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Open Access 01-01-2010 | Original Article

Preoperative Chemoradiotherapy Does Not Necessarily Reduce Lymph Node Retrieval in Rectal Cancer Specimens—Results from a Prospective Evaluation with Extensive Pathological Work-up

Authors: Thilo Sprenger, Hilka Rothe, Kia Homayounfar, Tim Beissbarth, B. Michael Ghadimi, Heinz Becker, Torsten Liersch

Published in: Journal of Gastrointestinal Surgery | Issue 1/2010

Abstract

Purpose

Preoperative chemoradiotherapy (CRT) is supposed not only to reduce lymph node metastases but also lymph node recovery in rectal cancer specimens. The objective of this prospective study was to determine the effects of chemoradiation on mesorectal lymph node retrieval under terms of a meticulous histopathological evaluation.

Methods

Specimens from 64 consecutive patients with stage II/III rectal cancer receiving preoperative 5-FU-based CRT were investigated. All patients were treated within the German Rectal Cancer Trial CAO/ARO/AIO-04. After surgery (including quality assessed total mesorectal excision), extensive pathological diagnostics was performed with embedding and microscopic evaluation of the whole mesorectal soft tissue compartment.

Results

A total number of 2,021 lymph nodes were recovered (31.6 per specimen) within pathological work-up. There was no significant correlation between the number of retrieved nodes and patient- as well as tumor-dependent parameters. Lymph node size constantly amounted for less than 0.5 cm. Twenty patients (31.3%) had persistent nodal metastases. A considerable incidence of residual micrometastatic involvement in lymph nodes <0.3 cm (in 9.4% of all patients) was detected by extensive pathologic work-up.

Conclusion

Reliable nodal staging with high numbers of detected nodes was feasible after neoadjuvant CRT. Micrometastases frequently occur in small lymph nodes detected by microscopic evaluation.

Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1998. CA Cancer J Clin 1998;48:6–29.CrossRefPubMed

Midgley R, Kerr D. Colorectal cancer. Lancet 1999;353:391–399.CrossRefPubMed

Enker WE, Thaler HT, Cranor ML, Polyak T. Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg 1995;181:335–346.PubMed

Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–1740.CrossRefPubMed

Rodel C, Liersch T, Hermann RM, Arnold D, Reese T, Hipp M, Furst A, Schwella N, Bieker M, Hellmich G, Ewald H, Haier J, Lordick F, Flentje M, Sulberg H, Hohenberger W, Sauer R. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 2007;25:110–117.CrossRefPubMed

Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.CrossRefPubMed

Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Pierart M, Calais G. Patients with curative resection of cT3–4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol 2007;25:4379–4386.CrossRefPubMed

Minsky BD. Adjuvant management of rectal cancer: the more we learn, the less we know. J Clin Oncol 2007;25:4339–4340.CrossRefPubMed

Quasar Collaborative G, Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 2007;370:2020–2029.CrossRef

10.

Leibold T, Shia J, Ruo L, Minsky BD, Akhurst T, Gollub MJ, Ginsberg MS, Larson S, Riedel E, Wong WD, Guillem JG. Prognostic implications of the distribution of lymph node metastases in rectal cancer after neoadjuvant chemoradiotherapy. J Clin Oncol 2008;26:2106–2111.CrossRefPubMed

11.

Liersch T, Langer C, Ghadimi BM, Kulle B, Aust DE, Baretton GB, Schwabe W, Hausler P, Becker H, Jakob C. Lymph node status and TS gene expression are prognostic markers in stage II/III rectal cancer after neoadjuvant fluorouracil-based chemoradiotherapy. J Clin Oncol 2006;24:4062–4068.CrossRefPubMed

12.

Sarli L, Bader G, Iusco D, Salvemini C, Mauro DD, Mazzeo A, Regina G, Roncoroni L. Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer. Eur J Cancer 2005;41:272–279.CrossRefPubMed

13.

Caplin S, Cerottini JP, Bosman FT, Constanda MT, Givel JC. For patients with Dukes’ B (TNM Stage II) colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis. Cancer 1998;83:666–672.CrossRefPubMed

14.

Cianchi F, Palomba A, Boddi V, Messerini L, Pucciani F, Perigli G, Bechi P, Cortesini C. Lymph node recovery from colorectal tumor specimens: recommendation for a minimum number of lymph nodes to be examined. World J Surg 2002;26:384–389.CrossRefPubMed

15.

Luna-Perez P, Rodriguez-Ramirez S, Alvarado I, Gutierrez de la Barrera M, Labastida S. Prognostic significance of retrieved lymph nodes per specimen in resected rectal adenocarcinoma after preoperative chemoradiation therapy. Arch Med Res 2003;34:281–286.CrossRefPubMed

16.

Tepper JE, O’Connell MJ, Niedzwiecki D, Hollis D, Compton C, Benson AB 3rd, Cummings B, Gunderson L, Macdonald JS, Mayer RJ. Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 2001;19:157–163.PubMed

17.

Tsai HL, Lu CY, Hsieh JS, Wu DC, Jan CM, Chai CY, Chu KS, Chan HM, Wang JY. The prognostic significance of total lymph node harvest in patients with T2–4N0M0 colorectal cancer. J Gastrointest Surg 2007;11:660–665.CrossRefPubMed

18.

Wichmann MW, Muller C, Meyer G, Strauss T, Hornung HM, Lau-Werner U, Angele MK, Schildberg FW. Effect of preoperative radiochemotherapy on lymph node retrieval after resection of rectal cancer. Arch Surg 2002;137:206–210.CrossRefPubMed

19.

Wijesuriya RE, Deen KI, Hewavisenthi J, Balawardana J, Perera M. Neoadjuvant therapy for rectal cancer down-stages the tumor but reduces lymph node harvest significantly. Surg Today 2005;35:442–445.CrossRefPubMed

20.

de la Fuente SG, Manson RJ, Ludwig KA, Mantyh CR. Neoadjuvant chemoradiation for rectal cancer reduces lymph node harvest in proctectomy specimens. J Gastrointest Surg 2009;13:269–274.CrossRefPubMed

21.

Baxter NN, Morris AM, Rothenberger DA, Tepper JE. Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis. Int J Radiat Oncol Biol Phys 2005;61:426–431.PubMed

22.

Habr-Gama A, Perez RO, Proscurshim I, Rawet V, Pereira DD, Sousa AH, Kiss D, Cecconello I. Absence of lymph nodes in the resected specimen after radical surgery for distal rectal cancer and neoadjuvant chemoradiation therapy: what does it mean? Dis Colon Rectum 2008;51:277–283.CrossRefPubMed

23.

Nagtegaal ID, van de Velde CJ, van der Worp E, Kapiteijn E, Quirke P, van Krieken JH. Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. J Clin Oncol 2002;20:1729–1734.CrossRefPubMed

24.

Sobin LH. TNM, sixth edition: new developments in general concepts and rules. Semin Surg Oncol 2003;21:19–22.CrossRefPubMed

25.

Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12:19–23.CrossRefPubMed

26.

Wittekind C, Tannapfel A. Regression grading of colorectal carcinoma after preoperative radiochemotherapy. An inventory. Pathologe 2003;24:61–65.PubMed

27.

Sobin LH. TNM classification: clarification of number of regional lymph nodes for pN0. Br J Cancer 2001;85:780.CrossRefPubMed

28.

Rinkus KM, Russell GB, Levine EA. Prognostic significance of nodal disease following preoperative radiation for rectal adenocarcinoma. Am Surg 2002;68:482–487.PubMed

29.

Thorn CC, Woodcock NP, Scott N, Verbeke C, Scott SB, Ambrose NS. What factors affect lymph node yield in surgery for rectal cancer? Colorectal Dis 2004;6:356–361.CrossRefPubMed

30.

Sermier A, Gervaz P, Egger JF, Dao M, Allal AS, Bonet M, Morel P. Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent. World J Surg Oncol 2006;4:29.CrossRefPubMed

31.

Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–646.CrossRefPubMed

32.

Marijnen CA, Nagtegaal ID, Klein Kranenbarg E, Hermans J, van de Velde CJ, Leer JW, van Krieken JH. No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol 2001;19:1976–1984.PubMed

33.

Perez RO, Seid VE, Bresciani EH, Bresciani C, Proscurshim I, Pereira DD, Kruglensky D, Rawet V, Habr-Gama A, Kiss D. Distribution of lymph nodes in the mesorectum: how deep is TME necessary? Tech Coloproctol 2008;12:39–43.CrossRefPubMed

34.

Koh DM, Chau I, Tait D, Wotherspoon A, Cunningham D, Brown G. Evaluating mesorectal lymph nodes in rectal cancer before and after neoadjuvant chemoradiation using thin-section T2-weighted magnetic resonance imaging. Int J Radiat Oncol Biol Phys 2008;71:456–461.PubMed

35.

Perez RO, Pereira DD, Proscurshim I, Gama-Rodrigues J, Rawet V, Sao Juliao GP, Kiss D, Cecconello I, Habr-Gama A. Lymph node size in rectal cancer following neoadjuvant chemoradiation–can we rely on radiologic nodal staging after chemoradiation? Dis Colon Rectum 2009;52:1278–1284.PubMed

36.

Fajardo LF. Effects of ionizing radiation on lymph nodes. A review. Front Radiat Ther Oncol 1994;28:37–45.PubMed

37.

Prall F, Wohlke M, Klautke G, Schiffmann L, Fietkau R, Barten M. Tumour regression and mesorectal lymph node changes after intensified neoadjuvant chemoradiation for carcinoma of the rectum. Apmis 2006;114:201–210.CrossRefPubMed

38.

Murphy J, Pocard M, Jass JR, O’Sullivan GC, Lee G, Talbot IC. Number and size of lymph nodes recovered from dukes B rectal cancers: correlation with prognosis and histologic antitumor immune response. Dis Colon Rectum 2007;50:1526–1534.CrossRefPubMed

39.

Perez RO, Habr-Gama A, Nishida Arazawa ST, Rawet V, Coelho Siqueira SA, Kiss DR, Gama-Rodrigues JJ. Lymph node micrometastasis in stage II distal rectal cancer following neoadjuvant chemoradiation therapy. Int J Colorectal Dis 2005;20:434–439.CrossRefPubMed

40.

Goldstein NS. Lymph node recoveries from 2427 pT3 colorectal resection specimens spanning 45 years: recommendations for a minimum number of recovered lymph nodes based on predictive probabilities. Am J Surg Pathol 2002;26:179–189.CrossRefPubMed

41.

Bilimoria KY, Bentrem DJ, Stewart AK, Talamonti MS, Winchester DP, Russell TR, Ko CY. Lymph node evaluation as a colon cancer quality measure: a national hospital report card. J Natl Cancer Inst 2008;100:1310–1317.CrossRefPubMed

42.

Kim YW, Kim NK, Min BS, Lee KY, Sohn SK, Cho CH. The influence of the number of retrieved lymph nodes on staging and survival in patients with stage II and III rectal cancer undergoing tumor-specific mesorectal excision. Ann Surg 2009;249:965–972.CrossRefPubMed

43.

Chang GJ, Rodriguez-Bigas MA, Eng C, Skibber JM. Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome. Cancer 2009. doi:10.1002/cncr.24622.

44.

Morris EJ, Maughan NJ, Forman D, Quirke P. Identifying stage III colorectal cancer patients: the influence of the patient, surgeon, and pathologist. J Clin Oncol 2007;25:2573–2579.CrossRefPubMed

Title: Preoperative Chemoradiotherapy Does Not Necessarily Reduce Lymph Node Retrieval in Rectal Cancer Specimens—Results from a Prospective Evaluation with Extensive Pathological Work-up
Authors: Thilo Sprenger
Hilka Rothe
Kia Homayounfar
Tim Beissbarth
B. Michael Ghadimi
Heinz Becker
Torsten Liersch
Publication date: 01-01-2010
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 1/2010
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-009-1057-6

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Preoperative Chemoradiotherapy Does Not Necessarily Reduce Lymph Node Retrieval in Rectal Cancer Specimens—Results from a Prospective Evaluation with Extensive Pathological Work-up

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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