1. Frontline Aggressive Surgical Approach To Primary Retroperitoneal STS: A Morbidity / Mortality Analysis From A Multi-Institutional Retrospective Review. Marco Fiore marco.fiore@istitutotumori.mi.it Sylvie Bonvalot sylvie.bonvalot@igr.fr Connective Tissue Oncology Society 15th Annual Meeting Miami, November 5-7th 2009

2. Aggressive surgery associated with improved local control

3. Liberal en-bloc visceral resections: –Nephrectomy and GI major surgery (with the exception of pancreato-duodenectomy and major hepatectomy, performed only if infiltrated) Loco-regional peritonectomy and miomectomy of the psoas: –To accomplish better en-bloc resection Vascular surgery and bone resection –Feasible but performed only if vessels/bone infiltrated “Aggressive surgical approach” Storm, Mahvi – Ann Surg 1990

4. Selection of cases / organs (due to expected morbidity): some but not all margins improve Data on short- and long-term morbidity not as yet provided

5. focus on safety the formal evidence is weak (retrospective) a randomized study (it will never be done!) “Aggressive surgical approach” routinely recommended ?

6. 249 primary RSTS (2000-2008) Median follow-up: 37 months (IQ range: 16-61) Median age: 55 years (IQ range: 45-66) Male/Female: 1/1 Median size: 17 cm (IQ range: 11-26) Lipo 57%; Leio 18%; MPNST 6%; SFT 6%; Other 13% Median post-operative stay: 13 days (IQ range: 11-16)

7. Best 5 yr overall survival and local control ever reported OS LR - DM

8. Study period n° of pts % complete resection 5 yrs overall survival 5 yrs LRFS Lewis, 19981982-1997231*80 %54 %59% Stoeckle, 20011980-1994145*65 %49 %42% Karakousis, 20031977-20017999 %65 %43% Kilkenny, 19961970-19946378 %48 %NR Gronchi, 20041982-20018288 %54 %63% Hassan, 20041983-19959778%51%56% Van Dalen, 20071989-199414355%39%NR Lehnert, 20091998-20027170%51%59% Current Series2000-200824993%65%78% 51%57%Previous (median) Current Series 93% 65% 78%

9. Number of organ resected Median # of organ resected: 2 (IQ range: 1-3) Type of organ resected

10. Morbidity & Mortality

11. Common Terminology Criteria for Adverse Events (CTCAE) v3.0 https://webapps.ctep.nci.nih.gov/webobjs/ctc/webhelp/welcome_to_ctcae.htm

12. Grade ≥ 3Grade ≥ 4Grade 5 18%12%3% 45 pts30 pts8 pts Anastomotic leakage 23154 Infected collection 1051 Haemorrage 662 Wound dehiscence 44 Pulmonary Embolism 11 Lower limb compartmental syndrome 1

13. Number of organs resected > 3 correlate with higher risk of morbidity # of organs resected Log odds

14. The organs resected correlate with the risk of morbidity Right Colon Left Colon Kidney Psoas Pancreas Spleen Uterus Ovary Diaphragm Parietal muscle Stomach Small bowel Bone Nerve Vein Artery OR 0.74 1.10 1.08 0.70 1.57 1.48 0.64 0.79 1.43 1.03 3.57 2.98 1.31 0.98 2.63 3.57 0123451020 Kidney Pancreas Spleen Uterus Ovary Diaphragm Parietal muscle Stomach Small bowel Bone Nerve Vein Artery OR 0.74 1.10 1.08 0.70 1.57 1.48 0.64 0.79 1.43 1.03 3.57 2.98 1.31 0.98 2.63 3.57 0123451020

15. Other prognostic factors for morbidity Patient Age (years): 66 vs 451.741.00 3.03 0.142 Side: Left vs Right Middle vs Right 0.98 2.07 0.48 0.53 2.01 8.00 0.550 Preoperative RT: Yes vs no 1.12 0.41 3.07 0.825 Preoperative CT: Yes vs no 1.47 0.64 3.36 0.364 Tumor size (cm): 26 vs 11 1.100.572.13 0.921 OR 95% C.I.Wald test

16. MorbidityMortality 18% (range 9-37%) 3% (range 1-7%) 30% (range 15-50%) 3% (range 1-5%) 10% (range 3-15%) 3% (range 2-4%) 5% (range 2-8%) 3% (range 2-4%) 18%3%

17. MorbidityReoperationMortality Lewis, 1998NR 4% Stoeckle, 2001NR Karakousis, 2003NR 0% Kilkenny, 1996NR Gronchi, 2004NR 3% Hassan, 20048%6%2% Van Dalen, 2007NR 5% Lehnert, 200924%NR7% Current Series18%12%3%

18. …in brief

19. Retroperitoneal STS are a challenging disease more for their anatomical location than for their biology Frontline approach is crucial: need for an aggressive surgery to minimize positive margins, often including adjacent uninvolved visceral organs. Safety is comparable to other major abdominal operations, if carried out at high-volume centers Need to refer these patients to high-volume centers to have the best ratio between aggressiveness and morbidity

20. marco.fiore@istitutotumori.mi.it