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Centralization of ovarian cancer surgery gives the patient better possibility to survive !

Centralization of ovarian cancer surgery gives the patient better possibility to survive !. Claes G Tropé Prof, MD, PhD Dept. of Gynecologic Oncology The Norwegian Radium Hospital, Oslo, Norway Annual Meeting April 20-21, 2007

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Centralization of ovarian cancer surgery gives the patient better possibility to survive !

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  1. Centralization of ovarian cancer surgerygives the patient better possibility to survive ! Claes G Tropé Prof, MD, PhD Dept. of Gynecologic Oncology The Norwegian Radium Hospital, Oslo, Norway Annual Meeting April 20-21, 2007 Dansk Selskab for Obstetrik & Gynækologi, Hindsgavl Slot, Middelfart

  2. Prognostic factors in early ovarian cancern=351 stage I / med. f.u. 9 yrs Patients: • staging complete (100), • peritoneal (107), • incomplete (144) • recurrence rate 15% • multivariate analysis: prognostic for S/DFS # tumor grade # completeness of staging Zanetta et al 1998; San Gerardo Monza

  3. Survival rates by staging performance and treatment in the ACTION trial Obs=observation; CT=chemotherapy;S+=optimal staging; S-=non optimal staging

  4. OVERALL SURVIVAL Meta-analysis of RCT’s of adjuvant CT vs controls in inadequately staged “EOC” • EORTC Action trial, 2/3 of patients23/148 37/147J Natl Cancer Inst 2003 • Icon 1, MRC42/241 61/236J Natl Cancer Inst 2003 • Trope et al, Scandinavia9/81 9/81Ann Oncol 2000 HR = 0.68 (0.52-0.89) 0.5 1 1.5 chemotherapy better no chemotherapy better

  5. OVERALL SURVIVAL Meta-analysis of RCT’s of adjuvant CT vs controls in adequately staged EOC • EORTC Action trial, 1/3 of patients10/76 8/75J Natl Cancer Inst 2003 • Bolis et al, GICOG8/42 9/41Ann Oncol 1995 • Young et al, GOG, OCSG, NCI2/43 4/38N Engl J Med 1990 HR = 0.91 (0.51-1.61) 0.5 1 1.5 chemotherapy better no chemotherapy better

  6. Lymphadenectomy in early ovarian cancer Progression-Free survival Overall survival Chemotherapy: 66 % control arm; 51 % lymphadenectomy group 90 % pos nodes; 56 % negative nodes Maggioni et al Br J Cancer (2006)

  7. Improved short-term survival for advanced ovarian cancer patients operated by specialized gynecologists Results from a prospective and population based Norwegian study

  8. Age adjusted incidence rate Ovarian cancer in Norway

  9. Survival in patients with ovarian cancer FIGO stage III without residual disease after surgery according to substage

  10. 34mo 25mo 25% 75% Primary Cytoreductive Surgery Bristow RE et al JCO 2002 - meta-analysis

  11. knife mitosis

  12. Background • Junor 1999 Specialist gynecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients • Olaitan 2001 The surgical management of women with ovarian cancer in the south west of England • Tingulstad 2003 The effect of centralization of primary surgery on survival in ovarian cancer patients

  13. Contributors • Torbjørn Paulsen,Cancer Registry of Norway • Claes Tropé,The Norwegian Radium Hospital • Kristina Kjærheim,Cancer Registry of Norway • Janne Kærn,The Norwegian Radium Hospital • Steinar Tretli,Cancer Registry of Norway

  14. Aim of the study • Population based prospective study • To investigate - surgical skill - type of hospital might influence short-term survival for advanced ovarian, tubal and peritoneal cancer patients

  15. Norway 4.58

  16. Inclusion criteria • Epithelial ovarian cancer FIGO IIIC • Advanced tubal • Advanced peritoneal • N = 198 • Primary diagnosis 2002 • Primary surgery

  17. Statistical analysis • Pearson chi-square test • Kaplan Meier • Cox proportional hazard model • Binominal logistic regression

  18. Operating physicians

  19. Operating physicians • Specialized gynecologists (n=16) • General gynecologists (n=63) • General surgeons (n=20)

  20. 1 .8 Spec.gyn. 75 (20) .6 Gyn. 99 (44) Cumulative Survival .4 Surgeon 24 (16) .2 0 0 200 400 600 800 1000 Survival in days Survival according to specialty

  21. Prognostic factors • Age • Differentiation of tumor • Histology • Ascites • Performance status (WHO) • CA125 • Serious comorbidity • Residual disease

  22. Hazard ratio after adjusting for prognostic factors - Cox regression Adjustment Specialist Gynecologist CI Surgeon CI . None 1 2.43 1.37 – 4.31 4.88 1.40 – 9.88 Residual disease 1 2.36 1.33 – 4.20 4.94 2.43 – 10.04 (cutoff 0 cm) Prognostic factors 1 2.11 1.13 – 3.95 3.08 1.26 – 7.52

  23. Hospital type • Teaching hospitals (TH = 4) - number of patients = 108 • Non-teaching hospitals (NTH = 34) - number of patients = 90

  24. 1 .8 .6 TH: 108 (37) Cumulative Survival NTH: 90 (43) .4 .2 0 0 200 400 600 800 1000 Survival in days Survival according to hospital level

  25. Survival byregional hospitals Pearson P = 0.015

  26. Hazard ratio after adjusting for prognostic factors - Cox regression Adjustments TH NTH CI . None 1 1.81 1.15–2.87 Residual disease 1 1.66 1.05–2.63 (cutoff 0 cm) Prognostic factors 1 1.83 1.11–3.01

  27. 1 .8 >10 operations .6 Cumulative Survival 1-10 operations .4 .2 0 0 200 400 600 800 1000 Survival in days Number of operations per physician

  28. Ovarialcancer DNR 1985 – 2000Epithelial, stadium IIIc Radikalitet av operasjon Total overlevelse Makro. Rad. Rest ≤ 2 cm Rest > 2 cm

  29. Ovarialcancer DNR 1985 – 2000Epithelial, stadium IIIc Periode, år Total overlevelse CIS single CIS kombi Taxol kombi Andre

  30. Centralization? • Important if you have a good center • Without a good center it does not help

  31. Tumor reduction surgery and long-term survival in advanced ovarian cancer: a DACOVA study 32% of the patients were operated at an oncologic center 50% at a general gynecologic department 18% at a general surgical department. Complete pathologic response and long-term survival were similar for all patients K Bertelsen: Gynecol Oncol. 1990 Aug;38(2):203-9

  32. Is centralization feasible? • Yes • RMI has a high specificity and a good sensitivity in advanced cases. • This has been proven in ”Nordjyllands amt” and in Trøndelag in Norway

  33. CA 125 The RMI algorithm Ultrasound criteria Score Multilocular cyst 1 Solid areas 1 Bilateral lesion 1 Ascites 1 Intraabd. mets. 1 Sum score 0-5 Menopausal status premenopausal M=1 postmenopausal M=3 Serum conc. (u/ml) Score 0-1: U=1 Score 2-5: U=3 RMI = U x M x CA 125

  34. What is the goal at primary surgery? • Complete removal of all tumor! • If not possible – removal to less than 1 cm

  35. What are the limitations to achieve total removal of tumor? • The pelvis can always be cleared !! • Lesions on peritoneum parietale can be removed • Lesions on the diaphragm can be removed • Lesions on the colon can be removed

  36. What are the limitations to achieve total removal of tumor? • Metastasis outside the abdominal cavity including liver metastasis • Pleural effusion ?? • Metastasis in the porta hepatis • Carcinosis on the small intestines ??

  37. Chemotherapy

  38. Chemotherapy % 100 80 Carbo-Pac 60 Carbo Others 40 None 20 0 Teaching hospitals Non-teaching hospitals n = 108 n = 90 Chi square P < 0.001

  39. Optimal chemotherapy % 100 ≥ 6 cycles 80 ≥ 6 cycles 60 < 6 cycles 40 < 6 cycles 20 0 Teaching hospitals Non-teaching hospitals n = 90 n = 108 Chi square P < 0.001

  40. Chance of receiving optimal chemotherapy (6 cycles) Adjustments TH NTH CI . None 1 0.24 0.13–0.48 Residual disease 1 0.27 0.14–0.52 (cutoff 0 cm) Prognostic factors 1 0.26 0.10–0.68

  41. Conclusion • Improved short-term survival among women operated by specialized gynecologists compared to general gynecologists and surgeons • Improved short-term survival among women with advanced ovarian cancer operated in teaching hospitals compared to non-teaching hospitals • Specialization and centralization of surgery probably improve the outcome for advanced ovarian cancer patients

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