Tertiary cytoreductive surgery in recurrent ovarian cancer: selection criteria and survival outcome.
ABSTRACT Studies of tertiary cytoreductive surgery (TCS) in recurrent epithelial ovarian cancer are limited, and appropriate patient selection remains a clinical challenge. We sought to evaluate the impact of TCS on survival and to determine predictors of optimal tertiary resection.
Between January 1997 and July 2004, 47 women with recurrent epithelial ovarian cancer underwent TCS at two institutions. All patients received initial platinum and taxane-based chemotherapy following primary cytoreductive surgery. Clinico-pathologic factors and survival were retrospectively abstracted from medical records. Optimal TCS was defined as microscopic residual disease.
Thirty of 47 (64%) patients underwent optimal TCS. Size of tumor implants<5 cm on preoperative imaging was the only significant predictor of achieving optimal TCS. Overall survival after TCS was statistically longer in patients with microscopic versus macroscopic residual disease (24 versus 16 months, p=0.03). After controlling for age, time to progression and optimal TCS, only the presence of diffuse disease at tertiary exploration remained a significant poor predictor of survival. However, in a cohort of patients with limited disease implants, multivariate analysis indicated that optimal TCS retained prognostic significance as a positive predictor of survival. Twelve patients (26%) experienced severe postoperative complications, including six with pulmonary embolism, four with fistulae and two with postoperative myocardial infarctions.
Size of disease implants on preoperative imaging may guide the selection of candidates for TCS. In those patients with limited disease implants at laparotomy, optimal TCS is associated with improved survival.
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ABSTRACT: Provide long-term follow-up data for women treated in a randomized multicenter study of pegylated liposomal doxorubicin compared with topotecan. Patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy were randomized to receive pegylated liposomal doxorubicin 50 mg/m(2) every 28 days (n = 239) or topotecan 1.5 mg/m(2) per day for 5 days every 21 days (n = 235). Patients were stratified prospectively based on response to initial platinum-based chemotherapy as well as the presence or absence of bulky disease. Most patients had been previously treated with platinum and taxanes (74% in the pegylated liposomal doxorubicin group and 72% in the topotecan group). Survival data are mature: 87% of patients have died (n = 413). There was an 18% reduction in the risk of death for patients treated with pegylated liposomal doxorubicin (median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients; HR = 1.216; 95% confidence interval (CI) 1.000-1.478; P = 0.050). The hazard ratio for all randomized subjects (includes those randomized, but never treated; n = 481) was 1.23 (median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients; 95% CI 1.01-1.50; P = 0.038). For patients with platinum-sensitive disease, there was a 30% reduction in the risk of death for the pegylated liposomal doxorubicin-treated group (median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients; HR = 1.432; 95% CI 1.066-1.923; P = 0.017). In patients with platinum-refractory disease, survival was similar between treatment groups. Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer. The survival benefit is pronounced in patients with platinum-sensitive disease.Gynecologic Oncology 11/2004; 95(1):1-8. · 3.93 Impact Factor
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ABSTRACT: The literature on the role of cytoreductive surgery beyond the secondary cytoreductive setting is limited. In this study, we reviewed the outcomes of patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction. We performed a retrospective chart review of all patients with recurrent epithelial ovarian carcinoma who underwent tertiary cytoreduction at our institution from 1/1/90 to 12/31/02. Disease-specific survival (DSS) was calculated from the time of tertiary cytoreduction to last follow-up. Univariate and multivariate analyses were used to analyze outcomes and to identify potential prognostic factors. A total of 26 patients were identified. The median follow-up after tertiary cytoreduction was 22.3 months (range, 0-71.7 months), with an overall median DSS of 33.4 months (95%CI, 20.4-46.4). On univariate analysis, treatment-free interval (TFI) before tertiary cytoreduction and residual disease after the procedure, as well as time to first recurrence, were found to be significant prognostic factors. Median DSS was 15 months for a TFI < or =12 months compared with 60.4 months for a TFI > 12 months (P = 0.002). The median DSS for patients with residual disease < or =0.5 cm was 36.3 months compared with 10.6 months for patients with residual disease >0.5 cm (P <0.0001). On multivariate analysis, TFI and residual disease after tertiary cytoreduction retained prognostic significance (P < 0.05 for both). Further cytoreductive surgery may offer a survival benefit in patients who experience a recurrence after secondary cytoreduction. This benefit appears to be greatest in patients with a longer TFI (>12 months) and in whom an optimal (< or = 0.5 cm) cytoreduction can be achieved.Gynecologic Oncology 11/2004; 95(1):181-8. · 3.93 Impact Factor
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ABSTRACT: BACKGROUND This study was performed to address patient selection criteria and the role of secondary cytoreductive surgery (SCR) in patients with epithelial ovarian carcinoma (EOC) who had relapsed tumors after a progression-free interval ⩾ 3 months.METHODS One hundred seventeen patients with relapsed EOC after a clinical complete remission duration ≥ 3 months who underwent SCR were entered on this prospective trial. Survival curves were generated using the Kaplan–Meier method, and statistical comparisons were performed using log-rank tests, logistic stepwise regression analyses, and a Cox stepwise regression model.RESULTSThe median patient age at the time of relapse was 53 years (range, 20–78 years). The median survival was 22 months and the estimated 5-year survival rate for the entire cohort was 17.2%. Tumor was confined to a solitary site in 33 patients and to ≥ 2 sites in 84 patients. After they underwent SCR, 11 patients were rendered macroscopically disease free, 61 patients had residual disease that measured ≤ 1 cm in greatest dimension, and 45 patients had bulky intraabdominal residual disease. Survival was influenced by the extent of relapse disease (solitary site vs. multiple sites; P < 0.0001), the size of residual disease after SCR (0 cm vs. ≤ 1 cm [P = 0.1211], ≤ 1 cm vs. > 1 cm [P = 0.0002], and 0 cm vs. > 1 cm [P = 0.0011]), Eastern Cooperative Oncology Group performance status (0 vs. 1 [P = 0.134], 1 vs. 2 [P = 0.007], and 0 vs. 2 [P = 0.0012]), and the number of cycles of salvage chemotherapy (1–2 cycles vs. 3–5 cycles [P = 0.0144]; 1–2 cycles vs. ≥ 6 cycles [P < 0.0001]; and 3–5 cycles vs. ≥ 6 cycles [P = 0.0009]). The outcome of SCR was influenced by the extent of relapse disease (multiple sites [51.2%] vs. solitary sites [87.9%]; relative risk [RR] = 9.1237; P = 0.0002) and by the use of bowel resection (yes [60.9%] vs. no [37.5%]; RR = 0.3828; P = 0.0106).CONCLUSIONSSCR was found to be safe for patients with relapsed EOC who achieved a clinical complete remission that lasted ≥ 3 months, with resectability similar to that of primary debulking surgery. Optimal surgical outcomes were achieved easily in patients who apparently had solitary tumor sites, with bowel resection making it possible to remove bulky tumors that involved the intestine. A survival benefit was provided by optimal SCR, particularly when surgery was supported by multiple courses of salvage chemotherapy. Cancer 2004. © 2004 American Cancer Society.Cancer 03/2004; 100(6):1152 - 1161. · 5.20 Impact Factor