GERM CELL OVARIAN TUMORS: AN ITALIAN EXPERIENCE

I.R.C.C.S SAN RAFFAELE HOSPITAL-MILAN

11/06/2010

Dott.ssa Giorgia Mangili

Gynecology and Obstetric Department,IRCCS San Raffaele Hospital – Milan.

PATIENTS CHARACTERISTICS

N = 123 patients

Duration of symptoms

Emergency 4,9% < 30 days 39,8% >30 days 26%No symptoms 15,4%

Unknown 13,8%

Mean Age (range)

27.7(11-76)

PresentingSign/symptom

Pelvic pain 52,8%

Abdominal enlargement

53,7%

Abdomino-pelvic mass

53,7%

Menstrual irregularities

11,4%

Amoenorrea 3,2%

Ascites 5,7%

Fever 2%

Hyrsutism 0,9%

HISTOLOGY AND STAGE

Histology N (%)

Dysgerminoma49(39,8%)

Immature Teratoma

35(28,5%)

Endodermal Sinus

26(21,1%)

Mixed12(9,8%)

Embrional Carcinoma

1(0,8%)

47,15%(58)

1,63%(2)

21,95%(27)

0,81%(1)

1,63%(2)

2,44%(3)

1,63%(2)

19,51%(24)

3,25%(4)

0

0,1

0,2

0,3

0,4

0,5

0,6

Frequenza

IA IB IC IIA IIB IIIA IIIB IIIC IV

Stadio

Stage

SURGICAL TREATMENT

MITO center 65,9%

Elsewhere 34,1%

Laparoscopy 17,9%

Laparotomy 82,1%

Fertility Sparing 74,8%

Radical 25,2%

24,7

36,7

Age and type of Surgery

T-test (p<0.05)

Fertility Sparing

Radical

Stage I 81,6% 18,4%

Stage II-III.IV 58,3% 41,7%

POSTOPERATIVE TREATMENT

Schedule N . (%)

PEB 70 (87,6)

PVB 8 (9,8)

EP 1 (1,2)

TAX-CARBO 1 (1,2)

CARBO 1 (1,2)

Chemoterapy in 66%

Histology N. (%)

Dysgerminoma 28 (57,1)

Immature Teratoma 15 (42,8)

Endodermal Sinus 26 (100)

Mixed 11 (91,7)

Embrional Carcinoma 1 (100)

REPRODUCTIVE FUNCTIONResume mestrual function

96,6%

Premature ovarian failure

3,4% Attempting conception 15

Failures 3

Conceving patients 12

Adjuvant chemotherpy 7

Conceptions 16

Normal pregnancy 10

Miscarriages 4

Terminations 2

Conceiving patients 12

Stage IA 7

Stage IC 3

Stage IIIC 2

Dysgerminoma 8

Teratoma immature 2

Endodermal Sinus 1

Mixed 1

2 patients with XY gonadal disgenesis delivered healty infants, with donor oocyte IVF

Miscarriage Rate= 25%

RECURRENCES

OVERALL RECURRENCE RATE= 17,8%

MEDIAN TIME TO RECURRENCE= 9 MONTHS

1. Immature teratoma: 25,7%

2. Endodermal Sinus Tumor: 19,2%

3. Mixed tumor: 16,6%

4. Dysgerminoma: 10,2%

RISK FACTORS FOR RECURRENCEFACTOR N. RECURRENCE RATE P (χ-square)

Primary Surgery in MITO center

Primary Surgery elsewhere

81

42

11,1%

30,9%0.006

Age < 45 years

Age>45 years

10

113

50%

15%0.027

Peritoneal Washing positive

Peritoneal Washing: negative

15

65

33,3%

10,8%0.006

Dysgerminoma

Non-dysgerminoma

49

74

10,2%

23%0.07

Stage I

Stage II-III-IV

87

36

13,8%

27,7%0.06

Conservative Surgery

Radical Surgery

92

31

17,4%

19,3%NS

OUTCOME

5 YEARS OVERALL SURVIVAL= 88,8%

MEDIAN FOLLOW UP TIME= 61 MONTHS

PROGNOSTIC FACTORS

FACTOR P value - RR

Non dysgerminoma histology 0.033 - 9,235

Elevated βHCG and αFP 0.043 - 4.05

Endodermal Sinus Tumor 0.001 - 6,31

Stage > I 0.004 - 5,576

Age >45 0.003 - 6,124

Residual disease 0.018 - 4,206

Capsular rupture 0.02 - 5,874

Tumor on serosal surface 0.015 - 4,95

Positive Peritoneal cytology 0.024 - 3,94

Cox Regression Univariate Analysis

FACTOR P value - RR

Endodermal Sinus Tumor 0.001 - 6,94

Stage > I 0.003 - 6,94

Cox Regression Multivariate Analysis

SURVIVAL ANALYSIS

Endodermal Sinus Tumor Other hystologies

Log rank p value=0.001

Endodermal Sinus versus Other hystologies

Other hystologies

Stage II-III-IV

Stage I

Log rank p value< 0.001

Stage I versus Stage II-III-IV

5y-OS Endodermal Sinus=69,6%5y-OS Other histologies= 94,2%

5y-OS stage I= 95,6%5y-OS advanced stages= 73,2%

PROGNOSTIC PREDICTORS IN RELAPSE PATIENTS

Factors P value-RR

Endodermal Sinus 8,69 - 0.004

Endodermal Sinus versus Other hystologies Debulking Surgery versus No surgery

Other hystologies

Endodermal Sinus

Debulking Surgery

No Surgery

Factors P value-RR

No debulking surgery 9,74 - 0.002

Log rank p value< 0.001Log rank p value< 0.001

GERM CELL OVARIAN TUMORS: MITO-9

Prognosis of MOGT is excellent

Older age, first treatment not in a MITO center are the main risk factors for recurrence

Endodermal sinus histology and stage are indipendent predictors of survival

Endodermal sinus histology and debulking surgery are predictor of survival at relapse

ROLE OF MULTICENTRIC RETROSPECTIVE STUDIES

Compare different terapeutic approaches when there are not established guidelines

Define guidelines in rare tumors as is not possible to performe prospective randomized studies

• Questions ?

• Is it warrented adiuvant chemotherapy in stage I T

• How to manage “clinical stage I A “dysgerminoma?

IS ADJUVANT CHEMOTHERAPY INDI CATED IN STAGE I PURE IMMATURE OVARIAN TERATOMA? IS ADJUVANT CHEMOTHERAPY INDI CATED IN STAGE I PURE IMMATURE OVARIAN TERATOMA?

Stage I Immature teratoma: 28 patients

Grade 1: 9 patients

Grade 2:12 patients

Grade 3: 7 patients

IA: 8 patients

IC: 1 patients

Surgery in 9 patients

No Relapse

IA: 5 patients

IB: 2 patients

IC:5 patients

IA: 6 patients

IC: 1 patients

Surgery in 8 patients

Surgery+ PEB in 4 patients

3 Relapse: IC

Surgery in 2 patients

Surgery+ PEB in 5 patients

3 Relapse: IA

Surgery in 3 :Mature teratoma

Surgeryin 1:

Mature teratoma

Surgery+ PEB in 2:

Immature teratoma

STAGE IA DYSGERMINOMA

Median Age (range) 22,5 (11-59)

Fertility Sparing Radical Surgery

65,4%34,6%

Surgical Staging

•Complete

•Lymph node dissection

• Peritoneal biopsies and/or omentectomy

• Peritoneal washing

19,2%

38,5%

46,2%

65,4%

Adjuvant Chemotherapy 27%

N =26 patients

STAGE IA DYSGERMINOMA

Surgical

treatmentSite of Relapse

Relapse

treatmentOutcome

TAH+BSO Pelvic Surgery+PEB NED

USO+

Washing

Abdomino-pelvic,

lymph-nodal PEB NED

USO+

peritoneal

biopsies

Abdomino-pelvic,

lymp-nodal,

controlateral ovarySurgery+PVB NED

STAGE IA DYSGERMINOMA

After a median follow up of 100 months all patients are NED

Conservative surgery with a complete surgical staging is the gold standard

Patients with incomplete staging could undergo surgical restaging

Chemotherapy should be reserved to relapse

Grazie a tutte le persone che in questi anni hanno lavorato con meUn ringraziamento particolare a Cristina Sigismondi per l’ aiuto profuso nel preparare tutte le relazioni in cui sono stati presentati i dati del MITO e a Jessica OttolinaUn saluto al Professor Ferrari e un augurio di buon lavoro al Prof Candiani