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RCPath Colorectal Cancer Pathology Standards and Datasets Professor Geraint Williams Cardiff University NBCSP Pathology Meeting 22 November 2007. Variable. Prognostically significant?. p value. Variable. Prognostically significant?. p value. Specimen/ operation type. YES. p<0.001.
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RCPath Colorectal Cancer Pathology Standards and Datasets Professor Geraint Williams Cardiff University NBCSP Pathology Meeting 22 November 2007
Variable Prognostically significant? p value Variable Prognostically significant? p value Specimen/ operation type YES p<0.001 CRM involvement YES p<0.001 Local invasion (pT) YES p<0.001 Distance to CRM YES p<0.001 No. lymph nodes examined YES p<0.001 Peritoneal involvement YES p<0.001 No. of positive nodes (pN) YES p<0.001 Extramural vascular inv. YES p<0.001 Validation of Minimum Dataset variables NYCRIS, 5604 cases, 7 years
New Information • Population data from Registries • Northern & Yorkshire • Large single centre studies • Gloucester • Multicentre randomised trials • CLASSIC • Dutch Rectal Cancer Study • CR07
Changes • Clarify features of therapeutic importance • Lymph nodes • Non-peritonealised surgical resection margins • Tumour perforation • Serosal involvement • Extramural venous invasion
Changes • Clarify features of therapeutic importance • Introduce new data items of proven prognostic importance • Measure the depth of extramural spread • Grade the quality of the resection plane in rectal cancer • Record complete or marked regression following neoadjuvant therapy for rectal cancer
Changes • Clarify features of therapeutic importance • Introduce new data items of proven prognostic importance • Introduce quality standards
Changes • Clarify features of therapeutic importance • Introduce new data items of proven prognostic importance • Introduce quality standards • Include recommendations for reporting local excisions
Changes • Clarify features of therapeutic importance • Introduce new data items of proven prognostic importance • Introduce quality standards • Include recommendations for reporting local excisions • Streamline the proforma
Features of Therapeutic Importance • Lymph node metastases • ALL nodes examined • care with those close to non-peritonealised margin • consider whether to embed whole nodes • count number of positive nodes • fat clearance, serial sections, immunostaining or molecular investigation for “micrometastases”, recording of extracapsular spread, not recommended
Lymph Node Sampling Pheby et al.J Clin Pathol 2004; 57: 43-47
Lymph Node Sampling • National Cancer Data Base, American College of Surgeons • 35,787 cases T3N0, 1985-91 • 5 year survival: • 64% if 1-2 nodes examined • 86% if >25 nodes examined • Significant differences in survival between • 1-7 • 8-12 • 13+ Swanson et alAnn Surg Oncol 2003; 10: 65-71
NICE 2004 “There is no consensus on the precise number of lymph nodes that need to be examined, but the research evidence suggests that it should be in double figures” RCPath STANDARD In a series of at least 50 cases of symptomatic colorectal cancer the mean number of lymph nodes examined is 12
Revised N Staging • Isolated Tumour Cells or Clusters (ITCs) • Single cells, or small clusters <0.2mm in lymph nodes detected by ICC or H&E do NOT affect pN stage. • They may be coded as pN0 (i+) • or pN0 (mol+) if detected by flow cytometry or molecular techniques • or pN0 (i+) (sn) in a sentinel node
5th edition TNM • A tumour nodule greater than 3mm in diameter in perirectal or pericolic adipose tissue without histological evidence of residual lymph node is classified as a regional lymph node metastasis. • However, a tumour nodule up to 3mm in diameter is classified in the T category as discontinuous extension, i.e. T3
6th edition TNM • “A tumour nodule in the pericolic/perirectal adipose tissue without histologic evidence of residual lymph node is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. • If the nodule has an irregular contour, it should be classified in the pT category, and also coded as V1 (microscopic venous invasion) or V2, if it was grossly evident, because there is a strong likelihood that it represents venous invasion” • An objective assessment (size) has been replaced by a subjective one (form and contour)
Impact of Changes • 80 cases pT3 colorectal cancer • Extramural nodules categorised into smooth and round or irregular by 23 pathologists • Agreement assessed by kappa statistics
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Impact of Changes • 80 cases pT3 colorectal cancer • Extramural nodules categorised into smooth and round or irregular by 23 pathologists • Agreement assessed by kappa statistics • Kappa = 0.36 (2:1 or worse in 10 nodules) • No difference between consultants and trainees • No difference between specialists and non-specialists
Impact of Changes • Using majority opinion for each nodule: • 5/80 cases upstaged from N0 to N1 • 4 more upstaged from N1 to N2 Howarth SM et al. Gut 2004; 53:A21
RCPath Recommendations • Retain 5th edition of TNM staging for colorectal cancer
Features of Therapeutic Importance • Non-peritonealised “Circumferential” margin positivity
Non-peritonealised Margin • “Bare” surgical margin • Completely different from the serosal surface
Non-peritonealised Margin Involvement (53/210 patients) Anterior 74% Lateral 13% Posterior 13% Direct spread 73.6% Nodes 20.8% Vascular 5.6% Boyle et al 2004
Non-peritonealised Margin Margin Local Recurrence Primary tumour 22.1% Lymph node 12.4% Nagtegaal et alAm. J. Surg. Pathol. 2002; 26; 350–357.
Non-peritonealised Margin Margin Local Recurrence > 2mm 5.8% 1-2mm 14.9% 0 16.4% Nagtegaal et alAm. J. Surg. Pathol. 2002; 26; 350–357.
Prognosis in Dukes B Colonic Carcinoma • Variable - good Bs and bad Bs • Many possible reasons: • encompasses T3 and T4 tumours • quality of lymph node sampling • Uncertainty with regard to adjuvant therapy
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: • Tumour perforation • Serosal involvement • Venous invasion • Circumferential margin involvement Petersen VC et alGut 2002; 51: 65-9
Prognosis in Dukes B Colonic Carcinoma • Tumour perforation 2 • Serosal involvement 1 • Venous invasion 1 • Circumferential margin involvement 1 HIGH RISK = 2 or more
Tumour Perforation • Automatically pT4b • Assessed macroscopically and confirmed microscopically • Excludes perforation of the colon proximal to an obstructing cancer • May be serosal or retro/infra-peritoneal
Serosal Involvement • Different from omental or mesenteric deposits (pM1) • Independent prognostic factor in rectal and colonic cancer • Predicts intraperitoneal and/or pelvic recurrence Shepherd et al 1995, 1997 Petersen et al 2002
Serosal involvement in Colon Cancer No % Lennon et al 118 30 Shepherd et al 173 43 Burdy et al 107 15 Merkel et al 611 12 Petersen et al 268 42 Morris 1306 22
RCPath STANDARD The frequency of cases with serosal involvement is at least 10% for rectal cancer and 20% for colon cancer
Serosal involvement (pT4) • Tumour cells visible on peritoneal surface or free in peritoneum with ulceration of visceral peritoneum • Tumour close to serosal surface with inflammatory reaction or mesothelial hyperplasia - examine more levels
Serosal involvement (pT4) • Blocks from areas of peritoneal irregularity, pallor, dulling or inflammation • At least two sections with levels if close or inflamed • Reflections, crevices, clefts
Features of Therapeutic Importance • Extramural venous invasion
Venous invasion (706 cases) • Definite in 52%, thick walled veins 15% • 5 yr survival: no VI 79% possible 70% definite 43% no VI 79% intramural 66% extramural thin 41% extramural thick 19% Talbot et al 1981
Venous Invasion “tumour within extramural endothelium-lined space that is either surrounded by a rim of muscle or contains red blood cells” Talbot et al 52% NYCRIS 29% Sternberg 52%