Pathologist and Prognosis in Colorectal Cancer Surgery.

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Pathologist and Prognosis in Colorectal Cancer
Surgery.

• Dr Bryan F Warren
• Consultant Gastrointestinal Pathologist
• Oxford
• M62 Course 2004

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Pathology of the formal colorectal cancer
resection specimen.

• Staging and prognosis
• What is the significance of theradial margin?
• How should I look for lymph nodes?
• What is a bad Dukes B cancer?

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• Cuthbert E Dukes
• Consultant PathologistSt Marks Hospital
• 1926-1956

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Evolution of pathological staging.

• UICC TNM 6th Edition 2002
• Major changes or minor changes?
• Likely that RCPath will recommend staying with
  TNM 5th edition.

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Reproduced from Schiller KFR, Cockel R, Hunt RH,
Warren BF 2001.
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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

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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 19868514996
• 14/52 LRM
• 12/14 local recurrence
• Specificity 92
• Sensitivity 95
• Positive predictive value 85

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How many slices for histology?
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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 19868514996
• Single slice chosen macroscopically
• 6/52 (12) LRM
• On embedding and sectioning the whole tumour
  using large blocks
• (10u HE stained sections cut on a sledge
  microtome)
• 14/52 (27) LRM

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• 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

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• 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 1998979-983.
• 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(p0.38)
• Disease free survival (p0.01) and mortality
  (p0.005) were related to CRM
• Patients with an involved CRM may die of distant
  disease before local recurrence is apparent.

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• 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
  2002235449-457.
• 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

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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.

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Trials CR07 quality of surgery
P Quirke et al
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Mode of CRM involvement

• Birbeck 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

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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?
  

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• 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

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• 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

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• 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

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• Prognosis in Dukes B Colonic Carcinoma
• Serosal involvement 1
• Venous invasion (intramural or 1extramural)
• Circumferential margin involvement (or inflamed
  in association with tumour) 1
• Tumour perforation 2
• HIGH RISK 2 or more

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• 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

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Right hemicolectomy specimen
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• Retroperitoneal Margin Involvement in Caecal
  Cancer
• 37 right hemicolectomies
• Retroperitoneal surgical margin involved in 4/37
  (11)
• Local recurrence approximately 10
• Bateman Warren 2001

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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

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• Features of Therapeutic Importance
• Tumour perforation
• Lymph node metastases
• Circumferential margin positivity (rectal cancer)
• Serosal involvement
• Extramural vascular invasion
• Poor differentiation

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Problems with regression

• Complete or partial
• Quantitation if partial
• Significance of mucus pools
• Poor relationship to TNM stage

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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 macroscopic disease Wheeler et al
Dis Colon Rectum 2002451051-6
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• 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

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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