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Original Investigation
September 30, 2021

Association Between Overall Survival and the Tendency for Cancer Programs to Administer Neoadjuvant Chemotherapy for Patients With Advanced Ovarian Cancer

Author Affiliations
  • 1Department of Obstetrics and Gynecology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
  • 2NewYork-Presbyterian/Columbia University Irving Medical Center, New York, New York
  • 3Herbert Irving Comprehensive Cancer Center, New York, New York
  • 4Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston
  • 5Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
  • 6Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York
  • 7Department of Health Policy, Harvard Medical School, Boston, Massachusetts
  • 8Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
JAMA Oncol. Published online September 30, 2021. doi:10.1001/jamaoncol.2021.4252
Key Points

Question  Was the differential adoption of neoadjuvant chemotherapy by US cancer centers for advanced-stage epithelial ovarian cancer associated with differences in overall survival?

Findings  In this difference-in-differences comparative effectiveness research study that included 39 299 patients treated in 664 cancer programs, patients treated in programs that markedly increased administration of neoadjuvant chemotherapy achieved greater improvements in short-term mortality and equivalent gains in median overall survival compared with patients who were treated in programs that continued to use the treatment infrequently.

Meaning  The study findings suggest that neoadjuvant chemotherapy may be an appropriate first-line treatment strategy for many patients with advanced-stage ovarian cancer.


Importance  Randomized clinical trials have found that, in patients with advanced-stage epithelial ovarian cancer, neoadjuvant chemotherapy has similar long-term survival and improved perioperative outcomes compared with primary cytoreductive surgery. Despite this, considerable controversy remains about the appropriate use of neoadjuvant chemotherapy, and the proportion of patients who receive this treatment varies considerably among cancer programs in the US.

Objective  To evaluate the association between high levels of neoadjuvant chemotherapy administration and overall survival in patients with advanced ovarian cancer.

Design, Setting, and Participants  This difference-in-differences comparative effectiveness analysis leveraged differential adoption of neoadjuvant chemotherapy in Commission on Cancer–accredited cancer programs in the US and included women with a diagnosis of stage IIIC and IV epithelial ovarian cancer between January 2004 and December 2015 who were followed up through the end of 2018. The data were analyzed between September 2020 and January 2021.

Exposures  Treatment in a cancer program with high levels of neoadjuvant chemotherapy administration (more often than expected based on case mix) or in a program that continued to restrict its use after the 2010 publication of a clinical trial demonstrating the noninferiority of neoadjuvant chemotherapy compared with primary surgery for the treatment of patients with advanced ovarian cancer.

Main Outcomes and Measures  Case mix–standardized median overall survival time and 1-year all-cause mortality assessed with a flexible parametric survival model.

Results  We identified 19 562 patients (mean [SD] age, 63.9 [12.6] years; 3.2% Asian, 8.0% Black, 4.8% Hispanic, 82.5% White individuals) who were treated in 332 cancer programs that increased use of neoadjuvant chemotherapy from 21.7% in 2004 to 2009 to 42.2% in 2010 to 2015 and 19 737 patients (mean [SD] age, 63.5 [12.6] years; 3.1% Asian, 7.7% Black, 6.5% Hispanic, 81.8% White individuals) who were treated in 332 programs that marginally increased use of neoadjuvant chemotherapy (20.1% to 22.5%) over these periods. The standardized median overall survival times improved by similar magnitudes in programs with high (from 31.6 [IQR, 12.3-70.1] to 37.9 [IQR, 17.0-84.9] months; 6.3-month difference; 95% CI, 4.2-8.3) and low (from 31.4 [IQR, 12.1-67.2] to 36.8 [IQR, 15.0-80.3] months; 5.4-month difference, 95% CI, 3.5-7.3) use of neoadjuvant chemotherapy after 2010 (difference-in-differences, 0.9 months; 95% CI, −1.9 to 3.7). One-year mortality declined more in programs with high (from 25.6% to 19.3%; risk difference, −5.2%; 95% CI, −6.4 to −4.1) than with low (from 24.9% to 21.8%; risk difference, −3.2%, 95% CI, −4.3 to −2.0) use of neoadjuvant chemotherapy (difference-in-differences, −2.1%; 95% CI, −3.7 to −0.5).

Conclusions and Relevance  In this comparative effectiveness research study, compared with cancer programs with low use of neoadjuvant chemotherapy, those with high use had similar improvements in median overall survival and larger declines in short-term mortality.

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