Pathologist and Prognosis in Colorectal Cancer Surgery.

Dr Bryan F WarrenConsultant Gastrointestinal

PathologistOxford

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 PathologistSt 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. Circumferentialmargin involvement after mesorectal excision of rectal cancer with curative intent. Predictorof survival but not local recurrence? Dis Colon Rectum 1998;979-983.

218 patients152 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 circumferentialresection margin involvement vary between surgeons and predict outcomes inrectal 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. Macroscopicevaluation of rectal cancer resection specimen: clinical significance of the pathologist inquality 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 involvementBirbeck et al

6 types of CRM involvement Direct tumour spread 46 pts 52.17% local recurrence Discontinuous tumour spread 110pts 45% Tumour within a lymph node 19pts 10.53%(caution pt. no.

small) Tumour within a blood vessel 23pts 30.43% Tumour within lymphatics 14pts 71.43% Perineural tumour 11pts 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

Shepherd et al 1997

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 1– Venous invasion (intramural or 1

extramural) – Circumferential margin involvement

(or inflamed in association with tumour) 1– Tumour perforation 2

HIGH RISK = 2 or more

Years

0 1 2 3 4 5 6 7 8 9 10

0.00

0.25

0.50

0.75

1.00

Low risk

High risk

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%

Bateman & Warren 2001

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 Tumour ‘sterilised’ or only microscopic foci,marked fibrosis

2 Marked fibrosis with macroscopic tumour

3 Little or no fibrosis, abundant macroscopicdisease

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