Survival impact of cytoreductive surgery ın advanced stage EOC

Transcription

1 Survival impact of cytoreductive surgery ın advanced stage EOC Ayhan Ali, MD Baskent University School of Medicine Department of Obstetrics and Gynecology, Division of Gynecologic Oncology 1

2 OVARIAN CANCER The sd most common pts worldwide every year 75% advanced stage Most lethal Currently OAS up to 50%

3 Ovarian Cancer World Turkey GLOBOCAN

4 The First 10 Women Cancers with in years

5 End-Points of Treatment 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

6 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

7 van Altena AM et al. Gynecol Oncol 2012 FIGO data 5y OAS 1958 % %49,7 advanced ovarian cancer survival showed a 29% improvement (hazard ratio of 0.71) improvement in the optimal debulking rate from 43% to 66% Bristow RE, meta-analysis of 6885 patients. J Clin Oncol 2002;20(5):

8 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)

9 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?)

10 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

11 Team-Work-up: Gyneco, Med Onc, Rad Onc, Gyn Pathol Advanced EOC (Stage II, III, IV) Surgery (Cytoreduction-Debulking) + Adjuvant (Chemo) (Platin + Taxane + Bev) Follow-up

12 Cytoreductive Surgery PDS IDS SDS Middle & Lower Abdominal Hysterectomy Oopherectomy Bowel resection Appendectomy LND (Pelvic,aortic) Upper Abdominal Diaphragm Splenectomy Distal Pancreatectomy Liver resection Porta Hepatis resection Others VATS

13 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

14 Median survival increases at least 5.5% for each 10% increase of CYTOREDUCTİON Gynecol Oncol 1992 Am J Obstet Gynecol 1986

15 Median Survival (mts) Study N Definition Optimal Suboptimal Liu et al. 47 <2cm Curtin et al. 92 <2cm Mankarah et al. Winter et al. 92 <2cm No gross ,1-5cm 30 Zang et al. 71 <1cm 23 9 Aletti et al. 49 <1cm cm 22,6 Salani and Bristow, CLINICAL OBSTETRICS AND GYNECOLOGY Volume 55, Number 1, , Lippincott Williams & Wilkins

16 Overall survival, stage IIIC ovarian cancer, Residual disease Pts Median OS (mo) Micro <0,5cm ,5-1cm cm >2cm D.S. Chi et al. / Gynecologic Oncology 103 (2006)

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18 Median PFS by residual disease after PDS Cum Surv Cum Surv PFS (mts) Median OS by residual disease after PDS Residual Diss NG 1cm >1cm Residual Diss NG 1cm >1cm 24mts 17mts 13mts 78mts 50mts 36mts D.S. Chi et al. / Gynecologic Oncology 124 (2012) OS (mts)

19 Initial surgery group 5year OS(%) No residual tm 50 RT <1cm 30 RT>1cm 14 P.-E. Colombo et al. / EJSO 35 (2009) 135e143

20 Residual Tumor - mos Residual Tm OS (mts) None mm 31 >1cm 15 P. Harter et al. / Gynecologic Oncology 121 (2011)

21 396 patients FIGO stages IIB IV Surgery extends by time (51 pts) (86 pts) (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)

22 Extension of surgery - OS Median OS(mts) P. Harter et al. / Gynecologic Oncology 121 (2011)

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24 A review about cytoreduction Tumor Size N MOS No Gross Residu Residu tm <1cm Residu tm >1cm S.-J. Chang, R.E. Bristow / Gynecologic Oncology 125 (2012)

25 PCR vs ES Primary Cytoreduction Extended Surgery 5-year OS(%) Median OS(mts) 5-year PFS(%) Also significantly more optimal cytoreduction and less gross tumor in ES D.S. Chi et al. / Gynecologic Oncology 114 (2009) 26 31

26 Therapeutic Benefit of Lymphadenectomy in AOC No res. Tm. (n:996) Median S. (mts) 5-year S. (%) LNE (+) LNE (-) ,4 59,2 Lymphadenectomy associated with superior survival in patients with NO residual disease du Bois et al JOURNAL OF CLINICAL ONCOLOGY VOLUME 28 NUMBER 10 APRIL

27 suspect LN (n:527) LNE (+) LNE (-) Median S. (mts) year S. (%) 48,1 24,7 significant impact of lymphadenectomy ONLY IN PATIENTS WITH CLINICALLY SUSPECT NODES (HR 0.72; 95% CI, 0.53 to 0.98;P.0379) 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) du Bois et al JOURNAL OF CLINICAL ONCOLOGY VOLUME 28 NUMBER 10 APRIL

28 189 patients Os mnt Pfs mnt LND LND Patients with NGR OS and PFS higher in LND+ arm Patients with GR- B no diff in OS and PFS

29 Extended Surgery

30 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)

31 Prospective RCT : PDS vs NA CT n: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

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33 NACT+ID Advanced age Poor performance Unresectable tumor Open Laparascopy or small incision

34 Moleculer targeted treatment Angiogenesis inhibitors(bevacizumab) Tyrosinekinase inhibitors(cediranib,pazopanib,sorafenib,b IBF 1120) PolyRibose Polymerase (PARP) inhibitors(olaparib) M-TOR EFGR and HER2 inhibitors(transtuzubab,pertuzumab,getifi nib )

35 Conclusion 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

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38 Thank you for your attention