What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study. Effect of cytoreductive surgery on survival of patients with recurrent epithelial ovarian cancer. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Surgery in recurrent epithelial ovarian cancer: benefits on Survival for patients with residual disease of 0.1-1 cm after secondary cytoreduction. Prognostic factors of stage IV epithelial ovarian cancer: a multicenter retrospective study. Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: a case-control study.
Recent studies have suggested that the definition of optimal cytoreduction for advanced EOC should be changed from the current Gynecologic Oncology Group threshold of < or =1 cm residual disease to no gross residual disease owing to improved survival of patients (pts) rendered macroscopically disease-free. The objective of this study was to analyze survival rates at very specific residual disease diameters to determine the optimal goal of primary cytoreduction for bulky stage IIIC EOC.
                A prospectively kept database was used to identify and review the records of all pts with Stage IIIC EOC who underwent primary cytoreductive surgery at our institution between January 1989 and December 2003. To analyze a homogeneous cohort of cases, we excluded pts with stage IIIC disease based on nodal metastasis alone (without bulky abdominal tumor), fallopian tube or primary peritoneal carcinomas, and borderline tumors. Standard statistical analyses were utilized.
                The study cohort included 465 pts. The median age was 60 years (range, 25-87), and the median follow-up was 38 months (range, 1-199). Univariate and multivariate analyses, which included various prognostic factors, identified amount of residual disease as a significant prognostic factor (P < 0.001). Median overall survival in relation to the 5 residual disease categories was: no gross residual, 106 months; gross < or =0.5 cm, 66 months; 0.6-1.0 cm, 48 months; 1-2 cm, 33 months; >2 cm, 34 months. Statistical comparison between the 5 residual disease categories revealed 3 distinct groups with significantly different survival rates (P < 0.01). These 3 groups were: (1) no gross residual; (2) gross < or =1 cm residual; and (3) >1 cm residual. Although the difference in survival did not reach statistical significance, within the gross < or =1 cm residual group, there was a trend toward improved survival in pts left with smaller volume, < or =0.5 cm residual compared with those with 0.6-1.0 cm residual (P = 0.06).
                Our data suggest that removal of all evidence of macroscopic disease is associated with prolonged survival and should be the goal of primary cytoreductive surgery. If complete gross resection is not feasible, however, cytoreduction to as minimal residual tumor as possible should be the focus of cytoreductive efforts, as each incremental decrease in residual disease below 1 cm may be associated with an incremental improvement in overall survival. The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer, in which the maximum diameter of residual is < or = 1 cm, and suboptimal residual cancer, in which the residual disease is > 1 cm. Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed. This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a randomized trial of intense versus standard chemotherapy.
                Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses, respectively. There was no difference in progression-free interval or survival between the two arms. Of the 458 stage III (with residual disease > 1 cm) and stage IV patients entered in this study, 294 stage III patients comprise the current analysis. Surgical reporting forms, operation reports, and pathology reports were reviewed to determine initial greatest tumor diameter and residual tumor diameter. Patients were grouped by residual diameter. Multivariate analysis considered residual diameter of disease, age, histologic characteristics, performance status, and ascites. An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group.
                Patients ranged in age from 20 to 80 years, with a median of 60 years. All patients were Gynecologic Oncology Group performance status 0 to 2. Fifty-two percent had grade 3 tumors, and 39% and 9%, respectively, had grade 2 or 1 tumors. All patients had stage III disease. Ninety percent had serous, endometrioid, or mixed epithelial cell type tumors. Multivariate analysis revealed a relative risk of dying as follows: residual disease < 2 cm, relative risk 1.00; 2 to 2.9 cm, relative risk 1.90; 3 to 3.9 cm, relative risk 1.91; 4 to 5.9 cm, relative risk 1.74; 6 to 7.9 cm, relative risk 1.85; 8 to 9.9 cm, relative risk 2.16; > or = 10 cm, relative risk 1.82. The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant (p < 0.01). There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm.
                Among patients with suboptimal (> 1 cm residual disease) epithelial ovarian cancer, those who have small diameter residual disease (< 2 cm) tend to survive longer than those who have larger residual disease. Among those with larger residual disease, size does not affect prognosis appreciably. Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer, relatively few undergo complete cytoreduction. This study was initiated to prospectively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact on survival.
                Between 1990 and 1996, 163 consecutive patients underwent primary cytoreduction. The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy. A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction (logistic regression) and survival (Cox proportional hazards model).
                One hundred thirty-nine patients (85.3%) underwent removal of all visible tumor, 22 (13.5%) had cytoreduction to </=1 cm residual disease, and 2 (1.2%) had unresected bulky disease. The median and estimated 5-year survival for the entire cohort was 54 months and 48%, respectively. The probability of achieving complete cytoreduction was influenced independently by the preoperative Gynecologic Oncology Group performance status (0-1 vs 2-3, P = 0.04), the number of mesenteric and intestinal serosal implants (</=75 vs >75 implants, P = 0.005), and stage (IIIC vs IV, P = 0.006). The probability of survival was independently influenced by age (</=61 vs >61 years, P = 0.003), volume of ascites (</=1 vs >1 liter, P = 0.01), stage (IIIC vs IV, P = 0.04), histology (clear cell and mucinous vs all other, P = 0.03), and the completeness of cytoreductive operation (complete vs incomplete cytoreduction, P = 0.02).
                Complete cytoreduction is possible for the majority of patients and improves survival, even compared to operations with minimal (</=1 cm) residual disease. Unless their medical condition prohibits anesthesia and surgery, patients with advanced epithelial ovarian cancer should undergo primary cytoreductive surgery with the intention of complete tumor removal.
                Copyright 1998 Academic Press. The value of secondary cytoreductive surgery is still controversial, especially in patients with recurrent epithelial ovarian cancer. In this retrospective study, we investigated the effect on survival of secondary cytoreduction for recurrent disease and variables influencing redebulking surgical outcome.
                Between 1986 and 1997, 60 patients who received primary cytoreductive surgery and platinum-based chemotherapy for stage III and IV epithelial ovarian cancer experienced disease recurrence at least 6 months after completion of primary therapy, and secondary surgical cytoreduction was performed. The optimal residual disease cutoff was 1.0 cm. The Cox proportional regression model and Logistic stepwise regression were used in statistical processing of the data.
                The median progression-free interval between the two operations was 13 months (range, 6-56 months). Optimal secondary cytoreduction was achieved in 23 patients (38.33%). There was a significant difference in survival between patients who were optimally cytoreduced compared to those suboptimally cytoreduced, with an estimated median survival in the optimal group of 19 months vs. 8 months in the suboptimal group (chi(2) = 22.04, P = 0.0000). Prognosis of survival for individuals with progression-free interval >12 months was better than that of those with the interval </=12 months (chi(2) = 5.22, P = 0.0224). Patients with ascites at disease recurrence suffered a pessimistic outcome, with an estimated median survival of 6 vs. 13 months in those without ascites (chi(2) = 13.99, P = 0.0002). Multivariate analysis strongly suggested that residual disease after second operation, ascites at disease recurrence, and progression-free interval were independent prognostic factors of survival. Logistic stepwise regression revealed that recurrent ascites (P = 0.0072, relative risk = 20.36) and residual disease after the second operation (P = 0.0096, relative risk = 5.16) were important determinants of secondary surgical outcome.
                Secondary cytoreductive surgery significantly lengthened survival for patients with recurrent epithelial ovarian cancer. Patients with ascites at disease recurrence, however, were not suitable for aggressive secondary surgery, and redebulking surgery for those with residual disease of >1.0 cm after primary operation should be considered prudently.
                Copyright 2000 Wiley-Liss, Inc. Residual disease after initial surgery for ovarian cancer is the strongest prognostic factor for survival. However, the extent of surgical resection required to achieve optimal cytoreduction is controversial. Our goal was to estimate the effect of aggressive surgical resection on ovarian cancer patient survival.
                A retrospective cohort study of consecutive patients with International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer undergoing primary surgery was conducted between January 1, 1994, and December 31, 1998. The main outcome measures were residual disease after cytoreduction, frequency of radical surgical resection, and 5-year disease-specific survival.
                The study comprised 194 patients, including 144 with carcinomatosis. The mean patient age and follow-up time were 64.4 and 3.5 years, respectively. After surgery, 131 (67.5%) of the 194 patients had less than 1 cm of residual disease (definition of optimal cytoreduction). Considering all patients, residual disease was the only independent predictor of survival; the need to perform radical procedures to achieve optimal cytoreduction was not associated with a decrease in survival. For the subgroup of patients with carcinomatosis, residual disease and the performance of radical surgical procedures were the only independent predictors. Disease-specific survival was markedly improved for patients with carcinomatosis operated on by surgeons who most frequently used radical procedures compared with those least likely to use radical procedures (44% versus 17%, P < .001).
                Overall, residual disease was the only independent predictor of survival. Minimizing residual disease through aggressive surgical resection was beneficial, especially in patients with carcinomatosis.
                II-2. The benefit of cytoreductive surgery for patients with recurrent epithelial ovarian cancer has not been defined clearly. The objective of this study was to identify prognostic factors for survival in patients who underwent secondary cytoreduction for recurrent, platinum-sensitive epithelial ovarian cancer and to establish generally applicable guidelines and selection criteria.
                The authors reviewed all patients who underwent secondary cytoreduction for recurrent epithelial ovarian cancer from 1987 to 2001. Potential prognostic factors were evaluated in univariate and multivariate analyses.
                In total, 157 patients underwent secondary cytoreduction, and 153 of those patients were evaluable. After secondary cytoreduction, the median follow-up was 36.9 months (range, 0.2-125.6 months), and the median survival was 41.7 months (95% confidence interval, 36.0-47.2 months). For patients who had a disease-free interval prior to recurrence of between 6 months and 12 months, the median survival was 30 months compared with 39 months for patients who had a disease-free interval between 13 months and 30 months and 51 months for patients who had a disease-free interval >30 months (P = .005). For patients who had a single site of recurrence, the median survival was 60 months compared with 42 months for patients who had multiple sites of recurrence and 28 months for patients who had carcinomatosis (P <.001). The median survival for patients who had residual disease that measured < or =0.5 cm was 56 months compared with 27 months for patients who had residual disease that measured >0.5 cm (P <.001). On multivariate analysis, disease-free interval (P = .004), the number of recurrence sites (P = .01), and residual disease (P <.001) were significant prognostic factors.
                In the authors' analysis of secondary cytoreduction for recurrent epithelial ovarian cancer, a significant survival benefit was demonstrated for residual disease that measured < or = 0.5 cm. The disease-free interval and the number of recurrence sites should be used as selection criteria for offering secondary cytoreduction. Recent retrospective trials stated that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a complete cytoreduction (R0) could be achieved. Most of them pointed out there was no difference in survival between residual disease of 0.1-1 cm (R1) and >1 cm (R2). The aim of this study was to evaluate survival benefits from cytoreduction to R1.
                Between 2002 and 2006, 123 patients with recurrent epithelial ovarian cancer undergoing secondary cytoreduction were identified from tumor registry databases.
                The median age at recurrence was 51 years (range: 28-84). Fifty-one (41.5%) patients had R0, 46 (37.4%) patients had R1, and 26 (21.1%) patients had R2 resection. The median survival of the entire cohort was 31.7 months, with an estimated 5-year survival of 31.1%. The median survival and estimated 5-year survival for patients with R1 were 31.1 months and 23.9%, and there were significant differences in survival when compared to 15.6 months and 6.4% in R2 (chi(2) = 7.45, P = 0.006), 63.2 months (mean survival) and 54.4% in complete cytoreduction (chi(2) = 8.93, P = 0.0028).
                Complete secondary cytoreduction is the strongest survival determinant in recurrent epithelial ovarian cancer, whereas patients with residual disease of 0.1-1 cm may also benefit from secondary cytoreduction.
                (c) 2010 Wiley-Liss, Inc. In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer.
                In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods.
                Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415).
                Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.
                Copyright 2001 Academic Press. To evaluate clinicopathological factors and survival outcome of patients with advanced epithelial ovarian carcinoma undergoing multiple bowel resections to achieve optimal (< or = 1 cm) cytoreduction.
                A case-control study was performed identifying patients undergoing optimal primary cytoreductive surgery with > or = 2 bowel resections between 10/1997 and 2/2006. The two control groups consisted of (1) patients undergoing optimal cytoreduction with < or = 1 bowel resections matched [1:2] for age and stage and (2) patients left with suboptimal disease. Cox proportional hazards model were used to evaluate the effects of demographic and surgico-pathologic factors on survival outcome.
                A total of 34 patients underwent > or = 2 bowel resections. Sixty-eight patients underwent < or = 1 bowel resections. All patients had optimal cytoreduction and 40/102 patients (39.2%) underwent complete cytoreduction. Patients undergoing multiple bowel resections experienced a higher EBL (700 v 500 mL, p=0.01) and longer LOS (10 v 7 days, p=0.01) compared to patients with < or = 1 bowel resections. Multivariate analysis revealed the amount of residual disease to be a statistically significant and radiation therapy to the right pelvic sidewall and cul-de-sac independent predictor of overall survival. The median overall survival time for patients undergoing > or = 2 bowel resections was 28.3 months, which was comparable to patients undergoing < or = 1 bowel resections, (37.8 months, p=0.09) but statistically significantly superior to patients left with suboptimal residual disease (12 months, p=0.02).
                Although primary surgery that includes > or = 2 bowel resections is associated with longer LOS and a higher EBL, such extensive procedures are warranted if they will contribute to an overall optimal residual disease state.
During primary surgery for advanced stage epithelial ovarian cancer all attempts should be made to achieve complete cytoreduction. When this is not achievable, the surgical goal should be optimal (< 1 cm) residual disease. Due to the high risk of bias in the current evidence, randomised controlled trials should be performed to determine whether it is the surgical intervention or patient-related and disease-related factors that are associated with the improved survival in these groups of women. The findings of this review that women with residual disease < 1 cm still do better than women with residual disease > 1 cm should prompt the surgical community to retain this category and consider re-defining it as 'near optimal' cytoreduction, reserving the term 'suboptimal' cytoreduction to cases where the residual disease is > 1 cm (optimal/near optimal/suboptimal instead of complete/optimal/suboptimal).