Alice C. Wei, MDCM, MSc, FRCSC, FACS Resectability in pancreatic cancer The surgeon’s definition and view Debate session: What is the best strategy to increase rates of resectability in pancreatic cancer Alice C. Wei, MDCM, MSc, FRCSC, FACS Princess Margaret Cancer Centre Assistant Professor of Surgery, University of Toronto, Canada Great Debates & Updates in GI Malignancies April 5-6, 2013

What is the best way to increase resectability rates in pancreas cancer?     Pre-op chemotherapy alone                         Jordan D. Berlin, MD                           Pre-op chemoradiation                         Chris Crane, MD

Role of surgery for pancreatic adenocarcinoma Resection offers potential for long term survival median OS ~ 14- 21 months 1, 2,3 Goals of surgery relief of symptoms complete tumor resection (R0) margin adequate node retrieval ≥ 12 nodes Multi-modality treatment recommended for all patients 4 Overall Survival following surgery (months)3 Lewis 424 pancreaticduodenectomies at 2 centres – U Pen and BI Deaconnes Mayo – seer database study that goes up to 2005 – 2461 patients median survival 14 months (12 time period 1 vs. 16 time period 2) Lewis R HPB (Oxford). 2013 Jan;15(1):49-60 Cleary SC, J Am Coll Surg. 2004 May;198(5):722-31 Mayo SC, J Am Coll Surg. 2012 January; 214(1): 33–45 Abrams RA, Ann Surg Oncol (2009) 16:1751–1756

Pancreatectomy has evolved 2 Patient selection is better staging is more sensitive  CT/ MRI/ EUS Pancreatectomy is safer  peri-operative mortality 14%-<2%1,2 marked volume-outcome relationship  volumes  better outcomes surgeons are better oncologists HPB sub-specialization collaboration with cancer centers 3  use of neo-adjuvant therapy 2 Van Heak, Ann Surg. 2005;242(6):781-8 Mayo SC, JACS, 2012; 214(1): 33–45 Nathan H,JACS, 2009; 208(4):528-538

Technical advances allow bigger resections Vascular resections PV resection routine arterial resections increasing experience Minimally invasive surgery staging laparoscopy laparoscopic/ robotic pancreatectomies More complex resections better margins Better perioperative care SMV and SMA resection with SFV graft graft SMV

Key principles of resectability Localized disease no evidence of metastatic disease Technically resectable with R0 intent Adequate performance status for major abdominal surgery

Resectable pancreatic cancer No metastases No superior mesenteric vein / portal vein distortion/ abutment/ encasement Normal tissue planes preserved around the celiac axis, hepatic artery, and SMA upfront resection recommended case 565 CTIS Callery MP, Ann Surg Oncol, 2009.16:1727–1733 NCCN guidelines version 2.2012, assessed March 18 13

Borderline resectable disease technically resectable but high risk for margin-positivity 3 classification systems differ in extent of venous involvement AHPBA/ SSO/ SSAT Criteria (2009)1 NCCN Guidelines (2.2012) 2 MD Anderson Cancer Center 3 MD Anderson Classification 3 Type A: anatomic classification Type B: potential metastatic disease Type C: poor performance status resected OS = 44 mo unresected OS=13 mo Katz 2008 - 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy ( 50% viable tumor) was seen in 37 (56%) of 66 patients. Median survival was 40 months for the 66 patients who completed all therapy and 13 months for the 94 patients who did not undergo pancreatectomy (p 0.001). OS borderline resectable pancreas cancer resected vs. unresected patients 3 Callery MP, Ann Surg Oncol, 2009.16:1727–1733 NCCN guidelines version 2.2012, assessed March 18 2013 Katz MH, J Am Coll Surg 2008;206:833–848.

NCCN (2012) criteria for borderline resectable1,2 No distant metastases Venous involvement of SMV/ PV tumor abutment with deformity or narrowing encasement or short segment venous occlusion of SMV/PV ** venous vessels amenable to safe resection and reconstruction GDA encasement up to hepatic artery +/- abutment or short-segment involvement of the hepatic artery Abutment of the SMA < 180° Figure 1. Tumor abutting SMA Figure 2. Short segment involvement of hepatic artery at takeoff of GDA. From Katz et al JACS 2008 No distant metastases. b. Venous involvement of the SMV/portal vein demonstrating tumor abutment with or without impingement and narrowing of the lumen, encasement of the SMV/portal vein but without encasement of the nearby arteries, or short segment venous occlusion resulting from either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection and reconstruction. c. Gastro duodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis. d. Tumor abutment of the SMA not to exceed[180 of the circumference of the vessel wall. 1. NCCN, guidelines version 2.2012, assessed March 18 2013 2. Callery MP, Ann Surg Oncol, 2009.16:1727–1733

Borderline resectable: differences between classification systems1 1. Katz MH, Ann Surg Oncol, 2013 Feb 23 (online version)

NCCN criteria for unresectable disease1,2 metastases tumor Distant metastases ≥180 degrees SMA or celiac encasement Non- reconstructible SMV/PV involvement Aortic invasion or encasement 1. NCCN, guidelines version 2.2012, assessed March 18 2013 2. Callery MP, Ann Surg Oncol, 2009.16:1727–1733

Conclusions Pancreatectomy Resectability depends on essential for best results Resectability depends on anatomic features of tumor cancer biology patient physiology Borderline resectable cancer needs multimodality approach vascular reconstruction often required results are encouraging