Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2012 Dec 12;12(12):CD008368.
doi: 10.1002/14651858.CD008368.pub2.

Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer

Kathryn McCarthy  1 , Katherine Pearson, Rachel Fulton, Jonathan Hewitt
Affiliations
Meta-Analysis

Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer

Kathryn McCarthy et al. Cochrane Database Syst Rev. .

Abstract

Background: This review sets out to assess the efficacy of pre-operative chemoradiation when compared to radiotherapy alone before surgery in the treatment of advanced non metastatic rectal surgery.

Objectives: To determine the efficacy of pre-operative chemoradiation (CRT) compared with radiation (RT) alone, in locally advanced rectal cancer with respect to overall survival, local recurrence and 30 day mortality, sphincter preservation and toxicity of treatment (both acute and late).

Search methods: In September 2011, we searched clinical trial registers, the Cochrane Central Register of Controlled Trials, Web of Science, EMBASE and MEDLINE and reviewed reference lists. Further hand searches were conducted of relevant journal proceedings. No language constraints were applied.The following search terms were used: colorectal, rectal, rectum, cancer, carcinoma, tumour, radiotherapy, chemotherapy, chemoradiotherapy, chemoradiation, 5-Fluorouracil, 5-FU, neo-adjuvant, preoperative, surgery, anterior resection, abdominoperineal resection, total mesorectal excision.

Selection criteria: Male and female patients aged over 18 years undergoing preoperative chemoradiation or radiotherapy followed by surgery for locally advanced non-metastatic rectal cancer. There was no upper age limit for participants. Locally advanced non-metastatic cancer was defined as stage 3 rectal tumours. These are tumours of any T stage with nodal involvement, without evidence of distant metastases.

Data collection and analysis: Primary outcome parameters included overall survival and local recurrence rate. Secondary outcome parameters included 30 day mortality, sphincter preservation, pathological response of tumour, acute and late toxicity of treatment. The outcome parameters were summarized using the odds ratio and 95% confidence intervals (CI).

Main results: There were 6 randomised controlled trials eligible for inclusion. A reduction in local recurrence was seen in the CRT group in comparison to the RT group (OR 0.56, 95% CI 0.42-0.75, P<0.0001). The results for overall survival were (OR=1.01 95%CI 0.85-1.20, P=0.88).The 30 day mortality was the same for both groups, CRT vs RT (OR 1.73, 95% CI 0.88-3.38). Sphincter preservation (stoma rate) was also similar for the two interventions (OR 1.02, 95% CI 0.85-1.21, P=0.64). An increase in acute grade 3/4 treatment related toxicity was seen in the CRT group versus the RT group (OR 3.96, 95% CI 3.03, 5.17, P<0.00001), although this result did display heterogeneity P=0.0005. Late toxicity events were similar between the two groups (OR 0.88, 95% CI 0.50, 1.54, P=0.65).

Authors' conclusions: RT was compared to the more intensive CRT in the treatment of T3-4, node positive (locally advanced) rectal cancer. While there was no difference in overall survival between RT and CRT, CRT was associated with less local recurrence.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

1
1
Forest plot of comparison: 1 Primary Outcome Parameters, outcome: 1.1 Overall Survival.
2
2
Forest plot of comparison: 1 Primary outcome: 1.2 Local Recurrence CRT versus RT. Due to potential interaction identified by the Bosset study authors this analysis does not include participants who underwent post‐operative chemotherapy.
3
3
Forest plot of comparison: 2 Secondary Outcome Parameters, outcome: 2.1 30 Day Mortality CRT versus RT.
4
4
Forest plot of comparison: 2 Secondary Outcome Parameters, outcome: 2.2 Sphincter Preservation CRT versus RT.
5
5
Forest plot of comparison: 2 Secondary Outcome Parameters, outcome: 2.3 Acute Toxicity CRT versus RT.
6
6
Forest plot of comparison: 2 Secondary Outcome Parameters, outcome: 2.4 Late Toxicity CRT versus RT.
1.1
1.1. Analysis
Comparison 1 Primary Outcome Parameters, Outcome 1 Overall Survival.
1.2
1.2. Analysis
Comparison 1 Primary Outcome Parameters, Outcome 2 Local Recurrence.
2.1
2.1. Analysis
Comparison 2 Secondary Outcome Parameters, Outcome 1 30 Day Mortality.
2.2
2.2. Analysis
Comparison 2 Secondary Outcome Parameters, Outcome 2 Sphincter Preservation.
2.3
2.3. Analysis
Comparison 2 Secondary Outcome Parameters, Outcome 3 Acute Toxicity.
2.4
2.4. Analysis
Comparison 2 Secondary Outcome Parameters, Outcome 4 Late Toxicity.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD008368

References

References to studies included in this review

Bosset 2004 {published data only}
    1. Bosset JF, Calais G, Daban A, Berger C Radosevic‐Jelci L, Maingon P, Bardet E, Pierart M, Briffaux A, EORCT Radiotherapy Group. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer 2004;40(2):219‐24. - PubMed
Bosset 2006 {published data only}
    1. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic‐Jelic L, Daban A, Bardet E, Beny A, Ollier JC. Chemotherapy with Preoperative Radiotherapy in Rectal Cancer. New England Journal of Medicine 2006;335:1114‐23. - PubMed
Boulis‐Wassif 1984 {published data only}
    1. Boulis‐Wassif S, Gerard A, Loygue J, Camelot D, Buyse M, Duez N. Final Results of a Randomised Trial on the Treatment of Rectal Cancer with Preoperative Radiotherapy Alone or in Combination with 5‐Fluorouarcil followed by Radical Surgery. Cancer 1984;53:1811‐1818. - PubMed
Bujko 2004 {published data only (unpublished sought but not used)}
    1. Bujko K, Nowacki MP, Nasierowska‐Guttmejer A, Michalski W, Bebenek M, Pudelko M, Kryj M, Oledzki J, Szmeja J, Sluszniak J, Serkies K, Kladny J, Pamucka M, Kukolowicz P. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short‐term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiotherapy and Oncology 2004;72:15‐24. - PubMed
Bujko 2005 {published data only (unpublished sought but not used)}
    1. Bujko K, Nowacki MP, Kepka L, Oledzki J, Bebenek M, Kryj M. Post operative complications in patients irradiated preoperatively for rectal cancer: report of a randomised trial comparing short‐term radiotherapy vs chemoradiation. Colorectal Disease 2005;7:410‐416. - PubMed
Bujko 2006 {published data only (unpublished sought but not used)}
    1. Bujko K, Nowacki MP, Nasierowska‐Guttmejer A, Michalski W, Bebenek M and M Kryj for the Polish Colorectal Study Group. Long‐term results of a randomized trial comparing preoperative short‐course radiotherapy with preoperative conventionally fractioned chemoradiation for rectal cancer. British Journal of Surgery 2006;93:1215‐1223. - PubMed
Gerard 2006 {published data only}
    1. Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon‐Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. 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. - PubMed
Latkauskas 2012 {published data only}
    1. Latkauskas T, Pauzas H, Gineikiene I, Janciauskiene R, Juozaityte E, Saladzinskas Z, et al. Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short‐course radiotherapy or long‐term chemoradiotherapy, both with delayed surgery. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 2012;14(3):294‐8. [PUBMED: 21899712] - PubMed
Ngan 2007 {published data only (unpublished sought but not used)}
    1. Ngan S, Fisher R, Mackay J, Soloman M, Burmeister B, Goldstein D, Schache D, Joseph D, Ackland S, McClure B. Acute adverse events in a randomised trial of short course versus long course preoperative radiotherapy for T3 adenocarcinoma of rectum: a Trans‐Tasman Raditaion Oncology Group trial (TROG 01.04). Eur J Cancer Suppl. 2007; Vol. 5/4:237.
Ngan 2010 {published data only (unpublished sought but not used)}
    1. Ngan S, Fisher D, Soloman M, Burmeister SP, Ackland DJ, Joseph B, McClure S, Mackay J, TROG, AGITG, CSSANZ, RACS. A randomised trial comparing local recurrence (LR) rates between short‐course (SC) and long‐course (LC) preoperative radiotherapy (RT) for clinical T3 rectal cancer: an intergroup trial (TROG, AGITG, CSSANZ, RACS). Journal of Clinical Oncology, ASCO Annual Meeting Proceedings. 2010; Vol. 28 No_15_suppl:No 3509.

References to studies excluded from this review

Liu 2005 {published data only}
    1. Lui JD, Du TH, Liu LY, Wei Wg. Comparison of long term efficacy between preoperative radiotherapy or radiochemotherapy followed by lower ‐ anterior resection and Miles abdominoperineal resection in patients with low rectal cancer. Chin J of Gastrointest Surg 2005;8:297‐300. - PubMed
Rutowski 2008 {published data only}
    1. A Rutkowski, K Bujko, M Nowacki, E Chmielik, A Nasiero‐Guttmejer, A Wojnar. Distal Bowel Surgical Margin Shorter than 1cm After Preoperative Radiation for Rectal Cancer: Is It Safe?. Annals of Surgical Oncology 2008;15:3124‐3131. - PubMed
Ulrich 2009 {published data only}
    1. Ulrich A, Weitz J, Slodczyk M, Koch M, Jaeger D, Munter M, Buchler W. Neoadjuvant treatment does not influence perioperative outcome in rectal cancer surgery. Int J Radiation Oncology Biol Phys 2009;75:129‐136. - PubMed

References to ongoing studies

Siegel 2009 {published data only}
    1. Siegal R, Burock S, Wernecke KD, Kretzschmar A, Dietel M, Loy V, Koswig S, Budach V, Schlag PM. Preoperative short‐course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi‐centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer 2009;9:50. - PMC - PubMed

Additional references

Beynon 1986
    1. Beynon J, Foy DM, Roe AM, Temple LN, Mortensen NJ. Endoluminal ultrasound in the assessment of local invasion in rectal cancer. British Journal of Surgery 1986;73:474‐7. - PubMed
Ceelen 2009
    1. Ceelen WP, Nieuwenhove Y, Fierens K. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858] - DOI - PubMed
Ferlay 2007
    1. Ferlay J, Autier P, Boniol M, Hennue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Annals of Oncology March 2007;3:581‐92. - PubMed
Folkesson 2005
    1. Fokesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. Journal of Clinical Oncology 2005;23:5644‐50. - PubMed
Glimelius 2002
    1. Glimelius B. Radiotherapy in rectal cancer. British Medical Bulletin 2002;64:141‐57. - PubMed
Gray 2001
    1. Gray R, Hills R, Stowe R, Clarke M, Peto R, Buyse M, Piedbois P. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8507 patients from 22 randomised trials. Lancet 2001;358:1291‐1304. - PubMed
Heald 1982
    1. Heald RJ, Husband EM, Ryall D. The mesorectum in rectal cancer surgery: the clue to recurrence?. Br J Surg 1982;69:613‐16. - PubMed
Higgins 2008
    1. Higgins JP, White IR, Wood AM. Imputation methods for missing outcome data in meta‐analysis of clinical trials. Clinical Trials 2008;3:225‐39. - PMC - PubMed
Higgins 2009
    1. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 [updated September 2009]. The Cochrane Collaboration. Wiley‐Blackwell, 2009.
Kapiteijin 2001
    1. Kapiteijin E, Marijnen CAM, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJT, Pahlman L, Glimelius B, Krieken J, Leer JWH, Velde CJH. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. New England Journal of Medicine 2001;345(9):638‐646. - PubMed
Luna‐Perez 2001
    1. Luna‐Perez P, Rodriguez‐Ramirez S, Rodriguez‐Coria DF, Fernandez A, Labastida S, Silva A, Lopez MJ. Preoperative chemoradiation therapy and anal sphincter preservation with locally advanced rectal adenocarcinoma. World Journal of Surgery 2001;25(8):1006‐11. - PubMed
Maier 2000
    1. Maier AG, Kersting‐Sommerhoff B, Reeders JW, Judmaier W, Schima W, Ann Weiler AA, Meusel M, Wallengren NO. Staging of rectal cancer by double‐contrast MR imaging using the rectally administered superparamagnetic iron oxide contrast agent ferristene and IV gadodiamide injection: results of a multicenter phase II trial. Journal of Magnetic Resonance Imaging 2000;12:651‐60. - PubMed
Mercury 2006
    1. The MERCURY study group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ 2006;333:779. - PMC - PubMed
Schiedler 2000
    1. Schiedler J, Reisser MF. MRI of the female and male pelvis: current and future applications of contrast enhancement. European Journal of Radiology 2000;34:220‐8. - PubMed
Scott 1995
    1. Scott N, Jackson P, Al‐Jaberi T, Dixon MF, Quirke P, Finan PJ. Total mesorectal excision and local recurrence; a study of tumour spread in the mesorectum distal to rectal cancer. British Journal of Surgery 1995;82:1031‐3. - PubMed
Sobin 2009
    1. Sobin L, Gospodarowics M, Wittekind C. TMN Classification of Malignant Tumours, 7th Edition. Wiley and Sons, 2009.
Urban 2000
    1. Urban M, Rosen HR, Holbling N, Feil N, Hochwarther G, Hruby W, Schiessel R. MR imaging for the preoperative planning of sphincter‐saving surgery for tumours of the lower third of the rectum: use of intravenous and endorectal contrast materials. Radiology 2000;214:503‐8. - PubMed

Publication types