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Complete Clinical Response After Preoperative Chemoradiation in Rectal Cancer: Is a “Wait and See” Policy Justified?

  • Original Contributions
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Diseases of the Colon & Rectum

Abstract

Purpose

A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of “waiting to see” and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery.

Results

In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a “wait and see” policy.

Discussion

It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response.

Conclusions

The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a “wait and see” policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery.

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References

  1. Gerard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–T4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006;24:4620–5.

    Article  PubMed  Google Scholar 

  2. Bosset JF, Calais G, Mineur L, et al. Enhanced tumoricidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results – EORTC 22921. J Clin Oncol 2005;23:5620–7.

    Article  PubMed  CAS  Google Scholar 

  3. Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006;355:1114–23.

    Article  PubMed  CAS  Google Scholar 

  4. Hiotis SP, Weber SM, Cohen AM, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg 2002;194:131–5.

    Article  PubMed  Google Scholar 

  5. Mawdsley S, Glynne-Jones R, Grainger J, et al. Can the histopathological assessment of the circumferential margin following pre-operative pelvic chemo-radiotherapy for T3/4 rectal cancer predict for three year disease free survival? Int J Radiation Oncol Biol Phys 2005;63:745–52.

    Google Scholar 

  6. Rich TA, Skibber JM, Ajani JA, et al. Preoperative infusional chemoradiation therapy for stage III rectal cancer. Int J Radiat Oncol Biol Phys 1995;32:1025–9.

    Article  PubMed  CAS  Google Scholar 

  7. Mehta VK, Cho C, Ford JM, et al. Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-Fluorouracil, and weekly CPT11, followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys 2003;55:132–7.

    Article  PubMed  Google Scholar 

  8. Glynne-Jones R, Sebag-Montefiore D, Maughan TS, et al. A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally advanced rectal cancer. Ann Oncol 2006;17:50–6.

    Article  PubMed  CAS  Google Scholar 

  9. Guillem JG, Chessin DB, Shia J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate endpoint. J Clin Oncol 2005;23:3475–9.

    Article  PubMed  Google Scholar 

  10. Chari RS, Tyler DS, Anscher MS, et al. Preoperative radiotherapy and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg 1995;221:778–87.

    Article  PubMed  CAS  Google Scholar 

  11. Seong J, Cho JH, Kim NK, Min JS, Suh CO. Preoperative chemoradiotherapy with oral UFT and leucovorin in unresectable primary rectal cancer. Int J Radiation Oncol Biol Phys 2001;50:435–39.

    Article  CAS  Google Scholar 

  12. Zmora O, Dasilva GM, Gurland B, et al. Does rectal wall tumor eradication with preoperative chemoradiation permit a change in the operative strategy? Dis Colon Rectum 2004;47:1607–12.

    Article  PubMed  Google Scholar 

  13. Tulchinsky H, Rabau M, Shacham-Shemueli E, et al. Can rectal cancers with pathological T0 after neoadjuvant chemoradiation (ypT0) be treated by transanal excision alone? Ann Surg Oncol 2006;13:347–52.

    Article  PubMed  Google Scholar 

  14. Habr-Gama A, de Souza PM, Ribeiro U, et al. Low rectal cancer: impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum 1998;41:1087–96.

    Article  PubMed  CAS  Google Scholar 

  15. Habr-Gama A, de Souza PM, Ribeiro U, et al. Multimodality therapy in low rectal cancer: long-term outcome of complete responders. Dis Colon Rectum 2001;44:A18.

    Article  Google Scholar 

  16. Heald RW, Brian D, O’Neill P, et al. MRI in predicting curative resection of rectal cancer. New dilemma in multidisciplinary team management. BMJ 2006;333:808.

    Article  PubMed  CAS  Google Scholar 

  17. Habr-Gama A, Perez RO, Nadalin W, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg 2005;9:90–101.

    Article  PubMed  Google Scholar 

  18. Wang Y, Cummings B, Catton P, et al. Primary radical external beam radiotherapy of rectal adenocarcinoma: long-term outcome of 271 patients. Radiother Oncol 2005;77:126–32.

    Article  PubMed  Google Scholar 

  19. Lezoche E, Guerreri M, Paganini AM, Balderelli M, De Sanctis A, Lezoche G. Long-term results in patients with T2–3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery. Br J Surg 2005;92:1546–52.

    Article  PubMed  CAS  Google Scholar 

  20. Steele GD Jr, Herndon JE, Bleday R, et al. Sphincter-sparing treatment for distal rectal adenocarcinoma. Ann Surg Oncol 1999;6:433–41.

    Article  PubMed  Google Scholar 

  21. Gerard JP. The use of radiotherapy for patients with low rectal cancer: an overview of the Lyon experience. ANZ J Surg 1994;64:457–63.

    Article  CAS  Google Scholar 

  22. Birnbaum EH, Ogunbiyi OA, Gagliardi G, et al. Selection criteria for treatment of rectal cancer with combined external beam and endocavitary radiation. Dis Colon Rectum 1999;42:727–33.

    Article  PubMed  CAS  Google Scholar 

  23. Zaheer S, Pemberton JH, Farouk R, Duzois RR, Wolff BG, Ilstrup D. Surgical treatment of adenocarcinoma of the rectum. Ann Surg 1998;227:800–6.

    Article  PubMed  CAS  Google Scholar 

  24. Chen E-T, Mohiuddin M, Brodovsky H, et al. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys 1994;30:169–75.

    PubMed  CAS  Google Scholar 

  25. Meterissian S, Skibber J, Rich T, et al. Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal cancer. Ann Surg Oncol 1994;1:111–6.

    Article  PubMed  CAS  Google Scholar 

  26. Keilholz L, Dworak O, Dunst J, et al. Preoperative radiochemotherapie bei primar inoperablen rektumkarzinomen. Strahlenther Onkol 1995;171:70–6.

    PubMed  CAS  Google Scholar 

  27. Picchiocci A, Claudio C, Paolo M, et al. Adjuvant treatment in operable stage II and III rectal cancer. Tumori 1995;81:109–13.

    Google Scholar 

  28. Bernini A, Deen KI, Madoff RD, et al. Preoperative adjuvant radiation with chemotherapy for rectal cancer:its impact onstage of disease and the role of endorectal ultrasound. Ann Surg Oncol 1996;3:131–5.

    Article  PubMed  CAS  Google Scholar 

  29. Grann A, Feng C, Wong D, et al. Preoperative combined modality for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2001;49:987–95.

    Article  PubMed  CAS  Google Scholar 

  30. Rossi BM, Nakagawa WT, Novaes PE, et al. Radiation and chemotherapy instead of surgery for low infiltrative rectal adenocarcinoma: a prospective trial. Ann Surg Oncol 1998;5:113–8.

    Article  PubMed  CAS  Google Scholar 

  31. Valentini V, Coco C, Cellini N. Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response and sphincter preservation. Int J Radiat Oncol Biol Phys 1998;40:1067.

    PubMed  CAS  Google Scholar 

  32. Burke SJ, Percapio BA, Knight DC, Kwasnik EM. Combined preoperative radiation and mitomycin/5-fluorouracil treatment for locally advanced rectal adenocarcinoma. J Am Coll Surg 1998;187:164–70.

    Article  PubMed  CAS  Google Scholar 

  33. De la Torre A, Ramos S, Valcarcel VJ, et al. Phase II study of radiochemotherapy with UFT and low dose oral leucovorin in patients with unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1999;45:629–34.

    PubMed  Google Scholar 

  34. Valentini V, Coco C, Cellini N. Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies. Int J Radiat Oncol Biol Phys 2001;51(2):371–83.

    PubMed  CAS  Google Scholar 

  35. Conzo G, Caraco C, Vacca R, et al. Chemio-radioterapia neoadiuvante nel trattamento del cancro del retto: risultati preliminary. Giorn Chir 2000;21:319–22.

    CAS  Google Scholar 

  36. Kim CJ, Yeatman TJ, Coppula D, et al. Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg 2001;234:352–8.

    Article  PubMed  CAS  Google Scholar 

  37. Grann A, Feng C, Wong D, et al. Preoperative combined modality for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2001;49:987–95.

    Article  PubMed  CAS  Google Scholar 

  38. Valentini V, Coco C, Cellini N. Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation. Int J Radiat Oncol Biol Phys 1999;45:1175–84.

    Article  PubMed  CAS  Google Scholar 

  39. Carraro S, Roca EL, Cartelli C, et al. Radiochemotherapy with short daily infusion of low-dose oxaliplatin, leucovorin and 5FU in T3–T4 unresectable rectal cancer: a phase II IATGI study. Int J Radiat Oncol Biol Phys 2005;54:397–402.

    Google Scholar 

  40. Schaffer M, Thoma M, Wilkowski R, et al. Radio-chemotherapy as a preoperative treatment for advanced rectal cancer. Evaluation of down-staging and morbidity. Onkologie 2002;25:352–6.

    Article  PubMed  CAS  Google Scholar 

  41. Uzcudun AE, Feliu JB, Velasco JF, et al. Efficacy of preoperative radiation therapy for respectable rectal adenocarcinoma when combined with oral tegafur-uracil modulated with leucovorin. Dis Colon Rectum 2002;45:1349–58.

    Article  PubMed  Google Scholar 

  42. Crane CH, Skibber JM, Birnbaum EH, et al. The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumour response, leading to increased sphincter preservation in locally advanced low rectal cancer. Int J Radiat Oncology Biol Phys 2003;57:84–9.

    Article  CAS  Google Scholar 

  43. Ratto C, Valentini V, Morganti AG, et al. Combined modality therapy in locally advanced primary rectal cancer. Dis Colon Rectum 2003;46:59–67.

    Article  PubMed  Google Scholar 

  44. Gerard JP, Chapet O, Nemoz C, et al. Improved sphincter preservation in low rectal cancer with high-dose preoperative therarpy: the Lyon R96-02 randomised trial. J Clin Oncol 2004;22:2402–9.

    Article  Google Scholar 

  45. Gambacorta MA, Valentini V, Morganti AG, et al. Chemoradiation with raltitrexed (tomudex) in preoperative treatment of stage II–III resectable rectal cancer: a phase II study. Int J Radiat Oncol Biol Phys 2004;60:130–8.

    Article  PubMed  CAS  Google Scholar 

  46. Benzoni E, Cerato F, Cojutti A, et al. The predictive value of clinical evaluation of response to neoadjuvant chemoradiation therapy for rectal cancer. Tumori 2005;91(5):401–5.

    PubMed  Google Scholar 

  47. Sebag-Montefiore D, Brown G, Rutten H, et al. An international phase II study of capecitabine, oxaliplatin, radiotherapy and excision (CORE) in patients with MRI-defined locally advanced rectal adenocarcinoma. Interim results [abstract 608]. Eur J Cancer 2005;2:170.

    Google Scholar 

  48. Chau I, Allen M, Cunningham D, et al. Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 2003;88:1017–24.

    Article  PubMed  CAS  Google Scholar 

  49. De Paoli A, Chiara S, Luppi G, et al. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentre phase II study. Ann Oncol 2006;17:246–51.

    Article  PubMed  Google Scholar 

  50. Ferrigno R, Novaes PE, Silva ML, et al. Neoadjuvant radiochemotherapy in the treatment of fixed and semi-fixed rectal tumours. Analysis of results and prognostic factors. Radiat Oncol 2006;1:5–17.

    Article  PubMed  Google Scholar 

  51. Roh MS, Colangelo L, Wieand S, et al. Response to preoperative multimodality therapy predicts survival in patients with carcinoma of the rectum. Proceedings of the American Society of Clinical Oncology [meeting abstract 3505]. J Clin Oncol 2004;22:246s.

    Google Scholar 

  52. Bujko K, Nowacki MP, Nasierowska-Guttmejer A. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 2004;72:15–24.

    Article  PubMed  CAS  Google Scholar 

  53. Onaitis MW, Noone RB, Fields R, et al. Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol 2001;8:801–6.

    Article  PubMed  CAS  Google Scholar 

  54. Mohiuddin M, Marks G, Bannon J. High does preoperative radiation full-thickness local excision: a new option for selective T3 distal rectal cancer. Int J Radiat Oncol Biol Phys 1994;30:845–9.

    PubMed  CAS  Google Scholar 

  55. Bonnen M, Crane C, Vauthey JN, et al. Long-term results using local excision after preoperative chemoradiation among selected T3 rectal cancer patients. Int J Radiat Oncol Biol Phys 2004;60:1098–105.

    Article  PubMed  Google Scholar 

  56. Schell SR, Zlotecki RA, Mendenhall WM, et al. Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy. J Am Coll Surg 2002;94:584–90.

    Article  Google Scholar 

  57. Bedrosian I, Rodriguez-Bias MA, Fieg B, et al. Predicting node-negative mesorectum after preoperative chemoradiation for locally advanced rectal carcinoma. J Gastrointest Surg 2004;8:56–62.

    Article  PubMed  Google Scholar 

  58. Read TE, Andujar JE, Caushaj PF, et al. Neoadjuvant therapy for rectal cancer: Histologic response of the primary tumour predicts nodal status. Dis Colon Rectum 2004;47:825–31.

    Article  PubMed  Google Scholar 

  59. Gavioli M, Luppi G, Losi L, et al. Incidence and clinical impact of sterilized disease and minimal residual disease after preoperative radiotherapy for rectal cancer. Dis Colon Rectum 2005;48:1851–7.

    Article  PubMed  Google Scholar 

  60. Pucciarelli S, Capirci C, Emmanuele U, et al. Relationship between pathologic T stage and nodal metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer. Ann Surg Oncol 2005;12(2):111–6.

    Article  PubMed  Google Scholar 

  61. Hughes R, Glynne-Jones R, Grainger J, et al. Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3–T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision? Int J Colorectal Dis 2006;21:11–7.

    Article  PubMed  CAS  Google Scholar 

  62. Chmielik E, Bujko K, Nasierowska-Guttmejer A, et al. Distal intramural spread of rectal cancer after preoperative radiotherapy: the results of a multicenter randomized clinical study. Int J Radiat Oncol Biol Phys 2006;65:182–8.

    PubMed  Google Scholar 

  63. Nakagawa WT, Rossi BM, De Ferreira F. Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe? Ann Surg Oncol 2002;9:568–73.

    Article  PubMed  Google Scholar 

  64. Gerard JP, Roy P, Coquard R, et al. Combined curative radiation therapy alone in (T1) T2–3 rectal adenocarcinoma: a pilot study of 29 patients. Radiother Oncol 1996;38(2):131-7.

    Article  PubMed  CAS  Google Scholar 

  65. Rider WD. The 1975 Gordon Richards Memorial Lecture. Is the Miles operation really necessary for the treatment of rectal cancer? J Can Assoc Radiol 1975;26:167–75.

    PubMed  CAS  Google Scholar 

  66. Horwitz H, Williams IG. The primary treatment of adenocarcinoma of the rectum by high voltage rroentgen xrays (1000Kv). Amm J Roetgenol Radium Ther Nucl Med 1956;76:919–28.

    CAS  Google Scholar 

  67. Rafla S, Turner S, Meleka F, Ghossein M. The role of radiotherapy in the definitive management of rectal carcinoma. AJR Am J Roentgenol 1976:127:841–5.

    PubMed  CAS  Google Scholar 

  68. Taylor RE, Kerr GR, Arnott SJ. External beam radiotherapy for rectal adenocarcinoma. Br J Surg 1987;74:455–9.

    Article  PubMed  CAS  Google Scholar 

  69. Papillon J. Rectal and anal cancers: conservative treatment by irradiation: an alternative to radical surgery. New York: Springer-Verlag, 1982.

    Google Scholar 

  70. Paty PB, Nash GM, Baron P, Zakowski M, et al. Long-term results for the excision of rectal cancer. Ann Surg 2002;236:522–30.

    Article  PubMed  Google Scholar 

  71. Garcia-Aguilar J, Mellgren A, Sirivongs P, Buie D, Madoff RD, Rothernberger DA. Local excision of rectal cancer without adjuvant therapy. Ann Surg 2000;231:345–51.

    Article  PubMed  CAS  Google Scholar 

  72. Van den Brink M, Stigglebout AM, van den Hout WB, et al. Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy. J Clin Oncol 2004;22:3958–64.

    Article  PubMed  Google Scholar 

  73. Nigro MD, Seydel Hg, Considine B, Vaitkevicius VK, Leichman L, Kinzie JJ. Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer 1983;51:1826–9.

    Article  PubMed  CAS  Google Scholar 

  74. Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following preoperative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol 2005;78:934–8.

    Article  PubMed  CAS  Google Scholar 

  75. Rodel C, Martus P, Papadopoulos T, et al. Prognostic significance of tumor regression after preoperative chemortherapy for rectal cancer. J Clin Oncol 2005;23:8688–96.

    Article  PubMed  Google Scholar 

  76. Habr-Gama A. Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy. Colorectal Dis 2006;8(Suppl 3):21–4.

    Article  PubMed  Google Scholar 

  77. Leichman L, Nigro N, Vaitkevicius VK, et al. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 1985;78:211–5.

    Article  PubMed  CAS  Google Scholar 

  78. Gerard JP, Chapet O, Ramaioli A, et al. Long-term control of T2-T3 rectal adenocarcinoma with radiotherapy alone. Int J Radiation Oncol Biol Phys 2002;54:142–9.

    Google Scholar 

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Correspondence to R. Glynne-Jones M.B.B.S., F.R.C.R..

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Glynne-Jones, R., Wallace, M., Livingstone, J.I.L. et al. Complete Clinical Response After Preoperative Chemoradiation in Rectal Cancer: Is a “Wait and See” Policy Justified?. Dis Colon Rectum 51, 10–20 (2008). https://doi.org/10.1007/s10350-007-9080-8

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