W. Douglas Wong, M.D.

Chief,Colorectal Service

Memorial Sloan Kettering Cancer Center

Professor of Surgery

Cornell University Medical School

4th East – West Colorectal Days

HungaryOct. 16-18, 2008

Ultra-Low Sphincter Saving Procedures -Re-defining the inferior resection limit

Sphincter preserving surgery should be considered the

standard for the majority of low rectal cancers

How much distal margin do you need?

• 5 cm rule*

• 2 cm rule**

• “end of the 2 cm rule”

*Williams et al. Reappraisal of the 5cm rule of distal excision for carcinoma of the rectum. Br. J Surg. 1983;70:150-154.**Pollett et al. The relationship between the extent of distal clearance and survival and local recurrence rates after curative anterior resection for carcinoma of the rectum. Ann Surg. 1983;198:159-163

What is an adequate distal margin for sphincter sparing rectal resection?

MSKCC Studies

1. Whole Mount Pathologic Analysis ( Annals of Surgery 2007)2. Distal Margin Analysis Study ( Unpublished 2008 )3. Coloanal / Intersphincteric Study ( Submitted 2008 )

A Prospective Pathologic Analysis Using Whole-Mount Sections of Rectal Cancer Following Preoperative Combined Modality Therapy

Implications for Sphincter Preservation

Jose Guillem, David Chessin, Jinru Shia, Arief Suriawinata, Elyn Riedel, Harvey Moore,

Bruce Minsky, and W. Douglas Wong

Annals of Surgery 2007;245(1):88-93

Study # 1

• To use whole mount pathologic analysis to characterize microscopic patterns of residual disease

• Circumferential margins

• Distal resection margins

• To identify clinicopathologic factors associated with residual disease

Aims of the Study

Methodology

• 109 patients prospectively accrued with ERUS staged locally advanced rectal cancer (T2-T4 and /or N1)

• Median distance of 7 cm. from anal verge

• Preoperative chemoradiation followed by TME based resection

• Comprehensive whole mount pathologic analysis was performed

Results

• Sphincter preserving resection was feasible in 87 patients (80%)

• Distal margins negative in all 109 pts – Median 2.1 cm; range 0.4 – 10 cm

• Intramural extension beyond gross mucosal edge of residual tumor was only in 2 patients (1.8 %)– Both < .95 cm

• No positive circumferential margins although 6 were less that 1 mm– Median 10 mm; range 1 - 28 mm

• On multivariate analysis, residual disease was observed more frequently in distally located tumors < 5 cm from the anal verge (p=.03)

Impact of distal margin

Distal Margin Rectal Cancer

1. Guillem JG, Ann Surg. 2007 Jan;245(1):88-93

MSK1: Whole mount analysis of 87 locally advanced RC after neoadjuvant CMT and LAR

No positive margins

2.2% had intramural extensionbeyond mucosal edge of tumor

9.5mm

3mm

Conclusions

• Following preoperative chemoradiation and TME, distal margins of 1 cm seems adequate

• Occult tumor beneath the mucosal edge was rare and when present was limited to less that 1 cm

• These results extend the indications for sphincter preservation as distal resection margins of only 1 cm may be acceptable for locally advanced rectal cancer treated with preoperative chemoradiation

Distal Margin Analysis

Nash G, Paty P, Guillem J, Temple L, Weiser M, and Wong D

( Unpublished Data 2008 )

Study # 2

Study Hypotheses

Margin of less than 8mm is associated

with higher risk of local recurrence (LR)

Mucosal recurrence (MR) is the

mechanism of higher LR

Distal margin rectal cancer

Study Cohort

• 627 patients with primary rectal cancer

• Study period: 1991-2004

• Curative resection

• No involvement of adjacent organs

• Low anterior resection – Stapled anastomosis– Hand-sewn coloanal anastomosis (HSCAA)

• Median follow up 5.8 years

Distal margin rectal cancer

Patient and Tumor Characteristics - LARDistal margin rectal cancer

Group 1 2 3 P value

Distal margin <8mm 8-19mm 20-60mm

n 103 230 294

Age ≤60 years 59% 53% 47% 0.07

Female 46% 39% 40% 0.40

2-6cm from AV 81% 57% 17% <0.001

pT3/4 16% 34% 54% <0.001

pN1/2 23% 29% 25% 0.48

M1 1% 2% 3% 0.47

LVI 9% 9% 10% 0.97

Preop CMT 58% 61% 60% 0.87

Any adjuvant rx 72% 76% 74% 0.73

DSS at 6 years 90% 87% 87% 0.76

OS at 6 years 84% 85% 83% 0.67

Local recurrenceDistal margin rectal cancer

Distal margin <8mm 8-19mm 20-60mm P-value

LR events 13/103 13/230 15/294

Absolute LR 12.6% 5.7% 5.1% 0.006

DM < 8mm *

DM = 8-19mm

DM = 20-60mm

* P = 0.008

103 95 78 45 23 13 5 230 217 167 99 47 21 9 294 281 220 133 71 35 15

103 97 81 46 25 13 5 230 222 170 99 47 21 9 294 283 222 134 71 35 16

Mucosal recurrenceDistal margin rectal cancer

Distal margin <8mm 8-19mm 20-60mm P value

MR events 8/103 4/230 4/294

Absolute MR 7.8% 1.7% 1.4% <0.001

DM < 8mm *

DM = 8-19mm

DM = 20-60mm

* P = 0.001

Pelvic recurrence (excludes iMR)Distal margin rectal cancer

Distal margin <8mm 8-19mm 20-60mm P value

PR events 7/103 11/230 13/294

Absolute PR 6.8% 4.8% 4.4% 0.63

DM < 8mm

DM = 8-19mm

DM = 20-60mm

P = 0.62

103 95 78 45 23 13 5 230 217 167 99 47 21 9 294 281 220 133 71 35 15

Changes over time: 1991-1997 and 1998-2004

Distal margin rectal cancer

Variation of LRDistal margin rectal cancer

n 1991-97 n 98-2004 P value

<8 mm 41 22% 62 6.5% 0.02

8-19 mm 74 6.8% 156 5.1% 0.62

20-60 mm 127 7.9% 167 3.0% 0.06

All patients 242 9.9% 385 4.4% 0.007

Variation of LRDistal margin rectal cancer

n 1991-97 n 98-2004 P value

<8 mm 41 22% 62 6.5% 0.02

8-19 mm 74 6.8% 156 5.1% 0.62

20-60 mm 127 7.9% 167 3.0% 0.06

All patients 242 9.9% 385 4.4% 0.007

n 1991-7 n 98-2004 P value

Preop CMT 286 46% 462 67% <0.001

Any adjuvant 286 65% 462 78% <0.001

Use of adjuvant therapy

Conclusions

• Sphincter sparing techniques do not compromise local control or survival

• Careful surveillance for MR is warranted in patients with close DM

• Salvage is feasible for most MR

Distal margin rectal cancer

Rationale for ultralow LAR/CAA

Ultralow LAR/CAA with Intersphincteric Dissection

Weiser et al. Adenocarcinoma of the Colon and Rectum. In Shackelford’s Surgery of the Alimentary Tract6th ed, 2007

1. We need less distal margin than we once thought

2. Internal sphincter is an extension of the rectal wall

Author Year nFollow-

upLocal

recurrence

Tiret et al 2003 26 39 mo 3.4%

Portier et al 2007 173 67 mo 10.6%

Saito et al 2006 228 41 mo 5.8%

Rullier et al 2005 92 >24 mo 2.0%

Tilney et al* 2007 612 9.5%

Oncologic Outcome of Coloanal Anastomosis

*literature review

Sphincter Preservation in low rectal cancer is facilitated by preoperative chemoradiation

and intersphincteric dissection

Weiser M, Quah HM, Shia J, Guillem J, Paty P, Temple L, Goodman K,

Minsky B and Wong D

( Submitted paper 2008 )

Study # 3

Aim of the Study

• To evaluate oncologic outcome in patients with locally advanced distal rectal cancer treated with preoperative chemoradiation followed by:

– LAR with stapled coloanal anastomosis– LAR with intersphincteric dissection and hand

sewn coloanal anastomosis– APR

Background Data

• From a cohort of 601 consecutive patients from 1998 – 2004 :

– 148 patients were identified with Stage II and III rectal cancers (ERUS Staged uT3-4 and/or N1) at or below 6 cm from the anal verge

– All treated with preoperative long course

chemoradiation and TME

Median Distal Margin

Median Distal Margin

• LAR Stapled Coloanal 1.1 cm ( 0.9 – 1.3 cm)• LAR Handsewn Intersphincteric 1.0 cm ( 0.9 – 1.3 cm)• APR 4.0 cm ( 3.5 – 4.6 cm)

Oncologic Outcome (MSKCC data)

LAR

Coloanal

n = 41

Intersphincteric dissection

n = 44

APR

n = 63

p-value

Age 60 54 67

Male 44% 57% 52% ns

Distance from anal verge 6 (3-6) 5 (3-6) 3 (0-6) 0.0001

Pathologic CR 24% 25% 6% 0.018

Poor differentiation 7% 5% 28% 0.003

+ circumferential margin 0% 5% 13% 0.11

MSKCC 2008

Oncologic Outcome (MSKCC data)

LAR Coloanal

n = 41

Intersphincteric dissection

n = 44

APR

n = 63

Crude recurrence rate 6(15%) 7(16%) 26(41%)

Local 1(2%) 0(0) 6(9%)

Distant 5(12%) 7(16%) 22(35%)

5 yr RFS (95% CI) 85% 83% 47%

5 yr DSS (95% CI) 97% 96% 59%

MSKCC 2008

Oncologic Outcome of Coloanal Anastomosis

N=149

MSKCC 2008

Conclusions

• In low rectal cancer, sphincter preservation is facilitated by significant response to chemoradiation and intersphincteric dissection without oncologic compromise

• APR is more likely required in those patients with lesser response to neoadjuvant therapy and is associated with poorer outcome

Functional outcome of ultralow LAR with coloanal anastomosis

Functional Outcome after LAR/CAA

• 81 patients• Median 2 BM / day• Continence

complete 51%

incontinent gas 21%

minor leak 23%

significant leak 5%• 56% excellent or good composite function

(continence, evacuation, #BMs)• 74% of patients were satisfied

Paty et al. Long-term functional results of coloanal anastomosis for rectal cancer. Am J Surg. 1994;167:90-95.

QOL: Anal Sphincter Preservation or Sacrifice

• Despite LAR patients suffering defecation problems, they had better QOL than APR patient

• Bowel function did not significantly impact on overall QOL• Stoma patients

– More limited everyday work and hobby activities (role functioning) – More disrupted social and family life (social functioning) – Less able to get about and look after themselves (physical

functioning)– Felt less attractive (body image)

• These changes persisted over time (4 years)• LAR scores improved with time while APR did not.• Greatest improvement in QOL was when temporary stomas were

reversed.

Engel et al. Quality of life in Rectal Cancer Patients. Ann Surg 2003;238:203-213.

• “Meta-analysis” – Validated instruments– Studies including APR and LAR

• Study included data from 11 studies – 1443 patients – 486 patients with APR– All retrospective– Validated instruments

• 4 SF-36, 7 EORTC 30, 8 EORTC – CRC38

Cornish et al. Ann Surg Onc, 2007; 14: 2056-2068

LAR vs APR

Quality of Life:Stoma vs Sphincter Preservation

QOL: SPS vs APR

Overall when comparing APR to LAR, no differences in general QOL were identified

Cornish et al. Ann Surg Onc, 2007; 14: 2056-2068

Conclusions

• A 1 cm distal margin is acceptable in patients undergoing neoadjuvant tx

• Ultra-low LAR/COLOANAL is oncologically sound

• Restores body image

• Majority of patients are satisfied with their QOL