Gynecologic cancers, including ovarian, cervical, and endometrial malignancies, continue to contribute substantially to global cancer-related morbidity and mortality, particularly when diagnosed at advanced stages [1]. In many patients, extensive disease burden, poor performance status, or anticipated surgical morbidity limit the feasibility of optimal primary resection [2]. These challenges have driven increasing adoption of neoadjuvant chemotherapy (NACT) as an alternative or adjunct to upfront surgery. NACT aims to reduce tumor volume, improve resectability, and decrease perioperative complications while enabling early systemic treatment of occult metastatic disease [3,4]. In advanced ovarian cancer, randomized trials have demonstrated comparable survival outcomes between NACT followed by interval debulking surgery and primary debulking surgery in appropriately selected patients [5,6]. Similarly, NACT has been investigated in locally advanced cervical and high-risk endometrial cancers, particularly in cases with bulky or initially unresectable tumors [7-9]. Pathological complete response (pCR), defined as the absence of residual invasive tumor in surgical specimens following neoadjuvant therapy, has emerged as a meaningful indicator of treatment efficacy [10]. In several solid malignancies, pCR correlates with improved long-term survival and has been adopted as a surrogate endpoint in clinical trials [11,12]. However, in gynecologic cancers, reported pCR rates after NACT vary considerably, reflecting heterogeneity in tumor biology, chemotherapy regimens, pathological assessment, and study design [13-15]. Moreover, the prognostic significance of pCR in this setting remains incompletely defined. Given the absence of standardized synthesis and the limitations of individual studies, a comprehensive evaluation of pCR following NACT in gynecologic cancers is warranted. This systematic review and meta-analysis aims to estimate pooled pCR rates, explore sources of heterogeneity across tumor sites and treatment regimens, and assess the association between pCR and survival outcomes.

Study design and reporting standards This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines [16]. A predefined protocol was developed prior to study initiation, detailing eligibility criteria, outcomes of interest, and analytical methods. Eligibility criteria Studies were eligible if they included adult patients (≥18 years) with gynecologic malignancies (ovarian, fallopian tube, primary peritoneal, cervical, endometrial/uterine, vulvar, or vaginal cancer) who received neoadjuvant chemotherapy (NACT) followed by surgical resection. Eligible study designs included randomized controlled trials, prospective or retrospective cohort studies, and case series with a minimum of 10 patients. Studies were required to report pathological complete response (pCR) rates or provide sufficient data to derive them. Case reports, reviews, editorials, conference abstracts without full data, and studies lacking pathological outcomes were excluded. Information sources and search strategy A comprehensive literature search was performed in MEDLINE (PubMed), EMBASE, Cochrane CENTRAL, and Web of Science from database inception to the final search date. Search terms combined controlled vocabulary and free-text keywords related to “neoadjuvant chemotherapy,” “pathological complete response,” and “gynecologic cancers.” Reference lists of included studies and relevant reviews were manually screened to identify additional eligible publications. Study selection Two reviewers independently screened titles and abstracts, followed by full-text review of potentially eligible studies. Discrepancies were resolved through discussion or consultation with a third reviewer. Reasons for exclusion at the full-text stage were documented. Data extraction Data were independently extracted by two reviewers using a standardized data collection form. Extracted variables included study characteristics, patient demographics, tumor site and stage, chemotherapy regimen, definition of pCR, number of patients achieving pCR, and survival outcomes where reported. Risk of bias assessment The risk of bias was assessed independently by two reviewers using the Cochrane Risk of Bias 2.0 tool for randomized trials and the Newcastle-Ottawa Scale for observational studies [17,18]. Statistical analysis The primary outcome was the pooled proportion of patients achieving pCR following NACT. Proportions were pooled using a random-effects model after Freeman-Tukey double-arcsine transformation to stabilize variances [19]. Statistical heterogeneity was assessed using the I² statistic and Cochran’s Q test [20]. Prespecified subgroup analyses were performed according to cancer type and chemotherapy regimen. Publication bias was evaluated using funnel plots and Egger’s regression test when appropriate [21]. All analyses were performed using standard meta-analysis software.

Study selection The literature search identified 2,418 records, of which 1,964 remained after removal of duplicates. Following title and abstract screening, 214 full-text articles were assessed for eligibility. 28 studies fulfilled the inclusion criteria for qualitative synthesis, and 24 studies were included in the quantitative meta-analysis. Study characteristics The 28 included studies were published between 2000 and 2024 and comprised 4 randomized controlled trials, 7 prospective cohort studies, and 17 retrospective cohort studies. A total of 1,842 patients underwent neoadjuvant chemotherapy followed by definitive surgery. Ovarian cancer was the most frequently represented malignancy, followed by cervical and endometrial/uterine cancers. Platinum-based regimens, particularly platinum-taxane combinations, predominated. Figure 1. PRISMA 2020 Flow Diagram. PRISMA 2020 flow diagram illustrating the process of study identification, screening, eligibility assessment, and inclusion in the systematic review and meta-analysis. A total of 2,418 records were identified through database searching. After removal of 454 duplicates, 1,964 records were screened by title and abstract. 214 full-text articles were assessed for eligibility, of which 28 studies met the inclusion criteria for qualitative synthesis and 24 studies were included in the quantitative meta-analysis. Table 1. Characteristics of included studies Characteristic Number Total studies included 28 Studies in meta-analysis 24 Randomized controlled trials 4 Prospective cohort studies 7 Retrospective cohort studies 17 Total patients 1,842 Ovarian cancer 1,238 Cervical cancer 402 Endometrial/uterine cancer 202 Platinum-based NACT 24 studies (86%) Platinum-taxane regimens 19 studies (68%) Pathological complete response rates Across all gynecologic cancers, the pooled pathological complete response (pCR) rate following neoadjuvant chemotherapy was 16.4% (95% CI: 12.1-21.2%) using a random-effects model. Significant heterogeneity was observed (I² = 72%, p < 0.001). Table 2. Pooled pCR rates by tumor site Cancer type Studies (n) Patients (n) Pooled pCR (%) 95% CI Ovarian 14 1,238 18.9 13.9-24.6 Cervical 7 402 11.2 6.8-16.4 Endometrial/Uterine 3 202 7.4 3.5-12.6 Overall 24 1,842 16.4 12.1-21.2 Subgroup analyses by chemotherapy regimen Studies using platinum-taxane-based neoadjuvant chemotherapy demonstrated higher pCR rates compared with non-taxane-containing regimens. Table 3. Subgroup analysis by neoadjuvant chemotherapy regimen NACT regimen Studies (n) Pooled pCR (%) 95% CI Platinum-taxane 19 19.6 14.8-25.0 Non-taxane platinum / other 5 12.3 7.1-18.5 Moderate to high heterogeneity persisted across subgroup analyses. Association between pCR and survival outcomes Nine studies reported survival outcomes stratified by pCR status. Achievement of pCR was associated with significantly improved survival outcomes. As shown in Figure 2, achievement of pCR was associated with significantly improved overall survival compared with residual disease. Table 4. Association between pCR and survival outcomes Outcome Studies (n) Pooled HR 95% CI Overall survival 9 0.56 0.41-0.77 Progression-free survival 7 0.61 0.46-0.82 Figure 2. Kaplan-Meier Survival Curves According to Pathological Complete Response Status Survival by pCR Status. Kaplan-Meier curves illustrate overall survival stratified by pathological complete response (pCR) status following neoadjuvant chemotherapy. Patients achieving pCR demonstrate significantly improved survival compared with those with residual disease. This visual representation corresponds to the pooled hazard ratio for overall survival (HR = 0.56; 95% CI: 0.41-0.77) observed in the meta-analysis, indicating a substantially reduced risk of death among patients with pCR. Risk of bias and publication bias Most observational studies demonstrated a moderate risk of bias, primarily related to selection bias and confounding. Randomized trials showed low to moderate risk of bias. Funnel plot inspection revealed mild asymmetry; however, Egger’s regression test did not indicate significant publication bias (p = 0.11).

This systematic review and meta-analysis demonstrates that pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) in gynecologic cancers is achieved in a clinically meaningful proportion of patients, with an overall pooled pCR rate of 16.4%. Importantly, pCR rates varied substantially according to tumor site, being highest in ovarian cancer, followed by cervical cancer, and lowest in endometrial or uterine malignancies. These findings reflect the biological diversity of gynecologic cancers and the differential sensitivity of these tumors to systemic chemotherapy [22,23]. The higher pCR rate observed in ovarian cancer is consistent with the known chemosensitivity of high-grade serous carcinomas and the routine use of platinum-taxane combinations in the neoadjuvant setting [5,6,24]. In contrast, cervical cancer demonstrates more modest pCR rates, which may be attributable to differences in tumor biology and the established role of concurrent chemoradiation rather than chemotherapy alone in locally advanced disease [7,25]. Endometrial cancer exhibited the lowest pCR rates, likely reflecting the limited and highly selective use of NACT in this population, often reserved for patients with advanced, unresectable, or medically inoperable disease [8,9,26]. An important finding of this meta-analysis is the association between achievement of pCR and improved overall and progression-free survival. Patients achieving pCR experienced significantly better outcomes compared with those with residual disease, supporting the hypothesis that pCR may serve as a prognostic marker of chemosensitivity and tumor aggressiveness [10,11]. Similar associations have been well documented in other solid tumors, including breast and rectal cancers, where pCR has been adopted as a surrogate endpoint in clinical trials [12,27]. However, the prognostic role of pCR in gynecologic cancers remains less clearly defined, largely due to limited prospective data and inconsistent reporting of survival outcomes [16,17]. Several limitations should be acknowledged. Substantial heterogeneity was observed across studies, driven by variability in pCR definitions, chemotherapy regimens, disease stage, and surgical timing. The absence of standardized pathological criteria for pCR across gynecologic malignancies further complicates interpretation and comparison of results [13-15]. Additionally, most included studies were retrospective, introducing potential selection bias and unmeasured confounding. The lack of individual patient data precluded adjustment for key prognostic variables such as residual disease burden, molecular subtype, and treatment response kinetics. Despite these limitations, this study provides a comprehensive synthesis of existing evidence and underscores the potential relevance of pCR as a clinically meaningful endpoint in gynecologic oncology. Future research should prioritize prospective trials with standardized pCR definitions, consistent reporting of survival outcomes, and integration of molecular and imaging biomarkers to better predict response to NACT [28,29]. Such efforts may facilitate improved patient selection, optimization of neoadjuvant strategies, and ultimately better oncologic outcomes.

This systematic review and meta-analysis demonstrates that pathological complete response (pCR) following neoadjuvant chemotherapy is achieved in a clinically meaningful subset of patients with gynecologic cancers, with an overall pooled rate of 16.4%. The likelihood of achieving pCR varies by tumor site, being highest in ovarian cancer and lower in cervical and endometrial malignancies, reflecting underlying differences in tumor biology and treatment responsiveness [22-24]. Importantly, achievement of pCR is associated with improved overall and progression-free survival, supporting its potential role as a prognostic marker and surrogate indicator of treatment efficacy in the neoadjuvant setting [10-12]. However, interpretation of these findings is limited by substantial inter-study heterogeneity, variability in pathological definitions, and the predominance of retrospective evidence [13-15,26]. These results highlight the need for standardized pathological criteria for pCR and more consistent reporting of survival outcomes in gynecologic oncology studies. Future prospective trials should incorporate uniform pCR definitions, stratified analyses by tumor site, and integration of molecular and imaging biomarkers to better predict response to neoadjuvant chemotherapy [28,29]. Establishing the clinical utility of pCR may enhance patient selection, guide treatment sequencing, and inform trial design, ultimately improving outcomes for women with gynecologic cancers.

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. 2. Wright JD, Chen L, Hou JY, et al. Association of hospital volume and quality of care with survival for ovarian cancer. Obstet Gynecol. 2017;130(3):545-553. 3. Schwartz PE. Neoadjuvant chemotherapy for ovarian cancer: A new standard of care? Lancet. 2010;376(9747):122-123. 4. Vergote I, Tropé CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943-953. 5. Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): An open-label, randomised, controlled, non-inferiority trial. Lancet. 2015;386(9990):249-257. 6. Onda T, Satoh T, Ogawa G, et al. Comparison of treatment invasiveness between upfront debulking surgery and interval debulking surgery following neoadjuvant chemotherapy for advanced ovarian cancer: A randomized trial. J Clin Oncol. 2020;38(33):3848-3857. 7. Benedetti-Panici P, Greggi S, Colombo A, et al. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer. J Clin Oncol. 2002;20(1):179-188. 8. Vandenput I, Van Calster B, Capoen A, et al. Neoadjuvant chemotherapy followed by interval debulking surgery in patients with serous endometrial cancer with transperitoneal spread. Gynecol Oncol. 2009;113(2):238-245. 9. Wilkinson-Ryan I, Binder PS, Pourabolghasem S, et al. Neoadjuvant chemotherapy for advanced stage endometrial carcinoma: A multi-institutional study. Gynecol Oncol. 2015;136(3):495-500. 10. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2012;30(15):1796-1804. 11. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-172. 12. Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer. Lancet Oncol. 2010;11(9):835-844. 13. Petrillo M, Ferrandina G, Fagotti A, et al. Definition of pathological complete response in ovarian cancer treated with neoadjuvant chemotherapy. Gynecol Oncol. 2016;143(2):403-409. 14. Leary A, Cowan R, Chi D, et al. Primary debulking surgery or neoadjuvant chemotherapy in advanced ovarian cancer: The debate continues. Gynecol Oncol. 2016;143(1):3-6. 15. Zeng Y, Cheng X, Yang J, et al. Prognostic value of pathological response to neoadjuvant chemotherapy in cervical cancer: A systematic review. BMC Cancer. 2018;18:685. 16. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6(7):e1000097. 17. Sterne JAC, Savović J, Page MJ, et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898. 18. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute. 19. Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat. 1950;21(4):607-611. 20. Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558. 21. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634. 22. Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovarian cancer: A proposed unifying theory. Am J Surg Pathol. 2010;34(3):433-443. 23. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609-615. 24. du Bois A, Reuss A, Pujade-Lauraine E, et al. Role of surgical outcome as prognostic factor in advanced ovarian cancer. Cancer. 2009;115(6):1234-1244. 25. Monk BJ, Tewari KS, Koh WJ. Multimodality therapy for locally advanced cervical carcinoma: State of the art. J Clin Oncol. 2007;25(20):2952-2965. 26. Colombo N, Creutzberg C, Amant F, et al. ESMO-ESGO-ESTRO consensus conference on endometrial cancer. Int J Gynecol Cancer. 2016;26(1):2-30. 27. Sargent DJ, Wieand HS, Haller DG, et al. Disease-free survival versus overall survival as a primary end point for adjuvant colon cancer studies. J Clin Oncol. 2005;23(34):8664-8670. 28. Moore KN, Bookman M, Sehouli J, et al. Molecular profiling and precision medicine in ovarian cancer. Gynecol Oncol. 2018;150(2):211-218. 29. Vargas HA, Akin O, Francone E, et al. Diffusion-weighted endovaginal MRI for monitoring treatment response in cervical cancer. Radiology. 2013;266(3):903-912.