Prolonged interruption of chemotherapy in patients undergoing delayed debulking surgery for advanced high grade serous ovarian cancer is associated with a worse prognosis

INTRODUCTION: The current standard of care for advanced high grade serous ovarian cancer (HGSC) comprises a combination of debulking surgery and platinum-based chemotherapy given in the neoadjuvant or adjuvant setting. In the neoadjuvant setting, patients usually undergo 3 cycles of chemotherapy followed by interval cytoreductive surgery (ICS), then 3 further cycles of chemotherapy. However, the optimum timeframe to administer chemotherapy before and after ICS remains unclear. We therefore examine the survival impact of the interval between pre- and post-operative chemotherapy in patients undergoing ICS in a well-established patient cohort. Factors leading to "delays" in recommencing post-operative chemotherapy were also examined.

METHODS: The study comprises of a retrospective cohort of 205 cases with FIGO stage III and IV HGSC undergoing ICS. The duration of the interval between pre-operative and post-operative chemotherapy was correlated with progression-free (PFS) and overall survival (OS). Univariate and multivariate analyses were constructed to identify factors associated with survival and prolonged chemotherapy interruption.

RESULTS: The median interval between pre-operative and post-operative chemotherapy was 63 days. Multivariate analyses revealed macroscopic residual disease (HR:2.280, 95% CI:1.635-3.177, p ≤ 0.001) and interruption of chemotherapy >10 weeks (HR:1.65, 95%CI:1.201-2.290, p = 0.002) were associated with poorer OS. Existing medical comorbidities and longer hospital stay were independent prognostic factors for prolonging the chemotherapy interruption.

CONCLUSION: Our study recommends that interruption to chemotherapy to allow patients to undergo ICS should be ≤10 weeks; otherwise, OS is significantly impacted. Patients with pre-existing medical comorbidities should receive additional support pre- and post-operatively to keep the chemotherapy interruption to a minimum.