Delay to Adjuvant Chemotherapy: Survival and Recurrence in Patients of Rectal Cancer Treated with Neo-adjuvant Chemoradiotherapy and Surgery



This aim of the study is to evaluate the survival function and hazard risks of delayed adjuvant chemotherapy (ChT) to distant recurrence risk in patients with non-metastatic rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) and surgery.


A single tertiary hospital retrospective cohort study of a duration of 5 years between January 2012 and December 2016 was performed. As no previous study shown a temporal relationship of delay to adjuvant/systemic ChT leading to increased risk of metastatic disease, we compared between our proposed cut-off with the median and mean value determined by our dataset. Time to event analysis and log rank tests were conducted.


A total of 269 patients with rectal cancer were identified. Two hundred eighteen patients were ineligible, leaving 51 patients for final analysis. Patients in the non-delayed group at 23 (proposed) and 25 (median) weeks’ cut-off reported better 5 years’ disease free survival (DFS) compared with the delayed group by 4.1% and 0.8%. Inversely, at the cut-off 28 (mean) weeks, the delayed group had a better DFS by 4.4%. Females and patients less than 60 years old had better 5-year DFS by 22.8% and 24%. Delayed group has a higher hazard risk ratio (HR) of 1.28 of distant recurrence compared with non-delayed at 23 weeks’ cut-off.


This study has demonstrated delaying a patient to adjuvant ChT will lower their DFS and increase their HR compared with those whose treatment is not delayed. We have long been too focused on local control; hence, priority needs to be shifted to efforts in managing potential distant disease in a timely manner.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. 1.

    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

    CAS  Article  Google Scholar 

  2. 2.

    Australian Institute of Health and Welfare. Australian Cancer Incidence and Mortality (ACIM) books: colorectal cancer 2017. Canberra. Available from: Accessed on 29 November 2018.

  3. 3.

    Australian Institute of Health and Welfare. Admitted patient care 2015–16: Australian hospital statistics. 2017. Available from Accessed on 29 November 2018.

  4. 4.

    Australian Institute of Health and Welfare. Australian Cancer Incidence and Mortality (ACIM) books: rectal cancer 2017. Canberra. Available from: Accessed on 29 November 2018.

  5. 5.

    Glynne-Jones R, Mawdsley S, Pearce T, Buyse M. Alternative clinical end points in rectal cancer--are we getting closer? Ann Oncol. 2006 Aug;17(8):1239–48.

    CAS  Article  Google Scholar 

  6. 6.

    Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620–5.

    Article  Google Scholar 

  7. 7.

    Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926–33.

    CAS  Article  Google Scholar 

  8. 8.

    Ludmir EB, Palta M, Willett CG, Czito BG. Total neoadjuvant therapy for rectal cancer: an emerging option. Cancer. 2017;123(9):1497–506.

    Article  Google Scholar 

  9. 9.

    Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, Rodel C, Cervantes A, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl_4):iv22–40.

    CAS  Article  Google Scholar 

  10. 10.

    Network NCC. NCCN Clinical Practice Guidelines for Rectal Cancer: National Comprehensive Cancer Network 2016. Available from: Accessed on 29 November 2018.

  11. 11.

    Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg. 2016 Mar;263(3):458–64.

    Article  Google Scholar 

  12. 12.

    Siegel R, DeSantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014 Mar-Apr;64(2):104–17.

    Article  Google Scholar 

  13. 13.

    Fazeli MS, Keramati MR. Rectal cancer: a review. Med J Islam Repub Iran. 2015;29:171.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Bosset J-F, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC, EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-1123.

  15. 15.

    Bujko K, Glimelius B, Valentini V, Michalski W, Spalek M. Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: a meta-analysis of randomized trials comparing surgery +/- a fluoropyrimidine and surgery + a fluoropyrimidine +/- oxaliplatin. Eur J Surg Oncol. 2015;41(6):713–23.

    CAS  Article  Google Scholar 

  16. 16.

    Sainato A. Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, et al. No benefit of adjuvant fluorouracil leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014;113(2):223–9.

    Article  Google Scholar 

  17. 17.

    Cui J, Fang H, Zhang L, Wu Y-L, Zhang H-Z. Advances for achieving a pathological complete response for rectal cancer after neoadjuvant therapy. Chronic Dis Transl Med. 2016;2(1):10–6.

    PubMed  PubMed Central  Google Scholar 

  18. 18.

    Bosset J-F, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun R-J, Bardet E., Beny A., Ollier J.C., Bolla M., Marchal D., van Laethem J., Klein V., Giralt J., Clavère P., Glanzmann C., Cellier P., Collette L., EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15(2):184-190.

  19. 19.

    Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. 2012;19(9):2822–32.

    Article  Google Scholar 

  20. 20.

    Petersen S, Harling H, Kirkeby L, et al. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. 2012.

  21. 21.

    Gollins S, Sebag-Montefiore D. Neoadjuvant treatment strategies for locally advanced rectal cancer. Clin Oncol (R Coll Radiol). 2016;28(2):146–51.

    CAS  Article  Google Scholar 

  22. 22.

    Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K, Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957-966.

  23. 23.

    Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Krynski J, et al. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016;27(5):834–42.

    CAS  Article  Google Scholar 

  24. 24.

    Gao YH, Lin JZ, An X, Luo JL, Cai MY, Cai PQ, et al. Neoadjuvant sandwich treatment with oxaliplatin and capecitabine administered prior to, concurrently with, and following radiation therapy in locally advanced rectal cancer: a prospective phase 2 trial. Int J Radiat Oncol Biol Phys. 2014;90(5):1153–60.

    CAS  Article  Google Scholar 

  25. 25.

    Zampino MG, Magni E, Leonardi MC, Petazzi E, Santoro L, Luca F, et al. Capecitabine initially concomitant to radiotherapy then perioperatively administered in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2009;75(2):421–7.

    CAS  Article  Google Scholar 

  26. 26.

    Fernandez-Martos C, Garcia-Albeniz X, Pericay C, Maurel J, Aparicio J, Montagut C, et al. Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trialdagger. Ann Oncol. 2015;26(8):1722–8.

    CAS  Article  Google Scholar 

  27. 27.

    Perez K, Shah N, Pricolo V, Vrees M, Roth L, Schechter S, et al. Complete neoadjuvant therapy in rectal cancer (CONTRE): a Brown University Oncology Research Group phase II study. J Clin Oncol. 2014;32(15_suppl):3530.

    Article  Google Scholar 

Download references


Dr. Da Wei Thong would like to acknowledge that this research was undertaken as part of the third year of the MSc in Surgical Sciences or Edinburgh Surgical Sciences Qualification

Author information



Corresponding author

Correspondence to Da Wei Thong.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Thong, D.W., Kim, J., Naik, A. et al. Delay to Adjuvant Chemotherapy: Survival and Recurrence in Patients of Rectal Cancer Treated with Neo-adjuvant Chemoradiotherapy and Surgery. J Gastrointest Canc 51, 877–886 (2020).

Download citation


  • Rectal neoplasm
  • Neoadjuvant therapy
  • Neoplasm metastasis
  • Time-to-treatment
  • Treatment delay