Primary Debulking Surgery Maintains Survival Advantage Amid Rising Popularity of NACT With Interval Debulking Surgery

Although primary debulking surgery (PDS) with adjuvant chemotherapy continues to offer the greatest overall survival (OS) benefit, increased use of neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS) for advanced epithelial ovarian cancer (EOC) is associated with higher complete gross resection rates and lower postoperative mortality.¹

The authors of the study published in Cancers highlighted that, in the mid-2010s, 3 international landmark surgical clinical trials involving patients with advanced stage IIIC or IV EOC found non-inferior OS using NACT with IDS vs PDS with adjuvant chemotherapy. Additionally, a Japanese clinical trial showed that NACT with IDS was associated with shorter operative times, fewer organ resections, and fewer surgical complications than PDS with adjuvant chemotherapy.

These 4 clinical trials prompted a shift in practice patterns and the sequencing of surgery and chemotherapy in advanced EOC. Since it has been about 15 years since the publication of these trials, the researchers performed a retrospective analysis of a real-world cohort to assess US practice patterns and surgical trends. To do so, they designed a large epidemiological retrospective study using the National Cancer Database (NCDB) to examine trends in OS, complete gross resection, and postoperative mortality following debulking surgery for advanced EOC.

Increased use of neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS) has changed surgical practice patterns, improving complete resection rates and reducing postoperative complications. | Image Credit: Dr_Microbe - stock.adobe.com

The NCDB is a hospital-based registry of US patients who received care at more than 1500 facilities accredited by the Commission on Cancer²; it represents about 70% of newly diagnosed ovarian cancer cases nationwide. From the database, the researchers identified patients with advanced stage III to IV EOC between 2010 and 2016 who underwent either PDS with adjuvant chemotherapy or NACT with IDS.¹

They calculated annual proportions of those receiving IDS and PDS. Additionally, median OS was estimated using the Kaplan-Meier method, and Joinpoint models were fitted to evaluate surgical trends.

The study population consisted of 34,982 eligible patients, of whom 10,460 (29.9%) underwent NACT with IDS and 24,522 (70.1%) underwent PDS with adjuvant chemotherapy. Compared with the PDS cohort, patients who underwent IDS were older (65 vs 61 years; P < .001), less likely to be White (85.6% vs 8.9%; P = .015), and more likely to have stage IV disease (51.3% vs 25.4%; P < .001) and be publicly insured (55.1% vs 44.5%; P < .001).

The rate of IDS increased from 18.9% to 40.6% during the study period (annual percentage change [APC], 11.8%; P < .05). However, median OS was significantly higher in patients undergoing PDS than IDS, at 54 vs 38.8 months (P < .001). Driven by outcomes in the PDS cohort, OS for all patients improved from 46.6 to 51 months between 2010 and 2017 (annual percentage change [APC], 1.9%; P < .05).

Postoperative 90-day mortality was lower in the PDS group (1.7% vs 2.4%; P < .001), whereas the IDS group had a lower 30-day readmission rate (6.2% vs 3.1%; P < .001). Overall, postoperative 90-day mortality decreased from 2.4% to 1.5% during the study period (APC, –4.64%; P < .05), primarily due to reductions among patients undergoing PDS (APC, –6.83%; P < .05).

Patients in the IDS cohort were less likely to undergo extensive surgery (27.4% vs 36.7%; P < .001) but were more likely to achieve complete gross resection (42% vs 38.6%; P < .001). Although the overall rate of extensive surgery remained stable during the study period, the complete gross resection rate increased from 34.8% to 41% (APC, 2.5%; P < .01). This was driven by improvements in patients undergoing PDS (annual improvement, 2.83%; P < .01), with no significant change in the IDS group.

The researchers acknowledged several limitations, including that the NCDB only represents data from about 30% of US hospitals. As a result, some populations are underrepresented, including American Indians, Alaska Natives, Hispanics, patients aged 86 years and older, and those from western states and rural areas. Still, they remained confident that their findings reflect improvements in patient triage and case selection.

“Triaging those patients with extensive disease burden at diagnosis to NACT and IDS may improve their chance of [complete gross] resection and therefore the optimal surgical outcomes when debulking is attempted,” the authors concluded.

References

1. Lamiman K, Silver M, Hayek J, et al. Trends in surgical outcomes and overall survival among women undergoing debulking surgery for advanced ovarian cancer in the US: analysis of the National Cancer Database. Cancers (Basel). 2025;17(17):2884. doi:10.3390/cancers17172884
2. Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15(3):683-690. doi:10.1245/s10434-007-9747-3