rapido rectal cancer and preoperative induction therapy followed by dedicated operation lars...
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RAPIDORectal cancer And Preoperative Induction therapy followed by Dedicated Operation
Lars Påhlman
Dept. Surgery, Colorectal unit,
University Hospital, Uppsala, Sweden
Rectal cancer treatmentMRI staging
Stage Irradiation
Good; No
Bad; 5 x 5 Gy
Ugly; Chemo-rad or 5 x 5 ?
Advanced Rectal CancerProblems !
Local recurrences solved ! Occult metastases the problem ! Survival not improved Chemo-rad. standard of care Chemotherapy too weak !
Advanced Rectal CancerStandard of care
Chemorad. 5 weeks Time to surgery 8 weeks Recovery after surgery; 4 weeks In total > 4 months until patients
receive decent chemotherapy !!
Neoadjuvant; Rectal cancer
The RAPIDO trial
Standard of care arm:
Chemorad. Surgery Chemo 4 m
Experimental arm:
5x5 Gy Chemo 5 m Surgery
The RAPIDO trialInclusion criteria
Biopsy proven rectal cancer Staging 5 weeks prior treatment No contra indication to chemotherapy ECOG performance < 1 Written informed consent 18 years Adequate for follow up
The RAPIDO trialInclusion criteria
Good quality MRI (T 3 c/d), T4 a/b EMVI + N2 N+ (outside the fascia plane) MRF +
The RAPIDO trialAt leased one of the criteria's
T4 overgrowth to adjacent organs T4b peritoneal involvement EMVI + vascular invasion N2 > 4 nodes which looks abnormal N+ lateral nodes > 1 cm MRF + threatened mesorectal fascia
The RAPIDO trialEndpoints
DFS at 3 years (Main endpoint) 880 patients (DFS 50 60 %) Toxicity + postop. complications pCR OS, Local recurrence rate QoL
The RAPIDO trialExperimental arm previous experience
Dutch M 1 Study
50 patients M1 (75% T3/4N+)5x5 Gy + XELOX + Bevacizumab (6 cycles) + surgery
83% received all chemo (90% >4 cycles)Low/acceptable toxicity
pCR in 26% of specimens‘No progression was seen on chemotherapy’
van Dijk et al. JCO 2009: p. ASCO GI 2010. Abstract 427
The RAPIDO trialExperimental armWhat are we treating ?
Local tumour Systemicgrowth disease
Surgery Radioth. Chemoth.
The RAPIDO trial
Possible concerns
Surgery difficult after > 20 weeks
Progressive disease during the delay
Local recurrence rateTrial / level Local recurrence
RT - RT + p value
SRCT < 5 cm 27 % 10 % 0.003TME < 5 cm 11 % 12 % 0.53CRO 7 < 5 cm 11 % 5 % < 0.001
SRCT 6 - 10 cm 26 % 9 % < 0.001TME 6 - 10 cm 15 % 4 % < 0.001CRO 7 6 - 10 cm 10 % 5 % < 0.001
SRCT > 10 cm 12 % 8 % 0.3TME > 10 cm 6 % 4 % 0.15CRO 7 > 10 cm 6 % 1 % < 0.001
Swedish Rectal Cancer Registry %
10
Dutch TME - trial Overall survival; eligible patients (n=1809)
Years since surgery
86420
Cu
m S
urv
iva
l
1,0
,9
,8
,7
,6
,5
,4
,3
,2
,1
0,0
64.2% vs 63.4% p = 0.87
TME alone
RT + TME
CRO7 - Overall survivalAll patients
Years
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5
Preop. RT
Postop. RT p = 0.07
%
Polish trial
Trial design
Preop. chemorad. 25 x 2 Gy
Preop. radiotherapy 5 x 5 Gy
Randomisation
Local
Recurr
Survival
Sphincter
preserv
Polish Trial Local Recurrences
Years
54321
20
15
10
5
Chemo-radiation
5 x 5 Gy
p = 0.23
16%
11%
Polish Trial - Overall Survival eligible patients (n=312)
p = 0.82
Years
543210
100
80
60
40
20
0,0
chemoradiation
5 x 5 Gy
Short - course radiotherapyStill an important option
Better than chemo-rad. ? Polish trial ! Australian trial ? Stockholm III !!!!
Stockholm III TrialOngoing trial in Sweden
3-armed trial
25 Gy / 1 week immediate surgery
25 Gy / 1 week delayed surgery
50 Gy / 5 weeks delayed surgery
Non-resectable rectal cancer
Non-resectable rectal cancer
Advanced Rectal CancerConclusion with 5x5 Gy
Delayed surgery is feasible Delayed surgery gives down –
sizing / staging ! Delayed surgery will not
increase complication rates