Prognostic factors for patients treated for a recurrent FIGO stage III ovarian cancer: A retrospective study of 108 cases

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EJSO 37 (2011) 971e977

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Prognostic factors for patients treated for a recurrent FIGO stage III ovarian cancer: A retrospective study of 108 cases J.M. Classe a,*, I. Jaffre a, J.S. Frenel b, V. Bordes a, M. Dejode a, F. Dravet a, G. Ferron c, F. Marchal d, D. Berton Rigaud b, D. Loussouarn e, L. Campion f a

Department of Surgical Oncology, Institut de Cancerologie de l’Ouest - Cancer Center Rene Gauducheau, Boulevard Jacques Monod, 44805 Nantes Saint Herblain, France b Department of Medical Oncology, Institut de Cancerologie de l’Ouest - Cancer Center Rene Gauducheau, Boulevard Jacques Monod, 44805 Nantes Saint Herblain, France c Department of Surgical Oncology, Institut Claudius Regaud, Avenue du Pont Saint Pierre, Toulouse, France d Department of Surgical Oncology, CRAN-Nancy-Universite, Center Alexis Vautrin, Avenue de Bourgogne Brabois, 54511 Vandoeuvre les Nancy, France e Department of Pathology, Hospital University, Laennec, Boulevard Jacques Monod, Nantes Saint Herblain 44805, France f Department of Statistics, Institut de Cancerologie de l’Ouest - Cancer Center Rene Gauducheau, Boulevard Jacques Monod, Nantes Saint Herblain 44805, France Accepted 28 August 2011 Available online 25 September 2011

Abstract Aims: To determine overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer, outside of randomized trial, with a long term follow-up and to identify prognostic factors. Materials and methods: A consecutive series of 108 patients treated for a first relapse of a FIGO stage III ovarian cancer was retrospectively included from December 1999 to November 2004. Each patient was treated with platinum-based chemotherapy in case of late (>6 months) relapse and with salvage chemotherapy without platinum in case of <6 months relapse. For statistical analysis the studied parameters were age, histological subtype, the completeness of initial surgery, disease-free period, localization of the relapse, clinical response to second-line chemotherapy, the completeness of secondary cytoreductive surgery (SCS) when it was performed. Results: Median follow-up from the first relapse was 40 months. From the 108 patients, 35 underwent SCS. Median overall survival from the first relapse was 13 months in case of no SCS or non-optimal SCS and 35 months for patient with an optimal SCS ( p ¼ 0.006). In a multivariate analysis age, disease-free period, the clinical presentation of the relapse, completeness of SCS and response to second line chemotherapy appeared to be independent prognostic factors. Conclusions: Prognostic factors of ovarian cancer relapse are directly or indirectly linked with the feasibility of a complete SCS. Thus in the case of an ovarian cancer relapse, the feasibility of SCS must be considered in order to give the patient the best chance to experience its complete removal. Ó 2011 Elsevier Ltd. All rights reserved. Keywords: Ovarian cancer; Relapse; Surgery; Prognostic factor; Survival

Introduction Epithelial ovarian cancer is the most lethal gynecologic neoplasm in France, with 4500 new cases and 3300 deaths, the majority of which due to peritoneal widespread at the time of diagnosis or relapse.1 * Corresponding author. Tel.: þ33 240679959; fax: þ33 240679759. E-mail address: [email protected] (J.M. Classe). 0748-7983/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.ejso.2011.08.138

The standard first-line treatment is based on cytoreductive surgery, followed by intravenous combined platinumbased chemotherapy.2,3 In a recent retrospective study of 1895 patients, extracted from GOG randomized trials, treated for a FIGO stage III ovarian cancer, 80% experienced a relapse. In this series age, performance status, tumor histology and residual tumor volume after initial surgery were independent prognostic factors, the median disease free survival was 17.1 month and the median

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overall survival was 45.3 months.4 In a retrospective series of 447 patients treated for a FIGO stage III-IV, outside of randomized trial, the median overall survival was 18 months.5 After the first relapse the median time to the second relapse is about 5e10 months.6,7 The standard treatment of the first relapse is mainly based on second-line intravenous chemotherapy. The choice of second-line chemotherapy is based on the disease-free interval between the end of initial treatment and the diagnosis of the first relapse. In case of a disease-free interval longer than 6 months, patients are generally offered a platinum-based chemotherapy.8 In ICON 4/AGO ovar 2.2 randomized trial, the overall survival of patients with a platinum sensitive relapse was 24e29 months.9 Unlike the initial treatment, secondary cytoreductive surgery (SCS) is not yet considered as a recommended standard treatment of the relapse outside of clinical trials, or in the case of palliative intent.10 Interestingly complete removal of the relapse without residual was associated with a long survival of patients with a first relapse in a recent meta-analysis and two large cohorts of patients.11,12 Survival of FIGO stage III patients with a first relapse was particularly studied through randomized trials or in retrospective series of patients who underwent a secondary surgical effort.9,13 The current study was based on a retrospective collection of a consecutive series of patient routinely treated for a relapsed FIGO stage III ovarian cancer in a single institution outside randomized trial. The objectives of our study were to assess overall survival of patients treated for a first relapse of FIGO stage III ovarian cancer in a consecutive mono institutional series of patients with a long follow-up and to identify factors predictive of poor outcome. Materials and methods We conducted a retrospective study of a consecutive series of patients with FIGO stage III ovarian cancer who had been treated in our Institution for a first relapse between December 1990 and November 2004. Clinical data were collected from a prospective clinical database, BERENIS (Banque de donnees pour l’Etude et la REcherche sur les Neoplasmes InfiltrantS), set up in our Institution. Inclusion criteria Inclusion criteria were the following: an initial diagnosis of a FIGO (Federation International of Gynecology and Obstetrics) Stage III epithelial ovarian cancer, first-line treatment consisting of a surgical resection, followed by 4e6 courses of an adjuvant platinum-based intravenous chemotherapy and at least one relapse. Exclusion criteria were initial treatment with chemotherapy first before surgery or chemotherapy alone without surgery.

Frontline and relapse treatment At the time of initial treatment, each patient had undergone FIGO classification according to clinical assessment, CT or MRI, serum CA 125 measurement and surgical assessment through a median laparotomy followed by at least a total hysterectomy with bilateral oophorectomy and omentectomy. Pelvic and aortico cava lymphadenectomy was not performed in all cases. All of the patients in this series experienced a relapse confirmed by one or more of the following criteria: a clinical tumor mass, ascitis, a new tumor seen at CT or MRI, coherent with new RECIST parameters and/or a confirmed increase in CA 125 level.14,15 SCS was not standard practice and was only performed in the case of a probable complete removal of the relapse for patients with a very good clinical status (performance status 0e1). The proposal for an SCS was always confirmed by the gynecologic oncologic multidisciplinary tumor board. When indicate, SCS was always performed in our Cancer Center. The amount of residual disease, at the end of the initial or secondary surgery, was systematically documented in the operative report, and categorized as follows according to the GOG rules16: complete cytoreduction correspond to the absence of any macroscopic residual disease (R0), optimal cytoreduction correspond to the presence of residual disease <1 cm (R1), suboptimal cytoreduction correspond to the presence of residual disease >1 cm (R2). Ovarian tumors were pathologically graded as well (G1), moderate (G2), or poorly (G3) differentiated. The end of initial treatment was determined as the day of the last course of first-line chemotherapy. Treatment response was evaluated through clinical assessment, CT scan and CA 125, and defined as follows: complete with no visible lesion, partial with >50% down-staging of initial lesions, stabilization with less than 50% down-staging of initial lesions, and progression. Relapse presentation was categorized as: pelvic masses only, retroperitoneal lymph nodes only (in this group some patients also had a pelvic mass), peritoneal carcinomatosis outside the pelvic area, and one distant metastasis or more. Studied parameters The studied parameters were age at diagnosis, tumor histology, amount of residual tumor at the end of surgery - initial and/or secondary- treatment response, presentation of the relapse, serum CA-125 levels at the time of recurrence, treatment of the first relapse (second-line chemotherapy, SCS), and time until death. The diseasefree interval was calculated from the end of initial treatment to the diagnosis of the first relapse, and total follow-up was the time from the end of initial treatment to death or to the last medical visit.

J.M. Classe et al. / EJSO 37 (2011) 971e977

Statistics Quantitative variables were described by median [range] and qualitative variables by distribution frequencies. The primary end-point (overall survival) was defined as the time between the date of the first relapse and the date of death (or last follow-up for living patients ¼ censored). Survival curves were estimated using the KaplaneMeier method. A univariate analysis of potential prognostic factors was performed with the log-rank test for categorical factors and with the univariate Cox analysis for continuous variables. Parameters with a p value < 0.15 at the univariate step were included in the multivariate regression Cox proportional hazards model. All tests were two-sided with statistical significance set at p < 0.05. All calculations were performed using SAS version 9.2 (SAS Institute, Cary, NC, USA) and STATA 10 SE (StataCorp, College Station, TX, USA). Results Patient characteristics A consecutive series of 108 patients were included during the study period. The patient characteristics are summarized in Table 1. Information concerning post-initial surgery residual tumor was available for all but 3 patients, with a complete surgery (R0) for 57 patients (57/105). Bowel surgery was performed at initial surgery in half of patients. The median follow-up from the end of initial treatment was 57 months (range 14e141). The median diseasefree interval was 9.1 months. The median follow-up, from the first relapse was 40 months (range 6e100). The median overall survival after the diagnosis of the relapse was 15.5 months. The median overall survival from initial treatment was 24 months (range, 4e161). At the time of the study only 13 patients were still alive. Only one third of the patients was purposed for SCS, with an optimal removal (R < 1 cm) in 21 patients (21/35). No mortality occurred within a 3 month period after SCS. The link between patient characteristics at initial treatment and the disease free interval from the end of initial treatment to the first relapse are summarized in Table 2. Suboptimal initial surgery was linked to a short disease-free interval. Overall survival and patient characteristics at the time of initial treatment The results of univariate and multivariate analyses addressing the link between patient characteristics at the time of initial treatment and survival are summarized in Table 3. Only the age of patients appeared to be statistically linked with survival in a multivariate analysis. No significant link was observed between the risk of death after the first relapse and the quality of initial surgery (neither completeness of initial surgery, nor the need for bowel surgery).

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Table 1 Patients characteristics. Variables

All patients (n ¼ 108)

Age (years) Histology Serous Mucinous Other R (after primary surgery) 0 1 2 NI Bowel surgery No Yes NI Disease-free interval (months) Type of relapse Peritoneal Carcinomatosis Extra abdominal metastasis Only in retroperitoneal lymph nodes Pelvic mass SCS No Yes R (residual) R0 R1 R2 Clinical response to second line chemotherapy Complete Partial Stabilization Progression Death Follow-up (months) Alive Death All

58.5 [33.8e82.9] 75 6 27 57 23 25 3 52 53 3 9.1 [0.1e83.8] 56 22 13 17 73 35 12 9 14 30 16 12 50 93/108 40 [6e100] 14 [4e102] 15 [4e102]

R after primary surgery: 0: no visible residual mass, 1: <1 cm residual mass, 2: >1 cm residual mass, SCS: Secondary Cytoreductive Surgery, NI: No Information.

Overall survival and patient characteristics at the time of the first relapse The results of univariate and multivariate analyses addressing the link between patient characteristics at the time of the first relapse and survival are summarized in Table 4. The multivariate analysis showed that young age, pelvic or lymph node relapse, optimal SCS, (R0-R1), delayed first relapse and response to second-line chemotherapy were independent prognostic factors for survival after the first relapse. Patients with an optimal SCS experienced a 35 month median overall survival from the first relapse and patients with non-optimal SCS or no SCS experienced a 13 month median overall survival ( p ¼ 0.006) (Fig. 1). Patient who underwent a non-optimal SCS experienced a median overall survival equivalent to that of patients who did not undergo any SCS.

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Table 2 Patient characteristics at initial diagnosis and relationship with disease free interval between the end of initial treatment to the first relapse. Variable

Age (years) Histological subtype Serous:Yes vs. No R stage 1 vs. 0 2 vs. 0 Bowel surgery Yes vs. No

Univariate analysis

Multivariate analysis

HR [95% CI]

Logrank p-value

HR [95% CI]

Cox p-value

1.02 [0.99e1.04]

0.071

1.02 [1.00e1.04]

0.040

0.90 [0.60e1.36]

0.625

0.84 [0.54e1.29]

0.422

1.36 [0.84e2.23] 1.82 [1.12e2.94]

0.217 0.015

1.19 [0.72e1.98] 1.97 [1.21e3.22]

0.496 0.007

1.32 [0.89e1.94]

0.164

1.48 [0.98e2.22]

0.061

R: tumor Residual after initial surgery: 0: no visible residual mass, 1: <1 cm residual mass, 2: >1 cm residual mass.

Discussion FIGO stage III: survival after the first relapse In the current study, patients with a FIGO stage III ovarian cancer, with at last one relapse, a follow-up of 57 months from the end of initial treatment, experienced a median overall survival of 24 months. In case of a complete SCS, median overall survival was 35 months, and 13 months in case of incomplete SCS or no SCS. Long term survival of a nonselected consecutive population of patient treated for a stage III ovarian cancer with a first relapse, outside of randomized trials, is hard to gather from literature. In a recent retrospective analysis of patients treated for a FIGO stage III ovarian cancer extracted from GOG randomized trials, with almost 80% of patients who experienced a relapse, the authors found a median overall survival of 45.3 months from the end of initial treatment.4 In the ICON 4/AGO-OVAR trial, including only patients with a first late relapse (>6 months) of an ovarian cancer, whatever initial FIGO stage, the best median overall survival was 29 months. 9 Considering that randomized trials are aimed to validate new treatments, the results of such treatments on cohorts of non-randomized patients appears to be the ultimate clinical goal. Clinical prognostic factors In the current study, in a multivariate analysis independent prognostic factors of survival after the first relapse

were young age, a delayed first relapse, a relapse limited to the pelvis or retroperitoneal lymph node, a good response to intravenous second-line chemotherapy and an optimal SCS. Those parameters characterize the biological aggressiveness of the tumor. Previous studies highlighted the prognosis value of the disease-free interval between the end of initial treatment and the first relapse.17 Disease free interval is an indirect marker of chemosensitivity. Relapse within 6 months of platinum-based therapy is an adequate definition of platinum-refractory ovarian cancer relapse.8 A longer time from initial treatment to the first relapse, from >12 months to 24 or 36 months, has been associated with an improved survival outcome.12,18,19 In those three studies, patients with a delayed relapse were put forward for a complete SCS. The long disease-free interval is an indirect marker of a non-aggressive relapse, making its complete removal feasible. In the current study the diseasefree interval was linked with young age and with complete initial surgery as compared with incomplete surgery, but none of the clinical characteristics at initial diagnosis appeared to be statistically linked with overall survival of relapsed patients in multivariate analysis. Relapse brings its own part of poor prognosis independently with initial characteristics. An isolated relapse, with a small number of tumor sites, located in the abdomen, the pelvis or in retroperitoneal lymph nodes without either peritoneal carcinomatosis, ascitis or extra abdominal metastasis, is linked with a long survival after the first relapse.20-22 In the recent study by Bae J

Table 3 Clinical-pathological characteristics at initial diagnosis and relationship with overall survival (from relapse diagnosis to death). Variable

Univariate analysis

Multivariate analysis

HR [95% CI]

Logrank p-value

HR [95% CI]

Cox p-value

Age (years) Histological subtype Serous:Yes vs. No R stage 1 vs. 0 2 vs. 0 Bowel surgery Yes vs. No

1.03 [1.01e1.05]

0.009

1.03 [1.01e1.05]

0.015

0.70 [0.45e1.08]

0.107

0.66 [0.42e1.05]

0.080

1.14 [0.68e1.92] 1.11 [0.66e1.87]

0.620 0.704

1.03 [0.59e1.79] 1.07 [0.63e1.81]

0.916 0.799

1.21 [0.80e1.84]

0.359

1.29 [0.85e1.97]

0.236

R: tumor Residual after initial surgery: 0: no visible residual mass, 1: <1 cm residual mass, 2: >1 cm residual mass.

J.M. Classe et al. / EJSO 37 (2011) 971e977

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Table 4 Clinical-pathological characteristics at relapse diagnosis and the univariate and multivariate relationship with the overall survival (from relapse to death). Variables

Univariate analysis HR [HR 95% CI]

Age (at first relapse) Histology Serous vs non serous Disease-free interval (months) 6e12 months vs. > 12 months < 6 months vs. > 12 months Type of relapse Peritoneal carcinomatosis or distant metastasis vs. pelvic or lymph node SCS Yes vs. no R R0eR1 vs. R2 or no SCS Clinical response to second-line chemotherapy Partial or, stabilization vs. complete Progression vs. complete

1.02 [1.01e1.04]

Multivariate analysis logrank P-value

HR [HR 95% CI]

Cox P-value

0.023

1.03 [1.01e1.05]

0.010

[0.42e1.02] [0.92e0.97] [1.69e4.86] [3.06e9.26]

0.067 <0.001 0.001 <0.001

0.66 [0.42e1.05] 0.97 [0.95e0.99]

0.078 0.010

2.07 [1.28e3.37]

0.003

2.17 [1.30e3.61]

0.003

0.49 [0.31e0.78]

0.003

0.34 [0.19e0.61]

<0.001

0.52 [0.27e0.99]

0.047

2.69 [1.47e4.92] 5.73 [3.31e9.92]

0.001 <0.001

1.90 [1.00e3.62] 3.88 [2.08e7.23]

0.051 <0.001

0.66 0.95 2.86 5.33

Secondary Cytoreductive Surgery (SCS), R: tumor Residual after SCS: 0: no visible residual mass, 1: <1 cm residual mass, 2: >1 cm residual mass.

et al, concerning 54 patients treated between May 2001 and October 2007, patients with a pelvic relapse experienced a better survival as compared to patients with other sites of relapse.23 Patients with metastasis, such as liver metastasis, experienced a poor prognosis.24,25 Secondary cytoreductive surgery In the current study complete SCS was an independent significant prognostic factor linked with the best prognosis. Even if SCS is not yet considered as standard treatment for ovarian cancer relapse, it appears that the main prognosis factors that determine a non-aggressive relapse, such as patient with a good performance status, a long disease-free

Probability of overall survival

1.00 0.75 P=0.006 0.50 P=0.006 0.25 P=NS

0.00 0

12

Number at risk NA 73 R 0 12 R1 9 R 2 14

40 10 9 8 NA

24 Follow-up (months) 16 8 5 4 R0

36

48

9 7 3 2

5 3 3 1

R1

R2

Figure 1. Overall survival and tumor residual after SCS, or non SCS. Secondary Cytoreductive Surgery (SCS), R: tumor Residual after SCS: 0: no visible residual mass, 1: <1 cm residual mass, 2: >1 cm residual mass. NA: non adapted, concerning patients not offered any SCS.

interval, and a limited presentation of the relapse, are linked with the feasibility of a complete SCS removal of the relapse leading to the best survival. Since the publication by Berek et al in 1983, which was the first to use “secondary cytoreductive surgery” (SCS) for the resection of an ovarian cancer relapse, numerous nonrandomized studies, resumed in a recent meta-analysis, have shown that surgery may allow for long survival in selected patients.26e28 It appears that we observe in the case of the first relapse the same link between complete surgery and long survival as in the case of initial treatment.28 The same biological arguments on which primary surgery is based, such as the development of drug-resistant cancer cell clones and enhanced host immunocompetence against the tumor, could remain valuable in the case of relapse.18 Selected patients with a complete removal of the relapse and platinumbased chemotherapy, may reach a very long overall survival, of up to 100 months.29 As in the case of initial surgery, the only statistically significant clinical variable independently associated with recurrent disease specific survival in a recent meta-analysis, was the proportion of patients undergoing complete SCS.11 In the current study of the 35 patients who experienced an SCS, 60% (21/35) underwent an optimal secondary surgery with no tumor residual or <1 cm tumor residual linked with the best overall survival. It is clear that the respective role of surgical skill and the biological characteristics of the relapse making the surgery feasible remain questionable. Surgery of the relapse must be considered only in the case of a complete removal. A recent retrospective study of 277 patients with an ovarian cancer relapse showed that a complete SCS was associated with a longer survival

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compared to surgery leaving any postoperative residual disease.18 In the current study, incomplete SCS provided no survival benefit compared with no SCS at all. Chemosensitivity of the relapse should be useful to select patients for SCS, allowing more frequent complete SCS. However the best schedule of second line chemotherapy before or after SCS is controversial. For Eisenkop et al, in a retrospective series of 106 patients, previous salvage chemotherapy before SCS was associated with a low survival.27 In the recent meta-analysis of 40 cohorts of patients undergoing SCS, surgery was performed before chemotherapy in 72% of cases.11 Bias associate with retrospectives studies do not allow any conclusion. Non-optimal SCS may have two origins: a non-resectable relapse, which is a sign of tumor aggressiveness or technical difficulties faced by an unspecialized surgeon. Tools are defined to select patients in order to limit the risk of useless incomplete SCS. Fagotti et al, described a laparoscopic scoring with an accuracy of 74% in identifying patient with no feasible complete SCS.30 The German AGO group described variables associated with complete SCS, as good performance status, a low initial FIGO stage IeII with no residual at initial surgery and no or a low volume of ascitis.18 Even for selected patients, SCS may require the use of complex abdominal techniques such as bowel resections, modified posterior pelvic exenterations, splenectomy and partial diaphragmatic resection.31 Such surgery justifies allocating the patient to surgical teams particularly specialized in retroperitoneal and upper abdominal surgery in order to limit post-operative mortality and to reduce severe morbidity rate to less than 10%,32 and to improve the chance of complete SCS.33 Death after SCS is associated with suboptimal surgery in the case of diffuse relapse.19 The specialization of the surgical team is associated both with a 69% reduction in the risk of in-hospital death and with a lower hospital related cost of care.34 An ongoing multi institutional randomized trial, DESKTOP III, from AGO group comparing SCS followed with second line chemotherapy versus chemotherapy alone in prospectively selected patients will assess overall survival only for pre selected patients with a good performans status, treated for a late relapse >6 months, with a complete initial surgery or an initial FIGO stage IeII, and a small volume of ascitis.18 Outside of this important trial the question of SCS remains particularly for patient non-eligible in this trial as in the case of initial FIGO stage III and or with a suboptimal initial surgery, with the hope of a long survival in the case of complete SCS. Seeking for patient preferences in recurrent ovarian cancer treatment, it appears that patients would switch from salvage therapy to palliative care when the median survival associated with salvage therapy was reduced to 5 months regardless of life satisfaction, quality of life or psychological or spiritual well-being.35

In conclusion, overall survival of FIGO stage III ovarian cancer with a first relapse is low, around 15 months after the diagnosis of the first relapse. An optimal SCS of the relapse is one of the independent prognosis factor for overall survival after the first relapse and the other parameters, such as young age, a relapse limited to the pelvic or lymph node, a long disease-free interval and a good response to second-line chemotherapy are indirectly linked to the feasibility of such surgery. Although it is clear that further progress is expected in the field of chemotherapy or targeted therapies, the large number of series showing an improvement in overall survival provided by a complete SCS for selected patients must convince multidisciplinary teams to consider complete SCS as an option for the treatment of ovarian cancer relapse. Conflict of interest statement None. Acknowledgments We would like to thank Mrs Nicole Andrieux, from the Department of database, Institut de Cancerologie de l’Ouest - Cancer Center Rene Gauducheau, for her database search. We would like to thank Doctor Christine Sagan, and Doctor Claire Toquet, from the Department of pathology, Hospital University, Laennec, Boulevard Jacques Monod, for their work on pathologic slides. We would thank Mrs Joana Ashton-Chess for the correction of english language. References 1. Hill C, Doyon F. The frequency of cancer in France in year 2002, and trends since 1968. Bull Cancer 2006;93(1):7–11. 2. Cannistra SA. Cancer of the ovary. N Engl J Med 2004;351(24):2519–29. 3. du Bois A, Quinn M, Thigpen T, et al. 2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004). Ann Oncol 2005;16(Suppl. 8): viii7–viii12. 4. Winter 3rd WE, Maxwell GL, Tian C, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007;25(24):3621–7. 5. Skirnisdottir I, Sorbe B. Prognostic factors for surgical outcome and survival in 447 women treated for advanced (FIGO-stages III-IV) epithelial ovarian carcinoma. Int J Oncol 2007;30(3):727–34. 6. Roland PY, Barnes MN, Niwas S, et al. Response to salvage treatment in recurrent ovarian cancer treated initially with paclitaxel and platinumbased combination regimens. Gynecol Oncol 1998;68(2):178–82. 7. Viens P, Petit T, Yovine A, et al. A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients. Ann Oncol 2006;17(3):429–36. 8. Markman M. "Recurrence within 6 months of platinum therapy": an adequate definition of "platinum-refractory" ovarian cancer? Gynecol Oncol 1998;69(2):91–2. 9. Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based

J.M. Classe et al. / EJSO 37 (2011) 971e977

10.

11. 12.

13.

14.

15.

16. 17.

18.

19.

20.

21.

22.

chemotherapy in women with relapsed ovarian cancer: the ICON4/ AGO-OVAR-2.2 trial. Lancet 2003;361(9375):2099–106. Leitao Jr MM, Kardos S, Barakat RR, Chi DS. Tertiary cytoreduction in patients with recurrent ovarian carcinoma. Gynecol Oncol 2004; 95(1):181–8. Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2009;112(1):265–74. Chi DS, McCaughty K, Diaz JP, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 2006; 106(9):1933–9. Bristow RE, Peiretti M, Gerardi M, et al. Secondary cytoreductive surgery including rectosigmoid colectomy for recurrent ovarian cancer: operative technique and clinical outcome. Gynecol Oncol 2009; 114(2):173–7. Ferrandina G, Ludovisi M, Corrado G, Carone V, Petrillo M, Scambia G. Prognostic role of Ca125 response criteria and RECIST criteria: analysis of results from the MITO-3 phase III trial of gemcitabine versus pegylated liposomal doxorubicin in recurrent ovarian cancer. Gynecol Oncol 2008;109(2):187–93. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92(3):205–16. Berman ML. Future directions in the surgical management of ovarian cancer. Gynecol Oncol 2003;90:S33–9. Munkarah AR, Coleman RL. Critical evaluation of secondary cytoreduction in recurrent ovarian cancer. Gynecol Oncol 2004;95(2):273– 80. Harter P, Bois A, Hahmann M, et al. Surgery in recurrent ovarian cancer: the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann Surg Oncol 2006;13(12):1702–10. Tay EH, Grant PT, Gebski V, Hacker NF. Secondary cytoreductive surgery for recurrent epithelial ovarian cancer. Obstet Gynecol 2002; 99(6):1008–13. Salani R, Santillan A, Zahurak ML, et al. Secondary cytoreductive surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome. Cancer 2007;109(4):685–91. Munkarah A, Levenback C, Wolf JK, et al. Secondary cytoreductive surgery for localized intra-abdominal recurrences in epithelial ovarian cancer. Gynecol Oncol 2001;81(2):237–41. Gadducci A, Iacconi P, Cosio S, Fanucchi A, Cristofani R, Riccardo Genazzani A. Complete salvage surgical cytoreduction improves

23.

24.

25.

26.

27.

28.

29. 30.

31.

32.

33.

34.

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further survival of patients with late recurrent ovarian cancer. Gynecol Oncol 2000;79(3):344–9. Bae J, Lim MC, Choi JH, et al. Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer. J Gynecol Oncol 2009;20(2):101–6. Vaccarello L, Rubin SC, Vlamis V, et al. Cytoreductive surgery in ovarian carcinoma patients with a documented previously complete surgical response. Gynecol Oncol 1995;57(1):61–5. Onda T, Yoshikawa H, Yasugi T, Yamada M, Matsumoto K, Taketani Y. Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection. Br J Cancer 2005;92(6):1026–32. Berek JS, Hacker NF, Lagasse LD, Nieberg RK, Elashoff RM. Survival of patients following secondary cytoreductive surgery in ovarian cancer. Obstet Gynecol 1983;61(2):189–93. Eisenkop SM, Friedman RL, Spirtos NM. The role of secondary cytoreductive surgery in the treatment of patients with recurrent epithelial ovarian carcinoma. Cancer 2000;88(1):144–53. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002;20(5):1248–59. du Bois A, Harter P. The role of surgery in advanced and recurrent ovarian cancer. Ann Oncol 2006;17(Suppl. 10):x235–40. Fagotti A, Ferrandina G, Fanfani F, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol 2008;199(6)(642):e1–6. Chi DS, Franklin CC, Levine DA, et al. Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach. Gynecol Oncol 2004;94(3):650–4. Zang RY, Li ZT, Tang J, et al. Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: who benefits? Cancer 2004;100(6):1152–61. Earle CC, Schrag D, Neville BA, et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst 2006;98(3):172–80. Bristow RE, Zahurak ML, Diaz-Montes TP, Giuntoli RL, Armstrong DK. Impact of surgeon and hospital ovarian cancer surgical case volume on in-hospital mortality and related short-term outcomes. Gynecol Oncol 2009;115(3):334–8. Donovan KA, Greene PG, Shuster JL, Partridge EE, Tucker DC. Treatment preferences in recurrent ovarian cancer. Gynecol Oncol 2002;86(2):200–11.