Download Laparoscopic Colectomy

A COMPARISON of LAPAROSCOPICALLY
ASSISTED and OPEN COLECTOMY for COLON
CANCER
The Clinical Outcomes of Surgical
Therapy Study Group
(Cost Study)
NEJM, May 13, 2004
•BACKGROUND
•METHODS
•RESULTS
•CONCLUSIONS
•EVIDENCE BASED MEDICINE
Ranking of the Study
BACKGROUND
Phillips, Ann, Surg, 1992
First to report laparoscopic approach to colectomy
for colon cancer in 24 patients
Berends, Lancet, 1994
Reported 3 of 14 patients developed trocar wound
site recurrences in series of laparoscopically
assisted resections for colon cancer.
Reilly, Disease Colon Rectum, 1996
Reported less than 1% wound site
recurrences following laparoscopically
assisted resections for colon cancer.
Questions Raised
1) Could a proper oncologic resection be
performed with the laparoscopic approach?
2) Were there staging inaccuracies with the
laparoscopic approach?
3) Were patterns of tumor cell dissemination
altered by the laparoscopic approach?
Questions Raised
4) Were wound site recurrence rates truly higher
with the laparoscopic approach?
5) Were overall recurrence rates higher with the
laparoscopic approach?
6) Were disease free and overall survival rates
lower with the laparoscopic approach?
Questions Raised
7) Were post operative complication rates
higher with the laparoscopic approach?
8) Was post operative recovery faster with
the laparoscopic approach?
COST STUDY
•Initiated in 1994 to ensure that the laparoscopic
approach to colon cancer was properly tested before
its use became wide spread.
•Surgeons generally adopted a virtual moratorium
on laparoscopic resection for colon cancer outside
of this trial.
METHODS
Design
•Noninferiority trial
•Prospective randomized trial
•Involved 66 credentialed surgeons from 48
institutions in the USA and Canada.
•Compared laparoscopic vs open approach to
colon cancer
Patients
Inclusion Criteria
•18 years of age or older
•Diagnosed clinically with colon
adenocarcinoma and had histologic
confirmation at surgery
•Right or left colon cancer
Patients
Exclusion Criteria
•Pregnancy
•Inflammatory bowel disease
•Familial polyposis
•Previous malignant tumor
•Current malignant tumor
•Severe medical illness
•Prohibitive abdominal adhesions
Patients
Exclusion Criteria
•Transverse colon cancer
•Rectal cancer
•Acute bowel obstruction
•Perforation from cancer
•Advanced local disease
•Metastatic disease
Quality Control
•66 credentialed surgeons at 48 institutions
•Each surgeon was required to have had
performed at least 20 laparoscopically
assisted colorectal surgeries prior to entry
into the trial
Quality Control
Prior to entry into trial, each surgeon submitted a
videotape of a laparoscopic colectomy that was
reviewed for:
•thoroughness of abdominal exploration
•identification of critical adjacent structures
•oncologic techniques
•degree of avoidance of direct tumor handling
•level of mesenteric ligation
Quality Control
•Random audits of videotapes during trial
•Assessment of bowel resection margins during trial
TECHNIQUE OF LAPAROSCOPIC COLON RESECTION
1) Pneumoperitoneal/ intracorporeal approach to:
•
abdominal exploration
•
mobilization of colon
•
identification of critical structures
•
ligation of vascular pedicles
2) Exteriorization of bowel through small incision for
resection/ anastomosis
INDICATIONS FOR COVERSION FROM
LAPAROSCOPIC TO OPEN SURGERY
•Presence of associated conditions
•Findings of advanced disease
•Massive adhesions
•Technical difficulties
•Inadequate oncologic margins
•Surgeons descretion for patient safety
Adjuvant chemotherapy was
allowed at the physicians or patient’s
descretion
RANDOMIZATION
• Performed centrally at the North Central
Cancer Treatment Group statistical office
• Patients randomly assigned to:
a) laparoscopically assisted colectomy
b) open laparotomy and colectomy
RANDOMIZATION
• Through use of minimization algorithm,
treatment assignment was balanced with respect to
three stratification variables:
1) surgeon
2) primary tumor site – right, left, sigmoid
RANDOMIZATION
3) American Society of Anesthesiologists Class
• Class I
– patient appears healthy
• Class II – patient has systemic, well
controlled disease
• Class III – patient has multiple symptoms
of disease, or well controlled
major system disease
FOLLOW – UP:
COMPLICATIONS
•Assessed by single reviewer
•Reviewer unaware of patient’s treatment assignment
•Assessed at date of discharge, 2 months, and 18 months
Follow – Up
Classification of Complications
Grade
Definition
1
Non-life threatening and temporary
2
Potentially life threatening, but temporary
3
Causing permanent disability
4
Fatal
FOLLOW – UP:
TUMOR RECURRENCE
•Physical exam including inspection of wound sites
•CEA every 3 months for first year, then every 6 months for 5 years
•CxR every 6 months for 2 years, then every year
•Colonoscopy, or proctosigmoidoscopy and barium enema every 3 years
•Recurrence had to be confirmed with imaging or endoscopy
STATISTICAL ANALYSIS
Designed to compare the following end points in the
laparoscopic vs the open colectomy groups:
1) Primary end point
•
Time to tumor recurrence defined as the time from
randomization to first confirmed recurrence
2) Secondary end points
•
Variables related to recovery
•
Complications
•
Disease free survival
•
Overall survival
RESULTS
Characteristics of Patients and Tumors
•872 patients underwent randomization from
August 1994 to August 2001 over 7 years
•2 patients subsequently declined surgery
•7 patients subsequently were ineligible
•This left 863 patients for final analysis
Characteristics of Patients
and Tumors
Age
Median
Open Colectomy
N = 428
69y
Laparoscopic Colectomy
N = 435
70y
Range
29-94y
28-96y
Characteristics of Patients
and Tumors
Sex
Female
Open Colectomy
N = 428
220 (51%)
Laparoscopic Colectomy
N = 435
212 (49%)
Male
208 (49%)
223 (51%)
Characteristics of Patients
and Tumors
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
1 or 2
367 (86%)
373 (86%)
3
61 (14%)
62 (14%)
American Society of
Anesthesiologists Class
Characteristics of Patients
and Tumors
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
0
233 (54%)
246 (57%)
1
120 (28%)
113 (26%)
>1
37 (9%)
41 (9%)
Unknown
38 (9%)
35 (8%)
Number of Previous
Operations
Characteristics of Patients
and Tumors
# of patients
Total
Benign disease
Malignant disease
•Stage I, II, III
•Stage IV
863
53 (6%)
810 (94%)
784 (97%)
26 (3%)
Characteristics of Patients
and Tumors
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
Right side of Colon
232 (54%)
237 (54%)
Left side of Colon
32 (7%)
32 (7%)
164 (38%)
166 (38%)
Location of Primary Tumor
Sigmoid Colon
Characteristics of Patients
and Tumors
Grade of Differentiation
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
•Grade 1 (well)
•Grade 2 (moderately)
44 (10%)
271 (63%)
36 (8%)
315 (72%)
•Grade 3 (poorly)
72 (17%)
51 (12%)
6 (1%)
5 (1%)
33 (8%)
2 (<1%)
20 (5%)
8 (2%)
•Grade 4 (undifferentiated)
•Not applicable (benign)
•Unknown
Characteristics of Patients
and Tumors
Depth of Invasion
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
•Submucosal
•Muscularis
59 (14%)
76 (18%)
67 (15%)
105 (24%)
•Serosal
237 (55%)
226 (52%)
•Beyond serosa,
involvement of
contiguous structure
•Not applicable (benign)
23 (5%)
12 (3%)
33 (8%)
20 (5%)
•Unknown
0 (0%)
5 (1%)
Characteristics of Patients
and Tumors
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
TNM Stage
0
I
33 (8%)
112 (26%)
20 (5%)
153 (35%)
II
146 (34%)
136 (31%)
III
121 (28%)
112 (26%)
IV
16 (4%)
10 (2%)
Unknown
0 (0%)
4 (1%)
SURGERY
Total Surgery Patients
# of patients
Total patients
863
Open colectomy
428 (49.6%)
Laparoscopic Colectomy
435 (50.4%)
•
Successful laparoscopic colectomy
345 (79%)
•
Converted to open colectomy
90 (21%)
SURGERY
Reasons for conversion
# of patients
•Advanced disease
22 (24%)
•Other
21 (23%)
•Adhesions
14 (16%)
•No visualization
12 (13%)
of critical structures
•Unable to mobilize colon
10 (11%)
•Complicating disease
3 (3%)
•Inadequate resection margins
4 (4%)
•Intraoperative complications
4 (4%)
SURGERY
Conversion Rates
P Value
High vs low volume surgeons
>0.05
Early vs late trial entry surgeons
>0.05
SURGERY
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
•Length of incision
<0.001
Median
18 cm
6 cm
Range
3 – 35 cm
2 – 35 cm
•Duration of Surgery
Median
Range
P Value
<0.001
95 min
27 – 435 min
150 min
35 – 450 min
SURGERY
Open
Colectomy
N = 428
Laparoscopic
Colectomy
N = 435
•Proximal Margin
P Value
0.38
Median
12 cm
13 cm
Range
3 – 50 cm
2 – 78 cm
•Distal Margin
0.09
Median
11 cm
Range
1 – 42 cm
10 cm
2 – 40 cm
SURGERY
•Margin Less than 5 cm
•Median # of lymph
nodes examined
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
P Value
26 (6%) pts
22 (5%) pts
0.52
12
12
SURGERY
•Other organs resected
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
62 (14%) pts
33 (8%) pts
0.001
Gyn organs
24 (39%)
8 (24%)
Gall bladder
10 (16%)
10 (30%)
Other
9 (15%)
5 (15%)
Liver
9 (15%)
1 (3%)
Bladder and
abdominal wall
6 (10%)
1 (3%)
4 (6%)
6 (18%)
Small bowel
•Malignant histologic
findings resected organs
14 (3%) pts
6 (1%) pts
P Value
RECOVERY
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
•Duration of parenteral narcotics
P Value
<0.001
Median
4 days
3 days
Interquartile range
3 – 5 days
2 – 4 days
•Duration of oral analgesics
0.02
Median
2 days
1 day
Interquartile range
1– 3 days
1 – 2 days
•Duration of hospitalization
<0.001
Median
6 days
5 days
Interquartile range
5 - 7 days
4 – 6 days
Complications
•Intraoperative Complications
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
8 (2%) pts
16 (4%) pts
Spleen injury
2 pts
0 pt
Bleeding
1 pt
8 pts
Bowel injury
2 pts
6 pts
Miscellaneous
3 pts
2 pts
•Postoperative Complications
before discharge
80 (19%) pts
81 (19%) pts
P Value
0.10
0.98
Complications
Open
Colectomy
Laparoscopic
Colectomy
N = 428
N = 435
P Value
Grade of post operative
complications before
discharge
Total
80 (19%) pts
81 (19%) pts
Grade 1
44 (55%) pts
42 (52%) pts
Grade 2
33 (41%) pts
34 (42%) pts
Grade 3
0 (0%) pts
2 (2%) pts
Grade 4
3 (4%) pts
3 (4%) pts
0.73
Complications
Open
Colectomy
Laparoscopic
Colectomy
(N = 428)
(N = 435)
P Value
92 (21%) pts
0.66
43 (10%) pts
52 (12%) pts
0.27
•Rate of reoperation
8 (<2%) pts
8 (<2%) pts
1.0
•30 day postoperative
mortality
4 (1%) pts
2 (<1%) pts
0.4
•Overall complications 85 (20%) pts
•Rate of readmission
RECURRENCE
(after median follow-up of 4.4 years)
Open
Colectomy
Laparoscopic
Colectomy
(N = 428)
(N = 435)
Recurrence in surgical
1 (0.2%) pts
wounds
2(0.5%) pts
P Value
0.5
RECURRENCE
(after median follow-up of 4.4 years)
Overall recurrence
Open
Colectomy
(N = 428)
Laparoscopic
Colectomy
(N = 435)
P Value
84 (20%) pts
76 (17%) pts
0.32
•Stage I
0.65
•Stage II
0.50
•Stage III
0.49
Cumulative Incidence of Recurrence among Patients with Colon Cancer of Any Stage (Panel
A), Stage I (Panel B), Stage II (Panel C), or Stage III (Panel D)
The Clinical Outcomes of Surgical Therapy Study Group, N Engl J Med 2004;350:2050-2059
SURVIVAL
(after median follow-up of 4.4 years)
Open
Colectomy
(N = 428)
Laparoscopic
Colectomy
(N = 435)
P Value
Deaths
•Total
95 (22%) pts
91 (21%) pts
•Before tumor
recurrence
34 (36%) pts
43 (47%) pts
•After tumor
recurrence
61 (64%) pts
48 (53%) pts
0.51
0.25
Survival
(after median follow-up of 4.4 years)
Open Colectomy vs Laparoscopic Colectomy
P Values
All Stages
0.51
Stage I
0.31
Stage II
0.58
Stage III
0.25
Overall Survival among Patients with Colon Cancer of Any Stage (Panel A), Stage I (Panel B),
Stage II (Panel C), or Stage III (Panel D)
The Clinical Outcomes of Surgical Therapy Study Group, N Engl J Med 2004;350:2050-2059
CONCLUSIONS
•The conversion rate from laparoscopic to open
colectomy was 21%
•The duration of surgery was significantly longer for
laparoscopic colectomy
•There was no significant difference in margins or in the
number of lymph nodes removed
CONCLUSIONS
•Postoperative recovery is significantly faster with
laparoscopic colon resection in terms of duration of
parenteral narcotic use and duration of hospitalization
•No significant difference in the incidence or severity
of intraoperative and postoperative complications.
CONCLUSIONS
•No significant difference in wound site tumor recurrence rates
•No significant difference in time to recurrence
•No significant difference in recurrence rates per tumor TNM stage
•No significant difference in overall recurrence rates
CONCLUSIONS
•No significant difference in disease free survival rates for each TNM stage
•No significant difference in overall disease free survival rates
•No significant difference in overall survival rates for each TNM stage
•No significant difference in overall survival rates
CONCLUSIONS
•The study was not designed to test whether
laparoscopic assisted colectomy is superior to open
colectomy for cancer
•The study did demonstrate that laparoscopic
assisted colectomy is not inferior to open
colectomy for cancer
•The study demonstrates that it is safe to proceed
with laparoscopic assisted colectomy for colon
cancer
EVIDENCE BASED MEDICINE
•The evidence based effort to improve patient care began in
the late 1980’s at McMaster University
•Founded on the idea that more emphasis could be placed on
the benefits and risks therapy
•Founded on the idea that it was best to treat patients with
therapies from the top of pyramids of research information
with methodologically weak studies at the base and strong
studies at the top of the pyramid
JAMA, 1992
Endo Clin, 2002
MODIFIED McMASTER CLASSIFICATION
Grade 1 -
benefits clearly outweigh harms
and cost
Grade 2 -
weaker recommendation
JAMA, 1992
MODIFIED McMASTER CLASSIFICATION
Grade A -
randomized controlled trial with consistent
results
Grade B -
randomized trials with less consistent
results
Grade C -
observational studies, or the generalization
of randomized trial results from one group
of patients to a different group
Grade C+ -
observational studies with compelling
results
JAMA, 1992
A COMPARISON of LAPAROSCOPICALLY ASSISTED
and OPEN COLECTOMY for COLON CANCER
McMaster Classification
GRADE IA
•Strong recommendation