain. 8. CEU Cardenal Herrera University, Department of Medicine, Valencia, Spain. *Corresponding author: M. Teresa Dawid de Vera, MD. Gynecological Tumours, Breast and Hereditary Cancer Research Group, La Fe Health Research Institute (IIS La Fe), Avinguda de Fernando Abril Martorell, 106, 46026, Valencia, Spain. Email: [email protected] ORCID: 0000-0002-5259-335X Phone: +34628754050 ABSTRACT Objective: To evaluate the prognostic value of Chemotherapy Response Score (CRS) in relation to Homologous Recombination (HR) status and PARP inhibitor (PARPi) maintenance in advanced high-grade serous carcinoma (HGSC) Design: retrospective cohort study Setting: University Hospital La Fe, Valencia, Spain, June 1st 2009– January 31st 2025. Population or sample: 168 patients with FIGO stage III–IV HGSC treated with neoadjuvant chemotherapy and interval debulking surgery Methods: Patients were stratified by CRS (1/2 vs. 3), HR status, and maintenance therapy. Survival was analysed using Kaplan–Meier curves and multivariate Cox models. Main Outcome Measures: Progression-free survival and overall survival. Results: CRS3 (37.5%) was associated with higher complete cytoreduction rates (p<0.001). Overall, CRS3 patients showed longer median progression-free survival (24 months, 95% CI 18–32 vs. 16 months, 95% CI 15–20; p=0.008) and overall survival (62 months, 95% CI 46–NA vs. 39 months, 95% CI 32–47; p=0.003). In stratified analysis, the prognostic benefit of CRS3 was exclusively maintained among BRCA -wild-type/HR-proficient patients and those not receiving PARPi maintenance (p<0.01). In multivariate analysis, BRCA -mutated/HR-deficiency was the primary independent factor for progression-free survival (HR 0.49, 95% CI 0.28–0.88; p=0.016), while CRS3 was the only independent predictor for overall survival (HR 0.53, 95% CI 0.31–0.90; p=0.019). Conclusions: CRS3 is associated with improved surgical outcomes and survival. However, its independent prognostic value is primary maintained for overall survival, particularly in BRCA -wild-type/HR-proficient patients or those without PARPi maintenance, suggesting its utility should be interpreted alongside molecular profiling for refined risk stratification. Funding: None declared Keywords: Ovarian Neoplasms; Neoadjuvant Chemotherapy; Chemotherapy Response Score; BRCA Mutations; PARP Inhibitors TITLE: Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study INTRODUCTION Ovarian cancer is the eighth leading cause of cancer-related mortality in women worldwide and a major cause of morbidity and mortality among gynaecologic malignancies, with a 5-year survival rate of approximately 40% (1) . High-grade serous carcinoma (HGSC) is the most frequent histological subtype, representing 70% of all malignant ovarian neoplasms. Approximately 50% of HGSC present homologous recombination deficiency (HRD), which confers increased sensitivity to platinum-based chemotherapy and to poly-ADP ribose polymerase inhibitors (PARP inhibitors, PARPi), which have been shown to improve survival as maintenance therapy (2) . Current treatment for ovarian cancer is based on a combination of primary debulking surgery, followed by adjuvant platinum-based chemotherapy (3,4) . However, for patients with high tumour burden or those medically unfit for extensive surgical procedures, current guidelines recommend neoadjuvant chemotherapy followed by interval debulking surgery (5) . While large randomised clinical trials have demonstrated non-inferiority between these strategies (6–9) , recent data from the TRUST trial and the SUROVA study have challenged these findings, suggesting a survival advantage for primary debulking surgery in high-volume centres when complete cytoreduction is achieved without complications (10,11) . Despite this ongoing debate, neoadjuvant chemotherapy remains an essential strategy for patients with high tumour burden or significant comorbidities (12) , and enables histopathological assessment of the chemotherapy response score. The chemotherapy response score (CRS), proposed by Böhm et al. in 2015, evaluates the proportion of viable tumour cells and fibro-inflammatory changes after neoadjuvant chemotherapy. It categorises response into three groups: no or minimal response (CRS1), partial response (CRS2), or complete or near-complete response (CRS3) (13) . The CRS has demonstrated prognostic value in patients undergoing interval debulking surgery and is included in pathology reports according to international guidelines (14) . Although previous studies have evaluated the BRCA status, most lack comprehensive data on HRD status or the impact of PARPi maintenance. As these factors are critical determinants of survival, the prognostic relevance of the CRS needs to be re-evaluated within this new therapeutic landscape. The aim of this study was to evaluate the prognostic value of chemotherapy response score as an independent variable and its specific relevance in relation to HRD status and the use of maintenance PARP inhibitors. METHODS A retrospective observational study was conducted including patients who underwent surgery for suspected ovarian cancer at a single centre between June 1 st 2009 and January 31 st 2025 in the Gynaecologic Oncology Department of Hospital Universitario y Politécnico La Fe, Valencia (Spain) after local ethics committee approval (Institutional Review Board: Comité de Ética de Investigación con Medicamentos; approval ID: 2025-0172-1). Written informed consent was obtained from all living patients included in the study. For deceased patients, a waiver of informed consent was granted by the Institutional Review Board in accordance with local regulations for retrospective research. All data were anonymised to ensure patient confidentiality. Patients with advanced ovarian cancer [Federation of Gynecology and Obstetrics (FIGO) stages III–IV] who received 3 or 4 cycles of neoadjuvant chemotherapy prior to interval debulking surgery were included. Patients with synchronous neoplasms, less than 3 or more than 4 cycles of neoadjuvant chemotherapy, those not operated after neoadjuvant chemotherapy, those with histological subtypes different from high-grade serous carcinoma, and those who did not undergo omentectomy during interval debulking surgery were excluded. All patients included in the final analysis completed adjuvant treatment and had a minimum follow-up of 6 months after surgery. The following clinical, surgical, and histopathological variables were collected: age, body mass index, parity, hormonal status (pre- or postmenopausal), date of diagnosis, FIGO stage, status of homologous recombination (HR) genes, surgical time, type of surgery, length of hospital stay, CRS, maintenance therapy with bevacizumab or PARP inhibitors, date of recurrence, death, or loss to follow-up. HR status was assessed through BRCA mutations and HRD testing. Germline mutations were analysed by heteroduplex analysis and capillary gel selective electrophoresis as described by Ganguly et al. (1997). Somatic mutations were evaluated using the Ion Torrent Oncomine BRCA panel (Thermo Fisher Scientific, Waltham, MA, USA). Additionally, HRD status was determined using the SOPHiA DDM Dx Homologous Recombination Deficiency Solution (SOPHiA GENETICS, Saint-Sulpice, Switzerland), with sequencing performed on the NextSeq 500/550 platform (Illumina, San Diego, CA, USA). Patients harbouring pathogenic mutations in BRCA 1/2 or showing HRD were classified as BRCA -mutated/HRD. Conversely, patients with no detectable mutations or those with unavailable test results were collectively categorised as BRCA -wild-type/HR-proficient/unknown. Complete cytoreduction was defined as absence of macroscopic residual disease. Optimal cytoreduction (1 cm macroscopic residual disease) were grouped as incomplete cytoreduction. Regarding core outcome sets, the primary and secondary outcomes of this study (progression-free survival and overall survival) align with established standards in ovarian cancer research to facilitate data synthesis and comparison across studies. Patients or the public were not involved in the design, conduct, or reporting of this research due to the retrospective nature of the study based on institutional clinical databases. Histological review To assess CRS, representative omental sections were included, and the slide with the poorest response to neoadjuvant chemotherapy was evaluated. All cases were evaluated by a pathologist dedicated to gynaecologic oncology (MTDV). CRS scoring was performed according to Böhm et al. (2015): CRS1 (minimal response with abundant residual tumour or minimal chemotherapy effect), CRS2 (partial response with residual tumour and evident fibroinflammatory changes), and CRS3 (complete or near-complete response, with no residual tumour or only scattered microscopic nests <2 mm). In accordance with the literature, patients with CRS1 and 2 were grouped together. Statistical analysis An exploratory analysis was performed to verify variable quality and missing data. Statistical significance was set at p<0.05 for all tests. Univariate analysis of qualitative variables was performed using the Chi-square test, applying Fisher’s exact test when expected frequencies were <5. For quantitative variables, a normality test (Kolmogorov–Smirnov) was performed first. If normal distribution was confirmed, Student’s t test was used to compare means and variances; otherwise, a non-parametric test (Wilcox test) was applied. Survival outcomes were estimated using Kaplan–Meier curves, and differences between groups were assessed using the log-rank test. To identify independent prognostic factors for progression-free survival and overall survival, a multivariate analysis was performed using Cox proportional hazards regression models. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. All statistical analyses were performed using R Studio, version 4.5.1. In accordance with the journal’s guidelines, we will make our data available for independent analysis by a team selected by the Editorial Board, either for additional analyses or to assess the reproducibility of this study in other centers, upon reasonable request. RESULTS During the study period, 1,212 patients with ovarian cancer were surgically treated. After applying the specified inclusion and exclusion criteria, 168 patients were included in the final analysis (Supplementary Figure 1). Baseline characteristics are presented in Supplementary Table 1. The mean age of the patients was 62 ± 4.2 and the majority presented FIGO stage III disease (72.6%). Molecular profiling was performed in 77.3% of the cohort (n=130). In the remaining cases, testing was not feasible due to limited availability or lack of clinical indication at the time of diagnosis. Based on these assessments, 42 patients (25.0%) were classified as BRCA- mutated/HRD, while 24 patients (14.2%) were BRCA- wild-type/HR-proficient. HR status was unknown in 64 patients (38.1%) with BRCA -wild-type tumours ( BRCA- wild-type/HR unknown). Complete and optimal cytoreduction was achieved in 67.8% and 20.8% of patients respectively. Regarding maintenance therapy, 57 patients (33.9%) received PARPi, and 36 (21.4%) received bevacizumab. Patients were categorised into CRS1/2 (n=105, 62.5%) and CRS3 (n=63; 37.5%) (Table 1). No statistically significant differences were observed between groups regarding the clinical variables age, body mass index, parity, or menopause status. Concerning surgical variables, CRS3 was associated with a higher rate of complete cytoreduction (87.3% vs. 56.2%; p<0.001), shorter surgical time (mean 258 ± 84.1 min vs. 297.4 ± 109.5 min; p=0.028) and reduced hospital stay (median 5 ± 2.8 days vs. 7.2 ± 4.2 days; p<0.001). Although patients with CRS3 showed a higher trend toward BRCA- mutated/HRD tumours compared with the CRS1/2 group (33.3% vs 20%), this did not reach statistical significance (p=0.053). The Kaplan–Meier curves for progression-free survival and overall survival are shown in Figure 1. Regarding CRS, the analysis was performed grouping CRS1 and CRS2 vs. CRS3 categories. Patients in the CRS3 group had significantly longer median progression-free survival (24 months, 95% CI 18–32 vs. 16 months, 95% CI 15–20; p=0.008) and overall survival (62 months, 95% CI 46–NA vs. 39 months, 95% CI 32–47; p=0.003) compared with those in CRS1/2 (Figures 1A and 1B, respectively). Complete cytoreduction was also associated with improved progression-free survival (22 months, 95% CI 18–26 vs. 16 months, 95% CI 13–18; p<0.001) and overall survival (47 months, 95% CI 46–62 vs. 34 months, 95% CI 26–53; p= 0.009) (Figures 1C and 1D). A stratified analysis was performed based on BRCA /HR status and use of maintenance PARPi o evaluate the prognostic value of CRS. Among BRCA- wild-type/HR-proficient or unknown status patients, CRS3 was associated with longer progression-free survival (20 months, 95% CI 16–27 vs. 15 months, 95% CI 13–18; p=0.007) and overall survival (62 months, 95% CI 44–NA vs. 35 months, 95% CI 30–47; p=0.006) (Figure 2A-B). Conversely, in BRCA- mutated/HRD subgroup, no significant differences were observed for progression-free survival (p=0.91) or overall survival (p=0.6). Regarding maintenance therapy, in the subgroup of patients who did not receive PARPi, CRS3 was associated with a significantly longer median progression-free survival (20 months, 95% CI 17–32 vs. 15 months, 95% CI 14–18; p=0.005) and overall survival (61 months, 95% CI 46–NA vs 38 months, 95% CI 32–47; p= 0.006) compared with CRS1/2 (Figure 2C-D). On the other hand, no differences were observed in progression-free survival (p=0.75) or overall survival (p=0.37) in those patients receiving PARPi maintenance. In the multivariate Cox regression model for progression-free survival, BRCA- mutated/HRD was the primary independent prognostic factor (HR=0.49, 95% CI 0.28–0.88; p=0.016). Although clinical trends were observed for type of surgery (HR=1.46; 95% CI 0.97–2.19; p=0.072) and CRS3 (HR=0.70, 95% CI 0.47–1.05; p=0.083), they did not reach statistical significance. In this time-to-event model, maintenance treatment with PARPi did not show a significant independent effect after adjusting for molecular status (HR=0.84, 95% CI 0.51–1.41; p=0.513) (Table 2A). For overall survival, CRS3 emerged as the only independent predictor of reduced mortality (HR=0.53, 95% CI 0.31–0.90; p=0.019). BRCA- mutated/HRD tumours (HR=0.56; 95% CI 0.26–1.19; p=0.131) and PARPi maintenance (HR=0.70; 95% CI 0.29–1.72; p=0.439) were not independently associated with overall survival (Table 2B). DISCUSSION Main Findings The present study evaluated the prognostic value of the CRS in a retrospective cohort of patients with advanced high-grade serous carcinoma undergoing interval debulking surgery after neoadjuvant chemotherapy. Our findings suggest that a complete pathological response in the omentum (CRS3) is associated with reduced surgical complexity, including higher rates of complete cytoreduction, shorter surgical times, and decreased hospital stay. While univariate analysis associated both CRS3 and complete cytoreduction with improved survival, this benefit appeared to be influenced by molecular status and maintenance therapy. Specifically, the prognostic value of CRS was primarily observed in patients with BRCA- wild-type/HR-proficient tumours or those who did not receive PARPi. In contrast, its impact was less evident among patients with BRCA- mutated/HRD or those treated with PARPi. In the multivariate Cox model, BRCA- mutated/HRD remained the primary independent prognostic factor for progression-free survival, with a 51% reduction in the risk of recurrence (HR 0.49; p=0.016), while CRS3 emerged as an independent predictor for overall survival, showing a 47% reduction in mortality risk (HR 0.53; p=0.019). PARPi maintenance and the type of surgery did not reach independent statistical significance after adjusting for molecular status and pathological response. Strengths and Limitations A major strength of this study is its clinical homogeneity, including only patients receiving 3–4 cycles of neoadjuvant chemotherapy at a single referral centre with consistent protocols. Furthermore, it provides critical data on the interplay between CRS, BRCA /HR status and PARPi maintenance, variables that remain poorly explored in pathological response studies. The use of Cox models allowed us to differentiate the independent drivers for overall survival versus progression-free survival. Nevertheless, limitations must be acknowledged. A significant proportion of the cohort (38% of BRCA -wild-type patients) lacked HRD testing due to the long recruitment period (2009-2025). While this represents the real-world clinical evolution of HGSC management, it introduces heterogeneity in the ‘unknown’ subgroup. Additionally, the number of patients treated with PARPi was small due to their relatively recent introduction as standard of care, which may have limited the statistical power to detect independent effects in the multivariate models. Finally, the retrospective, monocentric nature of the study means these findings should be interpreted as hypothesis-generating, requiring further validation in prospective, multi-institutional series. Interpretation (in light of other evidence) In our cohort, a trend toward higher frequency of BRCA mutations and/or HRD was observed in CRS3 patients (33.3% vs. 20% p=0.053). This aligns with the biological hypothesis that HRD tumours exhibit increased platinum sensitivity, consistent with the systematic review by Cohen et al. (15) and subsequent cohorts (16–18) . However, discrepancies exist. For instance, some studies found no link between CRS and germline BRCA1/2 mutations but found associations with somatic HRD (19) . Such lack of consensus in other publications may be due to several factors (20–26) . First, many studies evaluate only BRCA 1/2 status, which represent only about 20% of high-grade serous carcinoma mutations (2) underestimating the total contribution of the HRD pathway. Also, the practice of categorising CRS into three separate groups (CRS1, CRS2, CRS3) compromises sample sizes and statistical strength (21,23,26) . Recent data from Marchetti et al. suggest that CRS-based response does not fully reflect the HRD phenotype, as only 45.9% of BRCA-wild-type/CRS3 patients had HRD tumours (26) . Most series published since the validation of Böhm et al. (13) lack molecular or maintenance therapy data. Our study addresses this gap by including PARPi use, which is relevant given its relationship with BRCA- mutated/HRD tumours. Leveraging this integrated clinical and molecular dataset, we first assessed the general prognostic value of CRS. Our results demonstrated that CRS3 is associated with longer progression-free survival (24 vs. 16 months; p=0.008) and longer overall survival (62 vs. 39 months; p=0.003). Moreover, CRS3 patients achieved higher rates of complete cytoreduction and shorter hospital stay, underscoring its utility as a marker of resectability and favourable perioperative outcomes. While the association between CRS3 and progression-free survival is nearly unanimous in both univariate (18,22,24–29) and multivariate analyses (15–17,21,23,30–33) , its impact on overall survival remains a point of divergence in the literature, with several series failing to confirm an independent association with long-term survival (25,27,28,31,34,35) . The lack of independent significance for PARPi in our Cox models likely stems from biological collinearity with molecular status; the clinical benefit of PARPi is intrinsically linked to BRCA or HRD status. When both are included, the molecular deficiency often captures the statistical weight, a phenomenon described in similar integrated analyses (26) . Stratified analysis clarified this: CRS lacked prognostic value among BRCA- mutated/HRD or PARPi-treated patients, suggesting a ‘ceiling effect’ where the profound benefit of targeted therapies may overcome the differentiation offered by the CRS. Conversely, CRS3 showed significantly better outcomes among patients with BRCA- wild-type/HR-proficient tumours or those not receiving PARPi. These findings are consistent with observations by Lee et al. (20,25) but somewhat contrast with Marchetti et al., who found that CRS does have prognostic value in progression-free survival among patients treated with PARPi; however, no results were provided for the group that did not receive maintenance therapy. In their analysis, patients were stratified into BRCA -mutated, BRCA -wild-type/HRD positive, and BRCA -wild-type/HRD negative, observing a prognostic value of CRS exclusively in BRCA -mutated patients (26) . This somewhat challenges the hypothesis of greater chemosensitivity in HRD tumours, although it should be interpreted cautiously given the small sample sizes of the comparison groups. Our results suggest that CRS is particularly useful for identifying a subset of patients who, despite lacking canonical molecular markers of sensitivity, still derive significant benefit from neoadjuvant chemotherapy. Given the scarcity of literature integrating molecular and maintenance data, further studies are essential to validate these findings in the PARP inhibitor era. Conclusions In this cohort, CRS3 was associated with higher rates of complete cytoreduction and improved survival. Multivariate analysis identified HRD status as the primary factor for progression-free survival, while CRS3 independently predicted overall survival. The prognostic impact of CRS was specifically limited to patients with BRCA -wild-type/HR-proficient tumours and those not receiving PARPi maintenance. Practical and Research Recommendations These results suggest that while molecular markers dominate therapeutic decisions, CRS3 remains an essential tool for postoperative risk-stratification in patients with limited therapeutic options. Clinically, since initial diagnostic laparoscopy offers a window for biological characterisation, future research should focus on developing pre-treatment predictive biomarkers—integrating genomic, transcriptomic, or proteomic data from diagnostic biopsies—to anticipate the likelihood of achieving CRS3. Identifying these high-responders at the time of diagnosis could optimise the selection for interval debulking surgery, avoiding the morbidity of primary debulking surgery in poor responders and maximising the probability of achieving no residual disease. Further studies are assential to validate these findings in the evolving PARPi era. Disclosure of interests: None declared Contribution to Authorship: VL and MTDV had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Conceptualisation: VL, MTDV. Methodology: VL. Investigation: MTDV, IR, BM, MA, MMA, LM. Data Curation: MTDV, VL. Formal analysis: VL, MTDV. Writing - Original Draft: MTDV, VL. Writing - Review & Editing: PP-I, AS, PE, SDP, VL. Supervision: VL Details of Ethics Approval: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board (Comité de Ética de Investigación con Medicamentos; date of approval: February 12 th 2025; reference number: 2025-0172-1). Written informed consent was obtained from all living patients prior to their inclusion in the study. For deceased patients, a waiver of informed consent was granted by the Institutional Review Board in accordance with local regulations for retrospective research involving pseudonymised data. Strict confidentiality and data protection measures were maintained throughout the study, ensuring that all patient-level data were fully anonymised. Funding sources: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. REFERENCES 1. Ovarian Cancer Key Stats*. World Ovarian Cancer Coalition [Internet]. [cited 2026 Jan 23]. Available from: https://worldovariancancercoalition.org/about-ovarian-cancer/key-stats/2. The Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011 Jun 30;474(7353):609–15. doi:10.1038/nature101663. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. 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Surg Oncol. 2020 Sep;34:40–5. doi:10.1016/j.suronc.2020.03.001 Supplementary Material File (figure captions_bjog.docx) Download 17.45 KB File (tables_bjog.docx) Download 18.16 KB Information & Authors Information Version history V1 Version 1 30 March 2026 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords carcinoma of the ovary: chemotherapy carcinoma of the ovary: surgery gynaecological oncology pathology: gynaecological Authors Affiliations M. Teresa Dawid de Vera 0000-0002-5259-335X [email protected] Instituto de Investigacion Sanitaria La Fe View all articles by this author Iria Rey Instituto de Investigacion Sanitaria La Fe View all articles by this author Beatriz Montero Hospital Universitari i Politecnic La Fe View all articles by this author Marta Arnáez De La Cruz Instituto de Investigacion Sanitaria La Fe View all articles by this author Manel Montesinos-Albert Instituto de Investigacion Sanitaria La Fe View all articles by this author Pablo Padilla Iserte Instituto de Investigacion Sanitaria La Fe View all articles by this author Luis Matute Instituto de Investigacion Sanitaria La Fe View all articles by this author Ana Santaballa Instituto de Investigacion Sanitaria La Fe View all articles by this author Pilar Eroles Fundacion para la Investigacion del Hospital Clinico de la Comunitat Valenciana View all articles by this author Santiago Domingo del Pozo Hospital Universitari i Politecnic La Fe View all articles by this author VICTOR LAGO Hospital Universitari i Politecnic La Fe View all articles by this author Metrics & Citations Metrics Article Usage 117 views 73 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation M. Teresa Dawid de Vera, Iria Rey, Beatriz Montero, et al. Chemotherapy response score retains prognostic value only in homologous recombination-proficient or PARP inhibitor–naïve high-grade serous carcinoma: a retrospective cohort study. Authorea . 30 March 2026. DOI: https://doi.org/10.22541/au.177485619.93731704/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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