Patient and treatment characteristics in advanced disease (stage III + IV) by treatment setting are shown in Table 3. There were no significant differences in the distribution of substages within FIGO stage III, in histologic type, or differentiation grade between cases and controls. All cases and 54% of the control subjects (25 of 46) underwent the standard minimum required surgical procedure: total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. None of the controls underwent pelvic lymphadenectomy, whereas four (17%) cases had this procedure performed (P = .003). Also, intestinal resection, to increase the extent of cytoreduction, was done more frequently at the teaching hospital (among cases) (30%) than at nonteaching hospitals (among control subjects) (9%) (P = .02). Nine of the control subjects underwent relaparotomy at the teaching hospital because of inadequacy of the first operation. Finally, control subjects were less likely to have been optimally cytoreduced during primary surgery as only 24% obtained less than 1-cm residual disease compared with 48% of cases (P = .04). A few more cases received platinum-based chemotherapy compared with controls (P = .2). There was no difference in proportion of patients who completed chemotherapy (received five or more courses) and no difference in the mean number of courses given between cases (mean 5.7, standard deviation [SD] 1.1, range 0–9) and controls (mean 5.2, SD 2.4, range 0–15). Furthermore, for patients with advanced disease, the mean duration of the postoperative hospital stay was 11.2 days for cases and 12.8 days for controls (P = .86). Among those receiving chemotherapy, 55% of the patients operated at the teaching hospital received first course before discharge, compared with only 10% of the patients operated at the nonteaching hospitals (P < .001). The remaining patients received chemotherapy after a period of convalescence. The mean ratio of survival days spent in the hospital was 15% (SD 10.5, median 12, range 1–33) for cases and 28% (SD 16.8, median 17, range 1–75) for controls (P = .04).
Prognostic factors of survival were assessed in a forward stepwise Cox regression model by entering treating hospital (case/control) as an obligate exposure variable. In a model including histology (epithelial, nonepithelial), differentiation grade (well, moderate, poor, not graded), residual disease at end of surgery (less than 1 cm, 1 cm or greater), platinum therapy (non = 0, received = 1), and completeness of chemotherapy (less than five, five or more courses), only completeness of chemotherapy and residual disease were significant predictors of survival, whereas treating hospital became borderline significant (P = .11). There was no interaction between completeness of chemotherapy and residual disease. However, the analyses revealed a significant interaction between residual disease and treatment hospital (cases/controls) (P = .01), implying that survival varied among cases and controls by size of residual disease. Therefore, we explored a model by entering a combined variable of treating hospital and residual disease: teaching hospital/residual disease less than 1 cm, teaching hospital/residual disease 1 cm or greater, non-teaching hospital/residual disease less than 1 cm, and nonteaching hospital/residual disease 1 cm or greater. The results are shown in Table 4. With reference to those patients who were optimally operated on at the teaching hospital (residual disease less than 1 cm), patients operated on at the teaching hospital who did not reach this optimal surgical goal (left with residual disease 1 cm or greater) had a nine-fold increased risk of death within 5 years. These patients had a similar risk of mortality as patients undergoing primary surgery at a nonteaching hospital; there was no difference in mortality between patients treated in a nonteaching hospital setting by residual disease.
This report evaluates a policy of centralization of primary surgery for ovarian cancer in a population-based setting. The hospitals in the present study were the only ones in the health region where gynecologic surgery was performed (no private hospitals); thus, the study population was unselected. Despite the small sample size, the results show an improved survival among women with advanced disease who were operated on at a gynecologic–oncology subspecialty unit by gynecologic–oncologists compared with matched historical controls who were operated on at nonteaching hospitals by general gynecologists.
The size of residual disease after cytoreductive surgery has been reported by many authors to be the most consistent variable to predict prognosis.6,11,15,16 By combining the variables hospital setting (cases/controls) and residual disease (Table 4), patients at the teaching hospital not reaching treatment goal (residual disease less than 1 cm) had an equivalent mortality as patients treated at a nonteaching hospital regardless of residual tumor size. These data suggest that the overall management undertaken in the teaching hospital, aggressiveness in surgery by complete omentectomy, lymphadenectomy, and, if necessary, intestinal resection are important procedures to obtain a more correct estimation of residual disease. This phenomenon is shown by the difference in survival for the subgroup of patients who attained optimal cytoreduction (less than 1-cm residual tumor) operated on at nonteaching hospitals compared with those operated on at the teaching hospital.
The impact on survival of platinum-containing chemotherapy compared with surgical cytoreduction has been an issue of discussion.1,6,17 In our study, the hazard ratio of dying was three times higher for stage III/IV patients receiving less than five courses of chemotherapy in comparison with patients receiving five courses or more, independent of size of residual disease. However, there was no significant difference between cases and controls regarding type of chemotherapy or the number of courses of chemotherapy received. This indicates that the difference in survival among cases and controls in advanced stage disease could not be explained by the chemotherapy effect.
Patients who have undergone suboptimal primary surgery at a nonteaching hospital may be offered a second laparotomy at a more specialized oncology unit. In our study, nine of the patients in the control group (20%) were reoperated on such an indication at the teaching hospital, and seven of them obtained optimal cytoreduction (residual disease less than 1 cm). None of these patients received chemotherapy before relaparotomy. The median survival for these nine control patients, however, did not differ from the median survival rate for the whole control group (14 versus 12 months, respectively). This observation could indicate a superior effect of first versus second attempt to optimize cytoreductive surgery.
The need to maintain a critical volume of work to sustain surgical expertise has been a controversial issue.1,2,18,19 Olaiten et al reported that patients treated in hospitals managing fewer than ten ovarian cancer cases per year (P = .02) were less likely to obtain optimal cytoreduction compared with those treated in hospitals with ten or more cases per year.5 Trimbos et al have demonstrated a long learning curve associated with infrequent and complicated radical surgery for gynecologic cancer.20 In our setting, general gynecologists at the nonteaching hospitals operated on average five ovarian cancer patients per year (range 1–9), compared with a volume of 29 operations at the teaching hospital (range 20–41).11
The overall postoperative mortality was low, as no cases and two control subjects died within the first 28 days of surgery. It is noteworthy that the immediate postoperative mortality was not different between the two groups, despite the more extensive surgery performed in the cases. In addition, the fact that the duration of the hospital stay was similar for cases and controls reflects that more extensive surgery in the cases did not result in increased postoperative morbidity. In correspondence with our results, others have reported that radical surgery, including intestinal anastomosis, urologic procedures, and retroperitoneal lymphadenectomy to increase cytoreduction in advanced ovarian cancer surgery, did not increase operative mortality when patients were operated on by trained gynecologic–oncologists.21–23
Cases with advanced disease spent significantly less time of their overall survival time in hospitals compared with control subjects. Both the length of survival and the quality of life are important for cancer patients. Provided that the amount of survival time spent at home is a valuable experience for patients, our results suggest that primary surgery at a teaching hospital may add quality to life in addition to prolongation of survival. Although few studies have directly addressed the effect of surgical cytoreduction on the quality of the patient's life, Blythe and Wahl showed that ovarian cancer patients after extensive debulking surgery (to less than 2-cm residual tumor) enjoyed a better quality of life than patients rendered with tumor size greater than 2 cm.24 Centralization of primary surgery was introduced in the whole Health Region IV, Norway, from 1995 and onwards. To change the current referral practice of ovarian cancer patients in the health region for the benefit of a prospective randomized trial would ethically be questionable. Therefore, a pragmatic approach of applying a historical prospective design is the best scientific achievement in our setting. During the 10-year period 1987–1996, the health service in the health region has been reasonably stable, including surgical staff.11 Additionally, chemotherapy regimens have not been changed over the study period.
We conclude that centralization of ovarian cancer surgery to gynecologic–oncology subspecialty unit has improved survival, and may also have positively influenced the quality of life for patients with advanced disease. Therefore, our data suggest that patients with apparent advanced ovarian cancer should be referred to a subspecialty unit, and every effort should be made to obtain as complete cytoreduction as possible during primary surgery.4–6,11
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© 2003 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
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