A comprehensive analysis of over 70,000 patients with advanced ovarian cancer reveals that cancer centers with higher utilization of neoadjuvant chemotherapy (NACT) achieve significantly lower postoperative mortality rates and improved long-term survival outcomes, according to research published in JAMA Network Open.
The study examined treatment patterns across 1,333 US cancer programs between 2010 and 2019, analyzing data from 70,707 women with stage III or IV epithelial ovarian cancer. Researchers found that institutions with high NACT utilization (59% of patients received treatment) had substantially lower 90-day mortality rates compared to centers with low utilization (22% of patients).
Mortality Benefits Across All Hospital Types
The protective effect of NACT utilization was observed across all hospital volume categories, though the magnitude varied significantly. At high-volume hospitals, high NACT use was associated with a 74% reduction in odds of 90-day mortality (OR, 0.26; 95% CI, 0.17-0.41), with standardized mortality rates of 2.9% versus 10.0% at low-utilization centers.
Average-volume hospitals showed a 51% reduction in mortality odds (OR, 0.49; 95% CI, 0.33-0.72), with rates of 3.7% versus 7.3%. Even low-volume hospitals demonstrated a 52% reduction (OR, 0.48; 95% CI, 0.39-0.6), with mortality rates of 4.8% versus 9.5%.
"Neoadjuvant chemotherapy mattered everywhere," said Alexander Melamed, MD, MPH, gynecologic oncologist at Massachusetts General Hospital and lead researcher. "Irrespective of where you are, centers that tend to underuse neoadjuvant chemotherapy see higher rates of postoperative mortality."
Long-Term Survival Advantages
The survival benefits extended beyond immediate postoperative outcomes. At high-volume centers, patients treated at programs with high NACT utilization had a 4.0-month longer 60-month life expectancy compared to those at low-utilization centers (42.2 versus 38.1 months; 95% CI, 1.6-6.5). However, this long-term survival advantage was not observed at average- or low-volume centers.
The study population included 24,157 patients treated at low-volume centers (treating 12 cases per year), 24,095 at average-volume centers (12 to 23.9 cases), and 22,455 at high-volume centers (24 or more cases). Overall, 87.9% of patients underwent surgery.
Challenging Current Practice Patterns
The findings contradict concerns about NACT overutilization in the United States. "There's no evidence that there is a problem with overutilization of neoadjuvant chemotherapy in the United States," Melamed stated. "If anything, there continues to be a problem with underutilization."
Over the past 15 years, four randomized clinical trials have demonstrated that adding neoadjuvant chemotherapy reduces patient morbidity without compromising long-term survival outcomes. However, uptake has remained low due to persistent beliefs that primary surgery should remain the first-line treatment.
Clinical Implications for Treatment Selection
The research challenges the traditional approach of reserving NACT primarily for patients deemed too sick or with too extensive disease for primary surgery. Melamed emphasized that while not every patient requires neoadjuvant chemotherapy, "many, if not most, patients with advanced ovarian cancer should" receive it.
"For me, it's very clear that on the borderline case, you should definitely err toward neoadjuvant chemotherapy because you're very unlikely to harm the patient in any way," he explained. "With primary surgery, there's plenty of evidence, both randomized and observational, that there is measurable harm in terms of postoperative infection, stoma formation and even postoperative mortality."
The study's limitations include its retrospective design and lack of information about why specific patients did not receive neoadjuvant chemotherapy. Despite these constraints, the researchers expressed confidence in their findings, noting consistency with previous randomized trials and observational studies demonstrating NACT's benefits for postoperative morbidity and mortality.
An estimated 20,890 women will be diagnosed with ovarian cancer in 2025, with most presenting with stage III or IV disease, making these findings particularly relevant for current clinical practice and treatment decision-making.
