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

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Thank you for your attention