1. Classification of advanced rectal cancer
Gina Brown
The Royal Marsden Hospital
Imperial College

2. Developments in MRI based management of Rectal Cancer
The unimportance of nodal status
The importance of extramural depth of spread as a biomarker
Recognition and effective preoperative treatment of mrCRM involvement
Recognition and effective preoperative treatment of mrEMVI – impact on survival
Staging and assessment of low rectal cancer

3. Developments in MRI based management of Rectal Cancer
Advanced Rectal Cancer Classification
Using the post treatment MRI TRG assessment as a biomarker for further preoperative treatment stratification

4. A good prognosis tumour?
Looks like a T1sm3

5. Discontinuous EMVI in ERC
And a pelvic sidewall tumour deposit

6. Beyond TME
In a significant proportion of patients (15-20%), tumour extends beyond the achievable TME planes and requires more extensive surgery to achieve clear margins.

7. Exenterative surgery
Radical resection can achieve complete tumor clearance. Reported R0 rates range from 22%-67%.
Can significantly increase survival, enhancing the prospects for long term cure.
High rate of post-operative adverse effects/morbidity.
A.G. Heriot. Colorectal Dis,2006;8(9):

9. Beyond TME Collaborative project
To demonstrate that a validated staging system can be employed,
Establish scale and scope of pelvic exenterative surgery in advanced rectal cancer beyond TME
Assess quality of life and outcomes
Develop prognostic classification to assist in counselling patients

10. Beyond TME trial flow
Participating/opening
Sites and PIs:
Royal Marsden (P Tekkis)
St Marks (I Jenkins)
Oxford (C Cunningham)
Southampton (A Mirnezami)
Swansea (D Harris)
Edinburgh/Glasgow (M Duff)
Eindhoven (H Rutten)
Arhus (B Ginnerup)
Melbourne (A Heriot)

11. Normal Anatomy Lateral Central Posterior Central Posterior Anterior
Infra-levator

12. Reporting Proforma Advanced Tumour Requiring Surgery Beyond TME
Primary tumour
The primary tumour is demonstrated as an [ Annular | Semi-annular | Ulcerating | | Polypoidal | Mucinous] mass with a [nodular / smooth] infiltrating border.
The distal edge of the luminal tumour arises at a height of [ ] mm from anal verge:
The distal edge of the tumour lies [ ]mm [Above,at, below] the top of the puborectalis sling
The tumour extends craniocaudally over a distance of [ ] mm
The proximal edge of tumour lies [above at below] the peritoneal reflection
Invading edge of tumour extends from [ to ] O’clock
Tumour is [confined to] [extends through] the muscularis propria:
Extramural spread is [ ] mm
mrT stage: [T1 ] [ T2 ] [ T3a] [ T3b ] [ T3c] [ T3d ] [T4visceral ] [T4 peritoneal]  
Lymph node assessment
Only benign reactive and no suspicious nodes shown [N0]
[ ] mixed signal/irregular border nodes [N1/N2]
Extramural venous invasion: [ No evidence ] [ Evidence]
[ ] Small [ ]Medium [ ]Large vein invasion is present
Peritoneal deposits: [ No evidence] [ Evidence]
Pelvic side wall lymph nodes: [ None] [ Benign] [ Malignant mixed signal/irreg border]
Location: [Obturator fossa • R •L ] . [External Iliac Nodes • R •L] .[internal iliac • R •L ]

13. Pelvic fascia are free of disease
Laterally
Pelvic fascia are free of disease
Pelvic sidewall compartment are free of disease
Internal/external iliac arterial /venous branches are free of disease
Sacrotuberous/sacrospinous
Piriformis/Obturator
Infralevator compartment
Levator muscles are free of disease
Sphincter complex are free of disease
Anterior urogenital triangle/Perineum
Vaginal introitus/urethra : free of disease
Retropubic space: : free of disease
Summary:
MRI Overall stage: T N M , [ EMVI positive] [EMVI negative],[PSW positive ] [PSW negative], Total number of compartments, Closest potential surgical margins are located, Resection would require:
Disease affects central compartment
Above the peritoneal reflection within the pelvis
Disease is present/ absent
Ureters are free of disease
Below the Peritoneum anteriorly
Bladder /Uterus/Vagina/Ovaries Prostate/Seminal vesicles/Urethra are free of disease
Posteriorly
The bony cortex/periosteum from S1-S2 is / is not involved by disease
The bony cortex/periosteum from S3-S5 /coccyx is/ is not involved by disease
Presacral fascia (S1/S2/S3/S4/S5) is not involved by disease
Sciatic nerve/ S1/S2 nerve roots
No disease
Disease is present

14. Beyond TME?

15. Timing after CRT? When is maximum response reached?
6 weeks
ymrT3b
12 weeks
ymrT2
Baseline
mrT4
Final Pathology: ypT2N0

16. Assessing response Method Prospectively validated against DFS outcomes
MRI DWI
No – many retrospective quantitative cut-offs and qualitative assessments – none prospectively validated
DCE-MRI
No – many retrospective values proposed – none validated
PET-CT
No – but retrospective SUV cut-offs proposed – unverified prospectively
mrVolume assessment
Yes: >80% volume reduction
mrTRG
Yes : TRG1-5 validated prospectively and against outcomes
mrT and mrN stage
validated prospectively and against outcomes

17. TRG and Survival (Patel et al JCO 2011)
MRI TRG 1-3
72% at 5 yrs
MRI TRG 4-5
27% at 5 yrs
p=0.001
HR 3.28 (95%CI; 1.22–8.80).

18. MRI assessment

19. Royal Marsden n=208 patients
Yu et al , ESMO World GI Congress, Barcelona 2015

20. THESE CASES ARE VERY DIFFERENT FROM THE mrT1/T2 CASES – THEY LOOK DIFFERENT RADIOLOGICALLY AND WILL FEEL DIFFERENT – LOTS OF DENSE SCAR TISSUE/ FIBROSIS LEFT BEHIND – LIKELY TO HAVE DENSE SCAR TISSUE ETC. BUT JUST AS PATHOLOGISTS REPORT THIS IS OFTEN A pCR…

21. Selecting patients for deferral/watch and wait policy

22. How are the patients identified?
mrTRG 1-2
Highest detection
rate
PET/DWI
Too many false
positives
Clinically - DRE
+/- biopsy (too many false positives)
A TALK IN ITSELF – GIVEN BY SVETLANA….
Despite the use of preoperative radiotherapy in rectal cancer for many years – there is still considerable uncertainty regarding assessment of the effectiveness of treatment based on either imaging or pathology. In patients where complete
Triad –
PET

24. Diffusion does not contribute to mrTRG assessment
Diffusion results in false positives

25. TRG 2
Good response :dense fibrosis; no obvious residual tumour, signifies microscopic residual disease of questionable longterm viability and on continued surveillance may never regrow.

26. Patients deferring surgery

27. Patient accrual Proforma reporting mrTRG driven Trial Protocol FICARE
2007
Trial Protocol
Proforma reporting
mrTRG
driven
Discuss the blue bars…and the red bars…
Cumulative recruitment.
Ficare --?
Trial was established….
Synoptic reporting –
No events to trigger stopping rules…
Protocol amendments.
FICARE 2007

28. Proforma reporting

29. MRI detected more persistent EMVI post CRT than pathology
Chand M, Evans J, Swift RI, et al. Prognostic Significance of Postchemoradiotherapy High-Resolution MRI and Histopathology Detected Extramural Venous Invasion in Rectal Cancer. Ann Surg

31. mrTRG is a prognostic (and predictive) biomarker
Shows good interobserver radiology agreement and reproducibility
MERCURY trial (JCO 2011 – multiple radiologists)
EXPERT-C trial
GEMCAD study (17 radiologists)
CORE study (interobserver agreement)
MERCURY 2 trial – risk factor for CRM involvement
In EXPERT C trial identified 40% of patients with mrTRG1/2 – 89.8% overall survival. Compared with only 15% pathologic CR rate (90% survival).
Therefore mrTRG could be justified as a more clinically relevant endpoint

32. TRIGGER : randomised phase III trial patients will be randomised to an mrTRG based treatment strategy Training of Radiologists to undertake mrTRG

33. MRI reassessment after CRT
Philosophy of avoiding APE surgery if patient has had a good response to treatment
mrTRG used to identify patients suitable for deferral (many are falsely positive on biopsy, DWI and PET-CT)
Serial imaging – decision for deferral is not based on a single scan – uses the advantage of high resolution MRI monitoring
Employing serial MRI monitoring - gives opportunity to delay surgery until there is evidence of tumour regrowth rather than biopsy of tumour cells which are of uncertain viability

34. MRI Trials and the Colorectal Patient Pathway

35. 4th Annual rectal mri workshop for radiologists, surgons and oncologists – 12th 13th Jan 2017

36. Faculty Discussants 2016
Prof
John
Nicholls
Prof
Paris
Tekkis
Prof
Bill
Heald
Chris
Cunningham
Tan
Arulampalam
Roles: provoke discussion, share surgical and clinical experiences, highlight controversies,
Summarise Key Messages

37. 2016 Surgical, Oncology and Radiology participants
Country
number
Australia 2
Denmark 1
England 61
Germany 3
Greece
Italy
Japan
Lithuania
Netherlands
Norway 7
Poland
Portugal
Russia
Scotland
Sweden
USA
Wales
UNITED STATES of AMERICA
CANADA
ALASKA (USA)
MEXICO
COLOMBIA
VENEZUELA
BRAZIL
PERU
BOLIVIA
HONDURAS
NICARAGUA
ECUADOR
GUYANA
SURINAME
FRENCH GUIANA
COSTA RICA
PANAMA
GUATEMALA
CUBA
PARAGUAY
ARGENTINA
URUGUAY
CHILE
GREENLAND
ICELAND
UNITED KINGDOM
REPULIC OF IRELAND
NORWAY
SWEDEN
FINLAND
DENMARK
ESTONIA
LATVIA
LITHUANIA
POLAND
BELARUS
GERMANY
CZECH REPUBLIC
NETHERLANDS
BELGIUM
FRANCE
SPAIN
PORTUGAL
SWITZ.
AUSTRIA
SLOVAKIA
HUNGARY
ROMANIA
BULGARIA
ITALY
UKRAINE
TURKEY
GREECE
SYRIA
IRAQ
SAUDI ARABIA
YEMEN
OMAN
UAE
EGYPT
LIBYA
ALGERIA
MOROCCO
TUNISIA
WESTERN SAHARA
MAURITANIA
MALI
NIGER
CHAD
SUDAN
ETHIOPIA
SOMALIA
UGANDA
SENEGAL
GUINEA
LIBERIA
COTE D’IVOIRE
BURKINA
GHANA
NIGERIA
CAMEROON
CENTRAL AFRICAN REPUBLIC
GABON
CONGO
DEMOCRATIC REPUBLIC OF CONGO
KENYA
TANZANIA
ANGOLA
ZAMBIA
MOZAMBIQUE
NAMIBIA
BOTSWANA
ZIMBABWE
REPUBLIC OF SOUTH AFRICA
MADAGASCAR
RUSSIAN FEDERATION
KAZAKHSTAN
GEORGIA
IRAN
UZBEKISTAN
TURKMENISTAN
AFGHANISTAN
KYRGYZSTAN
TAHKISTAN
PAKISTAN
INDIA
CHINA
NEPAL
MYANMAR
THAILAND
SRI LANKA
MONGOLIA
NORTH KOREA
SOUTH KOREA
JAPAN
TAIWAN
CAMBODIA
LAOS
VIETNAM
PHILIPPINES
MALAYSIA
INDONESIA
PAPUA NEW GUINEA
AUSTRALIA
NEW ZEALAND

38. Reporting Minimum Standards