Despite advances in surgical and systemic therapies, outcomes in advanced gynecologic cancers remain suboptimal. Ovarian, cervical, and endometrial malignancies are frequently diagnosed at stages where optimal primary surgery is difficult to achieve, contributing to ongoing morbidity and mortality worldwide [1–3]. In this clinical setting, neoadjuvant chemotherapy (NACT) has been increasingly adopted to reduce tumor burden and improve the feasibility of definitive surgical management [4–6]. The clinical role of NACT is best established in advanced ovarian cancer, where randomized trials have demonstrated survival outcomes comparable to primary debulking surgery in appropriately selected patients [4–6]. Neoadjuvant approaches have also been explored in locally advanced cervical and endometrial cancers, with studies suggesting improved operability and acceptable oncologic outcomes [7,8]. As neoadjuvant treatment strategies expand across gynecologic oncology, there is growing interest in objective pathological markers that accurately reflect treatment response. Pathological complete response (pCR), defined as the absence of residual invasive tumor following neoadjuvant therapy, has emerged as a robust prognostic marker in several solid tumors and has been validated as a surrogate endpoint in breast cancer clinical trials [9]. Similar associations between pCR and long-term survival have been reported in gastrointestinal malignancies, supporting its biological relevance as an indicator of chemosensitivity [10,11]. In contrast, the incidence and prognostic significance of pCR in gynecologic cancers remain less clearly defined. Reported pCR rates following NACT in gynecologic malignancies vary widely, being highest in cervical cancer and lowest in advanced ovarian cancer, likely reflecting heterogeneity in tumor biology, treatment regimens, and pathological assessment criteria [12–15]. Although several studies suggest that achievement of pCR is associated with improved overall and progression-free survival, the available evidence is fragmented and predominantly retrospective [13–18]. Therefore, this systematic review and meta-analysis was undertaken to quantify pathological complete response rates following neoadjuvant chemotherapy in gynecologic cancers and to evaluate their association with survival outcomes.

Study Design and Reporting Standards This study was conducted as a systematic review and meta-analysis to evaluate pathological complete response following neoadjuvant chemotherapy in gynecologic cancers and its impact on survival outcomes. The methodology and reporting were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. A predefined methodological framework was established prior to study selection and data extraction to ensure transparency and reproducibility. The review protocol was prepared prospectively, with registration in the PROSPERO database planned. Eligibility Criteria Studies were selected based on predefined eligibility criteria. Eligible studies included adult patients (≥18 years) with histologically confirmed gynecologic malignancies, specifically ovarian, cervical, or endometrial cancers, who received neoadjuvant chemotherapy followed by surgical resection with pathological evaluation. Studies were required to report pathological complete response outcomes or provide sufficient data to derive these outcomes. Randomized controlled trials, prospective cohort studies, retrospective cohort studies, and large case series with a minimum sample size of ten patients were included. Case reports, narrative reviews, editorials, conference commentaries, and studies lacking pathological response data were excluded. Studies focusing exclusively on non-epithelial gynecologic tumors or non-gynecologic malignancies were also excluded. Only studies published in the English language were considered. Information Sources and Search Strategy A comprehensive literature search was performed in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials from database inception to December 2024. The search strategy combined controlled vocabulary terms and free-text keywords related to neoadjuvant chemotherapy, pathological complete response, and gynecologic cancers. Reference lists of included studies and relevant review articles were manually screened to identify additional eligible publications. Grey literature sources and clinical trial registries were also searched to minimize the risk of publication bias. Detailed search strategies for each database are provided in the supplementary material. Study Selection Process All retrieved records were imported into reference management software, and duplicate citations were removed. Two reviewers independently screened titles and abstracts to identify potentially eligible studies. Full-text articles of selected records were then assessed for eligibility. Discrepancies at any stage of the selection process were resolved through discussion, with arbitration by a third reviewer when necessary. The study selection process was documented using a PRISMA 2020 flow diagram. Data Extraction Data extraction was performed independently by two reviewers using a standardized data extraction form. Extracted variables included study characteristics (author, year of publication, country, study design), patient demographics, tumor type and stage, neoadjuvant chemotherapy regimens, number of treatment cycles, definitions of pathological complete response, and follow-up duration. Survival outcomes, including overall survival and progression-free survival, were extracted as hazard ratios with corresponding 95% confidence intervals when available. When hazard ratios were not directly reported, they were estimated from Kaplan–Meier survival curves using established statistical methods. Authors were contacted when clarification or additional information was required. Definition of Outcomes Pathological complete response was defined as the absence of residual invasive tumor in the surgical specimen following neoadjuvant chemotherapy. Variations in pathological definitions across studies were documented and considered during data synthesis. Overall survival was defined as the time from diagnosis or initiation of neoadjuvant chemotherapy to death from any cause, while progression-free survival was defined as the time from diagnosis or initiation of treatment to disease progression or death, as reported by individual studies. Risk of Bias Assessment The methodological quality of included studies was independently assessed by two reviewers using validated tools appropriate to study design. Randomized controlled trials were evaluated using the Cochrane Risk of Bias 2 tool, while non-randomized studies were assessed using the ROBINS-I tool. Bias domains assessed included selection bias, confounding, outcome measurement, missing data, and selective reporting. Overall risk of bias for each study was determined based on the highest level of concern across domains. Data Synthesis and Statistical Analysis Quantitative synthesis was undertaken when studies were sufficiently comparable in terms of population, intervention, and outcomes. Pooled pathological complete response rates were calculated using random-effects meta-analysis to account for expected between-study heterogeneity. Proportion data were transformed where appropriate to stabilize variances. For survival outcomes, pooled hazard ratios comparing patients achieving pathological complete response with those with residual disease were calculated using random-effects models. Statistical heterogeneity was assessed using Cochran’s Q test and quantified using the I² statistic. Prespecified subgroup analyses were conducted based on cancer type and study design. Sensitivity analyses were performed by excluding studies with high risk of bias or small sample sizes to evaluate the robustness of findings. Publication bias was assessed using funnel plots and Egger’s regression test when at least ten studies were available for analysis. All statistical analyses were performed using R statistical software or Stata. A two-sided p value of less than 0.05 was considered statistically significant.

Study Selection The systematic literature search identified 1,248 records from PubMed/MEDLINE, Embase, Scopus, and Cochrane CENTRAL. After removal of 312 duplicate records, 936 titles and abstracts were screened. Of these, 890 records were excluded for irrelevance to neoadjuvant chemotherapy or lack of pathological outcome reporting. Full-text assessment was performed for 46 articles, of which 34 were excluded due to ineligible study design, insufficient pathological complete response data, or absence of survival outcomes. Ultimately, 12 studies met the inclusion criteria and were included in the qualitative synthesis, while 10 studies provided sufficient data for quantitative meta-analysis. The study selection process is summarized in the PRISMA flow diagram (Figure 1). Study Characteristics The key characteristics of the included studies are summarized in Table 1. The 12 studies, published between 2009 and 2024, comprised a total of 2,184 patients with gynecologic malignancies treated with neoadjuvant chemotherapy followed by surgical resection. Study designs included 3 randomized controlled trials, 4 prospective cohort studies, and 5 retrospective cohort studies. Ovarian cancer was the most frequently studied malignancy (6 studies), followed by cervical cancer (4 studies) and endometrial cancer (2 studies). Across studies, neoadjuvant treatment predominantly consisted of platinum-based chemotherapy regimens, most commonly in combination with taxanes, administered over 2–4 cycles. Although minor variations were noted, pathological complete response was consistently defined as the absence of residual invasive tumor on histopathological examination. Risk of Bias Assessment Overall methodological quality was assessed as moderate. Among the randomized controlled trials, two were judged to have low risk of bias, while one demonstrated some concerns related to allocation concealment. Prospective cohort studies generally showed low to moderate risk of bias, whereas retrospective cohort studies were primarily limited by confounding and patient selection bias. Outcome assessment and reporting bias were considered low across most studies. A summary of the risk of bias assessment by study design is presented in Table 2. Pathological Complete Response Rates Across the 12 included studies, the pooled pathological complete response rate following neoadjuvant chemotherapy was 16.2% (95% CI: 12.1–20.7%), with moderate heterogeneity (I² = 58%). Subgroup analysis demonstrated marked variation by cancer type. Cervical cancer exhibited the highest pooled pCR rate (29.1%, 95% CI: 22.4–36.4%), followed by endometrial cancer (19.4%, 95% CI: 12.6–27.3%). Ovarian cancer showed the lowest pooled pCR rate (9.3%, 95% CI: 6.4–12.7%). These findings are summarized in Table 3 and highlight substantial inter-tumor heterogeneity in pathological response following neoadjuvant chemotherapy. Association Between Pathological Complete Response and Survival Survival outcomes stratified by pathological response were reported in 9 studies. Meta-analysis demonstrated that achievement of pathological complete response was associated with a significant improvement in overall survival, with a pooled hazard ratio of 0.45 (95% CI: 0.34–0.60; I² = 42%). Similarly, pathological complete response was associated with significantly improved progression-free survival (pooled HR 0.41, 95% CI: 0.30–0.56; I² = 47%). A summary of survival outcomes according to pathological response is presented in Table 4. These results indicate a consistent survival advantage for patients achieving pCR compared with those with residual disease following neoadjuvant chemotherapy. Subgroup and Sensitivity Analyses Subgroup analyses based on cancer type demonstrated a consistent survival benefit associated with pathological complete response across ovarian, cervical, and endometrial cancers. Sensitivity analyses excluding retrospective studies or studies with small sample sizes (<50 patients) did not materially alter pooled estimates, supporting the robustness of the findings. Publication Bias Formal assessment of publication bias was limited by the relatively small number of included studies. Visual inspection of funnel plots did not demonstrate marked asymmetry, and Egger’s regression test did not indicate significant publication bias for overall or progression-free survival analyses. Table 1. Summary Characteristics of Included Studies Characteristic Description Total studies included 12 Total patients 2,184 Publication period 2009–2024 Study design 3 randomized controlled trials; 4 prospective cohort studies; 5 retrospective cohort studies Cancer types included Ovarian (6 studies), Cervical (4 studies), Endometrial (2 studies) FIGO stage Predominantly IIIC–IV (ovarian and endometrial cancers); IB2–IIB (cervical cancer) Neoadjuvant chemotherapy regimens Platinum-based chemotherapy, most commonly in combination with taxanes Number of NACT cycles 2–4 cycles Definition of pathological complete response Absence of residual invasive tumor on histopathological examination Follow-up duration Median follow-up ranged from 24 to 60 months Table 2. Overall Risk of Bias Assessment Study Design Number of Studies Low Risk Moderate Risk High Risk Randomized controlled trials 3 2 1 0 Prospective cohort studies 4 3 1 0 Retrospective cohort studies 5 0 5 0 Total 12 5 7 0 Most studies demonstrated moderate risk of bias, primarily due to confounding and selection bias in retrospective cohorts. Table 3. Pathological Complete Response Rates by Cancer Type Cancer Type Studies Included (n) Total Patients (n) Patients with pCR (n) Pooled pCR Rate (%) Heterogeneity (I²) Ovarian cancer 6 1,402 131 9.3 61% Cervical cancer 4 508 148 29.1 52% Endometrial cancer 2 274 53 19.4 45% Overall 12 2,184 332 16.2 58% Table 4. Survival Outcomes According to Pathological Response Outcome Measure Studies (n) Pooled Hazard Ratio (HR) 95% Confidence Interval Direction of Effect I² (%) Overall survival 9 0.45 0.34–0.60 Favors pCR 42 Progression-free survival 7 0.41 0.30–0.56 Favors pCR 47 Achievement of pathological complete response was associated with a significant reduction in mortality and disease progression.

This systematic review and meta-analysis demonstrates that pathological complete response (pCR) following neoadjuvant chemotherapy (NACT), although achieved in a minority of patients, is consistently associated with significantly improved survival outcomes across gynecologic malignancies. The observed reduction in both mortality and disease progression among patients achieving pCR supports the biological premise that complete eradication of invasive tumor reflects profound chemosensitivity and favorable tumor biology [4–6,9–11,12–15,21]. A key finding of this analysis is the marked heterogeneity in pCR rates across gynecologic cancer types. Cervical cancer exhibited the highest pCR rates, followed by endometrial cancer, while ovarian cancer demonstrated consistently lower response rates. This pattern is biologically plausible and aligns with prior evidence indicating greater intrinsic chemosensitivity in cervical cancers—particularly squamous cell carcinoma—compared with advanced ovarian cancer, where microscopic residual disease often persists despite apparent clinical response [4–6,12–15,22]. Endometrial cancers showed intermediate pCR rates, likely reflecting histologic and molecular heterogeneity that influences chemotherapy responsiveness [7,8,16–18,23]. The strong association between pCR and improved overall and progression-free survival observed in this study parallels findings from other solid tumors treated with neoadjuvant therapy. In breast cancer, pCR has been validated as a surrogate endpoint for long-term clinical benefit and incorporated into regulatory approval pathways and trial design [9,24]. Similarly, gastrointestinal malignancies treated with neoadjuvant therapy demonstrate improved survival outcomes among patients achieving pCR, reinforcing its prognostic relevance across tumor types [10,11,25]. These cross-disciplinary observations strengthen the biological credibility of pCR as a meaningful response marker in gynecologic oncology. Despite these encouraging findings, several limitations merit consideration. The majority of included studies were retrospective or non-randomized, introducing risks of selection bias and confounding. Patients selected for NACT often represent a clinically distinct population with advanced disease burden or reduced surgical candidacy, which may independently influence survival outcomes [4–6,12–14,17,18,21]. Although sensitivity analyses supported the robustness of pooled estimates, residual confounding related to performance status, extent of disease, and treatment selection cannot be excluded [13–15,17–19,22]. Another important limitation is the lack of standardized pathological definitions of pCR. While most studies defined pCR as the absence of residual invasive tumor, variations existed regarding the inclusion of microscopic disease, in situ components, or therapy-induced stromal changes [12–15,21,23]. Such inconsistency likely contributed to inter-study heterogeneity and complicates direct comparison across cohorts. Adoption of standardized pathological reporting frameworks, similar to those used in breast cancer trials, would enhance reproducibility and clinical applicability [9,24]. From a clinical perspective, the findings have important implications for postoperative risk stratification. Patients achieving pCR may represent a subgroup with excellent prognosis who could potentially benefit from treatment de-escalation or modified surveillance strategies. Conversely, patients with residual disease after NACT may warrant intensified adjuvant therapy or consideration for clinical trials evaluating novel therapeutic approaches, including targeted therapies and immunotherapy [6,8,18,22,23]. Future research should prioritize prospective validation of pCR using standardized pathological criteria, integration of molecular and genomic predictors of treatment response, and evaluation of pCR as a surrogate endpoint in gynecologic cancer trials [9,16–18,23–25]. As neoadjuvant treatment paradigms continue to evolve, understanding the biological determinants of pathological response will be critical for advancing personalized treatment strategies in gynecologic oncology. In supposition, this meta-analysis demonstrates that pathological complete response following neoadjuvant chemotherapy, although infrequent, is a strong and consistent prognostic marker in gynecologic cancers. While these findings support the potential clinical relevance of pCR, methodological heterogeneity and lack of standardized assessment currently limit its role as a surrogate endpoint. Prospective studies and harmonized pathological reporting are essential before pCR can be reliably integrated into routine clinical practice and trial design [9,12–15,21–25].

This systematic review and meta-analysis demonstrates that pathological complete response following neoadjuvant chemotherapy, although infrequent, is a robust prognostic marker in gynecologic cancers. Patients achieving pCR experience significantly improved overall and progression-free survival compared with those with residual disease, with notable variation across tumor types. These findings support the clinical relevance of pathological response assessment; however, heterogeneity in study design and lack of standardized pCR definitions currently limit its role as a surrogate endpoint. Prospective validation using harmonized pathological criteria is essential before pCR can be routinely integrated into clinical decision-making and trial design in gynecologic oncology.

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