Sphincter preserving surgery after preoperative

treatment for ultra-low rectal carcinoma.

A French multicenter prospective trial:

GRECCAR 1

P Rouanet, M Rivoire, B Lelong, E Rullier, L Vanseymortier, L Mineur, P Lasser, M Pocard, JC Ollier, JL Faucheron, F Dravet, D Pezet,

JM Fabre, J Balosso, C Lemanski, S Gourgou, B Saint Aubert.

GRECCAR(French surgical research group of rectal carcinoma).

HDR (45 Gy + 18 Gy)

LRC R Surg CT if pN+

RCT (45 Gy + 5FU continuous)

GRECCAR 1 prospective muticentric randomised trial

Inclusion: LRC which requires APRTIP - LA < 2 cm / UT2-T3

PA : Incidence of conservative surgery

SA : - Oncological and functional results

- Down staging impact on survival - Quality of life

Classification of AnoproctectomyBased on : - mucosal resection

- endoanal resection

ISR partial

PISR

ISR complete

CISR

Mucosectomy

M

Intersphincteric Resection

Ano-Proctectomy

Mucosectomy

Partial ISR

Complete ISR

GRECCAR 1 : inclusion curves

4/2001 – 4/2005 : 207 patients in 13 centers

0

10

20

30

40

50

60

70

80

VA CLB IPC StA COL CSC IGR CRG CPS Gren CF Mtpl CAV

0

5

10

15

20

25

30

35

40

2001 2002 2003 2004 2005

HDR

RCT

Effectives

RANDOMISATIONn: 207

HDRn: 106

RCTn: 101

Excludedn: 3

Non opern: 3

Excludedn: 3

Non opern: 2

n: 100 n: 96

Patient characteristics

Rt High Dosen = 100

Rt Chemon = 96

X2 / p

Sex M/F 66/35 64/33 0.93

OMS 0 92% 92% 0.81

Age* 60 (28-83) 64 (21-80) 0.065

weight* (kg) 73 72 0.64

height* (cm) 169 168 0.54

BMI* (Kg/m2) 25.2 25.5 0.87

*median Results at 23 monthsData base ended Feb 06

Tumor characteristicsHDR

n = 100RCTn = 96

X2 / p

Distance ITP-LA* 0.5 (0-3) 0.5 (0-5) 0.35

Fixity 29% 45% 0.015

Circumference > ½ 40% 42% 0.85

Distance ITP-PL* 1.1 (0-3.8) 1.2 (0-5.5) 0.72

Tumor height * 5 4 0.07

T3 66% 75% 0.47

N + 57% 59% 0.75

ITP-LA* 0.5 (0-3) 0.5 (0-6) 0.37

Tumor height* 5 4 0.15

*Median in centimetres

RE

Colo

US

R

Evaluation of neoadjuvant treatments

HDRn = 100

RCTn = 96

X2 / p

Delay Random / Rt 13 (0-37) 13 (8-111) 0.59

Total irrad anal canal 68% 69% 0.16

Symptomatic improvement 55% 61% 0.67

TR: tumour regression 80% 87% 0.26

Distance IP-LA* 1 1 0.74

Fixity 23% 14% 0.14

Circumference 45% 40% 0.55

U IP-LA* 1 (0-4.5) 1 (0-6) 0.43

U Height T* 4 3 0.29

*Median in centimetres

RE

US

R

Treatment toxicities Grade 3-4

HDR RCT

• Peri anal Dermititis 75% 44% p : 0.21

• Diarrhea 53% 40% p : 0.51

• Prostatitis 25% 20% p : 0.74

• Nausea 4% 8% p : 0.49

• Cystitis 18% 28% p : 0.34

• Failure to continue TTT 7% 0

average 5 d (2-15)

Surgery: Conservative rate 85%

HDRn = 100

RCTn = 96

X2 / p

Delay Rt / Surgery 37 (7-88) 44 (13-136) 0.0001

Delay > 4 weeks 76% 89% 0.012

Protection of pelvic Nerves

88% 88% 1

APR 17 - 17% 14 – 14.6% 0.69

APR in second time 4 (1R1/3C) 3 (2R1/1C)

AP - Mucosectomy 12 12

AP – ISR partial 35 27 0.60

AP – ISR complete 36 43

CAA J pouch 76% 77%

CAA coloplasty 8% 12%

CAA direct 13% 7%

72%

Incidence of Conservation in relation to Topography

TIP-LA Cons rate

• 0 very low 76 84%

• ≤ 2 cm low 120 84%

Incidence and distribution of APR by center

0

10

20

30

40

50

60

70

80

90

CLB IGR CF CPS CRG IPC VA SA COL

APRpatients

Operative morbidity

• According to pre op TTT HDR RCTFistula 9% 3% p : 0.13Pelvic abscess 2% 4 % p : 0.40Colonic necrosis 3% 3% p : 0.99Anastomotic stenosis 5% 4% p : 0.75

• According to type of surgery APR M P ISR C ISRFistula 1 (3%) 4 (19%) 4 (6.9%) 2 (2.6%)

p:0.06 Pelvic abscess 1 (3%) 2 (9.5%) 1 (1.7%) 2 (2.6%)

p:0.36

Colonic necrosis 1 (3%) 0 2 (3.5%) 1 (1.3%) p:0.09

Anastomotic stenosis 0 2 (9.5%) 6 (10.3%) 1 (1.3%) p:0.06

Anatomical pathologyHDR

n = 100RCTn = 96

X2 / p

Tumor height* (cm) 2.5 2 0.047

Distal margin* (cm) 1 (0.1-6) 1.5 (0-8) 0.71

Lateral clearance* (mm) 5 (0-15) 4 (0-28) 0.80

pT0 8% 14.6% 0.45

pT1 / pT2 /pT3-4 8% - 39%- 45% 8%- 30%- 47% 0.45

pN0 / N1 / N2 61%-30%-9% 66%-25%-9% 0.72

pM1 3% 6% 0.27

R0 93% 94% 0.74

*median

RO Patients : 78%

Classical R1 patients n: 44 22%

• CRM = 0 n: 4 3 APR 1st, 1 APR 2nd

<1 n: 9 9 AP 1st , 1 APR 2nd

= 1 n : 29 DM

= 0 n : 2 2 AP 1st , 1 APR 2nd

"Real" R1 patients n: 15 7.6% ?

Relation between pT and pN staging

pT pN0 pN1 pN2 pN3 Total

0 22 0 0 0 22

1 14 2 0 0 16

2 49 12 6 1 67

3 36 39 12 1 88

4 2 1 0 0 3

Total 122 54 18 1 196

pN+ => pT0-pT1 : 2/38 – 5.2% , pT2: 19/67 – 28% , pT3-4: 53/91 – 59%

Oncologic results

HDR RCT

2-year OS 93% 95% p: 0.69

2-year DFS 78% 76% p: 0.70

2-year LR 6% 5% p: 0.94

2-year Mt 17% 21% p: 0.53

Stoma closure 90% 94% p: 0.40

Median FU : 23 months

Overall survival

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

0 6 12 18 24 30 36 42Months from start of RT

Arm = HDR Arm = RCT

p=0.69

Overall Survival

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

0 6 12 18 24 30 36 42Months from surgery

Surgery = APR Surgery = AP-MSurgery = Ap-ISRp Surgery = AP-ISRc

p=0.22

Disease-Free-Survival (DFS)

Survival according to the type of surgery

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

0 6 12 18 24 30 36 42Months from surgery

Surgery = APR Surgery = AP-MSurgery = Ap-ISRp Surgery = AP-ISRc

p=0.013

Overall Survival

Survival without local relapse

0.00

0.25

0.50

0.75

1.00

Pro

babi

lity

0 6 12 18 24 30 36 42Months from surgery

Surgery = APR Surgery = AP-MSurgery = Ap-ISRp Surgery = AP-ISRc

p=0.039

Local-Relapse Free Survival

Preliminary conclusions of GRECCAR 1

• 85% of sphincter conservation in respect with the oncological

quality criteria.

• No significant statistical difference between HDR and RCT arms

• Possible standardization of the surgery: the crucial impact of the

surgical technique (72% of ISR).

• Tumoral Down staging is an excellent prognostic factor : It can

modify an initial surgical indication of APR into conservative

surgery.

• More follow-up is needed in order to analyse the oncological safety

and the functional reliability of this treatment.