The optimal time for surgery in women with serous ovarian cancer

Abstract

Background: Advanced high-grade serous ovarian carcinoma (HGSC) is commonly treated with surgery and chemotherapy. We investigated the survival of patients treated with primary or interval surgery at different times following neoadjuvant chemotherapy. Their survival was compared with that of patients treated with primary cytoreductive surgery and adjuvant chemotherapy.

Methods: Patients with stage III or IV HGSC were included in this retrospective cohort study. Clinical data were obtained from patient records. Patients were divided into 2 groups based on treatment with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or with primary cytoreductive surgery and adjuvant chemotherapy (PCS). Study groups were stratified by several clinical variables.

Results: We included 334 patients in our study: 156 in the NAC and 178 in the PCS groups. Survival of patients in the NAC group was independent of when they underwent interval cytoreductive surgery following initiation of neoadjuvant chemotherapy (p < 0.001). Optimal surgical cytoreduction had no impact on overall survival in the NAC group (p < 0.001). Optimal cytoreduction (p < 0.001) and platinum sensitivity (p < 0.001) were independent predictors of improved survival in the PCS but not in the NAC group. Patients in the NAC group had significantly worse overall survival than those in the PCS group (31.6 v. 61.3 mo, p < 0.001).

Conclusion: Women with advanced HGSC who underwent PCS had better survival than those who underwent interval NAC, regardless of the number of cycles of neoadjuvant therapy. Optimal cytoreduction did not provide a survival advantage in the NAC group.

Fig. 1

Comparison of clinical characteristics of patients with high-grade serous ovarian carcinoma (HGSC) treated with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or primary cytoreductive surgery and adjuvant chemotherapy (PCS). (A) No significant difference in tumour stage was observed between the adjuvant and neoadjuvant groups. (B) Patients treated with neoadjuvant chemotherapy were significantly older (Student t test, p = 0.004). (C) Significantly more patients in the neoadjuvant group were optimally debulked (< 1 cm residual disease) than in the adjuvant group (Fisher exact test, p = 0.025). (D) Patients treated with neoadjuvant chemotherapy are more likely to demonstrate resistance to first-line platinum-based chemotherapy (i.e., progress on therapy or recurrence within 6 mo of completion of first-line therapy, Fisher exact test, p = 0.001). N/S = nonsignificant.

Fig. 2

Overall and progression-free survival of patients treated with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) compared with primary cytoreductive surgery and adjuvant chemotherapy (PCS). (A) Patients treated with neoadjuvant chemotherapy followed by surgery have a significantly worse overall survival than patients treated with primary surgery and adjuvant chemotherapy (p < 0.001). (B) The difference in overall survival was independent of the patients’ age at diagnosis (p < 0.001). (C) Patients treated with neoadjuvant chemotherapy had a significantly worse progression-free survival measured by radiologic imaging (i.e., clinical recurrence) (p < 0.001). (D) The significant difference in progression-free survival is independent of the age of the patient at diagnosis. All statistics were calculated with a log-rank (Mantel–Cox) test.

Fig. 3

Overall and progression-free survival stratified by the time to interval cytoreductive surgery. (A) Survival in the neoadjuvant group (NAC) was independent of the timing of surgery with respect to the number of cycles of neoadjuvant chemotherapy. Patients treated with neoadjuvant chemotherapy had a worse overall survival (p < 0.001), independent of whether they were treated with up to 3, 4, or 5 or more cycles before surgery (p = 0.92). (B) Patients treated with neoadjuvant chemotherapy had a significantly worse progression-free survival independent of the timing of interval cytoreductive surgery with respect to the number of cycles of neoadjuvant chemotherapy received (p < 0.001). All statistics were calculated with a log-rank (Mantel–Cox) test. PCS = primary cytoreductive surgery and adjuvant chemotherapy.

Fig. 4

Overall and progression-free survival of patients treated with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or primary cytoreductive surgery and adjuvant chemotherapy (PCS) stratified by surgical cytoreduction status. (A) Optimal surgical cytoreduction to less than 1 cm residual tumour had no significant impact on overall survival in the neoadjuvant group. In addition, within the suboptimally debulked group, neoadjuvant chemotherapy had no significant effect. However, within the optimal subgroup, the neoadjuvant patients had a worse overall outcome (p < 0.001). Within the adjuvant group, patients who were optimally debulked had a significantly improved survival (p = 0.001). (B) Optimal surgical cytoredcution resulted in better progression-free survival in patients treated with neoadjuvant chemotherapy or primary surgical cytoreduction (p = 0.020 and p = 0.002, respectively). However, in the optimally and suboptimally surgically debulked groups, the patients who received neoadjuvant chemotherapy had a significantly worse progression-free survival (p < 0.001 for both comparisons). All statistics were calculated with a log-rank (Mantel–Cox) test. Bonferroni corrections were applied for all multiple comparisons. N/S = nonsignificant.

Fig. 5

Overall and progression-free survival of patients treated with neoadjuvant chemotherapy and interval cytoreductive surgery (NAC) or primary cytoreductive surgery and adjuvant chemotherapy (PCS) stratified by sensitivity to platinum-based chemotherapy. All patients with first-line platinum-resistance had a worse (A) overall and (B) progression-free survival (p < 0.001). Treatment with neoadjuvant chemotherapy had no effect on the survival of the platinum-resistant patients. However, within the platinum-sensitive group, patients treated with neoadjuvant chemotherapy had worse overall and progression-free survival (p < 0.001). All statistics were calculated with a log-rank (Mantel–Cox) test. Bonferroni corrections were applied for all multiple comparisons. N/S = nonsignificant.