1. Controversies in Colorectal Surgery
Atthaphorn Trakarnsanga MD FRCST
Department of Surgery, Faculty of Medicine Siriraj Hospital
Mahidol University, Bangkok, Thailand
3. Topics
• Surgery for locally advanced rectal cancer
- Optimal timing of surgery after nCCRT
- Organ preservation
(Local excision, “wait and see”)
4. 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
5. Neoadjuvant Chemoradiation
nCCRT TME adj CMT
6-8 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
8. nCCRT TME adj CMT
6-8 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
9. nCCRT TME adj CMT
6-8 weeks 4-6 weeks
Increased waiting time
Waiting 10-11 weeks following nCCRT leads to highest chance for pCR
Sloothaak DA et al. Br J Surg 2013
Optimal Timing of Surgery after nCCRT
10. 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
11. 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(%)
12. 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)
13. Variable
Within 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(%)
14. 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
15. 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
16. • 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
17. 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
18. 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
19. Adding Chemotherapy in Waiting Period
nCRT TME adj CMT
10-12 weeks 4-6 weeks
Increase timing +
Add chemotherapy
20. 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
21. Trakarnsanga A et al. JNCI 2014; 106: dju248
Trakarnsanga 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
22. 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)
23. 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 MRI
Accuracy of T stage 65% (26-93) 52% (34-82)
Accuracy of N stage 73% (57-92) 72% (60-88)
24. 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
27. Topics
• Surgery for locally advanced rectal cancer
- Optimal timing of surgery after nCCRT
- Organ preservation
(Local excision, “wait and see”)
Notas do Editor
Actually, there are several topics that still be controlversial in colorectal cancer surgery. Unfortunately, because of limitation of the time, my topics today is focus in locally advanced rectal cancer including optimal time from neoadjuvant chemoradiation to surgery and any role of Organ preservation in this situation
Locally advanced rectal cancer is defined as clinically T3 or T4 and /or nodal positive disease
Preoperative clinical staging is crucial. DRE is still using even the accuracy is not great but DRE give you an idea where the tumor is and how bulky they are. Colonoscopy is mandatory for tissue biopsy and searching for synchronous lesions. CT scan is commonly using for distant metastases evaluation. ERUS and MRI are comparable accuracy for local staging evaluation. I personally use ERUS for small lesion and MRI for big bulky tumor because it will interfere the evaluation, causing by pain and discomfort to patients.
nCCRT is standard of practice for locally advanced rectal cancer with better local control compare to direct to surgery group
This is a schematic of common practice for nCCRT. You give them long course chemoradiation and waiting for 6-8 weeks and then operate them. After that you will wait for 4-6 weeks for recovery. Systemic chemotherapy is given regardless of their pathological reports. The recommendation of 6-8 weeks of waiting time come from The French Randomized study. They devided the patient who received radiotherapy in to 2 groups; Short and long interval means operate within 2 weeks and 6-8 wk after radiation, respectively. There was significant better tumor response in long interval group whereas no worse effect on toxicity.
One of the debated topic is if we extend the waiting time after nCCRT. The chance of pCR should be higher by increased tumor regression
However the complications may also increasing because of fibrosis formation
One of studies has nicely demonstrated the correlation of tumor regression by time. The UK work showed the having time of tumor regression is 14 days. If we use simple calculation in our head, but for me I need to use the calculator because I am not good with numbers and if the tumor shrink like a linear regression. Therefor, If we waiting more the tumor will go away nearly complete after 18-20 weeks after nCCRT
The data from Dutch registry demonstrated the effect of nCCRT. They found that surgery at 10-11 weeks after nCCRT has a highest chance for pCR
From our experience at Siriraj Hospital, we analyzed 60 patients of locally advanced rectal cancer who received long-course nCCRT
Majority of patients are clinically T3 and Nodal positive status. The tumor confine in the lower part of the rectum
There are no different in intraoperative and postoperative outcomes between both groups
The complications are comparable in both groups
The rate of R0 resection is significant higher in extended waiting time group and pCR is higher
One of the concerning issue that I need to point out. In extended waiting time group, the timing of full dose chemotherapy is delayed.
You can see in these schematics that systemic chemotherapy can be delayed like couple months if we compare to straight to surgery group. This effect may cause higher systemic recurrences or not, no data has been concluded yet.
Therefore, if we can added the full dose systematic chemo in the waiting period, this should be the ideal solution to solve my concern.
There are several phrase 2 trial about adding the chemotherapy to the waiting period. This is one of it, non randomized phrase 2 trial reported by Julio Garcia-Aguilar. As we are all expected. The pCR is significant higher in adding chemotherapy groups. The more you add, the more you get. However, the complication is also higher too. Therefor, the implication of this approach is still controversial. Randomized phrase III trial is needed to answer this question.
Actually, there are several topics that still be controlversial in colorectal cancer surgery. Unfortunately, because of limitation of the time, my topics today is focus in locally advanced rectal cancer including optimal time from neoadjuvant chemoradiation to surgery and any role of Organ preservation in this situation
