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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

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

slide3

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

slide4

Survival rates by staging performance and treatment in the ACTION trial

Obs=observation; CT=chemotherapy;S+=optimal staging; S-=non optimal staging

meta analysis of rct s of adjuvant ct vs controls in inadequately staged eoc

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

meta analysis of rct s of adjuvant ct vs controls in adequately staged eoc

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

lymphadenectomy in early ovarian cancer
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)

slide8

Improved short-term survival for advanced ovarian cancer patients operated by specialized gynecologists

Results from a prospective and

population based Norwegian study

slide10

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

slide11

34mo

25mo

25%

75%

Primary Cytoreductive Surgery

Bristow RE et al JCO 2002 - meta-analysis

slide12

knife

mitosis

background
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
contributors
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
aim of the study
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

norway
Norway

4.58

inclusion criteria
Inclusion criteria
  • Epithelial ovarian cancer FIGO IIIC
  • Advanced tubal
  • Advanced peritoneal
  • N = 198
  • Primary diagnosis 2002
  • Primary surgery
statistical analysis
Statistical analysis
  • Pearson chi-square test
  • Kaplan Meier
  • Cox proportional hazard model
  • Binominal logistic regression
operating physicians20
Operating physicians
  • Specialized gynecologists (n=16)
  • General gynecologists (n=63)
  • General surgeons (n=20)
survival according to specialty

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
prognostic factors
Prognostic factors
  • Age
  • Differentiation of tumor
  • Histology
  • Ascites
  • Performance status (WHO)
  • CA125
  • Serious comorbidity
  • Residual disease
hazard ratio after adjusting for prognostic factors cox regression
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

hospital type
Hospital type
  • Teaching hospitals (TH = 4)

- number of patients = 108

  • Non-teaching hospitals (NTH = 34)

- number of patients = 90

survival according to hospital level

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
hazard ratio after adjusting for prognostic factors cox regression28
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

number of operations per physician

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
slide30

Ovarialcancer DNR 1985 – 2000Epithelial, stadium IIIc

Radikalitet av operasjon

Total overlevelse

Makro. Rad.

Rest ≤ 2 cm

Rest > 2 cm

slide31

Ovarialcancer DNR 1985 – 2000Epithelial, stadium IIIc

Periode, år

Total overlevelse

CIS single

CIS kombi

Taxol kombi

Andre

centralization
Centralization?
  • Important if you have a good center
  • Without a good center it does not help
slide33

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

is centralization feasible
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
the rmi algorithm

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

what is the goal at primary surgery
What is the goal at primary surgery?
  • Complete removal of all tumor!
  • If not possible – removal to less than 1 cm
what are the limitations to achieve total removal of tumor
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
what are the limitations to achieve total removal of tumor38
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 ??
chemotherapy40
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

optimal chemotherapy
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

chance of receiving optimal chemotherapy 6 cycles
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

conclusion
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