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Survival impact of cytoreductive surgery ın advanced stage EOC
Baskent University School of Medicine
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology
Ayhan Ali, MD
1
OVARIAN CANCER•The sd most common
•225 000 pts worldwide every year
•75% advanced stage
•Most lethal
•Currently OAS up to 50%
Ovarian Cancer
GLOBOCAN
World Turkey
The First 10 Women Cancers with in years
• RR (response rate),
• PFS >>> OS,
• PRO (patient reported outcomes),
• CBR (clinical benefit rate),
• MOE (magnitude of effect)
QoL (quality of life),
should be included in evaluation
End-Points of Treatment
Surgeon Factor• 14 studies involving 19,043 pts
• Treatment by GYO showed higher
rates of:
– comprehensive staging of FIGO I/II (4
of 4 studies)
– ‘optimal’ debulking in FIGO III/IV (4 of 6
studies)
– state-of-the-art chemotherapy (2 of 2
studies)
– superior survival (5 of 9 studies)
• Significant advantage for at least 1
parameter in 13 of 14 studies
• advanced ovarian cancer survival showed a 29% improvement (hazard ratio of 0.71)
• improvement in the optimal debulking rate from43% to 66%
van Altena AM et al. Gynecol Oncol 2012
Bristow RE, meta-analysis of 6885 patients. J Clin Oncol 2002;20(5):1248-5.
FIGO data 5y OAS
1958 %26.8 2001 %49,7
Therapy depends on:
• Patients’ factor(Age, performance, fertility desire)
• Tumor factors(Histology, grade, molecular - genetic alterations)
• Clinical factors(Accurate diagnosis, extend of tumor,
experienced team, effective hospital supply)
Pre-operative work-up• History-Examination
– (systemic,abdominal,pelvic)
• Lab studies
– (cyto, chemical marker… etc )
• Imaging
– ( USG,CT,if needed MRI,PET)
• Laparascopy (open) or
• Small Incision laparatomy
– ( metastatic ,feasibility of surgery?)
Front-line therapy in EOC•Surgery
–(Staging -debulking)
•Adjuvant
–(IV or IV+IP comb)
•Doubled vs Tripled
–(anti-angiogenesis?)(PFS yes OS ?)
•Close follow up
Advanced EOC (Stage II, III, IV)
Surgery (Cytoreduction-Debulking)
+
Adjuvant (Chemo)(Platin + Taxane + Bev)
Follow-upTeam-Work-up: Gyneco, Med Onc, Rad Onc, Gyn Pathol
Cytoreductive Surgery
Middle & Lower Abdominal
Hysterectomy Oopherectomy Bowel resection Appendectomy LND (Pelvic,aortic)
VATS
Upper Abdominal
DiaphragmSplenectomy Distal Pancreatectomy Liver resectionPorta Hepatis resectionOthers
PDS IDS SDS
History of Optimal Cytoreduction• Griffith (1970) ≤ 1.6cm
(OS was inversely proportion to residual mass under 1.6cm)
• Than 2cm
• Definition was revised by GOG (97, 52, 158, 172) as a 1cm or less (optimal)
Today;NO MACROSCOPİC RESİDUAL DİSEASE
Median survival
increases
at least 5.5%
for each 10%
increase of
CYTOREDUCTİONGynecol Oncol 1992
Am J Obstet Gynecol 1986
Median Survival (mts)
Study N Definition Optimal Suboptimal
Liu et al. 47 <2cm 37 17
Curtin et al. 92 <2cm 40 18
Mankarahet al.
92 <2cm 25 15
Winter et al.
360 No gross 64 19
0,1-5cm 30
Zang et al. 71 <1cm 23 9
Aletti et al. 49 <1cm 38 11
1-2cm 22,6
Salani and Bristow, CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 55, Number 1, 75–95 © 2012, Lippincott Williams & Wilkins
D.S. Chi et al. / Gynecologic Oncology 103 (2006) 559–564
Overall survival, stage IIIC ovarian cancer, 1989–2003.
Residual disease Pts Median OS(mo)
Micro 67 106
<0,5cm 70 66
0,5-1cm 99 48
1-2cm 53 33
>2cm 176 34
17
Median PFS by residual disease after PDS
Median OS by residual disease after PDSPFS (mts)
OS (mts)
Cu
m S
urv
Cu
m S
urv
0 20 40 60 80 100 120
0 20 40 60 80 100 120
0.2
0.4
0.6
0.8
1
0.2
0.4
0.6
0.8
1
NG
Residual Diss
≤1cm
>1cm
NG
≤1cm
>1cm
Residual Diss
78mts
50mts
36mts
24mts
17mts
13mts
D.S. Chi et al. / Gynecologic Oncology 124 (2012)
P.-E. Colombo et al. / EJSO 35 (2009) 135e143
Initial surgery
group5year
OS(%)
No residual tm 50
RT <1cm 30
RT>1cm 14
Residual Tumor - mOS
Residual Tm OS
(mts)
None 69
1-10mm 31
>1cm 15
P. Harter et al. / Gynecologic Oncology 121 (2011) 615–619
• 396 patients FIGO stages IIB–IV
• Surgery extends by time
– 1997–2000 (51 pts)
– 2001–2003 (86 pts)
– 2004–2008 (259 pts)
• complete resection increased from 33% to 62%
• Residuals ≤1 cm increased from 65% to 86%
P. Harter et al. / Gynecologic Oncology 121 (2011) 615–619
Extension of surgery - OS
P. Harter et al. / Gynecologic Oncology 121 (2011) 615–619
Median
OS(mts)
1997–2000 26
2000–2003 37
2004–2008 45
• A review about cytoreduction
S.-J. Chang, R.E. Bristow / Gynecologic Oncology 125 (2012) 483–492
Tumor Size N MOS
No Gross Residu 3593 77.8
Residu tm <1cm 4780 39
Residu tm >1cm 3518 31.1
PCR vs ES
5-year
OS(%)
Median
OS(mts)
5-year
PFS(%)
Primary
Cytoreduction35 43 14
Extended
Surgery47 54 31
Also significantly more optimal cytoreduction
and less gross tumor in ES
D.S. Chi et al. / Gynecologic Oncology 114 (2009) 26–31
Therapeutic Benefit of Lymphadenectomy in AOC
du Bois et al JOURNAL OF CLINICAL ONCOLOGY VOLUME 28 NUMBER 10 APRIL 1 2010
No res. Tm. (n:996)
LNE (+) LNE (-)
Median S. (mts)
103 84
5-year S. (%)
67,4 59,2
Lymphadenectomy associated with
superior survival
in patients with NO residual disease
OS after LNE or no LNE in patients with postoperative residual tumor of 1 to 10 mm and with or without preoperative/intraoperative clinically uspect LNs (comparison 2A; cohort 2)
suspectLN (n:527)
LNE (+)
LNE (-)
MedianS. (mts)
57 32
5-year S. (%)
48,1 24,7
du Bois et al JOURNAL OF CLINICAL ONCOLOGY VOLUME 28 NUMBER 10 APRIL 1 2010
significant impact of lymphadenectomy ONLY IN PATIENTS WITH CLINICALLY
SUSPECT NODES (HR 0.72; 95% CI, 0.53 to 0.98;P.0379)
• 189 patients
Osmnt
Pfsmnt
LND+ 66 22
LND- 40 9
• Patients with NGR OS and PFS higher in LND+ arm
• Patients with GR-B no diff in OS and PFS
Extended Surgery
Alternatives for PDS (not standardized)
Interval debulking(suboptimal PDS +3 cycle chemo+surgery add
3 cycle chemo 1995 EORTC)
1.Neoadjuvant chemo +
Debulking(Biopsy proven EOC + 3 cycle chemo +
surgery+ 3 cycle chemo)
PDS vs NA CTn:704 pt ( in stage IIIc + IV)
PDS NACT
OS 29mo’s 30mo’s
PFS 11mo’s 11mo’s
Optimal CytR.R 42% 83%
Morbidity High Low
From Vergote I. et al 2008
Prospective RCT :
NACT+ID
•Advanced age
•Poor performance
•Unresectable tumor
•Open Laparascopy or
small incision
Moleculer targeted treatment
• Angiogenesis inhibitors(bevacizumab)
• Tyrosinekinase inhibitors(cediranib,pazopanib,sorafenib,BIBF 1120)
• PolyRibose Polymerase (PARP) inhibitors(olaparib)
• M-TOR
• EFGR and HER2 inhibitors(transtuzubab,pertuzumab,getifinib…)
• OC remains the most lethal GYN neoplasm
• Patient profile same
• Management and treatment has improved within years
• In last 30 yrs survival improved only 2yrs
• Maxımal cytoreductıon
Conclusion
36
37
Thank you for your attention