Innovations in Rectal Cancer Surgery

A. D’Hoore MD PhD, EBSQ-CR, (hon)FASCRSA. Wolthuis MD PhD, EBSQ-CR, FACS

G. Bislenghi MD

Departement of Abdominal SurgeryUniversity Hospitals Leuven, Belgium

No related disclosures

Local recurrence: persistent problem1984-1993 : 99 pts – low/mid rectal cancer

Intraoperative tumor break : 12 (13%) : LRR 45% despite postop RT

APR SSO

LRRat 1 yr 13% 5%at 5 yr 27% 21%

5 yr Survival 61% 67%

Leuven – dataD’Hoore A.

TME - concept

DRM : distal resection margin

CRM : circumferential resection margin

TN

Ejaculation

Erectile dysfunction

Urinary problems

TME quality: standardised method

Quality grading of surgery

Mesorectal plane

Intra-mesocolic plane

Muscularis proproa plane

Correlates with local recurrence and survival

TME implementation rsulted in a significant decrease in APR rate in Belgium

(significant differences remain for distal rectal cancer))

1995 – 1997

50 %2006 – 2009

22 %

Rectal carcinoma

Clinical staging (CT-scan)

Surgeryp staging

Adjuvant chemo - radiotherapy

MRI(DW-MRI)

patient

MD strategy

Radical SurgeryTME +/- proctectomy

Actual treatment in rectal cancer

Early rectal cancer(T1,T2,N0)

Advanced rectal cancer≥ T3, TxN1

Neoadjuvant(chemo)radiotherapy

TEM/TAETAMIS

T1sm1,(sm2)

cCR

“wait and see”organ sparing

MRI good

1

2

Evolution in SurgeryOpen surgery

Laparoscopic surgeryRobotic surgery

SSLNOSE

TAMIS

NOTEStime

EMREndoscopic polypectomy

Endoscopic biopsyDiagnostic endoscopy

inva

sive

ness

recent evidence

disruptiveincremental

Development of laparoscopic surgery

major disruptive change

first CCD-camera

Minimally Invasive surgery in evolution

IBD 2009

Hand-assisted + Pfannenstiehl Total Laparoscopic

COLOR II trial (non-inferiority phase III) 2004-2010

1044 patients randomised (2:1) 699 in laparoscopic surgery group345 in open surgery group

Locoregional recurrence rate at 3 years : 5.0% in both groups

DFS: 74.8% (laparoscopic) and 70.8% (open)

OS : 86.7% (laparoscopic) and 83.6% (open)

N Engl J Med 2015

Disease free survival Overall survival

Factors affecting suitability for lap TME

BMIPelvic anatomy

Previous surgeryCo-morbidity

Preference

T size, fixity, levelAnastomotic level

ExperienceQuality

Assurance

Colorectal Disease 2006; 8 (s3): 30-2

Conversion to laparotomyremains substantial

%

Grafiek1

ROLLAR

COLOR II

CLASSIC

conversions

10.2

17

30

Blad1

CRM positivity

CLASSIC16

COLOR II10.2

ROLLAR5.2

conversions

ROLLAR10.2

COLOR II17

CLASSIC30

Blad1

CRM positivity

conversions

Can robotics reduce conversions ?

Primary endpoint – conversion to open surgery

Lap(n=230)

Robotic(n=236)

Total (n=466)

Difference in rates(95% CI)

Conversion 28 (12.2%) 19 (8.1%) 47 (10.1%) 4.1% (-1.4%, 9.6%)

Overall conversion rate: 10.1%

Lap (n=28) Robotic (n=19)Reasons for intra-op conversion to open*Adhesions 1 (3.6%) 0 (0.0%)Advanced cancer 3 (10.7%) 4 (21.1%)Anaesthetic complication 0 (0.0%) 1 (5.3%)Completion of rectal/pelvic dissection 11 (39.3%) 9 (47.4%)Difficult colonic mobilisation 3 (10.7%) 2 (10.5%)Haemorrhage 3 (10.7%) 3 (15.8%)Obesity 6 (21.4%) 0 (0.0%)Robotic collisions 0 (0.0%) 1 (5.3%)Visceral injury 1 (3.6%) 2 (10.5%)

Pigazzi et al. ASCRS 2015 Boston

becoming more proficient : CRM positivity (%)

Robotic versus laparoscopic TME

Laparoscopic versus open TME

Laparoscopic versus open colon and rectum

Grafiek1

CLASSIC

COLOR II

ROLLAR

CRM positivity

16

10.2

5.2

Blad1

CRM positivity

CLASSIC16

COLOR II10.2

ROLLAR5.2

Blad1

CRM positivity

Understanding the shortcomings oflaparoscopic TME

- Difficult exposure deepest part pelvic dissection- Troublesome distal rectal transection- Uncontrolled distal margin

persistent high conversion to laparotomyIntracorporeal rectal stapling following laparoscopic totalmesorectal excision: overcoming a challenge.Brannigan AE, De Buck S, Suetens P, Penninckx F, D'Hoore A.Surg Endosc. 2006

https://www.ncbi.nlm.nih.gov/pubmed/16738989

Full laparoscopic dissection and transanal specimen extraction (TATA)

……a laparoscopic transanal abdominal transanalradical proctosigmoidectomy and a descending coloanalhandsewn anastomosis (TATA).

Laparoscopic low anterior resection and transanal pull-through for low rectal cancer: a Natural Orifice Specimen Extraction (NOSE) technique.D'Hoore A, Wolthuis AM. Colorectal Dis. 2011 Nov;13 Suppl 7:28-31

.Marks JH, Salem JF.Tech Coloproctol. 2016 Aug;20(8):513-5.

From TATA to notes, how taTME fits into the evolutionary surgical tree

https://www.ncbi.nlm.nih.gov/pubmed/22098514

Transanal Endoscopic Microsurgery( TEM)

Buess G et al. Surg Endosc 1988; 2: 245- 250

A new transanal platform

Endoluminal TAMIS

TEM TAMIS

Transanal TME (taTME)

Conceptual advantage taTMEvisual control of the distal margin

Human Pathol 2016; 52:164-172 distal spread beyond macroscopic tumor edge

Transanal natural orifice transluminal endoscopic surgery(NOTES) rectal resection: ‘‘down-to-up’’ total mesorectalexcision(TME)—short-term outcomes in the first 20 casesAntonio M. Lacy et al. Surg Endoscopy 2013

prostate

S3

R hypogastric nerve

Hybrid, laparoscopic procedure

New technologies

Expanding the applicability of the platform

- no

Transanal endoscopic proctectomyinnovative procedure for difficult resection of rectal tumorsin men with narrow pelvis (n=30, jan 2009- june 2011)

Laparoscopic assisted (splenic flexure)

Main causes for TAEP---

narrow pelvisfatty mesorectumlarge anterior tumor

231422

Morbidityurethral Injuries (n=2,reoperation (n=2, 7%)

7%)

Hospitalization 14d (19-25)Rouanet Ph et al. Dis Colon and Rectum 2013

The bulbar urethra ‘at risk’

Understanding the operative force vectors

Atalah S et al. Techn Coloproctology 2017

Operative vectors, anatomic distortion, fluid dynamics and theinherent effects of pneumatic insufflation encountered duringtransanal total mesorectal excision

Slide courtesy of John Monson

TA-TME Learning Curve - CUSUM

5 urethral injuries2 bladder injuries

1 vaginal perforation1 hypogastric nerve resection

2 macroscopic rectal tube perforations

Ann Surg. 2017; 266(1):111-117

2017

5 urethral injuries2 bladder injuries

1 vaginal perforation1 hypogastric nerve resection

2 macroscopic rectal tube perforations

20182018

1836 cases18.0%

Improved insufflation system in 80% 27% proctored

14 Urethral injuries2 bladder injuries

5 vaginal perforations11 rectal tube perforations

0.6% 0.9%

Incidence Anastomotic FailuretaTME Registry – International database

1594 patients

Overall anastomotic failure rate = 15.7% (and probably underreported)

- early leak rate 7.8%- delayed leak 2.0%

Independent risk factors- male sex - tumorbulk- obesity - intraoperative blood loss- smoking - manual anastomosis- diabetes mellitus - prolonged perineal operative time

Risk for a definitive stoma

11 % 26%

Risk factors : age > 65 yrspreoperative radiotherapyanastomotic morbidity and abscess

Celerier B. et al. Colorectal Dis 2015; 18

2017

Cancer patients (n=634)Quality TME specimen, n(%)

Intact 503 (85%)

Minor defects 65 (11%)

Majors defects 24 (4.1%)

Rectal tube perforations 12 (2%)

Distal Margin (mm)

Mean +/- SD 19 +/- 14.3

Median (range) 15 (0-97)

Positive DRM 2 (0.3%)

Circumferential Resection Margin (mm)

Mean +/- SD 9.2 +/- 8.6

Median (range) 8 (0-90)

Positive CRM 14 (2.4%)

Composite Optimal Pathological Outcome

CRM –, DM –, good specimen

92.6%

2017

20172017

PatientNone

TumourTumour height

Tumour locationmT stage

+ CRM MRIM+

nRCT

TechnicalSimultaneous operating

AR vs APEConversion

Blood loss > 1LExtent post abd dissection

Total operative time

Risk Factors for poor histological outcome after TaTMEUnivariate Analysis

4 Hospitals - 110 TaTME procedrues (2015-2017)

Local recurrences : > 9.5%

median time to recurrence 11 months

rapid, multifocal growth in the pelvis and side walls

Br J surg 2019

Rutgers M et al. (in preparation)

• Dutch Colorectal Audit Database• Mandatory audit• Limited core dataset

• Jan 2015 – dec 2018

• MIS procedure

• Primary low rectal Cancer -> (0-5 cm ARJ)

N= 3466• Lap : 2845• TaTME : 448 • Robot : 173

Patient/Tumour/Tx data

Primary outcome : R1

Secondary outcome- Peri-op morbidity- Conversion- Restorative procedure

ESCP Masterclass Cardiff | November 2019

Rutgers M et al. (in preparation)

0

10

20

30

40

50

60

Lap-LAR LAp-APE TA-LAR TA-APE R-LAR R-APE

complictions< 90 days

0 5 10 15 20 25

Lap-LAR

LAp-APE

TA-LAR

TA-APE

R-LAR

R-APE

anastomotic leakage

Rutgers M et al. (in preparation)

0123456789

Lap-LAR LAp-APE TA-LAR TA-APE R-LAR R-APE

CRM

CRM positivity : APR at risk

APE : optimizing surgical technique“cylindrical APE”

Tissue morphometry

Local recurrence after TaTME – 6 centres*

* Submitted Ann of Surg

• Consecutive TaTME cases from start (2013-2018)• Early adopters – Tertiary referral centres• Prospective kept databases

Oncologic Outcomes – Intermediate term• 2-3 yr LR-free• 2-3 yr DFS• 2-3 yr OS

Local recurrence after TaTME – 6 centres*

N = 767Baseline characteristics N (%)Male gender 72%

BMI >30 20%

Tumor height ARJ, median [IQR]≤ 1 cm

3 [1-5]28%

Anterior tumor 56%

mrCRM positive 41%

Neo-adjuvant therapy

mrTRG 1-2mrTRG 3-5

69%

47%53%

Variable, N (%) N=767

pT-stage ≥ 3 54%

pN-stage ≥ 1 31%

R1Only DRM+Only CRM+DRM+ & CRM+

8%0.7%6.3%

1%

TME quality CompleteNear-complete

Incomplete

81%12%7%

Rectal perforation 1%

Composite optimal pathology* 86%

*Composite optimal pathology: R0 and (near-) complete TME specimen and no perforations

Outcomes (1)

Local recurrence - free

LR 2y : 3.3%LR 3y : 4.4%

Median time to LR: 14 months

LR 2yACOSOG & ALACART:• Lap 4.6% and 5.4%• Open 4.5% and 3.1%

* submitted

Median FU: 25 months

Disease-free survival Overall survival

DFS 3y : 78% OS 3y : 93%

Predicted risk for pCRM+

Case selection learning curveIntensified neo-adjuvant therapyExtended TME / Beyond TME

cT1-3-stage cT4-stage

EMVI on MRI CRM on MRI Tumor >1cm ARJ Tumor ≤1cm ARJ Tumor >1cm ARJ Tumor ≤1cm ARJ

2% 3% 3% 5% 3% 5% 6% 10% 3% 4% 6% 9% 5% 9% 11% 17% 3% 5% 6% 10% 5% 9% 12% 18% 5% 8% 10% 16% 9% 15% 19% 28% not Anterior Anterior not Anterior Anterior not Anterior Anterior not Anterior Anterior

Surgical decision making in rectal cancer = complex

1. Type and extent of primary tumor

2. Response to chemo-radiation

3. Perceived ability to clear all tumor (adequate margins)DRM / CRM

4. Patient related factors (functional status, comorbidity)

5. Patients preferenceacceptance suboptimal functional outcome

Male patient: 75 yrs.Moderate operative risk, ASA 2well differentiated adenocarcinoma,juxta-anal (Rullier II) cT2 (3a) N?, M0

70

Functional outcome and QoL afterTME surgery

Battersby et al, Dis Colon Rectum 2016

Low rectal cancer & Radiotherapy:60% bowel-related QoL Impairment

Intentional organ preservationChemoradiation

Incidental organ preservationChemoradiation +TME = standard

Early, small Advanced tumors

Organ Preservation

> 50% 10-25%

Maas et al , Lancet Oncol 2010

Pre CRT 12 w post CRT

wait and follow upIncomplete response at 12 weeks

11 m 35 m Expand the Interval

local excision

radical surgery (TME)

From… MRI based (static process)

MDT decision on neoadjuvant treatment

Predefined surgery at 6-8 weeks interval

MRI plays pivotal role in defininga dynamic treatment process

- Upfront surgery

- Neoadjuvant chemo/radiation MR – response assessment

non-operative

cCR

resTumour specific Surgery

(flexible interval)

Call for centers of excellence in rectalcancer treatement

1. Complexity multidisciplinary decision making

2. Imaging, neoadjuvant treatment (none to TNT)

3. Complexity of minimally invasive TME surgery

Impact Hospital Volume (HV) and Surgeon Volume (SV) on QI in rectal cancer surgery

Hospital Volume Surgeon Volume

30 day mortality + +

Postopcomplications

+ -

Anastomotic leak + ++

LRR - +

5 yr survival - ++

J Gastrointest Oncol 2017; 8:534-546

Conclusion

The flexible transanal platform is the next step in MIS to rectal cancer

MR response assessment after neoadjuvant treatment first step in a dynamic process to define tailored surgical treatement

We should guide our patients through this dynamic process and take into account their preferences and expectations

Slide Number 1Slide Number 2Local recurrence: persistent problem�1984-1993 : 99 pts – low/mid rectal cancerTME - conceptSlide Number 5Slide Number 6Quality grading of surgeryTME implementation rsulted in a �significant decrease in APR rate in Belgium�(significant differences remain for distal rectal cancer))Rectal carcinoma�Actual treatment in rectal cancerSlide Number 11Slide Number 12Minimally Invasive surgery in evolutionCOLOR II trial (non-inferiority phase III) 2004-2010Slide Number 15Slide Number 16Slide Number 17Conversion to laparotomy�remains substantialCan robotics reduce conversions ?Primary endpoint – conversion to open surgery�becoming more proficient : CRM positivity (%) �Understanding the shortcomings of�laparoscopic TMESlide Number 23Slide Number 24Transanal Endoscopic Microsurgery( TEM)Slide Number 26Slide Number 27Transanal TME (taTME)Slide Number 29Slide Number 30Slide Number 31Slide Number 32Slide Number 33Slide Number 34Slide Number 35New technologiesSlide Number 37Slide Number 38Expanding the applicability of the platformSlide Number 40Slide Number 41The bulbar urethra ‘at risk’Understanding the operative force vectorsSlide Number 44Slide Number 45Slide Number 46Slide Number 47Slide Number 48Risk for a definitive stomaSlide Number 50Slide Number 51Slide Number 52Slide Number 53Slide Number 54Slide Number 55APE : optimizing surgical technique�“cylindrical APE”Slide Number 57Local recurrence after TaTME – 6 centres*Local recurrence after TaTME – 6 centres*Slide Number 60Slide Number 61Slide Number 62Slide Number 63Predicted risk for pCRM+Surgical decision making �in rectal cancer = complexMale patient: 75 yrs.�Moderate operative risk, ASA 2�well differentiated adenocarcinoma,juxta-anal (Rullier II) cT2 (3a) N?, M0�Slide Number 70Functional outcome and QoL after TME surgeryEarly, smallAdvanced tumorswait and follow upFrom… MRI based (static process) �MRI plays pivotal role in defining �a dynamic treatment processCall for centers of excellence in rectal cancer treatement�Impact Hospital Volume (HV) and Surgeon Volume (SV) �on QI in rectal cancer surgeryConclusion