Abstract
Purpose
The value of the lymph node ratio (LNR) in patients with rectal cancer has not yet been unequivocally established. This study aims to assess the effect of the lymph node ratio on the prognosis of rectal cancer in patients operated after short-course preoperative 25 Gy radiotherapy, at 10-year follow-up.
Methods
This is a substudy based on data from a prospective randomized clinical trial. A total of 141 patients with resectable rectal cancer were included. Lymph node yield was compared in patients with short and long time intervals between radiotherapy and surgery. Survival curves were compared between patients with different ypN and LNR categories. Univariate and multivariate analyses were performed to identify independent prognostic factors for overall survival and disease-free survival.
Results
Survival and recurrence data were available for a median follow-up of 11.6 years. The lymph node yield did not differ significantly between the patients in the short- and long-interval groups.
A greater difference in 10-year survival was observed in patients with LNR ≤ 0.41 and > 0.41 when compared to the ypN categories. Separate prognostic factor analyses were performed for the entire population and for subgroups that had < 12 and 12 lymph nodes resected. LNR was identified as an independent prognostic factor for overall survival, in multivariate analyses, for all patients and those with less than 12 retrieved lymph nodes.
Conclusion
The lymph node yield is comparable in patients with different time intervals between radiation therapy and surgery. LNR better discriminates patients in terms of overall survival than ypN categories.
Trial registration number
ClinicalTrials.gov Identifier: NCT01444495, date of registration: September 30, 2011.
Similar content being viewed by others
References
Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740. https://doi.org/10.1056/NEJMoa040694
Kapiteijn E, Marijnen CAM, Nagtegaal ID et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646. https://doi.org/10.1056/NEJMoa010580
Harisi R, Schaff Z, Flautner L et al (2008) Evaluation and comparison of the clinical, surgical and pathological TNM staging of colorectal cancer. Hepatogastroenterology 55:66–72
Glynne-Jones R, Wyrwicz L, Tiret E et al (2017) Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:iv22–iv40. https://doi.org/10.1093/annonc/mdx224
Morcos B, Baker B, Al Masri M et al (2010) Lymph node yield in rectal cancer surgery: effect of preoperative chemoradiotherapy. Eur J Surg Oncol 36:345–349. https://doi.org/10.1016/j.ejso.2009.12.006
Doll D, Gertler R, Maak M et al (2009) Reduced lymph node yield in rectal carcinoma specimen after neoadjuvant radiochemotherapy has no prognostic relevance. World J Surg 33:340–347. https://doi.org/10.1007/s00268-008-9838-8
Chen L, Huang X, Song Z (2018) The value of lymph node ratio in the prediction of rectal cancer patient survival after preoperative chemoradiotherapy. Int J Clin Exp Pathol 11:5992–6001
Tan L, Liu Z-L, Ma Z et al (2020) Prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: a meta-analysis. World J Gastrointest Oncol 12:1443–1455. https://doi.org/10.4251/wjgo.v12.i12.1443
Karaman S, Dagoglu RN, Kaval G et al (2019) Lymph node retrieval following neoadjuvant short course radiotherapy in patients with rectal cancer. Int J Radiat Oncol 105:E163–E164. https://doi.org/10.1016/j.ijrobp.2019.06.2138
Rosenberg R, Friederichs J, Schuster T et al (2008) Prognosis of patients with colorectal cancer Is associated with lymph node ratio a single-center analysis of 3026 patients over a 25-year time period. Ann Surg 248:968–977. https://doi.org/10.1097/SLA.0b013e318190eddc
Moug SJ, Saldanha JD, McGregor JR et al (2009) Positive lymph node retrieval ratio optimises patient staging in colorectal cancer. Br J Cancer 100:1530–1533. https://doi.org/10.1038/sj.bjc.6605049
Dekker JWT, Peeters KC, Putter H et al (2010) Metastatic lymph node ratio in stage III rectal cancer; prognostic significance in addition to the 7th edition of the TNM classification. Eur J Surg Oncol 36:1180–1186. https://doi.org/10.1016/j.ejso.2010.09.007
Jung W, Kim K, Kim J, Shim SJ (2020) Prognostic impact of lymph node ratio in patients undergoing preoperative chemoradiotherapy followed by curative resection for locally advanced rectal cancer. In Vivo 34:1247–1253. https://doi.org/10.21873/invivo.11898
Karjol U, Jonnada P, Chandranath A, Cherukuru S (2020) Lymph node ratio as a prognostic marker in rectal cancer survival: a systematic review and meta-analysis. Cureus 12:.https://doi.org/10.7759/cureus.8047
Pach R, Kulig J, Richter P et al (2012) Randomized clinical trial on preoperative radiotherapy 25 Gy in rectal cancer-treatment results at 5-year follow-up. Langenbeck’s Arch Surg 397:801–807. https://doi.org/10.1007/s00423-011-0890-8
Pach R, Sierzega M, Szczepanik A et al (2021) Preoperative radiotherapy 5 × 5 Gy and short versus long interval between surgery for resectable rectal cancer: 10-Year follow-up of the randomised controlled trial. Radiother Oncol 164:268–274. https://doi.org/10.1016/j.radonc.2021.10.006
Wittekind C, Compton C, Quirke P et al (2009) A uniform residual tumor (R) classification: integration of the R classification and the circumferential margin status. Cancer 115:3483–3488. https://doi.org/10.1002/cncr.24320
Zuo Z-G, Zhang X-F, Wang H et al (2016) Prognostic value of lymph node ratio in locally advanced rectal cancer patients after preoperative chemoradiotherapy followed by total mesorectal excision. Medicine (Baltimore) 95:e2988. https://doi.org/10.1097/MD.0000000000002988
Peschaud F, Benoist S, Julié C et al (2008) The ratio of metastatic to examined lymph nodes is a powerful independent prognostic factor in rectal cancer. Ann Surg 248:1067–1073. https://doi.org/10.1097/SLA.0b013e31818842ec
La Torre M, Mazzuca F, Ferri M et al (2013) The importance of lymph node retrieval and lymph node ratio following preoperative chemoradiation of rectal cancer. Color Dis 15:e382–e388. https://doi.org/10.1111/codi.12242
Van Cutsem E, Labianca R, Bodoky G et al (2009) Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol 27:3117–3125. https://doi.org/10.1200/JCO.2008.21.6663
Delbaldo C, Ychou M, Zawadi A et al (2015) Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial†. Ann Oncol Off J Eur Soc Med Oncol 26:1208–1215. https://doi.org/10.1093/annonc/mdv135
Mekenkamp LJM, Van Krieken JHJM, Marijnen CAM et al (2009) Lymph node retrieval in rectal cancer is dependent on many factors-the role of the tumor, the patient, the surgeon, the radiotherapist, and the pathologist. Am J Surg Pathol 33:1547–1553. https://doi.org/10.1097/PAS.0b013e3181b2e01f
Dienstmann R, Salazar R, Tabernero J (2015) Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol 33:1787–1796
Lee SDD, Kim THH, Kim DYY et al (2012) Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection. Eur J Surg Oncol 38:478–483. https://doi.org/10.1016/j.ejso.2012.03.002
Li Q, Li D, Zhuo C et al (2014) Metastatic lymph node ratio can further stratify prognosis in rectal cancer patients treated with preoperative radiotherapy: a population-based analysis. Tumor Biol 35:6389–6395. https://doi.org/10.1007/s13277-014-1817-0
Fajardo LF (1994) Effects of ionizing radiation on lymph nodes. A review Front Radiat Ther Oncol 28:37–45
Govindarajan A, Gönen M, Weiser MR et al (2011) Challenging the feasibility and clinical significance of current guidelines on lymph node examination in rectal cancer in the era of neoadjuvant therapy. J Clin Oncol 29:4568–4573. https://doi.org/10.1200/JCO.2011.37.2235
Li Q, Zhuo C, Liang L et al (2015) Lymph node count after preoperative radiotherapy is an independently prognostic factor for pathologically lymph node-negative patients with rectal cancer. Med (United States) 94:e395. https://doi.org/10.1097/MD.0000000000000395
Mechera R, Schuster T, Rosenberg R, Speich B (2017) Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: a systematic review and meta-analysis. Eur J Cancer. https://doi.org/10.1016/j.ejca.2016.10.031
Berger AC, Sigurdson ER, LeVoyer T et al (2005) Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 23:8706–8712. https://doi.org/10.1200/JCO.2005.02.8852
Peng J, Xu Y, Guan Z et al (2008) Prognostic significance of the metastatic lymph node ratio in node-positive rectal cancer. Ann Surg Oncol 15:3118–3123. https://doi.org/10.1245/s10434-008-0123-8
Klos CL, Bordeianou LG, Sylla P et al (2011) The prognostic value of lymph node ratio after neoadjuvant chemoradiation and rectal cancer surgery. Dis Colon Rectum 54:171–175. https://doi.org/10.1007/DCR.0b013e3181fd677d
Lykke J, Jess P, Roikjaer O, Danish Colorectal Cancer Group (2016) The prognostic value of lymph node ratio in a national cohort of rectal cancer patients. Eur J Surg Oncol 42:504–512. https://doi.org/10.1016/j.ejso.2016.01.012
Ren J, Xue F, Liu S et al (2015) Prognostic value of lymph node ratio and N stage in stage III colorectal cancer. Zhonghua Wei Chang Wai Ke Za Zhi 18:553–557
Kasi A, Abbasi S, Handa S et al (2020) Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer: a systematic review and meta-analysis. JAMA Netw open 3:e2030097. https://doi.org/10.1001/jamanetworkopen.2020.30097
Aoyama T, Oba K, Honda M et al (2017) Impact of postoperative complications on the colorectal cancer survival and recurrence: analyses of pooled individual patients’ data from three large phase III randomized trials. Cancer Med 6:1573–1580. https://doi.org/10.1002/cam4.1126
Author information
Authors and Affiliations
Contributions
Study conception and design: RP, PR, AS. Acquisition of data: RP. Analysis and interpretation of data: RP, AS, MS. Drafting of manuscript: RP, AS, MS, PR, MD. Critical revision of manuscript: AS, PR, RP, MD.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Pach, R., Szczepanik, A.M., Sierzega, M. et al. Prognostic value of lymph node ratio in resectable rectal cancer after preoperative short-course radiotherapy—results from randomized clinical trial. Langenbecks Arch Surg 407, 2969–2980 (2022). https://doi.org/10.1007/s00423-022-02603-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-022-02603-8