1. Defining the Colorectal Surgeons role in patients with colorectal cancer and limited metastatic disease Jose G. Guillem, MD, MPH Department of Surgery Memorial Sloan Kettering Cancer Center Great Debates & Updates in GI Malignancies March 28-29, 2014

2. Case 58M with 10lb weight loss, rectal pain/tenesmus, bleeding PMH: unremarkable DRE: palpable tethered mass with distal margin at 8cm from AV, 5cm above ring Flex sig: circumferential, ulcerated bulky near-obstructing mass CT scan: liver metastases

3. Stage IV Rectal Cancer

5. Management Options in Metastatic Rectal Ca Systemic Chemotherapy alone Stent and Chemotherapy Divert and Chemotherapy Resect and Chemotherapy Chemotherapy and Resect Chemotherapy, Chemoradiation and Resect

6. Central Issues Benefit of surgical resection over stent/diversion alone –Alleviation of bleeding, pain, tenesmus Morbidity and mortality of resection Delay in administering systemic chemo

7. Metastatic Rectal Cancer Bulky symptomatic primary with extensive liver mets Bulky symptomatic primary with limited liver metastases Non-bulky asymptomatic primary with extensive liver mets Non-bulky asymptomatic primary with limited liver mets

8. 33 successful stents out of 34 pts (97%) Palliation of malignant rectal obstruction with self-expanding metal stents Hünerbein M et al. Surgery. 2005 Overall, 18% required surgery because of stent complications Stent migration x 3 Intractable pain x 2 Incomplete stent expansion x 1 Incontinence x 1 Rectovesical fistula x 1 Incontinence x 1

9. Malignant rectal obstruction within 5cm of the anal verge: is there a role for expandable metallic stent placement? Group A: obstruction ≤ 5cm from AV Group B: obstruction > 5cm from AV Tx: PU or PTFE covered retrievable stents Song HY et al. Gastrointest Endosc. 2008

10. Radical resection of rectal cancer primary tumor provides effective local therapy in patients with stage IV disease N=80 with rectal CA resection without radiotherapy 12 (15%) surgical complications –1 death –4 reoperations 15 (19%) required colostomy at initial resection 5 (6%) local recurrences –Median time to local recurrence = 14 mos Median survival = 25 mos –11 patients died within 6 mos Nash GM et al, Annals of Surg Oncol, 2002.

11. <50% liver replacement Complete or near complete response of primary to first chemo regimen Able to receive subsequent aggressive, post- operative chemo Radical resection of primary in stage IV rectal cancer patients – who benefits? Nash GM et al, Annals of Surg Oncol, 2002.

12. Would modern, combination chemotherapy obviate the need for resection of the primary rectal cancer?

13. Combination chemotherapy without surgery as initial treatment 233 patients with synchronous metastatic colorectal cancer 93% of patients who received upfront chemotherapy never required palliative surgery for primary tumor 89% required no direct symptomatic management for intact primary tumor Poultsides et al. J Clin Oncol 2009

14. Combination chemotherapy without surgery as initial treatment Poultsides et al. J Clin Oncol 2009 Rectal Primary (n=78) No Emergent Intervention 85% (n=66) Emergent Primary- Directed Intervention 15% (n=12)

15. Would modern, combination chemotherapy obviate the need for resection of the primary rectal cancer? In some, initially yes, but if combinational chemotherapy converts unresectable liver mets to resectable, in the long run we may need to address the primary rectal cancer in more.

16. Anastomotic leak following low anterior resection in stage IV rectal cancer is associated with poor survival N = 123 pts resected with curative intent Smith JD et al. Ann Surg Oncol. 2013 Overall leak rate 6.5% 3y OS 72% 3y OS 32% Factors identified as significant in univariate analysis for Overall Survival (OS) Multivariate analysis for overall survival

17. Management Dilemma Morbidity Efficacy

18. Treatment Pathway Stage IV Rectal Cancer with Synchronous Liver Metastases ObstructedNon-obstructed ResectStentDivert Extrahepatic Metastases No Extrahepatic Metastases ChemotherapyResectable Liver MetastasesNonresectable Liver Metastases Isolated, Single, or Peripheral Bilobar or Multiple ChemotherapyResect Liver Resectable RectumNonresectable Rectum Chemoradiation TherapyResect Rectum Resect metastases and rectum if possible

19. Treatment Pathway Stage IV Rectal Cancer with Synchronous Liver Metastases ObstructedNon-obstructed ResectStentDivert Extrahepatic Metastases No Extrahepatic Metastases ChemotherapyResectable Liver MetastasesNonresectable Liver Metastases Isolated, Single, or Peripheral Bilobar or Multiple ChemotherapyResect Liver Resectable RectumNonresectable Rectum Chemoradiation TherapyResect Rectum Resect metastases and rectum if possible Synchronous vs. Staged Systemic vs. HAI Chemotherapy first, then radiation? Short-course vs. long-course? When, and in what order?

20. Management Options in Unresectable Metastatic Rectal Ca If symptoms of primary (bleeding, pain, tenesmus) are formidable and volume of liver mets limited (<50%) : Resect primary If patient cannot tolerate rectal resection: Laparoscopic diversion Defer stenting rectal cancer as last resort

21. Metastatic Rectal CA – Chemotherapy, Radiation, Divert, Stent or Resect First? Multidisciplinary approach throughout Colorectal surgeon: Bulk/lumen of primary, CRM, sphincter preservation, co-morbidities? Liver surgeon Resectability of mets, status of liver parenchyma, co-morbidities Medical/Radiation Oncologist Co-morbidities, volume:primary vs mets

22. Metastatic Rectal Cancer – Chemotherapy, Radiation, or Surgery First? Individualize, Individualize, Individualize