Pathology in Slovenian CRC screening programme:

Pathology in Slovenian CRC screening programme: Findings, organisation and quality assurance Snježana Frković Grazio University Medical Center Ljubljana, Slovenia

Slovenia s population: 2 million Incidence and mortality due to CRC among highest in Europe Organized national screening started in 2009 Invited: persons aged 50 69 yrs (from 2015 extended to 74) Targeted population: 600.000 (centralized invitations) Biannual FIT (all test readings in one central laboratory) Persons tested positive proceed to colonoscopy Colonoscopies performed in 26 accreditated centers Pathological examinations performed in 4 accreditated centers

Response rate to invitation: 60%, varies among regions, higher in females Positive test: 6 7% Colonoscopies performed in >90% of positives Cancer detection rate: 3.7/1000 in first round 2.0/1000 in second round

June 2009 to December 2015 51,369colonoscopies were performed in49,653 persons specimens were submitted in 66% of all colonoscopies (proportion stable over time) 33,903 pathology requests were submitted ( 5,200 per year) the number of submitted lesions per pathology request ranged from 1 to 26 mean 2.5 (the average number has steadily increased from2.1 in 2009 to 2.9in 2015) a total of 84,563 specimens were examined

Finding N % Carcinoma 1563 1.8% Suspicious for carcinoma 216 0.3% Adenoma 56530 66.8% Sessile serrated lesion 2575 3.0% Hyperplastic polyp 13518 16.0% Other (other tumors, other polyps normal, inflammation ) 10161 12.0% Total 84563 100.0%

Most advanced pathologic findingsin persons who underwent colonoscopy carcinoma suspicious for carcinoma advanced adenoma non-advanced adenoma SSL round 3 round 2 round 1 HPP other no histology 0% 5% 10% 15% 20% 25% 30% 35% 40%

Pathology in CRC screening the pathology service plays an important role in CRC screening since the management of participants depends on quality and accuracy of the diagnosis pathologic findings affect the decision to undergo further local or major resection as well as surveillance after screening

Factors that affect pathology endoscopists expertise and experience of pathologist quality control

Factors that affect pathology endoscopists expertise and experience of pathologist quality control

endoscopists E1 E2 pathologists P1 E3 E4 E5 P2 P3 E7 E8 E9 E10 E11 P4 P5 P6

Factors that affect pathology endoscopists expertise and experience of pathologist quality control

concentration of cases: 4 histopathology units (16 pathologists) with specific experience in gastrointestinal pathology, colorectal cancer diagnosis & treatment participation in MDT meetings each participating pathologists reports at least 300 screening biopsies per year double reading in cases of T1 cancer

TAT from admission to sign-up: >95% in 5 working days In addition to written reports, diagnoses and all necessary data are entered into structured online computer database system ->98% in 10 working days

For each lesion, pathology data are linked with corresponding endoscopic data Data can be easily retrieved and analyses performed (e.g., comparisons between pathologists, pathology units, etc.)

Education Introductory course Training course / workshop led by the leading British gastrointestinal pathologistsin October 2011 Refresher course planned in 2017

Factors that affect pathology endoscopists expertise and experience of pathologist quality control

Quality control analysis and comparison of data internal quality control Turnaround times (TAT) Proportion of various types of lesions Proportion of lesions with HG dysplasia Proportion of adenomas with HG dysplasia Proportion of adenomas with villous component. participation in an external quality assurance (EQA) programme

120% Proportion of pathology reports signed out within 5 working days by histopathology unit 100% 80% 60% A B C D 40% 20% 0% 2012 2013 2014 2015 2016

120% Proportion of pathology reports signed out within 5 working days by pathologists 100% 80% 60% 40% 20% 0% 2012 2013 2014 2015 2016

25% Proportion of adenomas with high-grade dysplasia 20% 15% 10% 5% 0% 2009 2010 2011 2012 2013 2014 2015 2016

60% Proportion of adenomas =>10 mm 50% 40% 30% 20% 10% 0% 2009 2010 2011 2012 2013 2014 2015 2016

40% 35% Proportion of adenomas with high-grade dysplasia training course / workshop 30% 25% 20% 15% all >=10 mm <10 mm 10% 5% 0% 2009 2010 2011 2012 2013

35% Adenomas with HG dysplasia by pathologist 30% 25% 20% 15% 2009-11 2012-13 2014-16 10% 5% 0% A B C D E F G H I J K L M N O P R S T

45% Adenomas with villous component by pathologist 40% 35% 30% 25% 20% 2009-11 2012-13 2014-16 15% 10% 5% 0% A B C D E F G H I J K L M N O P R S T

Quality contol analysis and comparison of data internal quality controle Turnaround times (TAT) Proportion of various types of lesions Proportion of lesions with HG dysplasia Proportion of adenomas with HG dysplasia Proportion of adenomas with villous component. participation in an external quality assurance (EQA) programme

UK BCSP EQA uses virtual slides (10 cases) slides accessed online http://www.virtualpathology.leeds.ac.uk/nbcs/bcsp_ circulations.php 4 possible answers for each slide Other Low grade dysplasia High grade dysplasia Adenocarcinoma

UK BCSP EQA A case is valid only if the diagnosis is agreed by 80% of the regional lead pathologists Points per case: 2 points for same diagnosis as consensus 1 point for one category removed (e.g. high grade dysplasia/carcinoma) 0 points otherwise Participant score is sum of points for the valid cases (score for 10 cases can be from 0 to 20)

13b run score 12 = poor performer score (0-16) SHA Leads 8 1 (N=9) 88,9% 11,1% 16 15 14 13 12 11 UK participants 221 156 52 16 3 2 (N=450) 49,1% 34,7% 11,6% 3,6% 0,7% 0,4% Slovenian participants 5 4 4 3 1 (N=17) 29,4% 23,5% 23,5% 17,6% 5,9%

15b run score 15 = poor performer score (0-18) 18 17 16 15 14 8 SHA Leads 10 2 (N=12) 83% 17% UK participants 304 87 9 2 1 (N=403) 75% 22% 2,2% 0,5% 0,3% Slovenian participants 11 3 1 (N=15) 73% 20% 7%

Pathology in CRC screening European guidelines for quality assurance in colorectal cancer screening and diagnosis (2010) Pathology: Chapter 7 & Annex 7a 23 recommendations

EG recommendations participating pathologists should have specific training in colorectal pathology pathologist should develop a network in order to share experience double reading in cases of T1 cancer participation in MDT meetings

EG recommendations mucosal neoplasia should be used instead of dysplasia only two grades of neoplasia should be used (low grade and high grade) adenomas should be classified as tubular, tubulovillous or villous, using 20% rule *

EG recommendations the terms intra-mucosal carcinoma or in situ carcinoma should not be used (= HG mucosal neoplasia) the WHO definition of carcinoma should be used: an invasion of neoplastic cells through the muscularis mucosae into submucosa

what should be reported -type of lesion -in case of adenoma: - type (tubular, tubulovillous, villous, traditional serrated) - grade of neoplasia / dysplasia (LG, HG) - size of adenoma - involvement of resection margins - in case of polyp cancer (pt1 cancer) - tumor grade (low 1, 2 or high 3) - lymphovascular invasion (present, absent, suspicious) - margin involvement ( 1 mm is generally regarded as an indication for further therapy - endoscopic or surgical) - substaging - Kikuchi / Haggitt levels or measurement of depth and width*

Kikuchi levels

Haggitt levels

EG recommendations all lesions should be reported by proforma or structured reporting and the data returned to the screening programme (in a minimum 90% of all cases) *departments and individual pathologists should audit their own reporting practices for key features -distribution of the type and size of lesions -frequency of grades of neoplasia and villousnes (not more than 10% of HG) -the number of LN retrieved (median 12), the frequency of extramural vascular invasion ( 25%), peritoneal invasion (colon 20%, rectum 10%)... in surgical resection specimens participation in an external quality assurance (EQA) programme

EG recommendations all lesions should be reported by proforma or structured reporting and the data returned to the screening programme (in a minimum 90% of all cases) *departments and individual pathologists should audit their own reporting practices for key features -distribution of the type and size of lesions -frequency of grades of neoplasia and villousnes (not more than 10% of HG) -the number of LN retrieved (median 12), the frequency of extramural vascular invasion ( 25%), peritoneal invasion (colon 20%, rectum 10%)... in surgical resection specimens participation in an external quality assurance (EQA) programme

2000 CRC crude incidence 1800 1600 1400 1200 1000 800 600 400 200 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014