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

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

Stage IV Rectal Cancer

Stage IV Rectal Cancer

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

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

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

• 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 3Intractable pain x 2Incomplete stent expansion x 1Incontinence x 1

Rectovesical fistula x 1Incontinence x 1

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

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.

• <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.

Would modern, combination chemotherapy obviate the need

for resection of the primary rectal cancer?

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

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)

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.

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

Management Dilemma

Morbidity

Efficacy

Treatment PathwayStage IV Rectal Cancer

with Synchronous Liver MetastasesObstructed Non-obstructed

Resect Stent Divert Extrahepatic Metastases

No Extrahepatic Metastases

ChemotherapyResectable Liver Metastases Nonresectable Liver Metastases

Isolated, Single, or Peripheral

Bilobar or Multiple

ChemotherapyResect Liver

Resectable Rectum Nonresectable Rectum

Chemoradiation TherapyResect Rectum

Resect metastases and rectumif possible

Treatment PathwayStage IV Rectal Cancer

with Synchronous Liver MetastasesObstructed Non-obstructed

Resect Stent Divert Extrahepatic Metastases

No Extrahepatic Metastases

ChemotherapyResectable Liver Metastases Nonresectable Liver Metastases

Isolated, Single, or Peripheral

Bilobar or Multiple

ChemotherapyResect Liver

Resectable Rectum Nonresectable Rectum

Chemoradiation TherapyResect Rectum

Resect metastases and rectumif possible

Synchronous vs. Staged

Systemic vs. HAI

Chemotherapy first, then radiation?Short-course vs. long-course?

When, and in what order?

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

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

Metastatic Rectal Cancer – Chemotherapy, Radiation, or Surgery First?

Individualize, Individualize, Individualize