The Time Between Chemoradiation and Surgery for Rectal Carcinoma Negatively Influences Mesorectal Excision Quality


Total mesorectal excision quality (TMEq) is a prognostic factor associated with local recurrence in rectal adenocarcinoma. Neoadjuvant chemoradiotherapy (NCRT) reduces the risk of tumor recurrence, but may compromise TMEq. The time between NCRT and surgery (TTS) and how it influences TMEq and tumor control were evaluated. In prospective registry, 236 patients after NCRT and TME were analyzed. NCRT involved radiotherapy with 45 Gy to the pelvis, plus tumor boost dose 5.4 Gy with concurrent 5-fluorouracil infusion. NCRT was followed by TME after 9 weeks on average (median 9.4 ± SD 2.5). TMEq was parametrically analyzed by standard three-grade system. With median follow-up of 47.5 months, 3-year overall survival (OS) was 83.8%, disease-free survival (DFS) was 77.7%, and 6.4% was the rate of local recurrence (LR). TTS was not associated with OS, DFS, or LR. TMEq was found to be associated with LR in univariate analysis, but not in multivariate, where pathological tumor stage and resection margins remained dominant predictors. TMEq was negatively influenced by inferior location of the tumor, longer TTS, higher tumor and nodal stage, presence of tumor perforation, perineural invasion, and close/positive resection margins. Nonetheless, TTS remained a strong predictor of TMEq in multivariate analyses. TTS was proven to be an independent predictor of TMEq. With longer TTS, fewer complete TME with intact mesorectal plane were observed. However, TTS was not associated with survival deterioration or tumor recurrence. These were negatively influenced by other factors interfering with TMEq, especially by pathological tumor stage and resection margins.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. 1.

    Parfitt JR, Driman DK (2007) The total mesorectal excision specimen for rectal cancer: a review of its pathological assessment. J Clin Pathol 60(8):849–855

    Article  Google Scholar 

  2. 2.

    Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1(8496):1479–1482

    CAS  Article  Google Scholar 

  3. 3.

    Kapiteijn E, Putter H, van de Velde CJ, Cooperative investigators of the Dutch ColoRectal Cancer Group (2002) Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in the Netherlands. Br J Surg 89(9):1142–1149

    CAS  Article  Google Scholar 

  4. 4.

    van Gijn W, Marijnen CA, Nagtegaal ID et al (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12(6):575–582

    Article  Google Scholar 

  5. 5.

    Bosset JF, Calais G, Mineur L et al (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol 15(2):184–190

    CAS  Article  Google Scholar 

  6. 6.

    Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740

    CAS  Article  Google Scholar 

  7. 7.

    Sauer R, Liersch T, Merkel S et al (2012) 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 30(16):1926–1933

    CAS  Article  Google Scholar 

  8. 8.

    Nagtegaal ID, van de Velde CJ, van der Worp E et al (2002) Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control. J Clin Oncol 20(7):1729–1734

    Article  Google Scholar 

  9. 9.

    Leonard D, Penninckx F, Fieuws S et al (2010) PROCARE, a multidisciplinary Belgian project on Cancer of the rectum. Factors predicting the quality of total mesorectal excision for rectal cancer. Ann Surg 252(6):982–988

    Article  Google Scholar 

  10. 10.

    Baik SH, Kim NK, Lee KY et al (2008) Factors influencing pathologic results after total mesorectal excision for rectal cancer: analysis of consecutive 100 cases. Ann Surg Oncol 15(3):721–728

    Article  Google Scholar 

  11. 11.

    Deng H, Chen H, Zhao L et al (2015) Quality of laparoscopic total mesorectal excision: results from a single institution in China. Hepatogastroenterology 62(138):264–267

    PubMed  Google Scholar 

  12. 12.

    Garlipp B, Ptok H, Schmidt U et al (2012) Factors influencing the quality of total mesorectal excision. Br J Surg 99(5):714–720

    CAS  Article  Google Scholar 

  13. 13.

    Bosch SL, Nagtegaal ID (2012) The importance of the Pathologist's role in assessment of the quality of the Mesorectum. Curr Colorectal Cancer Rep 8(2):90–98

    Article  Google Scholar 

  14. 14.

    Roh MS, Colangelo LH, O'Connell MJ et al (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27:5124–5130

    Article  Google Scholar 

  15. 15.

    Sautter-Bihl ML, Hohenberger W, Fietkau R et al (2013) Rectal cancer: when is the local recurrence risk low enough to refrain from the aim to prevent it? Strahlenther Onkol 189(2):105–110

    CAS  Article  Google Scholar 

  16. 16.

    Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2006) Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93(10):1215–1223

    CAS  Article  Google Scholar 

  17. 17.

    Hernando-Requejo O, López M, Cubillo A et al (2014) Complete pathological responses in locally advanced rectal cancer after preoperative IMRT and integrated-boost chemoradiation. Strahlenther Onkol 190(6):515–520

    Article  Google Scholar 

  18. 18.

    Wong RK, Tandan V, De Silva S, Figueredo A (2007) Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev 18(2):CD002102

    Google Scholar 

  19. 19.

    Foster JD, Jones EL, Falk S et al (2013) Timing of surgery after long-course neoadjuvant chemoradiotherapy for rectal cancer: a systematic review of the literature. Dis Colon Rectum 56(7):921–930

    Article  Google Scholar 

  20. 20.

    Sun Z, Adam MA, Kim J et al (2016) Optimal timing to surgery after neoadjuvant Chemoradiotherapy for locally advanced rectal Cancer. J Am Coll Surg 222(4):367–374

    Article  Google Scholar 

  21. 21.

    Pellizzon ACA (2019) Pre-operative radiotherapy to improve local control and survival in rectal cancer optimal time intervals between radiation and surgery. Pract Rep Oncol Radiother 24(1):1–2

    Article  Google Scholar 

  22. 22.

    Petersen C (2013) Optimal timing of surgery for rectal cancer after neoadjuvant chemoradiotherapy: which patients would benefit from waiting? Strahlenther Onkol 189(10):904–906

    CAS  Article  Google Scholar 

  23. 23.

    Sloothaak DA, Geijsen DE, van Leersum NJ et al (2013) Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg 100(7):933–939

    CAS  Article  Google Scholar 

  24. 24.

    Lefevre JH, Mineur L, Kotti S et al (2016) Effect of interval (7 or 11 weeks) between neoadjuvant Radiochemotherapy and surgery on complete pathologic response in rectal Cancer: a multicenter, randomized, controlled trial (GRECCAR-6). J Clin Oncol 34(31):3773–3778

    Article  Google Scholar 

  25. 25.

    Buka D, Dvorak J, Sitorova V et al (2017) The changes of tumour vascular endothelial growth factor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma. Contemp Oncol 21(1):48–53

    CAS  Google Scholar 

  26. 26.

    Hodek M, Sirák I, Ferko A et al (2016) Neoadjuvant chemoradiotherapy of rectal carcinoma : baseline hematologic parameters influencing outcomes. Strahlenther Onkol 192(9):632–640

    Article  Google Scholar 

  27. 27.

    Dvorak J, Sitorova V, Ryska A et al (2012) Prognostic significance of changes of tumor epidermal growth factor receptor expression after neoadjuvant chemoradiation in patients with rectal adenocarcinoma. Strahlenther Onkol 188(9):833–838

    CAS  Article  Google Scholar 

Download references


The review was supported by Progres Q40/06 – Charles University in Prague, and by Czech Republic Ministry of Health MHCZ-DRO (UHHK, 00179906). The authors would like to thank Dr. Ian McColl for proof-reading the manuscript. This paper contains data already published at ASTRO 2018 Annual Meeting (Int J Radiat Oncol Biol Phys 2018;102(3)S:E19, DOI:

Author information



Corresponding author

Correspondence to Milan Vošmik.

Ethics declarations

Conflict of Interest

All authors declare 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

Sirák, I., Pohanková, D., Ferko, A. et al. The Time Between Chemoradiation and Surgery for Rectal Carcinoma Negatively Influences Mesorectal Excision Quality. Pathol. Oncol. Res. 26, 1565–1572 (2020).

Download citation


  • Rectal carcinoma
  • Neoadjuvant chemoradiation
  • Mesorectal excision