The association between timing of initiation of adjuvant therapy and the survival of early stage ovarian cancer patients – An analysis of NRG Oncology/Gynecologic Oncology Group trials

Abstract

Objectives To determine the association between timing of adjuvant therapy initiation and survival of early stage ovarian cancer patients. Methods Data were obtained from women who underwent primary surgical staging followed by adjuvant therapy from two Gynecologic Oncology Group trials (protocols # 95 and 157). Kaplan-Meier estimates and Cox proportional hazards model adjusted for covariates were used for analyses. Results Of 497 stage I–II epithelial ovarian cancer patients, the median time between surgery and initiation of adjuvant therapy was 23 days (25th–75th%: 12–33 days). The time interval from surgery to initiation of adjuvant therapy was categorized into three groups: <2 weeks, 2–4 weeks, and >4 weeks. The corresponding 5-year recurrence-free survival rates were 72.8%, 73.9%, and 79.5% (p = 0.62). The 5-year overall survival rates were 79.4%, 81.9%, and 82.8%, respectively (p = 0.51; p = 0.33 - global test). As compared to <2 weeks, the hazard ratio for recurrence-free survival was 0.90 (95%CI = 0.59–1.37) for 2–4 weeks and 0.72 (95%CI = 0.46–1.13) for >4 weeks. Age, stage, grade, and cytology were important prognostic factors. Conclusions Timing of adjuvant therapy initiation was not associated with survival in early stage epithelial ovarian cancer patients.

The effect of adjuvant chemotherapy on survival in patients with FIGO stage I high-grade serous ovarian cancer

“…To minimize toxicity associated with paclitaxel, single-agent carboplatin, fewer courses, and the use of coldcap can be considered. The Gynecologic Oncology Group (GOG 157) compared the recurrence rate of high-risk FIGO stage I-II EOC after either three or six cycles of carboplatin and paclitaxel, and evaluated which patient would benefit most from more cycles of chemotherapy based on clinical and histological characteristics [29][30][31][32]. For patients with high-risk serous FIGO stage I-II, a significant improved RFS was demonstrated with six cycles of combination chemotherapy, compared with three cycles.…”

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

“…The potential importance of the timing of initiation of adjuvant therapy after surgery has been studied in patients with ovarian cancer [126][127][128][129][130][131][132][133][134][135][136]. However, all of these published studies except one [137] pertain to advanced disease or had a higher proportion of stage III-IV patients. Although this one report [137] of early-stage ovarian cancer patients from two RCTs (GOG 95 [138] and GOG 157 [117]) did not identify a benefit associated with earlier initiation of adjuvant therapy, it remains unclear if a significant delay in starting adjuvant therapy may worsen outcome.…”

Interval between secondary cytoreductive surgery and adjuvant chemotherapy is not associated with survivals in patients with recurrent ovarian cancer

“…To obtain more concrete results about the role of intervals on survival in subpopulations of EOC patients, some studies have been performed exclusively in patients with early-stage disease (FIGO I and II) [26], intraperitoneal (IP) chemotherapy [27], or neoadjuvant chemotherapy [16], which found no association between interval and survival. In the same context, studies including only older patients (more than 65 years) [28, 29] or those with high-grade serous ovarian carcinoma [12, 30] showed mixed results regarding the relationship between interval and survival.…”

“…One possible explanation for these results is that the study population consisted of patients with small-volume disease before and after SCS. For example, no effect of intervals on survival in FIGO stage I/II (relatively small volume disease as opposed to stage III and IV) at initial presentation or FIGO stage III/IV with no gross residual disease after primary cytoreductive surgery was reported [18, 26]. With longer median intervals (31 days reported by Tewari et al [15], 19 days reported by Mahner et al [13]) in more advanced EOC than that observed in our study (10 days), delayed chemotherapy was associated with poorer OS in patients with no gross residual disease after primary cytoreductive surgery, which suggests that our result may have been different if our median intervals were longer.…”