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Controversies in Colorectal Cancer

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Controversies in Colorectal Cancer. Atthaphorn Trakarnsanga

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Controversies in Colorectal Cancer

  1. 1. Controversies in Colorectal Surgery Atthaphorn Trakarnsanga MD FRCST Department of Surgery, Faculty of Medicine Siriraj Hospital Mahidol University, Bangkok, Thailand
  2. 2. No Disclosure
  3. 3. Topics • Surgery for locally advanced rectal cancer - Optimal timing of surgery after nCCRT - Organ preservation (Local excision, “wait and see”)
  4. 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. 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
  6. 6. Neoadjuvant Chemoradiation nCCRT TME adj CMT 6-8 weeks 4-6 weeks Increased waiting time Increased tumor regression (pCR?)
  7. 7. Neoadjuvant Chemoradiation nCCRT TME adj CMT 6-8 weeks 4-6 weeks Increased waiting time Increased tumor regression (pCR?) Increased fibrosis formation (complications?)
  8. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 19. Adding Chemotherapy in Waiting Period nCRT TME adj CMT 10-12 weeks 4-6 weeks Increase timing + Add chemotherapy
  20. 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. 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. 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. 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. 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
  25. 25. “Wait and see” Chawla S et al. Am J Clin Oncol 2014
  26. 26. Glynne-Jones R and Hughes R Br J Surg 2012;99:897-909
  27. 27. Topics • Surgery for locally advanced rectal cancer - Optimal timing of surgery after nCCRT - Organ preservation (Local excision, “wait and see”)

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