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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2012

01-09-2012 | Colorectal Cancer

Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis

Authors: Luigi Zorcolo, MD, Alan S. Rosman, MD, FACP, Angelo Restivo, MD, Michele Pisano, MD, Giuseppe R. Nigri, MD, FACS, Alessandro Fancellu, MD, Marcovalerio Melis, MD, FACS

Published in: Annals of Surgical Oncology | Issue 9/2012

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Abstract

Background

Complete pathologic response (CPR) after neoadjuvant chemoradiotherapy (combined modality treatment, CMT) for rectal cancer seems associated with improved survival compared to partial or no response (NPR). However, previous reports have been limited by small sample size and single-institution design.

Methods

A systematic literature review was conducted to detect studies comparing long-term results of patients with CPR and NPR after CMT for rectal cancer. Variables were pooled only if evaluated by 3 or more studies. Study end points included rates of CPR, local recurrence (LR), distant recurrence (DR), 5-year overall survival (OS), and disease-free survival (DFS).

Results

Twelve studies (1,913 patients) with rectal cancer treated with CMT were included. CPR was observed in 300 patients (15.6%). CPR and NPR patient groups were similar with respect to age, sex, tumor size, distance of tumor from the anus, and stage of disease before treatment. Median follow-up ranged from 23 to 46 months. CPR patients had lower rates of LR [0.7% vs. 2.6%; odds ratio (OR) 0.45, 95% confidence interval (CI) 0.22–0.90, P = 0.03], DR (5.3% vs. 24.1%; OR 0.15, 95% CI 0.07–0.31, P = 0.0001), and simultaneous LR + DR (0.7% vs. 4.8%; OR 0.32, 95% CI 0.13–0.79, P = 0.01). OS was 92.9% for CPR versus 73.4% for NPR (OR 3.6, 95% CI 1.84–7.22, P = 0.002), and DFS was 86.9% versus 63.9% (OR 3.53, 95% CI 1.62–7.72, P = 0.002).

Conclusions

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.
Literature
1.
2.
Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin. 1999;49:8–31.PubMedCrossRef
3.
van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12:575–82.PubMedCrossRef
4.
Kapiteijn E, Kranenbarg EK, Steup WH, et al. Total mesorectal excision (TME) with or without preoperative radiotherapy in the treatment of primary rectal cancer. Prospective randomised trial with standard operative and histopathological techniques. Dutch ColoRectal Cancer Group. Eur J Surg. 1999;165:410–20.PubMedCrossRef
5.
Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–46.PubMedCrossRef
6.
Gérard A, Buyse M, Nordlinger B, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Ann Surg. 1988;208:606–14.PubMedCrossRef
7.
Glimelius B, Grönberg H, Järhult J, Wallgren A, Cavallin-Ståhl E. A systematic overview of radiation therapy effects in rectal cancer. Acta Oncol. 2003;42:476–92.PubMedCrossRef
8.
Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet. 2001;358:1291–304.CrossRef
9.
Cammà C, Giunta M, Fiorica F, Pagliaro L, Craxì A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA. 2000;284:1008–15.PubMedCrossRef
10.
Myerson RJ, Genovesi D, Lockett MA, et al. Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment. Int J Radiat Oncol Biol Phys. 1999;43:537–43.PubMedCrossRef
11.
Påhlman L, Glimelius B. The value of adjuvant radio(chemo)therapy for rectal cancer. Eur J Cancer. 1995;31A:1347–50.PubMedCrossRef
12.
Petersen S, Hellmich G, Baumann M, Herrmann T, Henke G, Ludwig K. Brief preoperative radiotherapy in surgical therapy of rectal carcinoma. Long-term results of a prospective randomized study. Chirurg. 1998;69:759–65.PubMedCrossRef
13.
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.PubMedCrossRef
14.
Grann A, Feng C, Wong D, et al. Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2001;49:987–95.PubMedCrossRef
15.
Hartley A, Ho KF, McConkey C, Geh JI. Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol. 2005;78:934–8.PubMedCrossRef
16.
Pucciarelli S, Toppan P, Friso ML, et al. Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis Colon Rectum. 2004;47:1798–807.PubMedCrossRef
17.
Read TE, McNevin MS, Gross EK, et al. Neoadjuvant therapy for adenocarcinoma of the rectum: tumor response and acute toxicity. Dis Colon Rectum. 2001;44:513–22.PubMedCrossRef
18.
Uzcudun AE, Batlle JF, Velasco JC, et al. Efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma when combined with oral tegafur-uracil modulated with leucovorin: results from a phase II study. Dis Colon Rectum. 2002;45:1349–58.PubMedCrossRef
19.
Valentini V, Coco C, Cellini N, et al. 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;51:371–83.PubMedCrossRef
20.
Shivnani AT, Small W, Stryker SJ, et al. Preoperative chemoradiation for rectal cancer: results of multimodality management and analysis of prognostic factors. Am J Surg. 2007;193:389–93.PubMedCrossRef
21.
22.
Fleiss J. Statistical methods for rates and proportions. New York: Wiley-Interscience; 1981.
23.
Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983;249:1743–5.PubMedCrossRef
24.
Petitti D. Metaanalysis, decision analysis, and cost-effectiveness analysis: methods for quantitative synthesis in medicine. New York: Oxford University Press; 1994. pp. 90–130.
25.
26.
27.
Muncer S, Taylor S, Craigie M. Power dressing and meta-analysis: incorporating power analysis into meta-analysis. J Adv Nurs. 2002;38:274–80.PubMedCrossRef
28.
Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39:175–91.PubMedCrossRef
29.
Bedrosian I, Rodriguez-Bigas MA, Feig B, et al. Predicting the node-negative mesorectum after preoperative chemoradiation for locally advanced rectal carcinoma. J Gastrointest Surg. 2004;8:56–62.PubMedCrossRef
30.
Burke SJ, Percarpio 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.PubMedCrossRef
31.
Coco C, Valentini V, Manno A, et al. Long-term results after neoadjuvant radiochemotherapy for locally advanced resectable extraperitoneal rectal cancer. Dis Colon Rectum. 2006;49:311–8.PubMedCrossRef
32.
Crane CH, Skibber JM, Birnbaum EH, et al. The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2003;57:84–9.PubMedCrossRef
33.
Janjan NA, Crane C, Feig BW, et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol. 2001;24:107–12.PubMedCrossRef
34.
Onaitis M, Noone R, Fields R, et al. Complete response to neoadjuvant chemoradiation for rectal cancer does not influence survival. Ann Surg Oncol. 2001;8:801–6.PubMedCrossRef
35.
Rich TA, Skibber JM, Ajani JA, et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys. 1995;32:1025–9.PubMedCrossRef
36.
Quah HM, Chou JF, Gonen M, et al. Pathologic stage is most prognostic of disease‐free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113:57–64.PubMedCrossRef
37.
Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg. 2005;241:829–36.PubMedCrossRef
38.
Brown CL, Ternent CA, Thorson AG, et al. Response to preoperative chemoradiation in stage II and III rectal cancer. Dis Colon Rectum. 2003;46:1189–93.PubMedCrossRef
39.
Chan AKP, Wong A, Jenken D, Heine J, Buie D, Johnson D. Posttreatment TNM staging is a prognostic indicator of survival and recurrence in tethered or fixed rectal carcinoma after preoperative chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61:665–77.PubMedCrossRef
40.
Chari RS, Tyler DS, Anscher MS, et al. Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg. 1995;221:778–86.PubMedCrossRef
41.
García-Aguilar J, Hernandez 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.PubMedCrossRef
42.
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.PubMedCrossRef
43.
Kuo LJ, Liu MC, Jian JJM, et al. Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy? Ann Surg Oncol. 2007;14:2766–72.PubMedCrossRef
44.
Theodoropoulos G, Wise WE, Padmanabhan A, et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum. 2002;45:895–903.PubMedCrossRef
45.
Wiig JN, Larsen SG, Dueland S, Giercksky KE. Clinical outcome in patients with complete pathologic response (pT0) to preoperative irradiation/chemo-irradiation operated for locally advanced or locally recurrent rectal cancer. J Surg Oncol. 2005;92:70–5.PubMedCrossRef
46.
Biondo S, Navarro M, Marti-Rague J, et al. Response to neoadjuvant therapy for rectal cancer: influence on long-term results. Colorectal Dis. 2005;7:472–9.PubMedCrossRef
47.
Rödel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.PubMedCrossRef
48.
Crane CH, Skibber JM, Feig BW, et al. Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer. 2003;97:517–24.PubMedCrossRef
49.
Aschele C, Friso ML, Pucciarelli S, et al. A phase I–II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol. 2005;16:1140–6.PubMedCrossRef
50.
Carlomagno C, Farella A, Bucci L, et al. Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study. Ann Oncol. 2009;20:906–12.PubMedCrossRef
51.
Das P, Skibber J, Rodriguez-Bigas M, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109:1750–5.PubMedCrossRef
52.
Pucciarelli S, Capirci C, Emanuele U, et al. Relationship between pathologic T-stage and nodal metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer. Ann Surg Oncol. 2005;12:111–6.PubMedCrossRef
53.
Rengan R, Paty PB, Wong WD, et al. Ten-year results of preoperative radiation followed by sphincter preservation for rectal cancer: increased local failure rate in nonresponders. Clin Colorectal Cancer. 2006;5:413–21.PubMedCrossRef
54.
Rödel C, Liersch T, Hermann RM, et al. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol. 2007;25:110–7.PubMedCrossRef
55.
Rosenthal DI, Catalano PJ, Haller DG, et al. Phase I study of preoperative radiation therapy with concurrent infusional 5-fluorouracil and oxaliplatin followed by surgery and postoperative 5-fluorouracil plus leucovorin for T3/T4 rectal adenocarcinoma: ECOG E1297. Int J Radiat Oncol Biol Phys. 2008;72:108–13.PubMedCrossRef
56.
Roh MS, Colangelo LH, O’Connell MJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.PubMedCrossRef
57.
Stipa F, Chessin D, Shia J, et al. A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography. Ann Surg Oncol. 2006;13:1047–53.PubMedCrossRef
58.
Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72:99–107.PubMedCrossRef
59.
Suárez J, Vera R, Balén E, et al. Pathologic response assessed by Mandard grade is a better prognostic factor than down staging for disease-free survival after preoperative radiochemotherapy for advanced rectal cancer. Colorectal Dis. 2008;10:563–8.PubMedCrossRef
60.
Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys. 1999;44:1027–38.PubMedCrossRef
61.
Willett C, Duda D, Tomaso E, et al. Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer. Nat Clin Pract Oncol. 2007;4:316–21.PubMedCrossRef
62.
Kuremsky JG, Tepper JE, McLeod HL. Biomarkers for response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2009;74:673–88.PubMedCrossRef
63.
Glynne-Jones R, Mawdsley S, Pearce T, Buyse M. Alternative clinical end points in rectal cancer—are we getting closer? Ann Oncol. 2006;17:1239–48.PubMedCrossRef
64.
Quirke 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;2:996–9.PubMedCrossRef
65.
Mohiuddin M, Marks J, Marks G. Management of rectal cancer: short- vs. long-course preoperative radiation. Int J Radiat Oncol Biol Phys. 2008;72:636–43.PubMedCrossRef
66.
Beets GL MM, Nelemans PJ, Valentini V, et al. Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: a pooled analysis of 2724 patients. Presented at: 2011 ASCO Gastrointestinal Cancers Symposium, 20–22 Jan 2011, San Francisco, CA.
67.
Kim CJ, Yeatman TJ, Coppola D, et al. Local excision of T2 and T3 rectal cancers after downstaging chemoradiation. Ann Surg. 2001;234:352–8.PubMedCrossRef
68.
Coco C, Manno A, Mattana C, et al. The role of local excision in rectal cancer after complete response to neoadjuvant treatment. Surg Oncol. 2007;16(Suppl. 1):S101–4.PubMedCrossRef
69.
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.PubMedCrossRef
70.
Read TE, Andujar JE, Caushaj PF, et al. Neoadjuvant therapy for rectal cancer: histologic response of the primary tumor predicts nodal status. Dis Colon Rectum. 2004;47:825–31.PubMedCrossRef
71.
Borschitz T, Wachtlin D, Möhler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2–3 rectal cancer. Ann Surg Oncol. 2008;15:712–20.PubMedCrossRef
72.
Ota DM, Nelson H, ACOSOG Group. Local excision of rectal cancer revisited: ACOSOG protocol Z6041. Ann Surg Oncol. 2007;14:271.PubMedCrossRef
Metadata
Title
Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis
Authors
Luigi Zorcolo, MD
Alan S. Rosman, MD, FACP
Angelo Restivo, MD
Michele Pisano, MD
Giuseppe R. Nigri, MD, FACS
Alessandro Fancellu, MD
Marcovalerio Melis, MD, FACS
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-2209-y

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