Neoadjuvant Chemotherapy Becomes Leading Initial Treatment for Advanced Epithelial Ovarian Cancer

In 2021, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) overtook primary cytoreductive surgery (PCS) as the most popular approach for the initial treatment of patients with advanced epithelial ovarian cancer (EOC), according to a research letter published in JAMA Network Open.¹

Past single-institution observational studies found a survival advantage with PCS in patients with advanced EOC.² Conversely, past randomized clinical trials discovered that NACT followed by ICS achieves similar progression-free and overall survival as PCS but with decreased postoperative morbidity.³

However, national guidelines continuously recommend PCS as the preferred approach for patients with a high likelihood of achieving an optimal resection (< 1 cm).⁴ Despite this, the researchers noted that NACT utilization has increased in the US over time.⁵ Consequently, they conducted a study to describe temporal and age trends in the initial surgical treatment of patients with advanced EOC.¹

By 2021, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) became the most common initial treatment for advanced epithelial ovarian cancer (EOC). | Image Credit: Kiattisak - stock.adobe.com

To do so, the researchers analyzed patients diagnosed with stage III to IV EOC in the National Cancer Database (2010-2021). They separated patients into categories depending on whether they received PCS, NACT followed by ICS, or no cytoreductive surgery. Also, the researchers fit Poisson regression models with robust SEs to assess age and temporal trends in the prevalence of treatment modalities; these were used for data visualization and to estimate both RRs and 95% CIs.

They identified 87,449 patients with a mean (SD) age of 63.7 (12.4) years. Of the identified patients, 55,717 (63.7%) had stage III EOC. In terms of treatment, overall, 46,754 (53.5%) underwent PCS, 25,893 (29.3%) underwent ICS, and 14,802 (16.9%) received no surgery. The researchers observed that PCS and ICS use changed dramatically during the study period, with ICS overtaking PCS as the most frequent treatment approach by 2021.

From 2010 to 2021, the percentage of patients who underwent PCS fell from 70.1% to 37.2% (RR, 0.54; 95% CI, 0.52-0.55). More specifically, the number of patients with stage III disease who underwent PCS fell from 79.3% to 51.1% (RR, 0.65; 95% CI, 0.63-0.67) compared with 50.2% to 21.0% (RR, 0.42; 95% CI, 0.39-0.45) among those with stage IV disease.

Therefore, the researchers discovered substantial declines in PCS use throughout the age ranges in which EOC is most frequently observed. Conversely, overall, the percentage of patients who underwent ICS increased from 16.6% to 40.8% over the same period (RR, 2.49; 95% CI, 2.36-2.61).

Although this uptick in NACT followed by ICS was largely observed among those with stage IV disease, the researchers noted that it has increased significantly across all stages and ages. Historically, NACT was reserved for older patients, but these age-related findings show that the trend of increasing NACT was not associated with a particular age group.

Based on their findings, the researchers hypothesized different reasons why PCS use declined among this population.

“The decline of PCS may be driven by recognition of the excess operative morbidity and mortality that results from this treatment approach,” the authors concluded. “Additionally, the timing with which NACT overtook PCS as the major initial approach may be partially explained by the COVID-19 pandemic and initial limited operating room capabilities that resulted nationally.”

References

1. Bercow A, Stewart T, Bregar AJ, et al. Utilization of primary cytoreductive surgery for advanced-stage ovarian cancer. JAMA Netw Open. 2024;7(10):e2439893. doi:10.1001/jamanetworkopen.2024.39893
2. Chi DS, Musa F, Dao F, et al. An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). Gynecol Oncol. 2012;124(1):10-14. doi:10.1016/j.ygyno.2011.08.014
3. Coleridge SL, Bryant A, Kehoe S, Morrison J. Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev. 2021;7(7):CD005343. doi:10.1002/14651858.CD005343.pub6
4. Ovarian cancer: NCCN clinical practice guidelines in oncology. NCCN. Accessed October 21, 2024. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf
5. Knisely AT, St. Clair CM, Hou JY, et al. Trends in primary treatment and median survival among women with advanced-stage epithelial ovarian cancer in the US from 2004 to 2016. JAMA Netw Open. 2020;3(9):e2017517. doi:10.1001/jamanetworkopen.2020.17517