The role of Surgical and Chemotherapeutic Treatment in Ovarian … · 2019-04-07 · The GYN...
Transcript of The role of Surgical and Chemotherapeutic Treatment in Ovarian … · 2019-04-07 · The GYN...
Current approaches to diagnosis and treatment of ovarian cancer
Poznań 24-11-2011
ESGO Workshop
The role of Surgical and Chemotherapeutic
Treatment in Ovarian Carcinoma
P. Zola
Department of Gynaecologic Oncology
University of Turin
Ovarian Cancer: clinic and biological aspects
advanced disease at diagnosis (65-75% stage III and IV)
Intraperitoneal dissemination with ascites (55-60%)
low risk of ematogenous spread (2-3%)
chemosensitivity (60-90% of PR, 20-40% of CR)
Gynecology Oncology 2008
OVARIAN CANCER SURVIVAL FIGO Annual Report: Carcinoma of the Ovary: 5-yr Survival Rates
Annual Report: stage and survival distribution
Annual Report 2008
STAGE N° of PATIENTS 5 YEARS SURVIVAL
St. I
St. II
St. III
St. IV
3073 79.3 %
1469 57.0 %
2342 24.9 %
1740 11.1 %
aggressive primary cytoreductive surgery
platinum and taxane combination chemotherapy
Ovarian Cancer: standard management
PRIMARY CYTOREDUCTION
maximal cytoreduction and primary surgery: standard initial
treatment for the management of epithelial ovarian cancer
the amount of residual disease at the end of a
cytoreductive surgery is directly correlated with survival
practice of cytoreduction surgery after a maximal primary surgical attempt has
been unsuccessful in decreasing tumor burden to an optimal status after
chemotherapy in unresectable ovarian cancer at first surgery
controversal role
Interval debulking
Neoadjuvant chemotherapy
Administrating of chemotherapy for two or three cycles and at time up to six
cycles, prior to cytoreductive surgery
Chemotherapy in biopsy-proven stage IIIc or IV invasive epithelial ovarian
carcinoma
Ovarian Cancer: management controverses
NEOADJUVANT
CHEMOTHERAPY
EXTENSIVE
SURGERY
The survival benefit of cytoreductive surgery is well estabilished by almost
every retrospective and prospective study performed to date. The amount of
residual disease after cytoreductive surgery is among the most important
prognostic factors when predicting survival in women advanced ovarian cancer.
1992 – GICOC: 529 patients RESIDUAL DISEASE RR p value (cm)
< 2 1 n.s.
2-5 1.96 < 0.001
5-10 2.03 < 0.001
> 10 3.00 < 0.001
1993 – Markman et al. RESIDUAL DISEASE SURVIVAL (cm) (months)
0 39
0 – 0.5 29
0.6 -1.5 18
> 1.5 11
1994 – Baker et al.: 136 patients
RESIDUAL DISEASE PROGRESSION FREE SURVIVAL
(cm) 5-year (%) 8-year (%)
< 1 40.3 36.2
1-2 17.1 12.8
> 2 4.3 4.3
1995 – GONO: 512 patients RESIDUAL DISEASE RR p value
(cm)
mycroscopic 1
< 2 1.77
2-5 2.64
> 5 4.29 < 0.0001
1994 – G.O.G Hoskins et al.: 637 patients
Percent Maximum Cytoreductive Surgery
20
22
24
26
28
30
32
34
36
38
40
0 10 20 30 40 50 60 70 80 90 100
%MaxCyto
Weig
hte
d M
edia
n S
urv
ival (
mo
nth
s)
Maximum Cytoreductive Surgery - Multiple Regression Model
Bristow et.al. JCO March 2002
Access to Care
Experienced
Ovarian Cancer Surgeon
Suspected
Ovarian Cancer
The GYN oncologist
“ The outcome of ovarian cancer treatment are better
when provided by gynecologic oncologists
and in specialized hospitals: a systematic review ”
Vernooij F., Heintz P., Witteven E., Van der Graaf Y.
Gynecology Oncology Jun;105 (3):801-121 2007
Metanalysis on 37 studies (01/1991- 01/2006): relationship between CARE SETTINGS
(GYN vs GYN Oncologist; General hospital vs Referral Centre)
and CARE OUTCOMES
Gyn Oncologist: stadiation
ARTICOLO OUTOCOME GIN. ONCOLOGI GIN. GENERALI p value
Grossi et al. % adequate staging 47 % 15 % < 0.001
Engelen et al. % adequate staging 43 % 22 % < 0.001
Earle et al. % lymph node dissection 60 % 36 % < 0.001
Kumplainen et al. % pelvic lymph node dissection 78 % 33 % < 0.001
Kumplainen et al. % paraortic lymph node dissection 61 % 26 % < 0.001
Gyn Oncologist: optimal cytoreduction
OPTIMAL DEBULKING = T.R. < 2 cm OPTIMAL DEBULKING = T.R. microscopic
Optimal cytoreduction: what it means?
1978: OPTIMAL Debulking: < 1.5 cm Griffit, Fuller et al.
1986 – 1992: OPTIMAL Debulking: < 0.5 cm Heinz, Hoskins et al.
1998: OPTIMAL Debulking: microscopic Vergote et al.
2002: OPTIMAL Debulking: microscopic Bristow et al.
Optimal cytoreduction: controverses
2001: optimal debulking
OPTIMAL Debulking = T.R. microcopic 12 % U.S. GYN
OPTIMAL Debulking = T.R. < 0. 5 cm 13.7 %
OPTIMAL Debulking = T.R. ≤ 1 cm 60.8 %
OPTIMAL Debulking = T.R. ≤ 1.5 - 2 cm 12.3 %
Eisenkop et al. 82; 489-97 Gynecology Oncology 2001
EARLY STAGE: lymphnodal involvement
PAPER Stage 1 (ovary)
Wu et al. (1986)
Pickel et al. (1989)
Burghardt et al. (1991)
Di Re et al. (1989)
7
28
37
128
Stage 2 (pelvic involvement)
1 (14%)
7 (29%)
9 (24%)
16 (17%)
8
14
14
26
3 (37%)
4 (29%)
7 (50%)
6 (23%)
N N + (%) N N + (%)
Benedetti et al. (1997)
TOTAL
73
273
1 (16%)
44 (16%)
10
72
2 (20%)
22 (31%)
“ Randomised study of systematic
lymphadenctomy in patients with epithelial
ovarian cancer macroscopically confined to
the pelvis”
Maggioni A., Benedetti Panici P et al
95,699-704 British Journal of Cancer 2006
EARLY STAGE: lymphonodal involvement
EARLY STAGE and LYMPHADENECTOMY: Results
Lymphnodal involvement:
OVERALL
STAGE 1
STAGE 2
9 % 22 % P < 0.007
ARM 1: sampling ARM 2: lynphadenectomy
VS
4 % 18 % VS
20 % 31 % VS
P.F.S.: 73.4% vs 78.3% p = 0.166
Overall Survival: 81.6% vs 84% p = 0.513
21% pelvic lfn
54% aortic lfn
25% both
ADVANCED STAGE: lymphnodal involvement
PAPER Stage 3 (abdomen)
Wu et al. (1986)
Pickel et al. (1989)
Burghardt et al. (1991)
Di Re et al. (1989)
59
98
114
82
Stage 4 (methastasys)
38 (64%)
69 (70%)
84 (74%)
46 (56%)
3
13
15
17
3 (100%)
8 (61%)
11 (73%)
11 (65%)
N N + (%) N N + (%)
Benedetti et al. (1997)
TOTAL
73
426
52 (72%)
289 (68%)
- -
48
- -
33 (69%)
“ Systematic aortic and pelvic
lymphadenectomy versus resection of bulky
nodes only in optimally debulked advanced
ovarian cancer: a randomized clinical trial”
Benedetti Panici P, Maggioni A. et al
97(8): 560-566 Journal of National Cancer Institute 2005
ADVANCED STAGE: lymphnodal involvement
Benedetti Panici et al 97(8): 560-566 Journal of National Cancer Institute 2005
P.F.S. medio: 22.4 m vs 27.4 m p = 0.022
O.S.. medio: 56.3 m vs 62.1 m p = 0.768
ADVANCED STAGE: lymphnodal involvement
ADVANCED STAGES: CYTOREDUCTION
Morbidity
Fader et al. Jul 10 ;25 (20):2873-83 Journal of Clinical Oncology, 2007
Citoriduzione primaria nei tumori maligni epiteliali dell’ovaio
ADVANCED STAGE: predictive criteria of sub-optimal surgery
“ rate of optimal debulking after
sub-optimal prediction”
Bristow et al. 104 (2007) 480 – 490 Gynecology Oncology 2007
ADVANCED STAGE: neoadjuvant chemotherapy
Background
increase of optimal debulking rate
less aggressive surgical approach
intra-operative complicances decrease
mortality and morbidity decrease
QOL improvement
Rose PG et al. 21 201a Abstract 802 Proc ASCO 2002
Neoadiuvant chemotherapy of primary surgery: are
there similar results? YES
P. Zola Dipartimento Discipline Ginecologiche e Ostetriche
Università degli Studi di Torino
Ospedale Mauriziano “ Umberto I ”, Torino
50% full members SGO Chen et al. Int J Gynecol Cancer 2004
ADVANCED STAGE: neoadjuvant chemotherapy
Retrospective studies
Donadio et al 24 NACT increase the chances of optimal debulking
Surwit et al 29 Median survival = 22 months (= primary debulking)
Swartz et al 59 Similar survival with treated with primary debulking
Ansquer et al 54 Better survival with NACT vs nondebulked tumors
Kaicgoglu et al 45 NACT followed by IDS does not woersen prognosis
Shibata et al. 29 Long term NACT outcome wasn’t statiscally different
Morice et al 34 IDS offers same survival as PDS but better tolerated
Mazzeo et al 45 NACT + IDS is safe treatment in unresectable cancer
Chan et al 17 Overall quality of life improves after NACT
Hegazy et al. 27 NACT + IDS is safe and does not worsen prognosis
Lee et al. 18 NACT provides equivalent survival with less morbidity
AUTHOR n MAIN CONCLUSION
ADVANCED STAGE: sub-optimal surgery
Trial EORTC 1995
CR, PR, NC PD
randomization Out of study
3 cycles CP
278 Patients stage IIb-IV (T.R. >1 cm)
3 cycles CP
evaluation
Cytoreductive surgery NO
P.F.S. 56% (C.C. arm) vs 46% p < 0,05
O.S. 38% (C.C. arm) vs 26% p < 0,05
Van der Burg, N Engl J Med, 322, 1995
Trial G.O.G. 152
CR, PR, NC PD
randomization Out of study
3 cyclesTP
3 cycles TP
evaluation
Cytoreductive surgery NO
425 Patients stage III-IV (T.R. >1 cm)
P.F.S. medio 10.5 m (C.C. arm) vs 10.8 m N.S.
O.S. medio 33 m (C.C. arm) vs 32 m N.S.
Rose PG et al. 21 201a Abstract 802 Proc ASCO 2002
ADVANCED STAGE: sub-optimal surgery
EORTC vs G.O.G. 152
EORTC GOG152
Chemotherapy
Stage IV
Performance status 2
CP TP
21% 6 %
17 % 7 %
T.R. (cm) after primary surgery
- 1 - 2
- 2 - 5
- 5 -10
- > 10
6 %
30%
38 %
26 %
12 %
56 %
23 %
9 %
Vergote et al. 18 (Suppl.1); 11-19 Int J Gynecol Cancer 2008
Carcinoma Ovarico: trattamento neoadiuvante?
The role of surgical outcome as
prognostic factor in advanced
epithelial ovarian cancer
A combined analysis of 3 prospectively
randomized phase III multicenter trials
Andreas du Bois (AGO-ovar and GINECO)
IGCS Meeting 2008
Population:
• 3 randomized studies in FIGO IIB-IV ovarian cancer pts. receiving
6 courses platinum-paclitaxel +/- third drug after initial surgery:
• AGO-OVAR 3 (Cisplatin/Paclitaxel vs. Carbolatin/Paclitaxel) - A du Bois et al. JNCI 2003
• AGO-OVAR 5 / GINECO (Carboplatin/Paclitaxel +/- Epirubicine) – A du Bois et al JCO 2006
• AGO-OVAR 7 / GINECO (Carboplatin/Paclitaxel +/- Topotecan) - J Pfisterer et al. JNCI 2006
• 3,126 of 3,388 randomized pts. (92.3%) included of whom 1,837
(58.8%) had died within a median observation period of 53.9 months.
• pts. characteristics:
surgical outcome:
1,105 pts.
975 pts.
1,046 pts.
no post-OP residuals
residuals 1-10mm
residuals >10mm
Age [median; range] 58.9 (19.6-83.6) yrs
PS ECOG 0 1,190 38.1
ECOG 1 1,592 50.9
ECOG 2 326 10.4
Stage FIGO IIB-IIIA 448 14.4
FIGO IIIB 366 11.7
FIGO IIIC 1,779 56.9
FIGO IV 530 17.0
Grading G1 244 7.8
G2 998 31.9
G3 1,702 54.4
Histology Serous 2,296 73.4
Endometrioid 272 8.7
Mucinous 147 4.7
0%
25%
50%
75%
100%
0 12 24 36 48 60 72 84 96 108 120 132 144
% p
rog
res
sio
n-f
ree
su
rviv
al
0 mm
1-10 mm
> 10 mm
HR (95%CI)
1-10 mm vs. 0 mm: 2.52 (2.26;2.81)
>10 mm vs. 1-10 mm: 1.36 (1.24;1.50)
log-rank: p < 0.0001
0%
25%
50%
75%
100%
0 12 24 36 48 60 72 84 96 108 120 132 144
% o
ve
rall
su
rviv
al
0 mm
1-10 mm
> 10 mm
HR (95%CI)
1-10 mm vs. 0 mm: 2.70 (2.37; 3.07)
>10 mm vs. 1-10 mm: 1.34 (1.21; 1.49)
log-rank: p < 0.0001
The impact of residual tumor: What is optimal debulking?
Initial
FIGO stage
No macroscopic residual
tumor
Any residual
tumor
HR
(95% CI)
No residual
tumor
Any
residual
tumor
HR
(95% CI)
Pts. (n) PFS (mos) Pts (n) PFS
(mos)
Median OS (mos)
FIGO IIB-IIIB 497 91.7 317 19.1 0.37 (0.31; 0.45) 108.6 48.3 0.37 (0.30; 0.47)
FIGO IIIC 486 35.0 1293 14.5 0.39 (0.35; 0.45) 81.1 34.2 0.36 (0.31; 0.42)
FIGO IV 63 19.2 467 12.1 0.53 (0.39; 0.72) 54.6 24.6 0.49 (0.34; 0.70)
HR = Hazard Ratio, reference class for HR is “Any residual tumor”
Initial FIGO
stage
residual tumor
1-10 mm
residual tumor
> 10 mm
HR
(95% CI)
residuals
1-10 mm
residuals
> 10 mm
HR
(95% CI)
FIGO IIB-IIIB 205 22.2 112 16.7 0.73 (0.56; 0.95) 52.3 41.0 0.75 (0.55; 1.01)
FIGO IIIC 613 15.9 680 13.7 0.78 (0.70; 0.88) 35.6 30.7 0.80 (0.70; 0.91)
FIGO IV 156 13.5 311 11.5 0.84 (0.69; 1.03) 26.2 23.9 0.86 (0.69; 1.07)
HR = Hazard Ratio, reference class for HR is “residual tumor > 10 mm”
Which surgical outcome does improve prognosis in which FIGO stage?
Can surgical resection
correct for inital tumor burden?
0%
25%
50%
75%
100%
0 12 24 36 48 60 72 84 96 108 120 132 144
0%
25%
50%
75%
100%
0 12 24 36 48 60 72 84 96 108 120 132 144
res. tum. =0, FIGO IIB-IIIB
res. tum. =0, FIGO IIIC
res. tum. =0, FIGO IV res. tum. >0, FIGO IIB-IIIB
res. tum. >0, FIGO IIIC
res. tum. >0, FIGO IV
… only partially…
both initial and post-op tumor
burden have a prognostic impact
PFS
OS
PFS analysis No residual
post-OP tumor
Residual tumor
1-10 mm
Residual tumor
> 10 mm
Parameter HR 95%-CI p-value HR 95%-CI p-value HR 95%-CI p-value
Age [10yrs] 1.17 (1.08, 1.27) 0.0002 1.02 (0.95, 1.09) 0.5969 1.06 (0.99, 1.13) 0.0912
ECOG 2 vs. 0-1 1.53 (1.11, 2.11) 0.0091 1.14 (0.91, 1.42) 0.2567 1.09 (0.91, 1.30) 0.3486
FIGO IIIC-IV vs. IIB-IIIB 1.52 (1.28, 1.81) <.0001 1.47 (1.22, 1.77) <.0001 1.41 (1.13, 1.75) 0.0022
grading G2/3 vs. G1 2.13 (1.56, 2.91) <.0001 1.26 (0.89, 1.79) 0.1910 1.38 (0.97, 1.96) 0.0693
Mucinous vs. serous 1.53 (1.05, 2.25) 0.0282 2.17 (1.52, 3.11) <.0001 2.16 (1.62, 2.87) <.0001
Ascites yes vs. no 1.70 (1.39, 2.07) <.0001 1.19 (1.00, 1.43) 0.0515 1.19 (1.02, 1.40) 0.0273
Does residual tumor overrule other prognostic factors?
Significant loss of prognostic factors with increasing tumor residuals
Post-operative residual tumor overrules patient characteristics‘ and
tumor biology associated factors (except mucinous histo type)
AIM: to validate the performance of a laparoscopy-based model to
predict optimal cytoreduction in advanced ovarian cancer
patients. STUDY DESIGN: 113 advanced ovarian cancer patients
INCLUSION CRITERIA: presence of omental cake, peritoneal and
diaphragmatic extensive carcinosis, mesenteric retraction,
bowel and stomach infiltration, spleen and/or liver superficial
Metastasis. By summing the scores relative to all parameters, a
laparoscopic assessment for each patient (total predictive index
value PIV) has been calculated.
Prospective validation of a laparoscopic
predictive model for optimal cytoreduction in
advanced ovarian carcinoma. Fagotti Am J Obstet Gynecol 2008
RESULTS:
Accuracy rate of the laparoscopic procedure: (77.3% infiltrazione intestinale, 100% carcinosi peritoneale)
NPV: 17 FN bowel involvement
PPV: 2FP gastric infiltration
RESULTS: At a PIV 8 the probability of optimally
resecting the disease at laparotomy is equal to 0, and the rate of
unnecessary exploratory laparotomy is 40.5%.
CONCLUSIONS: The proposed laparoscopic model
appears a reliable and flexible tool to predict optimal
cytoreduction in advanced ovarian cancer
:
“ Neoadjuvant Chemotherapy or Primary Surgery in
stage IIIc or IV ovarian cancer”
Vergote et al. N Engl J Med, september 2, 2010
ADVANCED STAGE: neoadjuvant chemotherapy
3 cycles CP PD
Interval debulking Out of study
Second look*
718 Patients Stage IIIC-IV (biopsy-proven epithelial ovarian carcinoma
PRIMARY
SURGERY
3cyclesCP
evaluation
NACT3cyclesCP
RANDOM
Randomised EORTC-GCG/NCIC-CTG
trial on NACT + IDS versus PDS
Baseline Characteristics (ITT)
PDS NACT -> IDS
FIGO Stage
IIIc
IV
77%
23%
81.4%
24.3%
Serous 65.5% 58%
Age 62 (25-86) 62 (33-81)
CA125 > 30 KU/L 98% 99%
Largest metastasis (mm) 80 (0-400) 80 (0-389)
Randomised EORTC-GCG/NCIC-CTG
trial on NACT + IDS versus PDS Protocol Compliance (PP1)
PDS
(n = 336)
NACT -> IDS
(n = 334)
Primary debulking 100 % 0%
Interval debulking 19% 90%
Second look surgery 5% 4%
At least 6 courses CT 83% 86%
Randomised EORTC-GCG/NCIC-CTG trial
on NACT + IDS versus PDS
Surgical findings and results (PP1)
PDS
(n = 336)
NACT -> IDS
(n = 334)*
Metastases before > 2 cm 95% 68%
Metastases before > 10 cm 62% 27%
No residual after surgery 21% 53%
≤ 1 cm after surgery 46% 82%
* % calculated on the 306 patients who underwent IDS.
Randomised EORTC-GCG/NCIC-CTG
trial on NACT + IDS versus PDS
<= 1cm residual per country (PP1)
Total PDS
(n = 336)
NACT -> IDS
(n = 334)*
Belgium (n=133) 83% 72% 94%
Argentina (n=48) 71% 68% 74%
The Netherlands(n=104) 59% 40% 77%
Sweden (n=23) 59% 40% 75%
Norway (n=82) 55% 35% 73%
Italy (n=38) 52% 40% 64%
Spain (n=62) 49% 44% 58%
UK (n=101) 47% 37% 63%
Canada (n=84) 44% 29% 59%
Randomised EORTC-GCG/NCIC-CTG
trial on NACT + IDS versus PDS
Surgical characteristics (PP1)
PDS
(n = 336)
NACT -> IDS
(n = 334)*
Postoperative mortality
(< 28 days)
2,7% 0,6%
Postoperative fever Gr 3-4 8% 2%
Fistula (bowel/GU) 1,2% / 0,3% 0,3% / 0,6%
Operative time (minutes) 180 180
Red blood cell transfusion 51% 53%
Hemorhage Grade 3/4 7% 1%
Venous Gr 3/4 2,4% 0,3%
NACT + IDS versus PDS: ITT
Median PFS
PDS: 12 months
IDS: 12 months
HR for IDS:0.99 (0.87, 1.13)
(years)
0 1 2 3 4 5 6 7 8
0
10
20
30
40
50
60
70
80
90
100
O N Number of patients at risk : Treatment
320 360 168 60 39 26 17 7 2
320 357 177 60 36 20 13 3 1
Upfront debulking surgery
Neoadjuvant chemotherapy
Progression-free survival
NACT + IDS versus PDS: ITT
(years)
0 2 4 6 8 10
0
10
20
30
40
50
60
70
80
90
100
O N Number of patients at risk : Treatment
259 361 183 68 16 2
251 357 191 56 11 1
Upfront debulking surgery
Neoadjuvant chemotherapy
Overall survival
Median survial
PDS: 29 months
IDS: 30 months
HR for IDS:0.98 (0.85, 1.14)
NACT + IDS versus PDS: Per Protocol
Median survial
PDS: 30 months
IDS: 31 months
HR for IDS:1.00 (0.86, 1.16)
(years)
0 2 4 6 8 10
0
10
20
30
40
50
60
70
80
90
100
O N Number of patients at risk : Treatment
235 329 175 66 16 2
239 339 186 56 11 1
Upfront debulking surgery
Neoadjuvant chemotherapy
Overall survivalPP1
NACT + IDS versus PDS: ITT
EORTC 55971Events / Patients
Upfront debulking Neo-adj. ChemoStatistics
(O-E) Var.HR & CI*
:(Upfront debulking Neo-adj. Chemo)|1-HR|
% ± SD
Surv ival time: Figo stageSurv ival time: Figo stage
*90% CI everywhere
Treatment effect: p>0.1
better betterChi-square=0.5, df=1: p>0.1
Upfront debulking Neo-adj. ChemoTest for heterogeneity
0.25 0.5 1.0 2.0 4.0
IV 68 /81 59 /83 4 31.4
Total 258/357 250/356 2.2 126.1
(72.3 %) (70.2 %)
2% ±9
increase
III 190 /276 191 /273 -1.8 94.7
NACT + IDS versus PDS: ITT
EORTC 55971Events / Patients
Upfront debulking Neo-adj. ChemoStatistics
(O-E) Var.HR & CI*
:(Upfront debulking Neo-adj. Chemo)|1-HR|
% ± SD
Surv iv al time: AgeSurv iv al time: AgeSurv iv al time: Age
*90% CI everywhere
Treatment effect: p>0.1
better betterChi-square=2.59, df=2: p>0.1
Upfront debulking Neo-adj. ChemoTest for heterogeneity
0.25 0.5 1.0 2.0 4.00.8
>70 53 /71 59 / 80 -2.6 26.9
Total 259/361 251/357 3.5 125.1
(71.7 %) (70.3 %)
3% ±9
increase
50-70 172 /244 161 / 221 0 82.7
<50 34 /46 31 / 56 6.1 15.5
NACT + IDS versus PDS: ITT
EORTC 55971Events / Patients
Upfront debulking Neo-adj. ChemoStatistics
(O-E) Var.HR & CI*
:(Upfront debulking Neo-adj. Chemo)|1-HR|
% ± SD
Surv iv al time: WHO PSSurv iv al time: WHO PSSurv iv al time: WHO PS
*90% CI everywhere
Treatment effect: p>0.1
better betterChi-square=0.09, df=2: p>0.1
Upfront debulking Neo-adj. ChemoTest for heterogeneity
0.25 0.5 1.0 2.0 4.00.8
2 33 /41 33 /45 1.3 16.4
Total 259/358 250/356 4.3 125.9
(72.3 %) (70.2 %)
4% ±9
increase
1 109 /151 112 /156 0.3 54.4
0 117 /166 105 /155 2.8 55.1
NACT + IDS versus PDS: ITT
EORTC 55971
Events / PatientsUpfront debulking Neo-adj. Chemo
Statistics (O-E) Var.
HR & CI*:(Upfront debulking Neo-adj. Chemo)
|1-HR|% ± SD
Survival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: HistologySurvival time: Histology
*90% CI everywhere
Treatment effect: p>0.1
better betterChi-square=5.08, df=8: p>0.1
Upfront debulking Neo-adj. ChemoTest for heterogeneity
0.25 0.5 1.0 2.0 4.00.8
unknown 12 /17 23 /27 -3.1 8.5
Total 259/361 251/357 10.1 123.3
(71.7 %) (70.3 %)
9% ±9
increase
other 1 /2 7 /7 -0.5 1.1
mixed 4 /6 0 /2 0.9 0.6
unclassifiable 22 /26 25 /31 1.9 11.4
undifferentiated 29 /45 40 /58 -2 16.7
endometroid 8 /16 3 /7 0.9 2
clear cell 6 /7 3 /4 0.6 2.1
mucinous 10 /11 9 /13 2 4.5
serous 167 /231 141 /208 9.4 76.4
NACT + IDS versus PDS: ITT
EORTC 55971
Events / Patients Upfront debulking Neo-adj. Chemo
Statistics (O-E) Var.
HR & CI* : (Upfront debulking Neo-adj. Chemo)
|1-HR| % ± SD
Survival time: Country Survival time: Country Survival time: Country Survival time: Country Survival time: Country Survival time: Country Survival time: Country Survival time: Country Survival time: Country
*90% CI everywhere
Treatment effect: p>0.1 better better Chi-square=20.96, df=8: p<0.01
Upfront debulking Neo-adj. Chemo Test for heterogeneity 0.25 0.5 1.0 2.0 4.0 0.8
Canada (44%) 26 / 41 37 / 43 -9.4 15.2
Total 245 / 341 234 / 334 0.8 116.1 (71.8 %) (70.1 %)
1% ±9 increase
UK (47%) 38 / 53 38 / 48 -2.1 18.7
Spain (49%) 20 / 32 24 / 30 -4.4 10.6
Italy (52%) 15 / 20 15 / 18 -2.1 6.9
Norway (55%) 26 / 40 26 / 42 0 12.9
Sweden (59%) 9 / 11 4 / 12 3 3.2
The Netherlands (59%) 42 / 55 28 / 49 12.2 16.7
Argentina (71%) 19 / 25 14 / 23 2 7.9
Belgium (83%) 50 / 64 48 / 69 1.6 24.1
Multivariate analysis for OS(PP1)
P values
Optimal debulking 0.0001
Histological type (9 categories) 0.0003
Largest tumor size at
randomisation
0.0008
Figo Stage (IIIc vs IV) 0.0008
Country (14 categories) 0.0014
Age 0.0020
WHO PS NS
Differentiation Grade NS
Treatment arm NS
Conclusions (1) 1. In Stage IIIc-IV OVCA, NACT followed IDS produces
similar OS and PFS outcomes compared to standard
primary debulking followed by chemotherapy in FIGO
Stage IIIc-IV ovarian carcinoma.
2. There does not seem to be a subgroup based on
1. Stage IIIc or IV
2. Age
3. WHO performance
4. Histological type ovarian cancer
5. Countries with high or low optimal debulking rate
for which PDS or NACT -> IDS result in better
survival.
Conclusions (2) 3. Optimal debulking surgery is the
strongest independent prognostic factor for overall survival. Hence, optimal debulking (to no residual tumor) should
remain the goal of every surgical effort. The
timing of this procedure (PDS or IDS) does not seem to play a role.
4. Due to the lower morbidity of IDS compared
with PDS and the similar survival, NACT can be considered as the preferred treatment in patients, as included in this study, with Stage IIIc-IV ovarian, peritoneal and fallopian tube carcinoma.
Thank you