Ovarian Cancer Prof. Christina Fotopoulou Department of Surgery - PowerPoint PPT Presentation

Imperial College London Surgery ry for Advanced Ovarian Cancer Prof. Christina Fotopoulou Department of Surgery & Cancer Imperial College London, UK

Topic ics  Tumor dissemination patters in primary advanced OC  Prognostic value of postoperative residual disease  Interaction of surgical effort and tumorbiology  Value of pelvic and paraaortic LND  surgical quality assurance criteria, morbidity and surgical evolution over time  Timing of surgery

Topic ics  Tumor dissemination patters in primary advanced OC  Prognostic value of postoperative residual disease  Interaction of surgical effort and tumorbiology  Value of pelvic and paraaortic LND  surgical quality assurance criteria, morbidity and surgical evolution over time  Timing of surgery

Peritonectomy of involved +/- resection of paracardiac nodes peritoneum +/- splenectomy +/- liver capsule resection +/- Bowel resection Infragastric omentectomy Complete exploration of the Assessment of pelvic and abdomen paraaortic LN TAH, BSO

Tumor dis issemin inatio ion patterns in in consecutiv ive ovaria ian cancer patie ients FIGO-stage I: 8.4% stage II: 2.4% stage III: 70.6% stage IV: 16.4% ≤ 2c 0 >2cm m 5JOS 60% 25% 9% OS 85 23 mon mon (median) Sehouli et.al. J Surg Oncol 2009

In Intraoperativ ive tu tumor dis issemination pattern in in ad advanced OC requirin ing multivis isceral rese section techniques Procedure performed N patients (%) (N = 118) Pelvic LN dissection 47 (40.0 %) Para-aortic LN dissection 47 (40.0 %) Colostomy 14 (11.8 %) Ileostomy 2 (1.7 %) 83.1% Bowel resection (any) 84 (71.0 %) Small bowel 32 (27.1 %) Large bowel 81 (68.6 %) Liver/liver capsule resection 46 (39.0 %) Resection stomach/lesser sack 31 (26.3 %) 95.8% Cholecystectomy 3 (2.5 %) Coeliac trunc/subdiaphragmatic LN removal 9 (8.0 %) Partial pleura resection 20 (17 %) Splenectomy 23 (19.5 %) 97.5% Peritonectomy 115 (98.0 %) Diaphragmatic stripping/resection 79 (67.0 %) Operative morbidity/mortality Fotopoulou et.al. Arch Obst & Gyn 2016 fistula/perforation fistula first 13–101) fistula 6–104 fluid

How did all beginn? • Meigs (1934) / Maximal tumour reduction Mannel (1968) • Griffith (1975) „ Debulking- Surgery“ residual mass and median survival: 0.5cm 40 months, 1.5 cm 18 months, >1.5cm 6 months • Hoskins (1994) residual tumour mass< 2cm: significant benefit • Lichtenegger (1998) residual tumour mass< 2cm: significant benefit

1 AGO-OVAR databasis metaanalysis 0,75 (OVAR 3, OVAR 5, OVAR 7) 2,924 pts with OC FIGO IIB-IV and post- 0,5 OP Carbo/Taxol (+) 0,25 Residual tumor size pts death Median survival p-value Hazard Ratio p-value 5-YSR [%] Mos. (95%-CI) Logrank (95%-CI) Wald (95%-CI) 0 mm 1003 297 - (73.2; - ) 1 63.7 (59.7;67.4) 1-10 mm 932 580 36.3 (34.5;40.0) <0.0001 2.81 (2.44;3.23) <0.0001 28.6 (24.9;32.4) 0 > 10 mm 989 709 29.6 (27.4;32.4) 3.74 (3.26; 4.28) <0.0001 21.3 (18.2;24.6) 0 1 2 24 36 48 60 72 84

Ø <2cm Bristow et al. JCO 2002

Residual tu tumor outranks FIG IGO-stage 3126 patients duBois et al. Cancer 2009

How much tumor needs to be resected in every tumor stage? Any HR HR No macroscopic Any residual No residual residual Initial residual tumor tumor (95% CI) tumor (95% CI) tumor FIGO stage PFS median OS (months) Pts. (n) PFS (mos) Pts (n) (mos) + 60,3 Mon. 0.37 (0.31; 0.45) 0.37 (0.30; 0.47) FIGO IIB-IIIB 497 91.7 317 19.1 108.6 48.3 + 46,9 Mon. FIGO IIIC 486 35.0 1293 14.5 0.39 (0.35; 0.45) 81.1 34.2 0.36 (0.31; 0.42) + 30,0 Mon. 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” residual tumor residual tumor HR residuals residuals HR Initial FIGO 1-10 mm > 10 mm (95% CI) 1-10 mm > 10 mm (95% CI) stage + 11,3 Mon. 0.73 (0.56; 0.95) 0.75 (0.55; 1.01) FIGO IIB-IIIB 205 22.2 112 16.7 52.3 41.0 + 4,9 Mon. FIGO IIIC 613 15.9 680 13.7 0.78 (0.70; 0.88) 35.6 30.7 0.80 (0.70; 0.91) + 2,3 Mon. 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” duBois et al. Cancer 2009

RECTUM UTERUS

Topic ics  Tumor dissemination patters in primary advanced OC  Prognostic value of postoperative residual disease  Interaction of surgical effort and tumorbiology  Value of pelvic and paraaortic LND  surgical quality assurance criteria and surgical evolution over time  Timing of surgery

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Value of systematic LND vs removal of only bulky LN ( P. Benedetti Panici et al., JNCI 97, 2005) Systematic LND  pelvic  25 LN  para-aortic  15 LN FIGO IIIB - IV (pleura)  75 years R intraabdominal  systematic LND residual disease  1 cm  only: removal of“bulky nodes”

Removal of bulky nodes only: inferior PFS, same OS Panici et al. J Natl Cancer Inst 2005 PFS OS % 5 years: 31.2 vs. 21.6 % 49.5 vs. 48 % HR all : 0.75 (p = 0.01) 0.97 (n.s.) HR per protocol : 0.69 0.93 + 7 months + 2.4 months median HR : (22.4 vs. 29.4) (56.3 vs. 58.7) median roh : + 5 months + 5,6 months

AGO – OVAR OP.3 (LION) L ymphadenectomy I n O varian N eoplasms • Epithelial Ovarian ca system. LND • FIGO IIB - IV  pelvic • ECOG 0/1 and no  para-aortal contraindication for LND R • R0 • NO “bulky” Lymphknoten no LND endpoints: OS, PFS, QoL Strata: centre, age, PS

Centre random screened AGO-OVAR OP.3 (31.1.12) IGA IGA IGA Charite Berlin (Sehouli) 78 201 HSK Wiesbaden (du Bois -> Hils) 57 161 Düsseldorf Diakonie (Lampe) 48 113 Milano (Raspagliesi) 32 57 EVK Düsseldorf (Meier) 30 94 Praha (Cibula) 26 52 KEM Essen (du Bois) 23 46 UFK Greifswald (Mustea) 22 61 UKE Hamburg (Mahner) 21 68 UFK Jena (Runnebaum) 21 60 München rdI (Schmalfeldt) 21 43 München-Großhadern (Burges) 20 51 I.E.O. Milano (Landoni) 19 45 UFK Essen (Kimmig) 17 64 Roma (Scambia) 16 143 Napoli (Greggi) 16 39 UFK Kiel (Hilpert) 15 35 UFK Freiburg (Hasenburg) 14 39 MHH Hannover (Hillemanns) 12 50 Aviano (Giorda) 12 27 Leuven (Vergote) 12 26 650 Patients Albertinen Hamburg (von Leffern) 10 32 UFK Ulm (Kreienberg) 7 19 Wolfsburg (Petry) 7 15 Malteser Bonn (Gropp -> Hampel) 6 21 UFK Dresden (Schindelhauer) 6 20 UFK Bonn (Pölcher -> Zivanovic) 6 18 Monza (Buda) 6 16 Median LN Khs Lich (Kullmer) 6 14 Fürth (Hanf) 5 18 UFK Göttingen (Emons) 5 16 number: Seoul (Kim) 5 13 UFK Tübingen (Solomayer -> Rothmund) 5 11 Innsbruck (Marth) 5 9 28 paraaortic UFK Regensburg (Enzinger) 4 23 Ravensburg (Gropp-Meier) 4 10 19 each pelvic side UFK Erlangen (Thiel) 3 38 UFK Frankfurt (Kaufmann) 3 16 UFK Marburg (Wagner) 3 11 Martin Luther Berlin (Ulrich) 3 11 Deggendorf (Stuth) 3 9 Torino (Biglia) 3 7 Remscheid (Forner) 2 9 Berlin Lichtenberg (Glaser -> Elling) 2 6 Bad Homburg (Denschlag) 2 5 SKS Solingen (Pfisterer) 1 10 Aalen (Gnauert) 1 6 Graz (Tamussino) 1 6 Wien (Reinthaller) 1 4 Donauwörth (Both) 1 4 München 3.Orden (von Koch) 1 2 UFK Köln (Valter) 1 1 Roma (Ferrandina) - 8 Carpi (Marchesin) - 4 Wels (Bogner) - 2 Lüneburg (Boetel) - 1 Neumarkt (Scholz) - 1 Offenburg (Schwörer) - 1 Ansbach (Hornbacher) - 1 JoHo Wiesbaden (Hoffmann) - 1 Bremen (Aydoglu) - 1 Sum 650 1.895

Topic ics  Tumor dissemination patters in primary advanced OC  Prognostic value of postoperative residual disease  Interaction of surgical effort and tumorbiology  Value of pelvic and paraaortic LND  surgical quality assurance criteria, morbidity and surgical evolution over time  Timing of surgery

Surgical morbidity aft fter ultraradical procedures Operative morbidity/mortality Pleural effusion Major complications 22 (18.6 %) Deep venous thrombosis 2 (1.7 %) Pneumothorax Pulmonary embolism 4 (3.4 %) Pneumonia, ARDS Anastomotic leak 1 (0.8 %) Pancreatic leakage GI fistula/perforation 4 (3.4 %) Pancreatitis/pancreatic pseudocyst Myocardial infarction 1 (0.8 %) Intra-abdominal collection requiring drainage Intraabdominal abscess formation 1 (0.8 %) Persistent lymphorrhea 7 (5.9 %) Pulmonary embolus / DVT Nerve compression injury 3 (2.5 %) Subphrenic abscess and pancreas - pleural fistula Fulminant liver failure 1 (0.8 %) Renal failure 2 (1.7 %) Anastomotic leak/ Bowel obstruction Postoperative bleeding 2 (1.7 %) Reoperation (hemorrhage) Systemic sepsis 4 (3.4 %) Coagulopathy Secondary wound healing (vacuum dressing) 2 (1.7 %) Reoperation 4 (3.4 %) Sepsis Readmission 28 days 12 (10 %) Gastro-intestinal bleeding Mortality 2 (1.7 %) Perforated duodenal ulcer Cardiopulmonary failure Fotopoulou et.al. Arch Obst Gyn 2016 fistula first 13–101) fistula 6–104 fluid

Quali lity & radic icality of of surgery ry: Evolu lution over tim ime • En bloc rectosigmoid • Coeliac trunk and crura resections diaphragmatica resections • Peritoneal stripping • Pleura resections • Infrarenal LND • Paracardiac LN resections • Diaphragmatic resections • Extra-abdominal LN • Splenectomy resections • Liver resections • ?? Chi DS et al, Gynecol Oncol 2009 - MSKCC