Transcript Pathologist and Prognosis in Colorectal Cancer Surgery. Dr Bryan F Warren Consultant Gastrointestinal

Pathologist and Prognosis in
Colorectal Cancer Surgery.
Dr Bryan F Warren
Consultant Gastrointestinal
Pathologist
Oxford
M62 Course 2004
Pathology of the formal colorectal
cancer resection specimen.
 Staging and prognosis
 What is the significance of the“radial
margin”?
 How should I look for lymph nodes?
 What is a ‘bad Dukes B cancer’?
Cuthbert E Dukes
Consultant Pathologist
St Mark’s Hospital
1926-1956
Evolution of pathological staging.
UICC TNM 6th Edition 2002
Major changes or minor changes?
Likely that RCPath will recommend staying
with TNM 5th edition.
Reproduced from Schiller KFR, Cockel R, Hunt RH, Warren BF 2001.
Rectal cancer-How I do it
The specimen is received fresh, and
inspected by me +/- surgeon
+/- trainee pathologists and surgeons.
I/we inspect:
• Mesorectal margin
• Close distal margin
• Tumour on peritoneal surface/mesorectal
margin
Mesorectal margin and local
recurrence in rectal cancer
Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma
due to inadequate surgical resection. Histopathological study of lateral tumour spread and
surgical excision Lancet 1986;8514:996





14/52 LRM +
12/14 local recurrence
Specificity 92%
Sensitivity 95%
Positive predictive value 85%
How many slices for histology?
How many slices for histology?
Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma
due to inadequate surgical resection. Histopathological study of lateral tumour spread and
surgical excision Lancet 1986;8514:996
Single slice chosen macroscopically:
6/52 (12%) LRM +
On embedding and sectioning the whole tumour using large blocks:
(10u H&E stained sections cut on a sledge microtome)
14/52 (27%) LRM +
Adam IJ, Mohamdee MO, Martin IG, Scott NA, Finan PJ, Johnston D, Dixon MF,
Quirke P. Role of circumferential margin involvement in the local recurrence of
rectal cancer. Lancet 1994; 344(8924):707-711.
190 patients
CRM + in 25%(35/141) potentially curative resections
CRM + in 36%(69/190) of all cases
Local recurrence after potentially curative resection in 25%
CRM+ independently influenced both local recurrence and
survival
Confirms the need to examine CRM carefully
Hall NR, Finan PJ, Al-Jaberi T, Tsang CS, Brown SR, Dixon MF, Quirke P. Circumferential
margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor
of survival but not local recurrence? Dis Colon Rectum 1998;979-983.
218 patients
152 potentially curative resections.






20 (13%) tumour within 1mm CRM
50% disease recurrence CRM+ at 41 months
Local recurrence in 15%
24% disease recurrence CRM- at 41 months
Local recurrence in 11%(p=0.38)
Disease free survival (p=0.01) and mortality (p=0.005) were
related to CRM+
Patients with an involved CRM may die of distant disease
before local recurrence is apparent.
Birbeck KF, Macklin CP, Tiffin NJ, Parsons W, Dixon MF, Mapstone NP,
Abbott CR, Scott NA, Finan PJ, Johnston D, Quirke P. Rates of circumferential
resection margin involvement vary between surgeons and predict outcomes in
rectal cancer surgery. Ann Surg 2002;235:449-457.
608 patients





1986-1997
586 clinical follow up available
105 (17.9%) developed local recurrence
165 CRM positive 38.2% local recurrence
421 CRM negative 10% local recurrence.
CRM – had improved (75%) 5 year survival over
CRM+ (29%)
CRM+ immediate post surgical predictor of survival
(CR07)
Useful indicator of the quality of surgery-Audit
Pathologists’ assessment of the
mesorectum macroscopically.
Nagtegaal ID, van de Velde CJ, van der Worp E, Kapiteijn E, Quirke P, van Krieken JH;
Cooperative Clinical Investigators of the Dutch Colorectal Cancer Group. Macroscopic
evaluation of rectal cancer resection specimen: clinical significance of the pathologist in
quality control. J Clin Oncol 2002; 20: 1714-5.
180 patients
 24% (43) incomplete mesorectum
 36.1% local and distant recurrence vs 20.3% in the
group with a complete mesorectum
 2mm margin
 Survival is predicted by proper assessment of the
mesorectum, and judgement of the quality of TME.
Trials – CR07 quality of
surgery
P Quirke et al
Mode of CRM involvement
Birbeck et al







6 types of CRM involvement
Direct tumour spread
46 pts
Discontinuous tumour spread 110pts
Tumour within a lymph node 19pts
Tumour within a blood vessel 23pts
Tumour within lymphatics
14pts
Perineural tumour
11pts
52.17% local recurrence
45%
10.53%(caution pt. no. small)
30.43%
71.43%
54.55%
Lymph nodes
 Find all that are there
 Three contributors to lymph node numbers: patient, surgeon and
pathologist
 Sampling method must not compromise assessment of CRM
 Fat clearance? or
 30 minutes, hard seat, bright light, sharp knife?
Serosal Involvement in Colon
Cancer




found in 242/412 (58.7%)
most powerful independent prognostic marker
(greater than extent of spread or LN
involvement)
present in 45/46 patients who developed
intraperitoneal recurrence
present in all 6 patients who developed pelvic
recurrence
Serosal Involvement in Rectal
Cancer
–
–
–
–
anterior and lateral walls of mid and upper
rectum
found in 54/209 (25.8%)
independent prognostic marker
in 12 cases of local recurrence following
complete resection (CRM-), 6 had LPI
Shepherd et al 1995
Prognosis in Dukes B Colonic
Carcinoma
–
268 cases, continuous, unselected
–
Single pathologist (mean LNs 21, tumour blocks
5.7)
–
5 year survival rate 76% (95% CI 70-81%)
–
Logrank & Cox multivariate regression analysis:
• Serosal involvement
• Venous invasion (intramural or
extramural)
• Circumferential Margin involvement
• Tumour perforation
Prognosis in Dukes B Colonic
Carcinoma
–
–
–
–
Serosal involvement
Venous invasion (intramural or
extramural)
Circumferential margin involvement
(or inflamed in association with tumour)
Tumour perforation
HIGH RISK = 2 or more
1
1
1
2
1.00
Low risk
0.75
0.50
High risk
0.25
0.00
0
1
2
3
4
5
Years
6
7
8
9
10
Non-peritonealised
“circumferential” margin
involvement in colon cancer

Regions of the colon where a significant proportion
of the circumference is retroperitoneal
– caecum
– ascending colon
– descending colon
– distal sigmoid
Right hemicolectomy specimen
Retroperitoneal Margin
Involvement in Caecal Cancer
– 37 right hemicolectomies
– Retroperitoneal surgical margin
involved in 4/37 (11%)
– Local recurrence approximately
10%
Guidelines
Changes
(Courtesy of Professor GT Williams)




Highlight the features that are
of therapeutic importance
Clarify the definitions of
important prognostic features
and conventions for TNM
staging
Include recommendations for
reporting local excisions
Streamline the proforma
Features of Therapeutic
Importance






Tumour perforation
Lymph node metastases
Circumferential margin positivity (rectal cancer)
Serosal involvement
Extramural vascular invasion
Poor differentiation
Problems with regression




Complete or partial
Quantitation if partial
Significance of mucus pools
Poor relationship to TNM stage
Rectal Cancer Regression
Grade
1
2
3
Tumour ‘sterilised’ or only microscopic foci,
marked fibrosis
Marked fibrosis with macroscopic tumour
Little or no fibrosis, abundant macroscopic
disease
Wheeler et al Dis Colon Rectum 2002;45:1051-6
Change





Multidisciplinary teams
Sub-specialisation
Improved preoperative staging (MRI)
Better surgery for rectal cancer
Better evidence for the efficacy of
adjuvant and neoadjuvant chemotherapy
and radiotherapy
Summary
The pathologist and prognosis in colorectal cancer
surgery:
• To stage the tumour accurately
• To assess the surgical margins of the resected
specimen accurately
• To assess the quality of the surgery
• To sample lymph nodes adequately
• To be aware of features of a ‘bad’ Dukes B
tumour
• To communicate effectively with the
multidisciplinary team