Borderline Tumors of the Ovary: the ROBOTstudy(AGO-OVAR … · AGO-OVAR OP.5 Retrospective: data...
Transcript of Borderline Tumors of the Ovary: the ROBOTstudy(AGO-OVAR … · AGO-OVAR OP.5 Retrospective: data...
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Borderline Tumors of the Ovary:
the ROBOT study (AGO-OVAR OP.5) and more
Prof. Andreas du Bois, MD, PhDDirector Dept of Gynecology & Gynecological Oncology. KEM Essen
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Borderline Tumor (BOT) Ovarian Cancer (OC) 5-YSR BOT 5-YSR OC
Borderline Tumors and invasive Ovarian Carncer
FIGO World Report Vol. 16-26: 1963-2001
- relative Frequencies and 5-Year-Survival (5-YSR) -
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Clinical, pre-OP diagnosis in BOT= the majority of pts. are primarily operated inadequately
(at least 25% each understaged or overtreated)
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25%
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unclear might be CA probably benign might be BOT unknown
Spain: Cusido et al. 2007 Germany: Coumbos et al. 2006
Pre-OP diagnosisMultiple answers were allowed
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ROBOT AGO-OVAR OP.5
Retrospective:
data collection in clinical records/registries
Inclusion of all BOT pts. 1998-2008
Prospective: central pathology review
Prospective: actual follow-up
Exclusion, if paraffine blocks
were not available
Exclusion, if surgical reports
were not availlable
Prospective analysis plan
Retrospective/ prospective multicenter Outcome survey in Borderline Ovarian Tumours
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ROBOTcohort:
1,236 pts.
initially diagnosed
as BOT
1,042 pts.
with
reference pathology
194 pts.
reference pathology
not possible
950 pts. BOT
confirmed
92 pts. BOT
not confirmed
11.5 %11.5 % (Range: 0-43 %)*
92/803 (1042-126-77-36)*
52 x no BOT and benign
57 % of non-BOT
40 x invasive malignancies
43 % of non-BOT
(= 5.0 % of all with ref. path.)
StudyStudy cohortcohort
1,236 pts.
initially diagnosed
as BOT
1,042 pts.
with
reference pathology
194 pts.
reference pathology
not possible
950 pts. BOT
confirmed
92 pts. BOT
not confirmed
11.5 %11.5 % (Range: 0-43 %)*
92/803 (1042-126-77-36)*
52 x no BOT and benign
57 % of non-BOT
40 x invasive malignancies
43 % of non-BOT
(= 5.0 % of all with ref. path.)
StudyStudy cohortcohort
*HSK Wiesbaden, Berlin Charite and UFK Halle only enrolled pts.
who already had a reference pathology confirmation of BOT
excluded
Another trial from Denmark (CG Hannibal et al, Gynecol Oncol 2014):
265 / 1,259 (21%) pts. with presumed S-BOT re-classified by central pathology review
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HR 95 % CI p N E
BOT - - - 950 108
Malignant vs. BOT 3.60 2.09-6.19 < 0.0001 40 15
Benign vs. BOT 0.42 0.13-1.31 0.13 52 3
Log-rank test: p < 0.0001, N = 1042, E = 126
ROBOT: PFS pts. with reference pathology resultmedian follow-up alive: 4.1 yrs. (interquartile 1.5-6.1 yrs.)
[years]
% P
FS
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ROBOT S-BOT
644 pts.
M-BOT
290 pts.
Age median 48 y. median 50 y.
FIGO
I
II
III
489
68
87
75.9
10.6
13.5
279
3
8
96.2
1.0
2.8
Microinvasion 32 5.0 17 5.9
Micro-papillary type 97 15.1 - -
Intraepithelial carcinoma - - 23 7.9
Implants
- invasive implants
120
19
18.6
3.0
8
1
2.8
0.3
* P < 0.05
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Song T, et al. J Gynecol Oncol. 2013;24(1):44-51.
I. Surgical therapy
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ROBOT: PFS – initial surgical access:
No hint for higher risk after laparoscopy
[years]
% P
FS
Laparoscopy vs. Laparotomy: HR = 1.183, 95 % CI: (0.799 , 1.752)
Log-rank test: p = 0.4007
N E
Laparoscopy (incl. conversions) 364 41
Laparotomy 585 67
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ROBOT n %
All 950 100
Laparoscopy (LSC) 297 31.3
LSC -> Laparotomy 67 7.1
Laparotomy 585 61.6
Vaginal 1 0.1
Staging quality
Incomplete 720 75.8
Complete 230 24.2
Surgical
therapy:
1st
surgery
319 of 720 pts. (44.3 %) with initial incomplete staging
received a re-staging operation.
Re-staging led to up-staging in 10.2 % and finally
390 pts. (41 %) had a complete staging.
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ROBOT: PFS and final staging quality (n = 950)
Incomplete vs. complete staging: HR = 1.765, 95 % CI: (1.152, 2.706)
Log-rank test: p = 0.0091
N E
Complete 390 29
Incomplete 560 79
[years]
% P
FS
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ROBOT: PFS and FIGO stage
FIGO HR 95 % CI p N E
I 782 72
II vs. I 2.489 (1.444, 4.289) 0.0010 72 16
III vs. I 2.483 (1.511, 4.080) 0.0003 96 20
Total Log-rank test < 0.0001 950 108
[years]
% P
FS
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ROBOT: PFS and organ-preserving surgery
[years]
% P
FS
HR 95 % CI p N E
BSO 0.584 0.377-0.903 0.0129 708 63
USO (Ref) 1 - - 199 30
Cystectomy 3.306 1.741-6.278 0.0002 41 14
Log-rank test: p < 0.0001
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F Trillsch,…, A du Bois: Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from
a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study. Ann Oncol. 2014;25(7):1320-1327.
ROBOT: Multivariate analysis of prognostic factors
regarding progression-free survival (PFS)
* due to low numbers no OS analysis (follow up)
*
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du Bois A, Ewald-Riegler N, du Bois O, Harter P . Borderline-Tumoren des Ovars – eine systematische Übersicht, Geburtsh Frauenheilk, 6. 807-833, 2009 [German language]
Trillsch F, Mahner S, Ruetzel JD, Harter P, Jaenicke F, du Bois A . Clinical management of borderline ovarian tumors (BOT), Expert Review of Anticancer Therapy, 10: 1115-
1124, 2010 (English language)
Recurrence rate in BOT- a systematic review
(92 series including 10.971 patients)
FIGO I FIGO II-III
Localisation relapse (%) Localisation relapse (%)
ptsExtra-
gonadalovary all pts
Extra-
gonadalovary all
Conservative
surgery1543 2,0 10,6 12,6 210 19,7 25,1 44.8
Radical surgery 2162 2,4 - 2,4 366 13,7 - 13,7
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0-2 2-5 5-10 > 10
Years after diagnosis
invasive disease recurrent BOT
Fig. 3: Time course of invasive and non-invasive relapse after ürimary
diagnosis of a borderline tumour of the ovary – data from a systematic review
including 381 patients with known interval between diagnosis and relapse
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du Bois A, Ewald-Riegler N, du Bois O, Harter P . Borderline-Tumoren des Ovars – eine systematische Übersicht, Geburtsh Frauenheilk, 6. 807-833, 2009 [German language]
Trillsch F, Mahner S, Ruetzel JD, Harter P, Jaenicke F, du Bois A . Clinical management of borderline ovarian tumors (BOT), Expert Review of Anticancer Therapy, 10: 1115-
1124, 2010
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74 relapses
(7.8 % of 950)
52 (70 %) BOT
22 (30 %) invasive carcinoma
(2.3 % of 950)
8 (36 %)
high grade carcin.
10 + 1 (50 %)
low grade carcin.
3 (14 %) no grade available
7 x 2nd relapse 1 x 3rd relapse
ROBOT: Histology of relapse after initial BOT30 % malignant transformation (incl. 36 % high grade OC!)
1
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ROBOT: PFS and OS after first relapse – invasive CA vs. BOT(n = 74 pts. with 1. relapse)
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• (invasive) implants had a significant negative
impact on prognosis (overall survival)
• = advanced FIGO stage
World largest series of 1,042 pts. with confirmed S-BOT after central pathology review
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Prognosis and FIGO stage in S-BOT in Denmark
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II. Systemic therapy
http://www.apotheken-umschau.de
33 pts. received adjuvant therapy;
12 with FIGO I BOT and
21 (64 %) with FIGO stages II/III.
No evidence of efficacy!
PFS und adjuvante Therapie beim fort-
geschrittenen BOT (n = 168 pts. mit FIGO II/III)
N E
keine adjuvante Therapie 146 30
mit adjuvanter Therapie 22 6
N E
keine adjuvante Therapie 146 30
mit adjuvanter Therapie 22 6
mit vs ohne adjuvante Therapie: HR=1.359 95%CI: (0.563, 3.278)
Log-Rank: p=0.4940
% P
FS
[Jahre]
ROBOT: PFS and adjuvant therapy in
advanced BOT FIGO II/III (n = 168)
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Summary
• BOT has a good overall prognosis
• 5-year PFS 87.3 %
• malignant transformation in 2.3 %
• mainly in the 20-30 % of extragonadal relapses
• 5-year OS 95%, disease-specific survival: 98.1 %
• Prognostic factors
• Not modifiable: FIGO stage, histological features
• modifiable by therapy:
• Staging quality (mainly for PFS, minor impact on OS ?)
• Residual tumour
• Organ preservation (only for PFS, not for OS)
• mostly intra gonadal relapse, w/o impact on prognosis in FIGO I (?)
• completion surgery for „high risk“ / advanced stages only
• No evidence for efficacy of adjuvant chemotherapy