Post on 07-Sep-2019
Management of pT1 polyps
Maria Pellise
Logan RF etal. Gut 2012; You NC, Ann Surg 2007; Williams et al. Colorectal Dise 2013
0.75–5.6% of large-bowel polyps removed in general diagnostic colonoscopy practice
10% of detected cancers (British BCSP)
pT1 polyps
SM Invasive
adenocarcinoma
Early colorectal
cancer
Malignant polyp
Screening programmes Advances in diagnostic
& therapeutic endoscopy
Epithelial Layer
Lamina Propria
Muscularis Mucosae
Submucosa
m1 m2 m3 sm1 sm2 sm3
Muscularis Propria
Tis
T1sm
T2
Early Cancers Classification According to Depth of Invasion
T1
END
OSC
OP
IC TR
EATM
ENT
Lymp
hatic in
volvm
en
t
mpellise@clinic.cat
M, 57yo, FIT +
10mm rectal sessile polyp; 8cm from anal verge
mpellise@clinic.cat
mpellise@clinic.cat
Invasive adenocarcinoma within a tubular adenoma • Tumor size: 8mm • Adenoma size: 9mm • Depth of submucosal invasion: 2mm • Low grade histology (moderatelly differenciated) • Absence of lymphovascular invasion • Absence of perineural invasion • Negative margin • pTNM Staging: pT1
BANKER GAMBLER
SURGERY FOLLOW-UP
Morbidity
Anastomotic leak -
mortality rate up to 3-6%
Costs
Under-staging
Local recurrence
Systemic recurrence
Recurrence can be lethal
mpellise@clinic.cat
Recurrence rate: 1–5%
Management of pT1 polyps
No RCT
Heterogeneity and deficiencies in reporting histology
Heterogeneity and deficiencies in reporting endoscopic data
Surgical series
Different outcomes measures
Clinical significant outcomes are rare events
mpellise@clinic.cat
Incidence of synchronous LNM in pT1= 6–12%
Intermediate endpoint
Cancer related death • Local recurrence • Lymphatic spread • Vascular spread
mpellise@clinic.cat
poor differentiation lymphovascular invasion presence of positive (R1) or unable to determine (Rx) resection margins deep submucosal invasion (i.e., ≥1,000 μ m/SM2–3 in non-pedunculated tumors,
and Haggitt 4 in pedunculated tumors) presence of intense tumor budding Rectal location Sessile or flat morphology Clusters of undifferentiated cells
Risk factors for LNM in pT1 surgical series:
Bosch et al. Endoscopy 2013 mpellise@clinic.cat
Systematic review Risk of LNM
Bosch et al. Endoscopy 2013
Accuracy for predicting LNM
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Indications for additional treatment
NCCN ESMO JSCCR
Tumor differentiation + (grade 3,4) + (grade 3) + (poorly di; signet ring;mucinous)
Lymphatic invasion + + +
Vascular invasion + + +
Resection margin + + + (vertical)
Submucosal depth invasion + (Level 4) + (> 1mm)
Tumor budding + (grade 2 or 3)
Network NCC. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Rectal Cancer (Version 1.2017). 2017, DOI: Labianca R, Nordlinger B, Beretta GD et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2013; 24 Suppl 6: vi64-72 Watanabe T, Muro K, Ajioka Y et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. International journal of clinical oncology 2017,
mpellise@clinic.cat Ichimasa K et al. Endosocpy 2018
Artificial intelligence predictive model
It is not clear that surgery of a pT1 completely resected with high risk for LNM decreases mortality
mpellise@clinic.cat
mpellise@clinic.cat
Dutch T1 CRC working group
Backes Y et al. Am J Gastro 2017; Overwater et al. Gut 2018; Bakes Y Gastroenterol 2018
Patients with pT1 CRC 2000-2014
13 Hospitals N=2253
Patients included N=1691
708 pedunculated 905 sessile or flat morphology
Endoscopic resection of pT1CRC N= 925
Macroscopic complete resection N= 877
Primary surgical resection N=758
Including TAMIS N =105
Endoscopic resection only Wait and see
N= 519
Secondary surgery N= 358
High risk N= 602
Including N= 282 of secondary surgeries
Surgical resection and low risk or undefinable risk
N= 440 Including secondary surgeries low risk
N=19; unknown N=57
Low risk N= 121
High risk N= 198
Unknown N= 200
• Retrospective cohort study. Patients with T1 CRC diagnosed between 2000 and 2014 in 1 academic and 12 non-academic hospitals.
• Netherlands Cancer Registry. • Median follow-up time of 36.5 months (interquartile
range 16.0–68.3)
high-risk T1 CRC if one or more: • poor differentiation, • deep submucosal invasion (i.e., ≥1,000 μ
m/SM2–3 in non-pedunculated tumors, and Haggitt 4 in pedunculated tumors),
• lymphovascular invasion, • positive (R1) or unable to determine (Rx)
resection margins . R0 resectionwas defined as a cancer-free resection margin irrespective of distance in millimeters.
Backes Y et al. Am J Gastro 2017; Overwater et al. Gut 2018; Bakes Y Gastroenterol 2018
Endoscopic resection before surgical resection of a high-risk T1 CRC has no adverse effect.
Of all T1 CRCs treated with surgical resection, still 5% develops a local or distant recurrence.
CRC-related death among patients with recurrence: 41.7%
Dutch T1 CRC working group
The decision to conduct a wait-and-see policy in high-risk T1 CRC should be cautiously
made given the poor prognosis when cancer recurs
✓ Previous biopsies of the scar negative for cancerous tissue did not guarantee recurrence
free survival.
There is an increasing need for identification of malignant polyps before endoscopic
resection to guide resection technique and optimise specimen handling
Richards CH, Gut 2018
Scottish screening programme
Cancer related death = 1.3%-2.8% ONLY ! Systemic recurrence > local recurrence ¾ undergo surgery have no evidence of residual tumor independent predictors of residual tumour, disease recurrence and
cancer-related death: evidence of lymphovascular invasion Incomplete excision
N= 485 Follow up =50 months (minimum 16 months).
Therapeutic technique
F, 65, FIT(+) sigmoid
pT1 good prognosis. Margin < 1mmL
M, 65, FIT+ Sigmoid colon
mpellise@clinic.cat
mpellise@clinic.cat
Paris classification
Polypoid
Non polypoid
Slightly depressed
Lambert R, Lightdale C. Gastrointest Endosc 2003;58 suppl6 Lambert R et al. Endoscopy 2005;37:570-8. Kudo et al. Gastrointest endosc 2008;63:suppl3.
Pedunculated: 0-Ip
Sessile: 0-Is
Mixed: 0-Isp
Slightly elevated
Totally flat
11-15mm: 8% 16-20mm: 17% >20mm: more
6-10mm:44% 11-15mm: 67% 16-20mm: 90%
11-15mm: 2% 16-20mm: 10%
% sm invasion
Burgess et al. Gastroenterol 2018
mpellise@clinic.cat
Superficial focal interrogation: Pit & Microvascular pattern
Kudo S, J Clin Pathol 1994
Sano, Dig Endosc 2006
Japan NBI Expert Team (JNET) (2016) Sumimoto GIE 2017
Type 2 Type 3 Type 1
Color
Vessels
Surface
Most likely histology Hyperplastic Adenoma Deep submucosal
invasion
NBI International Colorectal Endoscopic classification (NICE)
n=1634 Participants included
n=1650 Elegible participants
n=2136 Lesions included
n=132 NICE 3
n=2004 No NICE 3
n=16 Excluded
n=7 No histology
n=4 No histology
Non-deep invasion
Deep invasion
Non-deep invasion
Deep invasion
n=1961 98.1% n=52 41.6% n=73 58.4% n=37 1.9%
mpellise@clinic.cat Puig et al. under revision
58 endoscopists 17 centers Polyps > 10mm Prediction of deep SM invasion
NICE classification p<0.001
p<0.001
LST-G nodular mixed type
Depressed area
p<0.001
NO YES
YES NO
Ulceration p=0.026
NO YES
p=0.007 Pedunculated
NO YES
1 2 3
1% 8.6% 9.7% 13%
44%
93%
n=1812 n=93 n=93 n=31 n=80 n=14
Non-deep invasion
Deep invasion
Puig et al. Under revision
Similar results for LNM risks
NICE classification
LST-G nodular mixed type
Depressed area
NO YES
YES NO
Ulceration
NO YES
Pedunculated
NO YES
1% 9% 10% 13% 44% 93%
1 2 3
Endoscopic treatment Uncertain (personalize)
Surgery
86,8%
12,5%
0,7%
Puig et al. under revision
• NICE type 2 with
depressed areas, • NICE type 2 nodular
mixed type • NICE type 3 non-
pedunculated polyps without ulceration
Final Remarks
mpellise@clinic.cat
(Too) Many open questions! Imperative need for:
standardisation of histological criteria, endoscopic description
Multidisciplinary consensus protocols
Large prospective cohort studies
Prospective randomised controlled trials?
Improve identification of malignant polyps before endoscopic resection: • In large polyps • in small polyps
Talk to your pathologist! Talk to your surgeon!
mpellise@clinic.cat
Thank you!!