Controversies in Colorectal Cancer
Transcript of Controversies in Colorectal Cancer
Controversies in Colorectal Surgery
Atthaphorn Trakarnsanga MD FRCSTDepartment of Surgery, Faculty of Medicine Siriraj Hospital
Mahidol University, Bangkok, Thailand
No Disclosure
Topics
• Surgery for locally advanced rectal cancer- Optimal timing of surgery after nCCRT- Organ preservation
(Local excision, “wait and see”)
Locally advanced rectal cancer • T3 or T4 and/or N +• Preoperative clinical staging
- CT scan - Endorectal ultrasonography - MRI
• Neoadjuvant chemoradiation (50.4 Gy combined with 5-FU based regimen)
Accuracy CT ERUS MRI
T Stage 73 87 82
N Stage 66 74 74
Kwok et al. Int J Colorectal Dis 2000;15:9-20
Neoadjuvant Chemoradiation
nCCRT TME adj CMT6-8 weeks 4-6 weeks
Francois Y J Clin Oncol 199917:2396
The Lyon R90-01 randomized trial - Short interval (within 2 wk) vs. Long interval (6-8 wk)- Significant better tumor response in long interval group (71.7% vs. 53.1%, p= 0.007)- No detrimental effect on toxicity
Neoadjuvant Chemoradiation
nCCRT TME adj CMT6-8 weeks 4-6 weeks
Increased waiting time
Increased tumor regression (pCR?)
Neoadjuvant Chemoradiation
nCCRT TME adj CMT6-8 weeks 4-6 weeks
Increased waiting time
Increased tumor regression (pCR?)
Increased fibrosis formation (complications?)
nCCRT TME adj CMT6-8 weeks 4-6 weeks
The median volume-halving time was 14 days
Week after CCRT
2 4 6 8 10 12 14 16 18 20
% regression
50 25 12.5 6.25 3.13 1.56 0.78 0.39 0.19 0.09
Tumor volume(cm3)
27 13.5 6.7 3.3 1.6 0.8 0.4 0.2 0.1 0.05
Mean Tumor volume = 54 cm3 Dhadda A.S. et al. Clinical Oncology 2009; 21: 23-31
Optimal Timing of Surgery after nCCRT
nCCRT TME adj CMT6-8 weeks 4-6 weeks
Increased waiting time
Waiting 10-11 weeks following nCCRT leads to highest chance for pCRSloothaak DA et al. Br J Surg 2013
Optimal Timing of Surgery after nCCRT
Siriraj’s experiences • Retrospective review from prospective
maintained data.
• Sixty patients of locally advanced rectal cancer
(T3-4 and/or N+ by CT scan, ERUS and/or MRI)
from Jun 2012 to Jan 2015
• Long-course chemoradiotherapy
Presented at World Congress of Surgery 2015, Bangkok, Thailand
Cilincal T staging
0.89
T3 14 (82%) 36 (83%)
T4 3 (18%) 7 (17%)
Clinical N positive 0.31
Negative 2 (12%) 10 (23%)
Positive 15 (88%) 33 (76%)
Distance from AV, cm 4.5 (3.4,5.7) 5.6 (4.9,6.3) 0.17
Variable Within 8 Wk (n=17)
More than 8 Wk (n=43)
P value
Values are presented as mean (95% CI), or number(%)
Values are presented as mean (95% CI), or number(%)
Variable Within 8 Wk (n=17) More than 8 Wk (n=43)
Duration after complete nCCRT to surgery ,weeks
6.4 (5.7 , 7.0) 11.7 (10.8 , 12.7)
VariableWithin 8 Wk
(n=17)More than 8 Wk
(n=43) P value
Operative time, min 277 (234, 320) 255 (223 , 286) 0.43 Estimate blood loss, ml 374 (196 , 551) 360 (239 , 481) 0.90 Blood transfusion, unit 0.4 (0 , 0.9) 0.3 (0.4 , 0.5) 0.5 Bowel movement, days 3 (2.3,3.6) 3.3 (2.7,4.0) 0.51 Full diet intake, days 4 (3,5) 3.7 (3.1,4.2) 0.58 Postoperative LOS, days 8.0 (6.0,10.1) 8.6 (6.0,11.1) 0.79
Values are presented as mean (95% CI), or number(%)
Grade 1 0 1
Grade 2 1 5
Grade 3a 0 0
Grade 3b 2 1
Grade 4 0 0
Grade 5 0 0
Total 3 7 0.19
Clavien-Dindo classification
Within 8 Wk (n=17)
More than 8 Wk (n=43)
P value
Tumor characteristics Within 8 Wk (n=17)
More than 8 Wk (n=43)
P value
Tumor grading
Well diff. 1 (5.9%) 1 (2.3%)
Mod diff. 14 (82.3%) 35 (81.3%)
Poor diff. 2 (11.8%) 2 (4.7%)
Circumferential margin
Positive 5 (30%) 4 (9.3%) 0.04
Invasion
Perineural invasion 7 (41.1%) 16 (37.2%) 0.77
Lymphovascular invasion
2 (11.7%) 8 (18.6%) 0.52
PCR 2 (11.7%) 8 (18.6%) 0.52
• Extend waiting time from nCCRT to surgery (> 8 weeks) did not increase perioperative complications.
• R0 resection (circumferential margin >1mm) and rate of pCR were higher in extended waiting time group.
• Prospective randomized controlled trial is needed.
Siriraj’s experiences
Presented at World Congress of Surgery 2015, Bangkok, Thailand
Controversy Issue
• Timing of full dose chemotherapy is delayed in extended waiting time group
Dx Surgery CMT CMT/RT CMT
DX nCCRT Surgery CMT
DX nCCRT Surgery CMT
4-6 wk
4-6 wk6-8 wk
10-12 wk 4-6 wk
Controversy Issue
• Timing of full dose chemotherapy is delayed in extended waiting time group
Dx Surgery CMT CMT/RT CMT
DX nCCRT Surgery CMT
DX nCCRT Surgery CMT
4-6 wk
4-6 wk6-8 wk
10-12 wk 4-6 wk
4-6 weeks
10-14 weeks
14-18 weeks
Adding Chemotherapy in Waiting Period
nCRT TME adj CMT10-12 weeks 4-6 weeks
Increase timing +Add chemotherapy
Garcia-Aguilar J et al. Lancet Oncol 2015;16:957-66.
pCR 18%
pCR 25%
pCR 30%
pCR 38%
60
67
67
65
Complications are higher in adding chemotherapy groups
Trakarnsanga A et al. JNCI 2014; 106: dju248Trakarnsanga A et al. World J Gastroenterol 2013
Pathological Complete Response• No viable tumor after
resection (15-20%) • The chances of recurrence
are extremely low • Clinical complete response
may not equivalent to pCR• Surgery may not be
needed
Surgery following nCCRT• LAR: diverting stoma is
needed to reduced leakage symptoms
• 50% of elderly patients have not undergone stoma reversal
• Majority of patients develop changing of bowel function
• APR: associated with morbidity to the patients Mass M et al. J Clin Oncol 2011;29(35)
Clinical Complete Response• Diagnosis is challenged• DRE is an accurate method for determining response, overall
concordance was 22%*
• Accuracy for restaging in T stage is low for early stage (ERUS: >80% for T3 vs. 25% for T1)**
• Diffusion-weighted MRI is more accurate***• PET/CT has pooled accuracy sensitivity 73% and specificity
77%*****Guillem JG et al. J Clin Oncol 2005;23:3475-9
** Memon S et al. Colorectal Dis 2015;17:748-61*** Lambregts DMJ, et al. Ann Surg Oncol 2011;18:2224-31
**** Mafflone AM et al. AJR Am J Roentgenol 2015;204:1261-8
ERUS MRIAccuracy of T stage 65% (26-93) 52% (34-82)
Accuracy of N stage 73% (57-92) 72% (60-88)
Local excision after nCCRT• To access pathological response accurately
Versevald M Br J Surg 2015;102: 853-60
TEM after nCCRT enabled organ preservation in one-half
“Wait and see”
Chawla S et al. Am J Clin Oncol 2014
Glynne-Jones R and Hughes R Br J Surg 2012;99:897-909
Topics
• Surgery for locally advanced rectal cancer- Optimal timing of surgery after nCCRT- Organ preservation
(Local excision, “wait and see”)