Does the time interval off neoadjuvant chemotherapy before and after interval debulking surgery affect the overall survival of women with advanced-epithelial ovarian cancer?

Purpose: Neoadjuvant chemotherapy followed by interval debulking surgery (IDS) is an alternative treatment option, compared to the current standard of care primary debulking surgery for treating advanced epithelial ovarian cancer (EOC). We present our institute experience of neoadjuvant chemotherapy strategy in the management of EOC which is one of the largest single institute experience. Methods: This is a retrospective analysis of patients with epithelial ovarian cancer who were treated in our institute between 2000 and 2006. Patient with advanced disease by clinical and imaging were treated with 3 cycles ofneoadjuvant chemotherapy and then taken up for interval debulking surgery (IDS) who had static or partial or complete response to chemotherapy. The remaining chemotherapy is delivered after the surgery. Patient who had limited disease had primary debulking surgery and then adjuvant chemotherapy according to institute protocol. Outcomes in terms of disease free and overall survival were analysed. Results: This retrospective analysis included 59 patients with limited disease who had primary debulking surgeryand 283 patients with advanced disease who recievedneoadjuvant chemotherapy. The median age was 50 years and majority are in the 50-59 years age group. Age more than 60 years represent 14.5%. Postmenopausal women were 55.3% and premenopausal women were 44.7 %. Multiparity is higher 70.2% than the uniparity 16.4% ornulliparity 11.7%. Abdomen distension 42% and pain 25% are the most common symptoms. Advanced stage was the most common presentation 71% with stage III-56.1% and stage IV-14.9%. Among the neoadjuvant chemotherapy group 126/283 (44.5%) had optimal cytoreduction, 44/283 (15.5%) had suboptimal cytoreduction and 113/283 (40%) not suitable for IDS. The 5 year disease free and overall survival was 30.8% and 41.5% in the NACT group with advanced disease and 58.5% and 75.8% in the primary cytoreduction group who had limited diseaserespectively. The 5 years overall survival among the IDS group with optimal cytoreduction was 57.1% and 11.7% for the suboptimal cytoreduction group. The 5 years survival was not affected by the number ofneoadjuvant chemotherapycycles delivered before surgery in the IDS group. Patient who received paclitaxol + carboplatin as first line chemotherapy had better survival than carboplatin alone or cyclophosphamide + cisplatin. Conclusion: NACT as an alternative option to primary debulking surgery in operable EOC is still debatable. But for patient with high disease burden where optimal cytoreduction is not possible NACT strategy is a valid option. Recent randomised controlled trials from Europe had shown the noninferiority of neoadjuvant chemotherapy followed by IDS when compared to the primary debulking surgery in operable advanced EOC.

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Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-001124 ◽

2020 ◽

Vol 30 (6) ◽

pp. 845-852 ◽

Cited By ~ 3

Author(s):

Yasmin A Lyons ◽

Henry D Reyes ◽

Megan E McDonald ◽

Andreea Newtson ◽

Eric Devor ◽

...

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Cytoreductive Surgery ◽

Residual Disease ◽

National Cancer Database ◽

Debulking Surgery ◽

Interval Debulking Surgery ◽

Advanced Epithelial Ovarian Cancer ◽

Significant Covariates

ObjectiveIn previous studies, neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary cytoreductive surgery as initial treatment for advanced epithelial ovarian cancer. Our study aimed to compare surgical and survival outcomes between the two treatments in a large national database.MethodsData were extracted from the National Cancer Database from January 2004 to December 2015. Patients with FIGO (International Federation of Gynecologists and Obstetricians) stage III-IV epithelial ovarian cancer and known sequence of treatment were included: primary cytoreductive (surgery=26 717 and neoadjuvant chemotherapy=9885). Tubal and primary peritoneal cancer diagnostic codes were not included. Residual disease after treatment was defined based on recorded data: R0 defined as microscopic or no residual disease; R1 defined as macroscopic residual disease. Multivariate Cox proportional HR was used for survival analysis. Multivariate logistic regression analysis was utilized to compare mortality between groups. Outcomes were adjusted for significant covariates. Validation was performed using propensity score matching of significant covariates.ResultsA total of 36 602 patients were included in the analysis. Patients who underwent primary cytoreductive surgery had better survival than those treated with neoadjuvant chemotherapy followed by interval surgery, after adjusting for age, co-morbidities, stage, and residual disease (p<0.001). Primary cytoreductive surgery patients with R0 disease had best median survival (62.6 months, 95% CI 60.5–64.5). Neoadjuvant chemotherapy patients with R1 disease had worst median survival (29.5 months, 95% CI 28.4–31.9). There were small survival differences between primary cytoreductive surgery with R1 (38.9 months) and neoadjuvant chemotherapy with R0 (41.8 months) (HR 0.93, 95% CI 0.87 to 1.0), after adjusting for age, co-morbidities, grade, histology, and stage. Neoadjuvant chemotherapy had 3.5 times higher 30-day mortality after surgery than primary cytoreductive surgery (95% CI 2.46 to 5.64). The 90-day mortality was higher for neoadjuvant chemotherapy in multivariate analysis (HR 1.31, 95% CI 1.06 to 1.61) but similar to primary cytoreductive surgery after excluding high-risk patients.ConclusionsMost patients with advanced epithelial ovarian cancer may benefit from primary cytoreductive surgery. Patients treated with neoadjuvant chemotherapy should be those with co-morbidities unfit for surgery.

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