Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지

Appropriate Timing of Surgery after Neoadjuvant Chemo-Radiation Therapy for Locally Advanced Rectal Cancer

  • Published : 2016.09.01
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Abstract

Background: Surgery is the corner stone for the management of rectal cancer. The purpose of this study was to demonstrate the optimal time of surgical resection after the completion of neoadjuvant chemo-radiotherapy (CRT) in treatment of locally advanced rectal cancer. Materials and Methods: This study compared 2 groups of patients with locally advanced rectal cancer, treated with neoadjuvant CRT followed by surgical resection either 6-8 weeks or 9-14 weeks after the completion of chemo-radiotherapy. The impact of delaying surgery was tested in comparison to early surgical resection after completion of chemo-radiotherapy. Results: The total significant response rate that could result in functional preservation was estimated to be 3.85% in group I and 15.4% in group II. Some 9.62% of our patients had residual malignant cells at one cm surgical margin. All those patients with positive margins at one cm were in group I (19.23%). There was less operative time in group II, but the difference between both groups was statistically insignificant (P=0.845). The difference between both groups regarding operative blood loss and intra operative blood transfusion was significantly less in group II (P=0.044). There was no statistically significant difference between both groups regarding the intra operative complications (P=0.609). The current study showed significantly less post-operative hospital stay period, and less post-operative wound infection in group II (P=0.012 and 0.017). The current study showed more tumor regression and necrosis in group II with a highly significant main effect of time F=61.7 (P<0.001). Pathological TN stage indicated better pathological tumor response in group II (P=0.04). The current study showed recurrence free survival for all cases at 18 months of 84.2%. In group I, survival rate at the same duration was 73.8%, however none of group II cases had local recurrence (censored) (P=0.031). Disease free survival (DFS) during the same duration (18 months) was 69.4 % for patients in group I and 82.3% for group II (P=0.429). Conclusions: Surgical resection delay up to 9-14 weeks after chemo-radiation was associated with better outcome and better recurrence free survival.

Keywords

References

  1. Allegra CJ, Ursiny CS, Yothers G, et al (2009). Pre-operative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: "NSABP R-03". J Clin Oncol, 27, 5124-30. https://doi.org/10.1200/JCO.2009.22.0467
  2. Brown G, Evans J, Patel U (2011). Rectal cancer: primary staging and assessment after chemoradiotherapy. Semin Radiat Oncol, 21, 169-77. https://doi.org/10.1016/j.semradonc.2011.02.002
  3. Buecher B, Bardet E, Rio E, et al (2006). Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer. Colorectal Dis, 8, 430-5. https://doi.org/10.1111/j.1463-1318.2006.00990.x
  4. Buskens CJ, Punt CJ, Geijsen DE, et al (2013). Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg, 100, 933-9. https://doi.org/10.1002/bjs.9112
  5. Cho CH, Kim H, Roh JK, et al (2006). Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumor-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival. Ann Surg, 244, 1024-30. https://doi.org/10.1097/01.sla.0000225360.99257.73
  6. Cohen AM, Minsky BD, Chessin DB, et al (2005). Long-term Oncologic Outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg, 241, 829-38. https://doi.org/10.1097/01.sla.0000161980.46459.96
  7. Cooper EJ, Jones EL, Foster JD, et al (2013). Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature. Dis Colon Rectum, 56, 921-30. https://doi.org/10.1097/DCR.0b013e31828aedcb
  8. Crimaldi A, Huntington CR, Boselli D, et al (2016). Optimal timing of surgical resection after radiationtherapy in locally advanced rectal adenocarcinoma: An analysis of the National Cancer Database. Ann Surg Oncol, 23, 877-87. https://doi.org/10.1245/s10434-015-4927-z
  9. D'Hoore A, Wolthuis AM, Van Cutsem E, et al (2012). Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol, 19, 2833-41. https://doi.org/10.1245/s10434-012-2327-1
  10. da Luz Moreira A, Dietz D, Geisler DP, et al (2011). Neoadjuvant therapy for rectal cancer: the impact of longer interval between chemoradiation and surgery. J Gastrointest Surg, 15, 444-50. https://doi.org/10.1007/s11605-010-1197-8
  11. Feig BW, Crane CH, Eng C, et al (2006). Clinical and pathologic predictors of locoregional recurrence, distant metastasis, and overall survival in patients treated with chemoradiation and mesorectal excision for rectal cancer. Am J Clin Oncol, 29, 219-24. https://doi.org/10.1097/01.coc.0000214930.78200.4a
  12. Fierens K, Pattyn P, Van Nieuwenhove Y, et al (2009). Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis. Int J Cancer, 124, 2966-72. https://doi.org/10.1002/ijc.24247
  13. Figer A, Shmueli E, Tulchinsky H, et al (2008). An interval & gt; 7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease free survival in patients with locally advanced rectal cancer. Ann Surg Oncol, 15, 2661-7. https://doi.org/10.1245/s10434-008-9892-3
  14. Figueredo A, Wong RK, De Silva S, et al (2007). Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev, 2, 2102.
  15. Giraudo G, and Morino M (2005). Laparoscopic total mesorectal excision-the Turin experience. Recent Results Cancer Res, 165, 167-79.
  16. Gittleman AE, Minsky BD, Wong D, et al (2004). Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection. Dis Colon Rectum, 47, 279-86. https://doi.org/10.1007/s10350-003-0062-1
  17. Glimelius B, Pahlman L (1990). Pre-or post operative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicentric trial. Ann Surg, 211, 187-95. https://doi.org/10.1097/00000658-199002000-00011
  18. Glynne-Jones R, Kerr SF, Norton S (2008). Delaying surgery after neoadjuvant chemoradiotherapy for rectal cancer may reduce postoperative morbidity without compromising prognosis. Br J Surg, 95, 1534-40. https://doi.org/10.1002/bjs.6377
  19. Gutman H, and Wasserberg N (2008). Resection margins in modern rectal cancer surgery. J Surg Oncol, 98, 611-5. https://doi.org/10.1002/jso.21036
  20. Hess CF, Rodel C, Wittekind C, et al (2004). German rectal cancer study group. preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med, 351, 1731-40. https://doi.org/10.1056/NEJMoa040694
  21. Hochhaus A, Leitner A, Leitner A, et al (2007). A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Br J Cancer, 96, 912-7. https://doi.org/10.1038/sj.bjc.6603645
  22. Holt A, Tran CL, Stamos MJ, et al (2006). Evaluation of safety of increased time interval between chemoradiation and resection for rectal cancer. University of California. Am J Surg, 192, 873-7. https://doi.org/10.1016/j.amjsurg.2006.08.061
  23. Kennelly RP, Heeney A, White A, Winter DC, et al (2012). A prospective analysis of patient outcome following treatment of T3 rectal cancer with neo-adjuvant chemoradiotherapy and transanal excision. Int J Colorectal Dis, 27, 759-64. https://doi.org/10.1007/s00384-011-1388-0
  24. Kim DY, Chang HJ, Choi HS, et al (2008). Optimal surgery time after preoperative chemoradiotherapy for locally advanced rectal cancers. Ann Surg, 248, 243-51. https://doi.org/10.1097/SLA.0b013e31817fc2a0
  25. Kulig J, Szura M, Richter P, et al (2012). Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer--treatment results at 5-year follow-up. Langenbecks Arch Surg, 397, 801-7. https://doi.org/10.1007/s00423-011-0890-8
  26. Martling A, Cedermark B, Glimelius B, et al (2015). Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg, 102, 972-8. https://doi.org/10.1002/bjs.9811
  27. Nemoz CJ, Partensky C, Baulieux J, et al (1999). Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol, 17, 2396. https://doi.org/10.1200/JCO.1999.17.8.2396
  28. Rodel C, Calvo FA, Beets GL, et al (2010). Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol, 11, 835-44. https://doi.org/10.1016/S1470-2045(10)70172-8
  29. Serrano A, Pellicer E, Valero G, et al (2003). Neoadjuvant radiation and chemotherapy in rectal cancer does not increase postoperative complications. Int J Colorectal Dis, 18, 495-9. https://doi.org/10.1007/s00384-003-0520-1
  30. Smith DD, Bergsland EK, Garcia-Aguilar J, et al (2011). Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg, 254, 97-102. https://doi.org/10.1097/SLA.0b013e3182196e1f
  31. Stamm B, Fasolini F, Bouzourene H, et al (2006). Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): is it a matter of days? Acta Oncol, 45, 1086-93. https://doi.org/10.1080/02841860600891317
  32. Volk B, Wolmark N, Peter M (2000). Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum. national surgical adjuvant breast and bowel project protocol R-02. J Natl Cancer Inst, 92, 388-96. https://doi.org/10.1093/jnci/92.5.388
  33. Wibe A, Svensson E, Myrvold HE, et al (2002). Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer. Br J Surg, 89, 327-34. https://doi.org/10.1046/j.0007-1323.2001.02024.x