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.