Neoadjuvant Chemotherapy for Advanced Ovarian Cancer Improves Short-term Survival Regardless of Hospital Case Volume

Hospitals that treat fewer cases of advanced ovarian cancer are known to have higher perioperative mortality because their ability to rescue patients after complications is limited. High utilization of neoadjuvant chemotherapy may be particularly important in low-volume centers, as it reduces surgical complexity, postoperative complications, and postoperative mortality compared with primary cytoreductive surgery alone.

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In a nationwide U.S. study, Alexander Melamed, MD, MPH, and Mary Kathryn Abel, MD, MAS, of the Center for Gynecologic Oncology at Mass General Brigham Cancer Institute, and colleagues linked high rates of neoadjuvant chemotherapy use to better 90-day mortality after surgery for advanced ovarian cancer, regardless of hospital case volume.

As they add in JAMA Network Open, though, both 90-day surgical mortality and 5-year life expectancy were best for patients who had surgery in high-volume centers with high use of neoadjuvant chemotherapy.

Methods

Using the National Cancer Database, the researchers identified 70,707 individuals with advanced epithelial ovarian cancer who were treated in 1,333 cancer centers between 2010 and 2019:

• 1,089 low-volume centers (<12 cases/year)—24,157 patients treated (20,114 underwent surgery)
• 175 average-volume centers (12–23.9 cases/year)—24,095 patients treated (21,864 underwent surgery)
• 69 high-volume centers (≥24 cases/year)—22,455 patients treated (20,237 underwent surgery)

Patient and Treatment Differences by Case Volume

Compared with high-volume centers, low-volume centers served older patients who had higher rates of stage IV disease and more cases with non-serous histology. In addition, patients in low-volume centers were more likely to have Medicare or Medicaid insurance.

Treatment patterns varied significantly by hospital-level case volume:

• Surgery—83% of patients in the low-volume center cohort, 91% in the average-volume center cohort, and 90% in the high-volume center cohort (P<0.001)
• Neoadjuvant chemotherapy—43%, 38%, and 43% (P<0.001)

90-Day Surgical Mortality

Treatment in a center with high rather than low use of neoadjuvant chemotherapy was associated with reduction in the odds of 90-day surgical mortality (death within 90 days of cytoreductive surgery):

• Low-volume centers—9.5% incidence of 90-day surgical mortality with low use of neoadjuvant chemotherapy vs. 4.8% with high use (OR, 0.48)
• Average-volume centers—7.3% vs. 3.7% (OR, 0.49)
• High-volume centers—10.0% vs. 2.9% (OR, 0.26)

These differences in the magnitude of the association between neoadjuvant chemotherapy use and 90-day mortality according to case volume were statistically significant (P for interaction, <0.001). However, there appeared to be a point after which higher rates of neoadjuvant chemotherapy in low-volume centers were not associated with further improvement in 90-day mortality.

5-Year Life Expectancy

Individuals treated in high-volume centers with high use of neoadjuvant chemotherapy had the best 5-year life expectancy (survival from the time of diagnosis):

• Low-volume centers—39.1 months with low use of neoadjuvant chemotherapy vs. 37.9 months with high use (difference, −1.2 months)
• Average-volume centers—39.4 vs. 39.6 (difference, 0.2 months)
• High-volume centers—38.1 vs. 42.2 months (difference, 4.0 months)

Interpreting the Results

It’s unclear why high use of neoadjuvant chemotherapy is associated with a larger reduction in 90-day surgical mortality in high-volume centers than in others. High-volume centers with high use of neoadjuvant chemotherapy may have disproportionately adopted other practices that reduce perioperative mortality, such as Enhanced Recovery After Surgery protocols. It may also be that low-volume programs care for patients with greater frailty.

However, a causal interpretation of these results is also plausible: treatment in a high-volume hospital that uses neoadjuvant chemotherapy liberally may be the safest setting for cytoreductive surgery for advanced ovarian cancer.

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