Reduced Lymph Node Yield in Rectal Carcinoma Specimen After Neoadjuvant Radiochemotherapy Has No Prognostic Relevance
Corresponding Author
Dietrich Doll
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
[email protected]Search for more papers by this authorRalf Gertler
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorMatthias Maak
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorJan Friederichs
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorKaren Becker
Institut für Pathologie und Pathologische Anatomie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorHans Geinitz
Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorMonika Kriner
Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorHjalmar Nekarda
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorJörg R. Siewert
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorRobert Rosenberg
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorCorresponding Author
Dietrich Doll
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
[email protected]Search for more papers by this authorRalf Gertler
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorMatthias Maak
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorJan Friederichs
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorKaren Becker
Institut für Pathologie und Pathologische Anatomie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorHans Geinitz
Klinik für Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorMonika Kriner
Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
Search for more papers by this authorHjalmar Nekarda
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorJörg R. Siewert
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorRobert Rosenberg
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany
Search for more papers by this authorD. Doll and R. Gertler contributed equally to this work.
Abstract
Background
In colorectal surgery UICC/AJCC criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. Neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined.
Methods
One hundred two patients with uT3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with uT3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. Total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival.
Results
After neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p < 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p = 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. Reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. Overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39% for 0, 1–3, and more than 3 positive lymph nodes (p < 0.0001).
Conclusion
The UICC/AJCC criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients.
References
- 1JemalA, SiegelR, WardE et al. Cancer Statistics 2007. CA Cancer J Clin (2007) 57: 43–661723703510.3322/canjclin.57.1.43
- 2TepperJE, O’ConnellMJ, PetroniGR et al. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of Intergroup 0114. J Clin Oncol (1997) 15: 2030–20399164215
- 3KobayashiH, UenoH, HashiguchiY et al. Distribution of lymph node metastasis is a prognostic index in patients with stage III colon cancer. Surgery (2006) 139: 516–5221662706110.1016/j.surg.2005.09.004
- 4BergerAC, SigurdsonER, LeVoyerT et al. Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol (2005) 23: 8706–87121631463010.1200/JCO.2005.02.8852
- 5TocchiA, MazzoniG, LepreL et al. Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences. Arch Surg (2001) 136: 216–2201117714510.1001/archsurg.136.2.216
- 6van den BrinkM, StiggelboutAM, van den HoutWB 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: 3958–39641545921810.1200/JCO.2004.01.023
- 7JohnsonPM, MalatjalianD, PorterGA Adequacy of nodal harvest in colorectal cancer: a consecutive cohort study. J Gastrointest Surg (2002) 6: 883–8881250422810.1016/S1091-255X(02)00131-2
- 8ChangGJ, Rodriguez-BigasMA, SkibberJM et al. Lymph node evaluation and survival after curative resection of colon cancer: systematic review. J Natl Cancer Inst (2007) 99: 433–4411737483310.1093/jnci/djk092
- 9GeorgeS, PrimroseJ, TalbotR et al. Will Rogers revisited: prospective observational study of survival of 3592 patients with colorectal cancer according to number of nodes examined by pathologists. Br J Cancer (2006) 95: 841–8471696934210.1038/sj.bjc.6603352
- 10SwansonRS, ComptonCC, StewartAK et al. The prognosis of T3N0 colon cancer is dependent on the number of lymph nodes examined. Ann Surg Oncol (2003) 10: 65–711251396310.1245/ASO.2003.03.058
- 11LeeHY, ChoiHJ, ParkKJ et al. Prognostic significance of metastatic lymph node ratio in node-positive colon carcinoma. Ann Surg Oncol (2007) 14: 1712–17171725310210.1245/s10434-006-9322-3
- 12MaurelJ, LaunoyG, GrosclaudeP et al. Lymph node harvest reporting in patients with carcinoma of the large bowel: a French population-based study. Cancer (1998) 82: 1482–1486955452410.1002/(SICI)1097-0142(19980415)82:8<1482::AID-CNCR8>3.0.CO;2-B
10.1002/(SICI)1097-0142(19980415)82:8<1482::AID-CNCR8>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- 13YoshimatsuK, IshibashiK, UmeharaA et al. How many lymph nodes should be examined in Dukes’ B colorectal cancer? Determination on the basis of cumulative survival rate. Hepatogastroenterology (2005) 52: 1703–170616334761
- 14Luna-PerezP, Trejo-ValdiviaB, LabastidaS et al. Prognostic factors in patients with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy and surgery. World J Surg (1999) 23: 1069–10741051294910.1007/s002689900625
- 15PrandiM, LionettoR, BiniA et al. Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg (2002) 235: 458–4631192360010.1097/00000658-200204000-00002
- 16 LH Sobin, C Wittekind (eds) (1997) TNM classification of malignant tumours, 5th edn. Wiley-Liss, New York
- 17SobinLH, GreeneFL TNM classification: clarification of number of regional lymph nodes for pN0. Cancer (2001) 92: 4521146670210.1002/1097-0142(20010715)92:2<452::AID-CNCR1342>3.0.CO;2-B
10.1002/1097-0142(20010715)92:2<452::AID-CNCR1342>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- 18SchmiegelW, PoxC, AdlerG et al. S3-Guidelines Conference “Colorectal Cancer” 2004. Z Gastroenterol (2004) 42: 1129–11771550805810.1055/s-2004-813699
- 19CammaC, GiuntaM, FioricaM et al. Preoperative radiotherapy for resectable rectal cancer. A meta-analysis. JAMA (2000) 284: 1008–10151094464710.1001/jama.284.8.1008
- 20KapiteijnE, MarijnenCA, NagtegaalID et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med (2001) 345: 638–6461154771710.1056/NEJMoa010580
- 21SauerR, BeckerH, HohenbergerW et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med (2004) 351: 1731–17401549662210.1056/NEJMoa040694
- 22RosenbergR, NekardaH, ZimmermannF et al. Histopathological response after preoperative radiochemotherapy in rectal carcinoma is associated with improved overall survival. J Surg Oncol (2008) 97: 8–131808561910.1002/jso.20844
- 23PartyMedical Research Council Rectal Cancer Working A trial of preoperative radiotherapy in the management of operable rectal cancer. Br J Surg (1982) 69: 513–51910.1002/bjs.1800690906
- 24HornA, MorildI, DahlO Tumour shrinkage and down staging after preoperative radiation of rectal adenocarcinomas. Radiother Oncol (1990) 18: 19–28219331810.1016/0167-8140(90)90019-S
- 25PartyMedical Research Council Rectal Cancer Working Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet (1996) 348: 1610–161410.1016/S0140-6736(96)05349-4
- 26MarijnenCA, NagtegaalID, Klein KranenbargE et al. No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol (2001) 19: 1976–198411283130
- 27SermierA, GervazP, EggerJF et al. Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent. World J Surg Oncol (2006) 4: 291674993110.1186/1477-7819-4-29
- 28WheelerJM, WarrenBF, MortensenNJ et al. Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system. Dis Colon Rectum (2002) 45: 1051–10561219518910.1007/s10350-004-6359-x
- 29WichmannMW, MullerC, MeyerG et al. Effect of preoperative radiochemotherapy on lymph node retrieval after resection of rectal cancer. Arch Surg (2002) 137: 206–2101182296110.1001/archsurg.137.2.206
- 30WijesuriyaRE, DeenKI, HewavisenthiJ et al. Neoadjuvant therapy for rectal cancer down-stages the tumour but reduces lymph node harvest significantly. Surg Today (2005) 35: 442–4451591229010.1007/s00595-004-2956-5
- 31BaxterNN, MorrisAM, RothenbergerDA et al. Impact of preoperative radiation for rectal cancer on subsequent lymph node evaluation: a population-based analysis. Int J Radiol Oncol Biol Phys (2005) 61: 426–43110.1016/j.ijrobp.2004.06.259
- 32 NIH consensus conferenceAdjuvant therapy for patients with colon and rectal cancer. JAMA (1990) 264: 1444–145010.1001/jama.264.11.1444
- 33O’ConnellMJ, MartensonJA, WieandHS et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med (1994) 331: 502–507804141510.1056/NEJM199408253310803
- 34BeckerK, MuellerJD, SchuhmacherC et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer (2003) 98: 1521–15301450884110.1002/cncr.11660
- 35FrancoisY, NernozCJ, BaulieuxJ et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol (1999) 17: 279–286
- 36MooreHG, GittlemanAE, MinskyBD et al. Rate of pathologic complete response with increased interval between preoperative combined modality and rectal cancer resection. Dis Colon Rectum (2004) 47: 279–2861499148810.1007/s10350-003-0062-1
- 37FarjardoLF Effects of ionizing radiation on lymph nodes. Front Radiat Ther Oncol (1994) 28: 37–45
- 38ShveroJ, KorenR, MarshakG et al. Histological changes in the cervical lymph nodes after radiotherapy. Oncol Rep (2001) 8: 909–91111410808
- 39ThornCC, WoodcockNP, ScottN et al. What factors affect lymph node yield in surgery for rectal cancer?. Colorectal Dis (2004) 6: 356–3611533537010.1111/j.1463-1318.2004.00670.x
- 40SarliL, BaderG, IuscoD et al. Number of lymph nodes examined and prognosis of TNM stage II colorectal cancer. Eur J Cancer (2005) 41: 272–2791566155310.1016/j.ejca.2004.10.010
- 41JassJR, O’BrienMJ, RiddellRH et al. Recommendations for the reporting of surgically resected specimens of colorectal carcinoma. Hum Pathol (2007) 38: 537–5451727024610.1016/j.humpath.2006.11.009
- 42KimNK, BaikSH, SeongJS et al. Oncologic outcomes after neoadjuvant chemoradiation followed by curative resection with tumour-specific mesorectal excision for fixed locally advanced rectal cancer: Impact of postirradiated pathologic downstaging on local recurrence and survival. Ann Surg (2006) 244: 1024–10301712262910.1097/01.sla.0000225360.99257.73
- 43RosenbergR, FriederichsJ, GertlerR et al. Prognostic evaluation and review of immunohistochemically detected disseminated tumour cells in peritumoural lymph nodes of patients with pN0 colorectal cancer. Int J Colorectal Dis (2004) 19: 430–4371471649510.1007/s00384-003-0559-z
- 44FriederichsJ, RosenbergR, MagesJ et al. Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumour progression. Int J Colorectal Dis (2005) 20: 391–4021588378310.1007/s00384-004-0722-1
- 45BeresfordM, Glynne-JonesR, RichmanP et al. The reliability of lymph node staging in rectal cancer after preoperative chemoradiotherapy. Clin Oncol (R Coll Radiol) (2005) 17: 448–455
