The prognosis impact of NACT-IDS and PDS in advanced ovarian cancer: a systematic review and meta-analysis

Abstract

Objective

We aimed to explore the prognostic implications of neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS) compared to primary debulking surgery (PDS) in patients diagnosed with advanced ovarian cancer by meta-analysis.

Methods

The search was conducted across PubMed, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure, and the Chinese BioMedical Literature Database to identify pertinent studies examining the prognostic implications of NACT-IDS versus PDS in patients with advanced ovarian cancer.

Results

As of September 11, 2023, a total of 29 articles were ultimately included, encompassing 12,916 patients with advanced ovarian cancer in this meta-analysis. NACT-IDS groups exhibited a higher satisfactory tumor reduction rate (odds ratio [OR]=2.06; 95% confidence interval [CI]=1.53 to 2.76; p<0.001). NACT-IDS effectively reduced the risk of adverse cardiac events (OR=0.36; 95% CI=0.17 to 0.80; p=0.012), surgical site infections (OR=0.42; 95% CI=0.29 to 0.60; p<0.001), and embolic complications (OR=0.43; 95% CI=0.24 to 0.75; p=0.003) in patients with advanced ovarian cancer. Compared to NACT-IDS therapy for International Federation of Gynecology and Obstetrics (FIGO) III–IV ovarian cancer patients (OR=1.66; 95% CI=1.24 to 2.23; p=0.009), NACT-IDS groups exhibited a higher satisfactory tumor reduction rate for FIGO IIIC–IV (OR=2.35; 95% CI=1.50 to 3.70; p<0.001).

Conclusion

NACT-IDS effectively enhances the satisfactory tumor reduction rate, especially for patients with stage IIIC and IV, and decreases postoperative complications among patients with advanced ovarian cancer.

INTRODUCTION

Ovarian cancer (OC) presents as a highly malignant tumor worldwide, characterized by a notably high fatality rate within the spectrum of malignancies affecting the female reproductive system. Research reports have consistently highlighted its global impact, with over 200,000 new cases of OC diagnosed annually [1]. OC is insidious in its onset, often manifesting nonspecific clinical symptoms in its early stages, compounded by ineffective early screening methods. Typically, the disease reaches an advanced stage by initial diagnosis, classified as stage III or IV by the International Federation of Gynecology and Obstetrics (FIGO) [2]. Gastrointestinal symptoms, including abdominal effusion, distension, and anorexia, mark late-stage presentations. Furthermore, some patients exhibit severe cachexia symptoms, such as weight loss and tumor-related anemia. The prognosis remains discouraging, with a 5-year survival rate of less than 30% [3].

The standard treatment approach in advanced OC entails primary debulking surgery (PDS) accompanied by adjuvant platinum-based chemotherapy [4]. The primary goal of PDS is the maximally feasible removal of observable disease, ideally to a state where no discernible residual disease exists within the abdominal cavity. Nevertheless, since most women present with widespread disease that cannot be entirely eradicated through PDS alone, platinum-based chemotherapy is also imperative for targeting unresectable or microscopically residual disease.

However, not all patients with advanced OC are eligible for achieving an optimal PDS. Some individuals with advanced OC present with a substantial tumor burden. The lesions have extensively infiltrated and metastasized throughout the pelvic and abdominal cavities, often accompanied by a significant volume of pleural and ascitic effusion, rendering complete resection challenging. Conversely, elderly patients with compromised overall health may manifest various contraindications for surgical intervention, rendering them unsuitable for immediate surgical management. Meantime, most OC patients exhibit sensitivity to chemotherapy, with chemotherapy efficacy reaching as high as 80%–90%. In this context, the concept of neoadjuvant chemotherapy (NACT) combined with interval debulking surgery (IDS) emerged. This approach entails administering a defined course of NACT before proceeding with IDS, followed by platinum-based chemotherapy as a foundational treatment [5]. NACT involves the administration of chemotherapy before surgical intervention for malignant tumors. The precondition for NACT is the acquisition of cytological or histological tumor evidence. NACT reduces the tumor burden to varying degrees, mitigates tissue reactive edema, diminishes adhesions between tumors and adjacent tissues, and establishes a favorable opportunity for effective tumor cytoreduction [6].

In recent years, the utilization of NACT-IDS in managing advanced OC patients has garnered considerable attention from numerous scholars. Multiple investigations have affirmed the capacity of NACT-IDS to enhance the rate of satisfactory tumor reduction [7,8,9,10]. For example, Zhang et al. showed that a defined course of NACT before proceeding with IDS can improve the surgical conditions of ovarian cancer patients, which is beneficial for increasing the Optimal debulking rate [9]. This was also confirmed by Bian et al. [8] reviewing 339 epithelial ovarian cancer patients treated at West China Women’s and Children’s Hospital. Additionally, a growing body of evidence underscores the association between NACT-IDS and an improved quality of life and reduced incidence of postoperative adverse events [9,11,12]. Studies also showed that the patients treated with NACT-IDS were not superior to those treated with PDS. A previous study showed that 670 among patients with epithelial ovarian carcinoma, survival after NACT followed by IDS is similar to survival after PDS followed by chemotherapy [12]. Most of the study populations were patients with stage III and IV OC or stage IIIC and IV OC. However, the difference in efficacy between NACT-IDS and PDS in patients with stage III and IV OC and stage IIIC and IV OC was not explored systematically. Meanwhile, the clinical adoption of NACT-IDS remains a topic of ongoing debate. This study undertakes a meta-analysis of postoperative factors pertinent and subgroups of patients to advanced OC patients subjected to NACT-IDS and PDS, aiming to deliver an objective and substantiated basis for evidence-based medical practice. The ultimate aim is to guide clinical application, thereby advancing survival rates and the overall quality of life among advanced OC patients.

METHODS

1. Search strategy

A systematic computerized search encompassing 6 online databases, including PubMed, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure, and the Chinese BioMedical Literature Database (CBM), was executed. The quest aimed to retrieve information related to NACT combined with IDS and PDS, as applied in advanced OC, and the search period ranged from the inception of these databases to September 11, 2023. The search strategy combined subject headings and keywords comprehensively. Subject headings included “ovarian neoplasms,” “ovarian cancer,” “neoadjuvant therapy,” “neoadjuvant chemotherapy,” “debulking surgery,” and “Cytoreduction Surgical Procedures.” Additionally, reference lists of retrieved documents and relevant meta-analyses and reviews were scrutinized to maximize document retrieval. A manual search was performed to mitigate the risk of overlooking pertinent documents in automated database searches, supplementing the results obtained from the computerized search.

2. Inclusion and exclusion criteria

Two researchers carried out the process of evaluation independently. They meticulously reviewed the retrieved studies’ titles, abstracts, and full texts, adhering to the predefined inclusion and exclusion criteria. Discrepancies arising between the 2 researchers regarding the inclusion of a study were settled through discussion.

Inclusion criteria for this study were as follows: 1) The research encompassed randomized controlled trials (RCTs) and observational studies conducted in either English or Chinese; 2) The study population consisted of patients previously diagnosed with primary FIGO stage III–IV OC who had not undergone radiotherapy or chemotherapy; 3) The study had the NACT-IDS experimental and PDS control groups. The NACT-IDS experimental group comprised patients with advanced OC who initially received no more than 4 cycles of platinum-based chemotherapy upon confirmed pathological diagnosis. Subsequently, they underwent IDS at appropriate intervals to achieve a satisfactory tumor reduction rate. The PDS control group included patients diagnosed with advanced OC who initially underwent cytoreduction surgery or laparotomy due to a significant pelvic mass, supplemented by 3–6 cycles of platinum-based chemotherapy to optimize survival; and 4) The clinical research must have clearly defined criteria for a satisfactory tumor reduction rate and a specific follow-up cutoff period. Furthermore, it should encompass relevant survival indicators, particularly overall survival (OS) and progression-free survival (PFS).

Exclusion criteria for this study included: 1) Studies that did not fall under RCTs, observational studies, or studies with inaccurate or incomplete literature information; 2) Studies involving patient populations not diagnosed with FIGO stage III–IV OC; 3) Studies that did not incorporate NACT; 4) Studies lacking a direct comparison between NACT-IDS and PDS; and 5) Studies with a less-than-rigorous research design, inappropriate statistical methods, or results reported with significant bias.

3. Data extraction and quality assessment

Using a pre-designed data extraction form, two researchers independently performed data extraction for the included studies and established a comprehensive database. This database encompassed the following details and pertinent information from the included studies: 1) Fundamental particulars of the included studies, including the first author’s name, publication year, study location, study design, sample size, and the OC stage of the study population, as well as the chemotherapy regimen; 2) Assessment of surgical procedures and prognostic survival indicators, comprising the satisfactory tumor reduction rate, postoperative complications, OS, and PFS. The 2 researchers completed data extraction, and cross-verified the extracted data to ensure data consistency.

The risk of bias in RCTs was evaluated using the modified Jadad scale. Non-randomized controlled trials were assessed for bias using the Newcastle-Ottawa Scale (NOS). Retrospective studies were evaluated using the JBI Case Series Critical Assessment Checklist. When the quality assessment outcomes of a particular study diverged between the two researchers, the inconsistency was resolved through discussion. This final evaluation was based on the assessments conducted by the initial two researchers and the accompanying rationales.

4. Statistical analysis

We utilized Stata 17.0 software to process the extracted literature data [13,14]. The results of each study were visually represented using forest plots. Heterogeneity among the included study results was assessed through two methods: the Q test (χ² test) and the I² test. These tests quantified the extent of heterogeneity by combining the p-value and I². Initially, the Q test assessed heterogeneity: if p>0.05, it indicated homogeneity among the studies; conversely, if p≤0.05, it indicated heterogeneity. Subsequently, quantitative analysis of heterogeneity was based on I²: if I²<50%, it signaled small heterogeneity within the acceptable range among the included studies; in contrast, I²≥50% suggested substantial heterogeneity among the studies. For meta-analysis, if between-study heterogeneity was low (p>0.05 and I²<50%), the fixed-effects model was employed, whereas if substantial heterogeneity was present between studies (p≤0.05 or I²≥50%), the random-effects model was used. Additionally, sensitivity analysis was conducted to assess the stability and reliability of the combined results. For dichotomous variables and continuous variables, the evaluation index was reported using odds ratio (OR) and standardized mean difference (SMD) with their 95% confidence intervals (95% CIs), respectively. Finally, we employed the Egger linear regression method to examine potential publication bias. A p-value ≤0.05 implied the presence of publication bias [15].

RESULTS

1. Literature screening process, research basic characteristics, and quality assessment

A total of 3,675 articles were detected in 6 databases, including 1,348 articles in PubMed, 494 articles in Cochrane, 1,678 articles in Web of Science, 119 articles in China National Knowledge Infrastructure, 27 articles in Wanfang Data, and 9 articles in CBM. Zero articles were obtained through manual search. After deleting 1,698 articles that were repeatedly retrieved, we retained 32 articles by reading the titles and abstracts. Then, 3 studies among the articles that participated in the full-text evaluation were excluded because the data could not be obtained or, provided or converted into data that could be effectively used. Finally, 29 articles were included in the meta-analysis (Fig. S1). This review included 12,916 patients with advanced OC for meta-analysis. And the chemotherapy regimens include paclitaxel and carboplatin, paclitaxel and cisplatin, cisplatin and cyclophosphamide, cisplatin, bleomycin and etoposide (BEP), etc. The primary characteristics of the 29 studies included in the meta-analysis after screening are shown in Table 1 [7,8,9,10,11,12,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40].

Table 1. Characteristics of the studies included in the meta-analysis.

Study, year	Nation	Study population	Number of patients			Mean age (yr)		Optimal debulking rate (%)		Outcomes
			NACT-IDS	PDS	Total	NACT-IDS	PDS	NACT-IDS	PDS
Ahmad et al., 2015 [16]	India	FIGO IIIC–IV	32	19	51	54.4	51.8	NA	NA	ACE, F, SSI
Zhang et al., 2023 [9]	China	FIGO III–IV	19	21	40	24	24	100	85.71	ODR, F, SSI, H.GE
Onda et al., 2016 [11]	Japan	FIGO III–IV	150	147	297	60.5	59	71.33	63.27	ODR, F, E, GE
Ren et al., 2015 [33]	China	FIGO IIIC–IV	32	376	408	60	55	56.25	53.46	ODR, OS
Mueller et al., 2016 [30]	USA	FIGO III–IV	154	432	586	65	62	55.03	47.00	ODR, PFS
Li and Du, 2019 [25]	China	FIGO IIIC–IV	94	84	178	NA	NA	NA	NA	OS, PFS
Vergote et al., 2010 [12]	Europe	FIGO IIIC–IV	334	336	570	63	62	71.26	39.00	ODR, SSI, E, H, GE
Stewart et al., 2016 [7]	Canada	FIGO III–IV	156	178	334	60	56	80.00	68.00	ODR
Skof et al., 2016 [35]	Slovenia	FIGO III	80	80	160	64.8	60.2	52.50	42.50	ODR
Rauh-Hain et al., 2017 [31]	USA	FIGO III–IV	2,935	2,935	5,870	56	56	NA	NA	ODR, OS
Luo et al., 2016 [27]	Korea	FIGO IIIC–IV	58	283	341	54.5	53.5	84.48	46.29	ODR
Georgeena et al., 2016 [21]	India	FIGO IIIC–IV	78	50	128	NA	NA	94.87	90.00	ODR
Bian et al., 2016 [8]	China	FIGO IIIC–IV	114	225	339	53	50.7	70.20	65.80	ODR, OS, PFS, ACE, SSI, E, H, GE
Zhao et al., 2015 [39]	China	FIGO III–IV	61	46	107	56	57.4	60.66	45.65	ODR
Rosen et al., 2014 [34]	Canada	FIGO IIIC–IV	143	183	326	61.6	56.7	78.32	63.93	ODR
Worley et al., 2013 [38]	USA	FIGO IIIC–IV	40	125	165	74	75	85.00	74.40	ODR, ACE, E, GE
Taşkın et al., 2013 [37]	Turkey	FIGO IIIC–IV	74	223	297	60.5	56.4	60.81	63.23	ODR
Zheng and Gao, 2012 [40]	China	FIGO IIIC–IV	30	37	67	55.8	54.5	60.00	32.43	ODR, OS
Rauh-Hain et al., 2012 [32]	USA	FIGO IV	45	176	221	62	62	71.11	57.95	ODR, OS
Milam et al., 2011 [29]	USA	FIGO III–IV	46	217	263	61	57	80.43	55.30	ODR
Hou et al., 2007 [22]	USA	FIGO IIIC–IV	63	109	172	64.1	62.7	95.24	70.64	ODR
Inciura et al., 2006 [23]	Lithuania	FIGO III–IV	213	361	574	NA	NA	62.91	67.04	ODR, OS, PFS
Kehoe et al., 2015 [24]	UK and New Zealand	FIGO IIIC–IV	219	255	474	65	66	67.12	37.65	ODR, ACE, F, SSI, E, H, GE
Markauskas et al., 2014 [28]	Denmark	FIGO IIIC–IV	167	165	332	66	65	72.46	84.24	ODR, ACE, SSI, E, H, GE
Nantasupha et al., 2022 [10]	Thailand	FIGO III–IV	75	128	203	56	55	65.33	39.06	ODR
Tan et al., 2023 [36]	China	FIGO III–IV	67	39	106	59.2	54.9	NA	NA	OS
Chen et al., 2020 [17]	China	FIGO III–IV	27	35	62	57.41	51.66	NA	NA	SSI, GE
Lu et al., 2023 [26]	China	FIGO IIIC–IV	52	72	124	60.87	59.25	84.62	25.00	ODR, SSI, E, GE
Fang and Tan, 2020 [20]	China	FIGO III–IV	67	54	121	52.8	55.1	71.64	59.26	ODR, SSI

ACE, adverse cardiac events; E, embolism; F, fever; FIGO, International Federation of Gynecology and Obstetrics; GE, gastrointestinal events; H, hemorrhage; IDS, interval debulking surgery; NA, not applicable; NACT, neoadjuvant chemotherapy; ODR, optimal debulking rate; OS, overall survival; PDS, primary debulking surgery; PFS, progression-free survival; SSI, surgical site infection.

A randomized study was assessed utilizing the modified Jadad scale, which appraises four key dimensions: random sequence generation, randomization concealment, blinding, and withdrawal [41]. Non-randomized studies were evaluated using the NOS, which categorizes studies into three dimensions based on eight items: population selection, comparability, and outcome assessment (for cohort studies) or exposure assessment (for case-control studies) [42]. Each study’s detailed quality assessment criteria and scores were provided in Table S1.

2. Optimal debulking rate

Twenty-four articles within the selected literature reported satisfactory tumor reduction rates for both surgical methods, encompassing 2,465 patients in the NACT-IDS group and 4,279 patients in the PDS group. Heterogeneity testing revealed significant heterogeneity among the studies (p<0.001, I²>82.6%). Consequently, a random-effects model was applied for the meta-analysis. As shown in Fig. 1, the OR for the satisfactory tumor reduction rate between the NACT-IDS and PDS groups was 2.06 (95% CI=1.53 to 2.76; p<0.001), signifying a statistically significant difference in favor of the NACT-IDS group, which exhibited a higher satisfactory tumor reduction rate.

Fig. 1. Forest plot about the pooled results of optimal debulking rate in total.

CI, confidence interval; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OR, odds ratio; PDS, primary debulking surgery.

3. Survival

A total of 7 papers provided statistical data on OS, encompassing 3,485 patients in the NACT-IDS group and 4,057 patients in the PDS group. The included studies exhibited substantial heterogeneity, with an I² statistic of 99.9% and a p-value <0.001. Accordingly, the random-effects model was employed for meta-analysis. The forest plot illustrated an SMD ratio of OS between the NACT-IDS and PDS groups (SMD=−1.79; 95% CI=−4.53 to 0.94; p=0.198) (Fig. 2A). This finding suggested no statistically significant difference in OS between the experimental and control groups (Table S2). In summary, the results indicated that NACT-IDS did not significantly prolong OS in patients diagnosed with advanced OC.

Fig. 2. Forest plot about the pooled results in total. (A) OS and (B) PFS.

CI, confidence interval; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OS, overall survival; PDS, primary debulking surgery; PFS, progression-free survival; SMD, standardized mean difference.

This study encompassed 4 documents that reported PFS, collectively covering 575 patients in the NACT-IDS group and 1,102 patients in the PDS group. The included studies displayed substantial heterogeneity, reflected in an I² statistic of 99.8% and p<0.001. Consequently, a random-effects model was employed for the analysis. The forest plot revealed an SMD ratio between the NACT-IDS and PDS groups (SMD=−0.56; 95% CI=−4.33 to 3.21; p=0.770) (Fig. 2B). In summary, the findings indicated that NACT-IDS did not significantly extend PFS in patients diagnosed with OC.

4. Postoperative complications

This research encompassed 9 articles that addressed postoperative complications, with a specific focus on 5 articles concerning cardiac adverse events, 4 articles on fever, 9 articles on surgical site infections, 7 articles on embolic events, 5 articles regarding bleeding, and 9 articles discussing gastrointestinal events. The patient count for the NACT-IDS and PDS groups was 572/789, 422/444, 1,031/1,182, 1,078/1,327, 853/1,002, and 1,124/1,383, respectively.

The heterogeneity (I²) among the studies in the adverse cardiac event subgroup was found to be zero, with p=0.810, as determined using a fixed-effects model. The forest plot demonstrated that, compared to the PDS group, the NACT-IDS group effectively reduced the risk of adverse cardiac events in patients with advanced OC (OR=0.36; 95% CI=0.17 to 0.80; p=0.012) (Fig. 3A). Similarly, within the postoperative surgical site infection subgroup, the I² for heterogeneity was zero, with p= 0.826, signifying low heterogeneity. As seen in the forest plot, compared to the PDS group, the NACT-IDS group significantly reduced the risk of surgical site infection in patients with advanced OC (OR=0.42; 95% CI=0.29 to 0.60; p<0.001) (Fig. 3A). The analysis revealed a heterogeneity (I²) of 22.2% among the included studies in the embolization subgroup, with a corresponding p=0.260. The fixed-effects model was employed for these calculations. Examination of the forest plot demonstrated that, when compared with the PDS group, the NACT-IDS group effectively mitigated the risk of embolism in patients with advanced OC (OR=0.45; 95% CI=0.25 to 0.80; p=0.007) (Fig. 3A). Within the postoperative fever subgroup, the I² for heterogeneity was also zero, with p=0.871, signifying low heterogeneity. Fig. 3A showed no statistically significant difference in postoperative fever between the experimental group and the control group (OR=0.78; 95% CI=0.27 to 2.23; p=0.637) (Fig. 3A).

Fig. 3. Forest plot about the pooled results of postoperative complications in total. (A) The adverse cardiac event, the postoperative surgical site infection, embolism, the postoperative fever and (B) bleeding complications, gastrointestinal complications.

CI, confidence interval; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OR, odds ratio; PDS, primary debulking surgery.

Heterogeneity, indicated by I², within the bleeding subgroup, was notably high at 73.7%, p=0.004, warranting the application of the random-effects model for combined item calculations. Fig. 3B showed that the difference in bleeding complications between the experimental group and the control group was not statistically significant (OR=0.86; 95% CI=0.41 to 1.84; p=0.706) (Fig. 3B). In contrast, the gastrointestinal complications subgroup displayed considerable heterogeneity with an I² of 50.4% (p=0.041). As seen in the forest plot, the distinction in gastrointestinal complications between the 2 groups was not statistically significant (OR=0.39; 95% CI=0.15 to 1.01; p=0.052) (Fig. 3B).

5. Subgroup analysis

Subgroup analyses were performed for optimal debulking rate, OS, and PDS according to the populations in the included studies.

The results demonstrated that the OR for the satisfactory tumor reduction rate between the NACT-IDS and PDS groups in patients with FIGO III–IV OC and FIGO IIIC–IV OC was 1.66 (95% CI=1.24 to 2.23; p=0.001) and 2.35 (95% CI=1.50 to 3.70; p<0.001), respectively (Fig. 4). These results revealed that compared to NACT-IDS therapy for FIGO III–IV ovarian cancer patients, NACT-IDS groups exhibited a higher satisfactory tumor reduction rate for FIGO IIIC–IV.

Fig. 4. Forest plots for the subgroup analysis of population-based optimal debulking rate.

CI, confidence interval; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OR, odds ratio; PDS, primary debulking surgery.

From the forest plot (Fig. 5A), the SMD of OS of FIGO III-IV ovarian cancer patients in the NACT-IDS group compared to the PDS group was −1.04 (95% CI=−3.83 to 1.75; p=0.465). The SMD of OS of FIGO IIIC–IV ovarian cancer patients in the NACT-IDS group compared to the PDS group was −2.79 (95% CI=−6.26 to 0.68; p=0.115). Subgroup analysis of PDS showed that the SMD between NACT-IDS group and PDS group for FIGO III-IV ovarian cancer patients and FIGO IIIC-IV ovarian cancer patients was −4.67 (95% CI=−10.05 to 0.70; p=0.089) and 3.55 (95% CI=−0.25 to 7.35; p=0.067), respectively (Fig. 5B). Neither of these differences was statistically significant.

Fig. 5. Forest plots for the subgroup analysis of population-based survivals. (A) OS and (B) PFS.

CI, confidence interval; IDS, interval debulking surgery; NACT, neoadjuvant chemotherapy; OS, overall survival; PDS, primary debulking surgery; PFS, progression-free survival; SMD, standardized mean difference.

6. Sensitivity analysis

Sensitivity analysis was executed by systematically excluding one study at a time to evaluate its influence on the aggregated outcomes. The outcomes of the sensitivity analysis revealed that the combined results, accompanied by their 95% confidence intervals, remained largely unaffected by the omission of any single study (Fig. S2). These findings implied that the results presented in this meta-analysis were relatively robust.

7. Publication bias

The Egger’s test was employed to detect publication bias, ensuring the integrity of the meta-analysis outcomes. There was no notable evidence of publication bias in the collective findings of all clinical indicators (Table S3). Similarly, the results of the Egger’s test for postoperative complications exhibited a comparable pattern (Table S4).

DISCUSSION

A woman’s lifetime risk of developing OC is estimated at 1 in 75, with a mortality rate of approximately 1 in 1,000. OC accounted for over 200,000 deaths in 2020 [43]. Late-stage OC, defined as stages III–IV by the FIGO standards, comprises the diagnosis for most OC patients (75%). The 5-year survival rate for patients at this stage is 20% to 40% [44]. A smaller fraction of cases (15%) is diagnosed with localized tumors (stage I), boasting a 5-year survival rate of 92%. Notably, the 5-year overall relative survival rate for advanced OC patients worldwide consistently falls within the range of 30% to 40%, having experienced only a marginal increase of 2% to 4% since 1995 [45]. The established international standard for treating advanced OC is comprehensive PDS coupled with platinum-based adjuvant chemotherapy [4]. The prognosis for stages III–IV remains particularly bleak, with average relative 5-year survival rates remaining dishearteningly low at 35% and 20%, respectively [46]. Surgical interventions must eradicate all visible lesions, as this has been demonstrably linked to significant extensions in patient survival [47]. Once the tumor reduction effect in advanced OC is satisfied, patients exhibit heightened chemotherapy response rates and improved survival prospects. Therefore, meticulous and satisfactory PDS merits due attention. Nonetheless, individuals with advanced OC might have a substantial tumor burden, involving extensive metastases within the pelvic, abdominal, and thoracic regions and multi-organ involvement. Such patients were not suitable candidates for PDS. A considerable proportion of OC patients exhibit high sensitivity to chemotherapy, with chemotherapy demonstrating efficacy rates as high as 80%–90%. Consequently, an initial course of chemotherapy can be administered for patients unsuitable for comprehensive PDS, followed by IDS. Three or more cycles of postoperative chemotherapy were administered.

In recent years, more patients diagnosed with advanced OC have been undergoing NACT-IDS, particularly those with a substantial tumor burden or multiple comorbidities. The widespread acceptance of NACT can be attributed to its ability to enhance the feasibility of surgery. It significantly augments the optimal tumor reduction rate during surgery, diminishes the extent of surgical resection, reduces surgical complications and mortality, and enhances the postoperative quality of life [7,8,9,10,11,12]. This strategy primarily involves the utilization of preoperative chemotherapy to mitigate adhesions between tumor tissue and adjacent structures, diminish tumor volume, lower tumor staging, manage pleural and ascitic effusion, and minimize tumor dissemination during surgery. These measures encourage tumor cells to enter a “dormant state,” ultimately decreasing intraoperative blood loss, surgical duration, and hospitalization duration. The veracity of this approach is corroborated by studies such as EORTC 55971 [12] and CHORUS [24]. Meantime, analogous outcomes have been consistently observed in numerous retrospective investigations [29,40]. Furthermore, several studies have demonstrated that NACT coupled with IDS offers comparable survival prospects to PDS followed by chemotherapy. Significantly, this approach does not exacerbate the overall prognosis, even among patients who typically present with poorer general health [8,23]. In addition, this study found that compared to NACT-IDS therapy for FIGO III–IV ovarian cancer patients, NACT-IDS therapy showed an advantage in improving the rate of satisfactory tumor reduction and enhancing survival benefits for FIGO IIIC–IV.

Meanwhile, the majority of scholars continue to maintain a cautious stance regarding the application of NACT-IDS therapy. Their perspective rests on the premise that NACT-IDS can enhance the favorable surgical tumor reduction rate. Nevertheless, this advantage in surgery has yet to translate into a discernible survival benefit. It is crucial to emphasize that the survival rate is the primary prognostic parameter for cancer patients. However, numerous retrospective investigations have consistently indicated that NACT does not extend OS or PFS among patients with advanced OC [39,48]. This study has also yielded the same findings. The principal factor contributing to the limited impact of NACT-IDS on the extension of survival in patients with advanced OC is its potential to induce chemotherapy resistance, thereby diminishing postoperative platinum chemotherapy sensitivity. Additionally, individuals undergoing NACT are at a heightened risk of tumor recurrence [49]. Consequently, despite the enhancement in the favorable tumor reduction rate and the mitigation of surgical risks in advanced OC patients when employing NACT alongside IDS, a viewpoint remains that implementing NACT in advanced OC patients carries inherent risks.

This study presents several limitations. Firstly, a substantial level of heterogeneity existed among the effect sizes, which, although not found to significantly affect the results upon performing sensitivity analyses, may have introduced errors and biases in the interpretation of some data. Secondly, only 6 RCT research documents met the inclusion criteria, and most of the studies were retrospective, which could introduce risks related to data gaps, selection bias, and unobserved confounding factors. Lastly, the potential impact of different chemotherapy regimens and the number of treatment courses on survival prognosis were uncertain. Nevertheless, based on the available reports, the diverse chemotherapy regimens featured in the included studies were unlikely to impact survival outcomes substantially.

In conclusion, NACT-IDS effectively enhances the rate of satisfactory tumor reduction, especially for patients with FIGO stage IIIC and IV, and diminishes postoperative complications among advanced OC patients.

SUPPLEMENTARY MATERIALS

Table S1

Quality assessment of the studies included in the meta-analysis

Table S2

Test for overall effect

Table S3

The Egger’s test result for publication bias of optimal debulking rate, OS and PFS

Table S4

The Egger’s test result for publication bias of postoperative complications

Fig. S1

Flow diagram of meta-analysis for inclusion/exclusion of studies.

Fig. S2

Sensitivity analysis. (A) Sensitivity analysis for optimal debulking rate; (B) Sensitivity analysis for overall survival; (C) Sensitivity analysis for progression-free survival; (D) Sensitivity analysis for adverse cardiac events; (E) Sensitivity analysis for fever; (F) Sensitivity analysis for respiratory complications; (G) Sensitivity analysis for surgical site infection; (H) Sensitivity analysis for embolism; (I) Sensitivity analysis for hemorrhage; and (J) Sensitivity analysis for gastrointestinal events.