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



Increased waiting time

Increased tumor regression (pCR?)




Increased tumor regression (pCR?)

Increased fibrosis formation (complications?)


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



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(%)


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


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)


P value

Tumor characteristics Within 8 Wk (n=17)


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


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



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”)

controversies in colorectal cancer

Education