Review ArticleReview
Open Access

Primary Debulking Surgery Versus Interval Debulking Surgery in the Management of Advanced-Stage Ovarian Cancer

JOHN P. MICHA, RANDY D. BOHART, JOSHUA P. GORMAN and BRAM H. GOLDSTEIN
Anticancer Research March 2026, 46 (3) 1175-1182; DOI: https://doi.org/10.21873/anticanres.18021

Abstract

Background/Aim: The improved overall survival rates associated with advanced-stage ovarian cancer primarily reflect the surgeon’s capacity to remove all residual disease following either primary debulking surgery (PDS) and chemotherapy or via neoadjuvant chemotherapy and interval debulking surgery (IDS). The aim of this study was to compare the survival rates in ovarian cancer following either PDS or IDS.

Materials and Methods: We conducted an extensive PubMed search incorporating review articles, retrospective studies, and randomized control trials on the topic of ovarian cancer, with specific terms that included ovarian cancer, PDS, IDS, overall survival, and intraoperative outcomes.

Results: While several investigations have indicated that PDS and IDS confer equivalent survival outcomes, additional results suggested that PDS is associated with improved survival compared to IDS, especially in patients amenable to a gross total resection.

Conclusion: Despite the reportedly similar overall survival outcomes in ovarian cancer, IDS is indicated with elderly or frail patients and in the presence of significant co-morbidities; alternatively, PDS may be preferable in ovarian cancer cases wherein an upfront gross total resection can be readily achieved.

Keywords:

Introduction

Ovarian cancer is the most aggressive gynecologic malignancy in the United States, accounting for 19,680 newly diagnosed cases and 12,740 patient deaths during 2024 (1). The primary management of advanced-stage ovarian cancer comprises debulking surgery and platinum-based chemotherapy, with the potential inclusion of maintenance therapy encompassing a poly (ADP-ribose) polymerase inhibitor (PARP) inhibitor and/or bevacizumab (2). Despite the clinically appreciable benefits derived from maintenance therapy, the 5-year survival rates in advanced-stage ovarian cancer remain inauspicious.

Primary debulking surgery (PDS) and adjuvant chemotherapy in ovarian cancer have historically been the sine qua non to improving patient survival rates (3, 4). Hence, in endeavoring to achieve no residual disease following optimal cyto-reductive surgery in ovarian cancer, the surgical approach frequently incorporates an intestinal resection, peritonectomy, diaphragmatic resection, retroperitoneal nodes resection, and splenectomy (5). Nevertheless, PDS can engender increased morbidity rates, especially with patients who are frail, of advanced age (e.g., >75 years), or have significant co-morbidities (6).

Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative surgical option in gynecologic oncology, particularly when there is a significant concern for patient intraoperative morbidity and postoperative complications (6-10). While NACT and IDS may be indicated under the aforesaid circumstances, the effect on patient overall survival has been associated with varying survival outcomes compared to PDS and adjuvant chemotherapy (8, 11, 12).

Materials and Methods

The purpose of this review was to compare the survival outcomes of PDS and IDS in advanced-stage ovarian cancer. We conducted a PubMed search comprising several review articles, retrospective studies, and randomized control trials (RCTs) on the topic of surgical approaches in ovarian cancer, with specific terms that included PDS, IDS, morbidity, and survival outcomes (Figure 1). The primary objective of this review was to further edify clinicians regarding the clinical outcomes associated with PDS and IDS in the management of advanced-stage ovarian carcinoma.

Figure 1.
Figure 1.

PRISMA flow diagram for new systematic reviews.

Results

Primary debulking surgery. Meigs initially described PDS in attempting to improve the postoperative clinical outcomes in ovarian cancer following radiation therapy (13). In patients whose surgery resulted in greater tumor regression following PDS, chemotherapy sensitivity was enhanced, presumably because of the decreased manifestation of tumor-induced resistance mechanisms (14). Thereafter, PDS was reportedly associated with a higher increase in overall survival (OS) in ovarian cancer with 0 cm to <0.5 cm of residual disease (an OS of 39 months) compared to >1.5 cm of residual disease (an OS of 11 months) (15).

Investigations have further corroborated that extent of macroscopic disease resection (e.g., optimal 0 cm; near-optimal <1 cm; sub-optimal >1 cm) is an independent prognostic factor for ovarian cancer survival (14, 16, 17). Chi et al. retrospectively evaluated 465 advanced-stage ovarian cancer patients to assess the impact of residual disease following PDS on patient survival (18). The patients with no gross residual disease exhibited a median OS of 106 months compared to 34 months in patients with >2 cm of residual disease.

Winter et al. evaluated the prognostic outcome associated with degree of post-operative residual disease in advanced-stage ovarian cancer (19). They documented that in contrast to microscopic disease, patients with greater (e.g., 0.1 to 1.0 cm and >1.0 cm) residual disease were at increased risk for tumor recurrence (HR=1.96; 95% CI=1.70 to 2.26; and HR=2.36; 95% CI=2.04 to 2.73, respectively) and death (HR=2.11; 95%CI=1.78 to 2.49; p<0.001; and HR=2.47; 95% CI=2.09 to 2.92, respectively). Chang et al. further recounted that conducting primary radical surgery and achieving no gross residual disease in stage IIIC-IV ovarian cancer were independent prognostic factors for improved OS (20). Currently, a complete gross resection is characterized by optimal (1-10 mm) residual disease or sub-optimal (>10 mm) residual disease (14).

Interval debulking surgery. When considering IDS, the contention is that following NACT, tumor size is appreciably decreased, thereby actuating improved chemotherapy perfusion (9). Smaller lesions also have a more efficient blood supply and theoretically respond more propitiously to initial chemotherapy exposure, theoretically minimizing the propensity for cytotoxic resistance (21). Select evaluations have also indicated that IDS and intraperitoneal chemotherapy significantly benefit progression-free survival (PFS) in advanced-stage ovarian carcinoma (22), especially in patients with stage III disease (23). Studies have also suggested that IDS may engender improved survival compared to PDS in the presence of extensive abdominal metastases, not to mention reduced intraoperative morbidity (10, 24, 25).

Improved survival with interval debulking surgery. Jacob et al. retrospectively compared the outcomes of ovarian cancer patients who underwent either 2-4 cycles of neoadjuvant cisplatin chemotherapy, IDS and six cycles of adjuvant cisplatin chemotherapy (n=22), primary surgery with >2 cm of residual disease and adjuvant cisplatin chemotherapy (n=22), or laparotomy and biopsy only, followed by debulking surgery and six cycles of cisplatin chemotherapy (n=18) (26). Median disease-free survival among the three groups was equivalent (p=0.58). However, in the IDS group, of whom 77% achieved optimal cytoreduction, the survival outcomes were significantly improved (18.1 months) compared to the sub-optimally debulked patients (7.5 months) (p=0.001).

Gill et al. (27) also sought to ascertain which clinical factors were most amenable to improving overall survival in advanced-stage ovarian cancer patients following NACT and IDS. In the 87 patients evaluated, older age (HR=1.60; 95% CI=1.18 to 2.16) and elevated CA-125 values (HR=2.30; 95% CI=1.25 to 4.23) correlated with inferior survival outcomes. Subsequently, patients with unresectable disease treated with IDS (n=45) were matched with sub-optimally debulked PDS (n=45) subjects to assess any outcomes differences; an improved OS benefit was borne out for patients treated with IDS (HR=0.53; 95% CI=0.32 to 0.88). Table I exhibits select prospective investigations and RCTs comparing ovarian cancer survival outcomes following IDS and PDS.

View this table:
Table I.

Prospective investigations and randomized control trials comparing ovarian cancer survival outcomes following IDS and PDS.

When considering surgical complications, Fagö-Olsen et al. reported that in their advanced ovarian cancer patients treated with IDS, they encountered reduced blood loss, attenuated operative morbidity and a lower incidence of residual tumor (p<0.05) compared to patients who underwent primary radical surgery (28). Similarly, in the Gill et al. study, they recounted that in comparison to the sub-optimally debulked patients, the IDS group experienced fewer postoperative complications than the PDS group (11% vs. 36%, p=0.01) (25).

Equivalent survival outcomes. In the Phase 3 Chorus study, 550 stage III/IV ovarian cancer patients were randomly assigned to undergo PDS followed by six cycles of chemotherapy (n=276) or NACT and IDS (n=274) (8). They remarked that median OS between the groups (22.6 months for PDS and 24.1 months with IDS) was non-significant but there was a reduced risk of death (HR=0.87) in favor of the IDS group; also, the incidence of grade 3/4 postoperative adverse events and deaths were lower in the IDS group (14%) compared to the PDS group (24%; p=0.001).

In a comparative study, Rauh-Hain et al. retrospectively evaluated 242 stage IV epithelial ovarian cancer patients who underwent either PDS (n=176), IDS (n=45) or chemotherapy alone (n=21) (11). The proportion of patients who ultimately obtained a complete resection with no residual disease was significantly greater with IDS than PDS (27% vs. 7.5%; p<0.001). Moreover, longer hospital duration (12 vs. 8 days; p=0.01) and a higher rate of postoperative complications (27% vs. 15%; p=0.08) were observed with the PDS patients.

Improved survival with primary debulking surgery. Mysona et al. compared the survival outcomes in advanced ovarian cancer patients who underwent either PDS or IDS in a propensity score matching study (29). The use of IDS was associated with an increased rate of complete gross resection (ptrend=0.02), but not with a decreased rate of suboptimal resection (ptrend=0.18). Moreover, IDS patients had inferior OS compared to PDS patients (HR=1.12, 95% CI=1.03 to 1.22, p=0.008), particularly after a complete gross resection was achieved (51 vs. 44 months, p<0.001).

Sørensen et al. (30) evaluated 681 stage IV ovarian cancer patients via a prospectively collected data registry, of whom 26% underwent PDS (n=177), 38% were treated with IDS (n=259), and 36% received chemotherapy only (n=245). The OS differences between the PDS (31.2 months) and IDS (32.3 months) groups were similar; however, there was a tendency for the stage IVB patients who achieved R0 (i.e., no macroscopic residual disease) following PDS (45.7 months, 95% CI=26.8 to 64.6 months) to exhibit a higher OS compared to IDS (35.9 months, 95% CI=31.4 to 40.5 months). Table II. illustrates select retrospective and observational studies comparing ovarian cancer survival outcomes following IDS and PDS.

View this table:
Table II.

Retrospective and observational studies comparing ovarian cancer survival outcomes following IDS and PDS.

In a RCT, Onda et al. (31) compared the survival outcomes between advanced-stage ovarian cancer patients who received either PDS (n=149) or IDS (n=152). The OS was 49.0 months and 44.3 months for the PDS and IDS groups, respectively (HR=1.052, 90.8% CI=0.835 to 1.326); a one-sided noninferiority p-value of 0.24 suggested that when appropriate (i.e., an increased probability for achieving optimal cytoreductive surgery), PDS may be preferable to IDS for engendering improved survival. Moreover, in a target trial, Jochum et al. (32) reported an improved PFS advantage for their stage IVA and IVB ovarian cancer patients treated with PDS [19.7 months (interquartile range=19.3-20.1)] compared to IDS [15.7 months (interquartile range=15.7-16.1)]; the PFS benefit coincided with enhanced OS in the PDS group [63.1 months (interquartile range=61.7-65.4)] compared to the IDS group [55.6 months (interquartile range=53.8-56.3)].

Conclusion

When considering the applicability of IDS and PDS in the management of advanced-stage ovarian cancer, both approaches are reportedly associated with equivalent survival rates (8, 11, 12, 33). Nevertheless, IDS coincides with fewer intraoperative events and is reportedly more amenable in patients who present with significant tumor burden (i.e., when an upfront debulking surgery is inadvisable) or have an unfavorable performance status (e.g., advanced age, frailty, or the presence of multiple co-morbidities) (34, 35). One may also consider IDS when using intraperitoneal chemotherapy to potentially further increase PFS intervals (23).

Alternatively, PDS may be indicated when endeavoring to maximize PFS and OS (36), especially when the initial radiologic findings suggest a favorable opportunity to obtain a gross total resection or in the presence of peritoneal carcinomatosis (29, 31, 37, 38). We acknowledge that when considering the aforesaid studies, deriving precise conclusions is complicated, particularly from retrospective and small population studies (11, 27, 29, 37). Moreover, we only included select reviews comparing PDS and IDS, and this may have eventuated in selection bias. Also, our study methodology limitations potentially restrict the ability to match and compare separate studies as patient and management characteristics can vary significantly (e.g., we did not use a meta-analysis to account for these confounders).

The acceptability of IDS in ovarian cancer has steadily increased in gynecologic oncology and while the data support this approach in managing advanced-stage ovarian cancer, oncology surgeons should continue to define the subset of ovarian cancer patients who are appropriate for either PDS and IDS, not to mention further consideration of surgical approaches that promote oncofertility and quality of life (39) in breast and other gynecologic malignancies. Ultimately, the relevant method is case-specific and patients should be comprehensively informed of the proposed benefits and risks inherent to both procedures (34).

Footnotes

  • Authors’ Contributions

    JM and MR planned and initiated the study. BG, RB JG, reviewed the study data and content analysis. MR and JG categorized the data set and created the tables. MR, JG, BG, RB, and JM drafted and critically revised the manuscript. All authors have read and approved the final manuscript and have agreed to be accountable for all aspects of the work.

  • Conflicts of Interest

    The Authors have no conflicts of interest to declare in relation to this study.

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received June 24, 2025.
  • Revision received December 9, 2025.
  • Accepted December 23, 2025.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Primary Debulking Surgery Versus Interval Debulking Surgery in the Management of Advanced-Stage Ovarian Cancer
JOHN P. MICHA, RANDY D. BOHART, JOSHUA P. GORMAN, BRAM H. GOLDSTEIN
Anticancer Research Mar 2026, 46 (3) 1175-1182; DOI: 10.21873/anticanres.18021
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