Secondary Surgery Versus Chemotherapy for Recurrent Ovarian Cancer.
ABSTRACT: The best course of treatment for recurrent ovarian cancer is uncertain. We sought to determine whether secondary cytoreductive surgery for first recurrence of ovarian cancer improves overall survival compared with other treatments.We assessed survival using Surveillance, Epidemiology and End Results-Medicare data for advanced stage ovarian cancer cases diagnosed from January 1, 1997 to December 31, 2007 with survival data through 2010 using multinomial propensity weighted finite mixture survival regression models to distinguish true from misclassified recurrences. Of 35,995 women ages 66 years and older with ovarian cancer, 3439 underwent optimal primary debulking surgery with 6 cycles of chemotherapy; 2038 experienced a remission.One thousand six hundred thirty-five of 2038 (80%) women received treatment for recurrence of whom 72% were treated with chemotherapy only, 16% with surgery and chemotherapy and 12% received hospice care. Median survival of women treated with chemotherapy alone, surgery and chemotherapy, or hospice care was 4.1, 5.4, and 2.2 years, respectively (P<0.001). Of those receiving no secondary treatments, 75% were likely true nonrecurrences with median survival of 15.9 years and 25% misclassified with 2.4 years survival. Survival among women with recurrence was greater for those treated with surgery and chemotherapy compared with chemotherapy alone (hazard ratio=1.67; 95% confidence interval, 1.13-2.47). Women who were older with more comorbidities and high-grade cancer had worse survival.Secondary surgery with chemotherapy to treat recurrent ovarian cancer increases survival by 1.3 years compared with chemotherapy alone and pending ongoing randomized trial results, may be considered a standard of care.
Project description:BACKGROUND:Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. METHODS/DESIGN:Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION:Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.
Project description:Background:Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). Methods:A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: "ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC". Seven studies were selected for analysis. Results:In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06-5.56; P=0.04; I2=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81-6.10; P<0.01; I2=0%), (OR 4.22; 95% CI, 2.07-8.60; P<0.01; I2=52%), (OR 5.17; 95% CI, 1.40-19.09; P=0.01; I2=82%). Conclusions:HIPEC seems to have an effective role to prolong survival in patients affected by ROC.
Project description:BACKGROUND:Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain. METHODS:We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. RESULTS:After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). CONCLUSIONS:Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.).
Project description:OBJECTIVE:To determine correlation between race and receipt of optimal treatment for ovarian cancer and the impact of this on overall survival. METHODS:Using SEER-linked Medicare database, women 66 and older diagnosed with advanced ovarian cancer between 2002 and 2011 were identified. Patients with unclear histology, diagnosed on autopsy and without Medicare Parts A and B were excluded. We used Chi-square test for categorical variables, F test for continuous variables, and multivariable logistic regression to identify characteristics associated with receipt of surgery and chemotherapy. Kaplan-Meier analysis was used to compare overall survival rates. Cox Proportional Hazards regression was performed to identify factors associated with 5-year survival. RESULTS:9016 ovarian cancer patients were included. 2638 had primary chemotherapy, 4854 had primary surgery, and 1524 had no treatment. 7653 (84.9%) were white, 572 (6.3%) black, 479 (5.3%) Hispanic, and 312 (3.5%) were of other race/ethnicity. More white patients (57.2%) received both chemotherapy and surgery compared to black (39.9%), Hispanic (48.9%), or other (54.2%) (p < .001). Receipt of either only surgery or chemotherapy, or receipt of neither, resulted in higher risk of death when compared to receipt of both. On multivariable analysis, black (OR 0.58 [0.46-0.73]) and Hispanic (0.69 [0.54-0.88]) patients were less likely to receive both chemotherapy and surgery. Being of black race was significantly correlated with worse overall survival [HR 1.13 (1.03-1.23); p = .02]. CONCLUSIONS:Non-white women are less likely to receive the standard of care treatment for ovarian cancer and more likely to die from their disease than white women.
Project description:BACKGROUND:Observational studies comparing neoadjuvant chemotherapy to primary surgery for advanced-stage ovarian cancer are limited by strong selection bias. Multiple methods were used to control for confounding and selection bias to estimate the effect of primary treatment on survival for ovarian cancer. METHODS:The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women ? 65 years of age with stage II-IV epithelial ovarian cancer who survived > 6 months from the date of diagnosis and received treatment from 1991 through 2007. Traditional regression analysis, propensity score-based analysis, and an instrumental variable analysis (IVA) using geographic location as an instrument were used to compare survival between neoadjuvant chemotherapy and primary surgery. RESULTS:A total of 9587 patients with stage II-IV ovarian cancer were identified. Use of primary surgery decreased from 63.2% in 1991 to 49.5% by 2007, whereas primary chemotherapy increased from 19.7% in 1991 to 31.8% in 2007 (P < .0001). In the observational cohort survival (hazard ratio [HR] = 1.27; 95% confidence interval [CI] = 1.19-1.35) was inferior for patients treated with neoadjuvant chemotherapy; both median survival (15.8 versus 28.8 months) and 2-year survival (36% versus 56%) were lower in the neoadjuvant chemotherapy group compared to those who underwent surgery. In the IVA, primary treatment had minimal effect on overall survival (HR = 1.04; 95% CI = 0.67-1.60). The median survival for patients with a value of the instrument less than the median (24.0 months, 95% CI = 23.0-25.0) and greater than or equal to median value of the IV (24.0 months, 95% CI = 23.0-26.0) were similar. CONCLUSIONS:Use of neoadjuvant therapy has increased over time. Survival with neoadjuvant chemotherapy did not differ significantly from primary surgery in elderly women in the United States.
Project description:INTRODUCTION:Adnexal or pelvic mass is a finding that commonly raises suspicion for malignancy, especially for ovarian cancer. Proper identification prior to surgery would permit appropriate referral to a specialty center in cases likely to be ovarian cancer, as optimal outcomes in such cases are obtained when surgical staging and treatment are provided at the time of initial surgery. METHODS:We compared the screening capabilities of two in vitro diagnostic multivariate index assays (IVDMIAs), a new IVDMIA (second-generation multivariate index assay: MIA2G) and a currently used triage algorithm (Risk of Ovarian Malignancy Assay: ROMA). RESULTS:Among 245 subjects (24.7%) determined to have a malignancy, ROMA misclassified 51 malignancies (including 10 high-grade ovarian malignancies), whereas MIA2G misclassified 22 (including 5 high-grade ovarian malignancies). Early stage cancers were more frequently misclassified by ROMA (20 vs. 8 cases). The rate of "test-negative" malignancies was significantly higher for ROMA, while the rate of "test-positive" benign cases was significantly higher for MIA2G. CONCLUSION:Triage algorithms play an important role in improving clinical outcomes for women presenting with an adnexal mass regardless of the eventual diagnosis. In this study, MIA2G was shown to correctly predict more cases of ovarian cancer than the ROMA algorithm. FUNDING:Aspira Labs/Vermillion Inc.
Project description:BACKGROUND:In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS:Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS:In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS:Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).
Project description:This study investigated the clinical significance of keratin 5 and 6 expression in serous ovarian cancer progression and chemotherapy resistance. KRT5 and KRT6 (KRT6A, KRT6B & KRT6C) gene expression was assessed in publically available serous ovarian cancer data sets, ovarian cancer cell lines and primary serous ovarian cancer cells. Monoclonal antibodies which detect both K5/6 or only K5 were used to assess protein expression in ovarian cancer cell lines and a cohort of high grade serous ovarian carcinomas at surgery (n = 117) and after neoadjuvant chemotherapy (n = 21). Survival analyses showed that high KRT5 mRNA in stage III/IV serous ovarian cancers was significantly associated with reduced progression-free (HR 1.38, P < 0.0001) and overall survival (HR 1.28, P = 0.013) whilst high KRT6 mRNA was only associated with reduced progression-free survival (HR 1.2, P = 0.031). Both high K5/6 (? 10%, HR 1.78 95% CI; 1.03-2.65, P = 0.017) and high K5 (? 10%, HR 1.90, 95% CI; 1.12-3.19, P = 0.017) were associated with an increased risk of disease recurrence. KRT5 but not KRT6C mRNA expression was increased in chemotherapy resistant primary serous ovarian cancer cells compared to chemotherapy sensitive cells. The proportion of serous ovarian carcinomas with high K5/6 or high K5 immunostaining was significantly increased following neoadjuvant chemotherapy. K5 can be used to predict serous ovarian cancer prognosis and identify cancer cells that are resistant to chemotherapy. Developing strategies to target K5 may therefore improve serous ovarian cancer survival.
Project description:Ovarian cancer (OC) is the fifth most common cause of cancer death in women. Although significant progress has been made in the treatment of OC, the majority of patients experience disease recurrence and receive second-line and sometimes several lines of treatment. Here we review the options available for the treatment of recurrent disease and discuss how different agents are selected, combined and offered in a rationale sequence in the context of multidisciplinary care. We reviewed published work between 1990 and 2013 and meeting abstracts related to the use of chemotherapy and surgery in patients with recurrent ovarian cancer. We discuss treatment regimens, efficacy endpoints and safety profiles of the different therapies. Platinum-based drugs are the most active agents and are selected on the basis of a probability of response to retreatment. Nonplatinum-based chemotherapy regimens are usually given in the 'platinum-resistant' setting and have a modest effect on outcome. Molecular targeted therapy of ovarian cancer given alone or integrated with chemotherapy is showing promising results. Many patients are now receiving more than one line of therapy for recurrent disease, usually platinum based until platinum resistance emerges. The sequential use of chemotherapy regimens and the incorporation of molecularly targeted treatments, either alone or in combination with chemotherapy, have over the last decade significantly extended the median survival of patients with ovarian cancer.
Project description:OBJECTIVE:Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed as a treatment in ovarian cancer. A recently published RCT demonstrated that HIPEC prolongs disease-free survival (DFS) and overall survival (OS) in ovarian cancer. The aim of the study was to investigate oncologic results of cytoreductive surgery+HIPEC compared with cytoreductive surgery alone in advanced primary ovarian cancer with a particular attention to the pattern of recurrence. METHODS:This is a retrospective case control study with a propensity score (PS) matching of the patients. All the patients treated for primary advanced ovarian cancer who underwent interval surgery with or without HIPEC were collected; a PS was calculated in order to match cases to controls. RESULTS:Among 77 eligible patients 56 patients were included in the study. Preoperative patients' characteristics were homogeneous. No difference in morbidity and mortality after surgery were recorded. DFS was not different among the 2 groups (13.2 vs. 13.9 months, p=0.454) but OS was better in patients treated with HIPEC with no median reached vs. 35.5 months (p=0.048). Patients treated with cytoreductive surgery alone were more likely to have a peritoneal recurrence (43% vs. 14%). CONCLUSION:HIPEC seems to affect the relapse pattern with lesser peritoneal recurrence. This difference in relapse pattern seems to affect the OS with better results in patients treated with HIPEC. Further studies are needed to confirm these findings.