Abstract
Purpose: The aim of this study was to evaluate the response to neoadjuvant long course chemoradiotherapy (CRT) for patients with locally advanced rectal cancer with or without lymph node metastasis.
Materials and Methods: Between 1993 – 2007, 126 patients with locally advanced rectal cancer with or without lymph node involvement were treated at Dokuz Eylul University Medical Faculty Hospital. Prospectively collected data of patients were analyzed. All patients received concurrent CRT. Curative intend surgical resection was performed 4 to 8 weeks after the completion of CRT. Response to neoadjuvant CRT was assessed by comparing the preoperative clinical staging and postoperative pathological evaluation. Histopathological complete response (pCR) was defined as no tumor cells within the specimen. Downstaging of T and/or N stage of the tumor was defined as partial response (PR).
Results: Mean age was 57.9 years and 40,5% of patients were female, 59,5% of patients were male. Preoperative staging revealed T3 tumor in 54 (42,8%) of patients and T4 tumor in 58 (46%) of patients. In 32 (25,4%) patients there were no lymph node metastases (cN0) whereas in 94 (74,6%) patients lymph node involvement was detected (cN+). Tumor was located at lower rectum in 61,1% of patients, at mid-rectum in 25,4% of patients, and at upper rectum in 13,5% of patients. Sphincter saving resection was performed in 62,7% of patients. Histopathological complete response was observed in 13 (10,3%) patients. T stage downstaging was observed in 63 (%63) patients, N stage downstaging was observed in 57 (45,2%) patients, and PR was observed in 76 (60,3%) patients. No significant difference was observed between the response to neoadjuvant CRT and tumor localization and sphincter saving resection (P>0.05).
Conclusion: Response to neoadjuvant CRT was obtained in majority of the patients. Downstaging was not associated with the rate of sphincter preserving surgery. Surgical resection is still the primary treatment of resectable rectal cancer.
Keywords:
Locally advanced rectal cancer, neoadjuvant chemoradiotherapy, downstaging
References
1Chen ET, Mohiuddin M, Brodovsky H, Fishbein G, Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys 1994; 30: 169–175.
2Minsky BD, Cohan AM, Enker WE, Paty P. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis. Int J Radiat Oncol Biol Phys 1995; 31: 553–559.
3Rouanet P, Fabre JM, Dubois JB, et al. Conservative surgery for low rectal carcinoma and high-dose radiation: functional and oncological results. Ann Surg 1995; 221: 67–73.
4Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351: 1731-1740.
5Buroker T, Nigro N, Correa J, Vaitkevicius VK, Samson M, Considine B. Combination preoperative radiation and chemotherapy in adenocarcinoma of the rectum: preliminary report. Dis Colon Rectum 1976;19: 660–663.
6Minsky BD, Cohen AM, Kemeny N, et al. Efficacy of preoperative 5-FU, high dose leucoverin, and sequential radiation therapy for unresectable rectal cancer. Cancer 1994; 73: 273–280.
7Wheeler JM, Dodds E, Warren BF, et al. Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade. Dis Colon Rectum 2004; 47: 2025-2031.
8Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 1986; 2: 996-999.
9Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986; 1: 1479-1482.
10Halefoglu AM, Yildirim S, Avlanmis O, Sakiz D, Baykan A. Endorectal ultrasonography versus phased-array magnetic resonance imaging for preoperative staging of rectal cancer. World J Gastroenterol 2008; 14: 3504-3510.
11Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997; 336: 980-987.
12Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001; 345: 638-646.
13http://www.ctu.mrc.ac.uk/studies/CR07.asp
14Bosset JF, Collette L, Calais G, et al; EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006; 355: 1114-1123.
15Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006; 24: 4620-4625
16Garcia-Aguilar J, Herna´ndez de Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003; 46: 298–304.
17Biondo S, Navarro M, Marti-Rague J, et al. Response to neoadjuvant therapy for rectal cancer: influence on long-term results. Colorectal Dis 2005; 7: 472-479.
18Devine RM, Dozois RR. Surgical management of locally advanced adenocarcinoma of the rectum. World J Surg 1992; 16: 486-489.
19Frykholm GJ, Påhlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 2001; 50: 427-434.
20Vestermark LW, Jacobsen A, Qvortrup C, et al. Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC). Acta Oncol 2008; 47: 428-433.
21Wong RK, Tandan V, De Silva S, Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev 2007; (2): CD002102.
22Bujko K, Kepka L, Michalski W, Nowacki MP. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol 2006; 80: 4-12.
23Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 2004; 72: 15-24.
24Bozzetti F, Baratti D, Andreola S, et al. Preoperative radiation therapy for patients with T2-T3 carcinoma of the middle-to-lower rectum. Cancer 1999; 86: 398-404.
25Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004; 240: 711-717.
26Schell SR, Zlotecki RA, Mendenhall WM, Marsh RW, Vauthey JN, Copeland EM 3rd. Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy. J Am Coll Surg 2002; 194: 584-590.
27Kim CJ, Yeatman TJ, Coppola D, et al. Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg 2001; 234: 352-358.
28Habr-Gama A, de Souza PM, Ribeiro U Jr, et al. Low rectal cancer: impact of radiation and chemotherapy on surgical treatment. Dis Colon Rectum 1998; 41: 1087-1096.
29Hiotis 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: 131-135.
30Guillem JG, Chessin DB, Shia J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol 2005; 23: 3475-3479.
31Chen CC, Lee RC, Lin JK, Wang LW, Yang SH. How accurate is magnetic resonance imaging in restaging rectal cancer in patients receiving preoperative combined chemoradiotherapy? Dis Colon Rectum 2005; 48: 722-7228.
32Capirci C, Rubello D, Chierichetti F, et al. Restaging after neoadjuvant chemoradiotherapy for rectal adenocarcinoma: role of F18-FDG PET. Biomed Pharmacother 2004; 58: 451-457.
33Meterissian S, Skibber J, Rich T, et al. Patterns of residual disease after preoperative chemoradiation in ultrasound T3 rectal carcinoma. Ann Surg Oncol 1994; 1: 111-116.
34Zmora 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: 1607-1612.
35Stipa F, Zernecke A, Moore HG, et al. Residual mesorectal lymph node involvement following neoadjuvant combined-modality therapy: rationale for radical resection? Ann Surg Oncol 2004; 11: 187-191.
36Nakagawa WT, Rossi BM, de O Ferreira F, et al. Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe? Ann Surg Oncol 2002; 9: 568-573.