Impact of increased cycles of neoadjuvant chemotherapy on interval debulking surgery outcomes (541)

Abstract

Objectives: Over the last two decades, the modern treatment paradigm for ovarian, fallopian, and primary peritoneal cancer has evolved to include increasing use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). However, the impact of extended cycles of NACT on outcomes remains an open question. This study aimed to evaluate the impact of the number of cycles of platinum-based NACT on cytoreductive surgery outcomes within a single institution. Methods: Four hundred and forty-one patients with stage III and IV ovarian cancer treated at a single institution were retrospectively identified. Of these patients, 64 received NACT followed by interval debulking surgery (IDS). Patients were divided into three groups based on the number of cycles of NACT received before interval debulking surgery: < 3 cycles, 4-5 cycles, or > 6 cycles. Clinical-pathologic data were assessed, and the impact of the number of cycles of NACT on the likelihood of optimal IDS was analyzed. Statistical analysis was performed using one-way ANOVA and Chi-square tests. Results: Of the 64 patients receiving NACT, 44%, 22%, and 34% received < 3 cycles, 4-5 cycles, or > 6 cycles, respectively. Based on this multivariate analysis, an increased number of NACT cycles was not associated with a statistically significant improvement in achieving R0 resection. However, there was a modest absolute difference in the cohort of patients receiving 4-5 cycles, of which 71% achieved R0 resection versus only 50% in both the < 3 cycles and > 6 cycles groups (p=0.44). Six or more cycles of NACT were associated with decreased overall survival (OS) (23 months, p=0.002). There was no significant difference in age, race, smoking rates, stage, grade, histology, CA-125 at diagnosis, or surgical approach across the groups. Receiving > 6 cycles of NACT was associated with increased median BMI (32, p=0.008). Comorbid conditions could not be adequately assessed given missing data; however, no difference was seen in chronic kidney disease rates (p=0.71). Conclusions: The use of NACT plays an important role in the care of women with ovarian, fallopian, or primary peritoneal cancer. It has been well described that the three or four cycles of platinumbased neoadjuvant chemotherapy regimen increase the likelihood of achieving an optimal debulking surgery. However, the impact of increased chemotherapy cycles is unknown. In this cohort of 64 patients, increased cycles of NACT do not significantly improve IDS outcomes but may negatively impact the overall survival. It is unclear if the reduced OS seen in patients receiving > 6 cycles of NACT represents a true treatment effect or reflects a treatment bias. Increased cycles of chemotherapy were used in patients with higher BMIs. This group may represent a subset of patients with more extensive disease or increased comorbid conditions. Further investigation is ongoing to assess the potential harm associated with NACT exceeding five cycles and the utility of surgery in this population. Objectives: Over the last two decades, the modern treatment paradigm for ovarian, fallopian, and primary peritoneal cancer has evolved to include increasing use of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). However, the impact of extended cycles of NACT on outcomes remains an open question. This study aimed to evaluate the impact of the number of cycles of platinum-based NACT on cytoreductive surgery outcomes within a single institution. Methods: Four hundred and forty-one patients with stage III and IV ovarian cancer treated at a single institution were retrospectively identified. Of these patients, 64 received NACT followed by interval debulking surgery (IDS). Patients were divided into three groups based on the number of cycles of NACT received before interval debulking surgery: < 3 cycles, 4-5 cycles, or > 6 cycles. Clinical-pathologic data were assessed, and the impact of the number of cycles of NACT on the likelihood of optimal IDS was analyzed. Statistical analysis was performed using one-way ANOVA and Chi-square tests. Results: Of the 64 patients receiving NACT, 44%, 22%, and 34% received < 3 cycles, 4-5 cycles, or > 6 cycles, respectively. Based on this multivariate analysis, an increased number of NACT cycles was not associated with a statistically significant improvement in achieving R0 resection. However, there was a modest absolute difference in the cohort of patients receiving 4-5 cycles, of which 71% achieved R0 resection versus only 50% in both the < 3 cycles and > 6 cycles groups (p=0.44). Six or more cycles of NACT were associated with decreased overall survival (OS) (23 months, p=0.002). There was no significant difference in age, race, smoking rates, stage, grade, histology, CA-125 at diagnosis, or surgical approach across the groups. Receiving > 6 cycles of NACT was associated with increased median BMI (32, p=0.008). Comorbid conditions could not be adequately assessed given missing data; however, no difference was seen in chronic kidney disease rates (p=0.71). Conclusions: The use of NACT plays an important role in the care of women with ovarian, fallopian, or primary peritoneal cancer. It has been well described that the three or four cycles of platinumbased neoadjuvant chemotherapy regimen increase the likelihood of achieving an optimal debulking surgery. However, the impact of increased chemotherapy cycles is unknown. In this cohort of 64 patients, increased cycles of NACT do not significantly improve IDS outcomes but may negatively impact the overall survival. It is unclear if the reduced OS seen in patients receiving > 6 cycles of NACT represents a true treatment effect or reflects a treatment bias. Increased cycles of chemotherapy were used in patients with higher BMIs. This group may represent a subset of patients with more extensive disease or increased comorbid conditions. Further investigation is ongoing to assess the potential harm associated with NACT exceeding five cycles and the utility of surgery in this population.