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Predictive factors of complete pathological response in patients with locally advanced rectal cancer



Patients with locally advanced rectal cancer who achieve pathologic complete response (pCR) following neoadjuvant therapy have better long-term outcomes and could be spared from the perioperative and long-term morbidity of rectal resection. The aim of this study was to identify factors that predict the ability to achieve pCR at completion of conventional neoadjuvant therapy, therefore determining their suitability for non-surgical management.


A retrospective analysis was performed on data obtained from a prospectively maintained colorectal neoplasia database. Patients treated for biopsy-proven primary rectal adenocarcinoma between January 1, 2010, and February 28, 2018, who received neoadjuvant radiotherapy or chemoradiotherapy and had undergone surgical resection, were included in this study. Five-year oncologic outcome data was also obtained for 144 patients. Clinicopathological tumour characteristics and treatment regimens were analysed for correlation to clinical outcome.


Three hundred fifty-four patients met inclusion criteria for this study. We identified significant differences between patients achieving a pCR and those that did not for tumour type (adenocarcinoma vs. mucinous/signet ring; p = 0.008), pre-treatment serum CEA level (</≥ 2.5 μg/L; p = 0.003), neoadjuvant therapy type (short-course radiotherapy and long-course chemoradiotherapy; p = 0.008) and preoperative lymph node status (node-negative versus node-positive disease; p = 0.031). Additionally, this is the first report to our knowledge to identify a significant correlation with pCR and the degree of tumour fixity (mobile vs. fixed/tethered; p = 0.038).


This retrospective analysis identified factors that significantly impact a patients’ ability to achieve a pCR, which may prove useful for prospectively selecting patients suitable for non-surgical management of disease.

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  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424.

    Article  Google Scholar 

  2. Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM (2017) Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol 14(6):356–365.

    CAS  Article  PubMed  Google Scholar 

  3. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324(11):709–715.

    CAS  Article  PubMed  Google Scholar 

  4. Gastrointestinal Tumor Study, G (1985) Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 312(23):1465–1472.

    Article  Google Scholar 

  5. Araujo RO, Valadao M, Borges D, Linhares E, de Jesus JP, Ferreira CG, Victorino AP, Vieira FM, Albagli R (2015) Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response. A comparative study. Eur J Surg Oncol 41(11):1456–1463.

    CAS  Article  PubMed  Google Scholar 

  6. Rauch P, Miny J, Conroy T, Neyton L, Guillemin F (2004) Quality of life among disease-free survivors of rectal cancer. J Clin Oncol 22(2):354–360.

    Article  PubMed  Google Scholar 

  7. Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11(9):835–844.

    Article  Google Scholar 

  8. de Campos-Lobato LF, Stocchi L, da Luz Moreira A, Geisler D, Dietz DW, Lavery IC, Fazio VW, Kalady MF (2011) Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol 18(6):1590–1598.

    Article  PubMed  Google Scholar 

  9. Hartley A, Ho KF, McConkey C, Geh JI (2005) Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. Br J Radiol 78(934):934–938.

    CAS  Article  PubMed  Google Scholar 

  10. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474.

    Article  PubMed  Google Scholar 

  11. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, Campos FG, Kiss DR, Gama-Rodrigues J (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240(4):711–717 discussion 717-8

    PubMed  PubMed Central  Google Scholar 

  12. Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, Temple LK, Nash GM, Paty PB (2012) Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg 256(6):965–972.

    Article  PubMed  Google Scholar 

  13. Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewe KW, Buijsen J, Beets GL (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29(35):4633–4640.

    Article  PubMed  Google Scholar 

  14. Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, Melis M (2012) Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol 19(9):2822–2832.

    Article  PubMed  Google Scholar 

  15. Cui J, Fang H, Zhang L, Wu YL, Zhang HZ (2016) Advances for achieving a pathological complete response for rectal cancer after neoadjuvant therapy. Chronic Dis Transl Med 2(1):10–16.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Perez RO, Habr-Gama A, Sao Juliao GP, Proscurshim I, Fernandez LM, de Azevedo RU, Vailati BB, Fernandes FA, Gama-Rodrigues J (2016) Transanal endoscopic microsurgery (TEM) following neoadjuvant chemoradiation for rectal cancer: outcomes of salvage resection for local recurrence. Ann Surg Oncol 23(4):1143–1148.

    Article  PubMed  Google Scholar 

  17. McMurrick PJ, Oliva K, Carne P, Reid C, Polglase A, Bell S, Farmer KC, Ranchod P (2014) The first 1000 patients on an internet-based colorectal neoplasia database across private and public medicine in Australia: development of a binational model for the Colorectal Surgical Society of Australia and New Zealand. Dis Colon Rectum 57(2):167–173.

    CAS  Article  PubMed  Google Scholar 

  18. Bagante F, Spolverato G, Beal E, Merath K, Chen Q, Akgul O, Anders RA, Pawlik TM (2018) Impact of histological subtype on the prognosis of patients undergoing surgery for colon cancer. J Surg Oncol 117(7):1355–1363.

    Article  PubMed  Google Scholar 

  19. Khan M, Loree JM, Advani SM, Ning J, Li W, Pereira AAL, Lam M, Raghav K, Morris VK, Broaddus R, Maru D, Overman MJ, Kopetz S (2018) Prognostic implications of mucinous differentiation in metastatic colorectal carcinoma can be explained by distinct molecular and clinicopathologic characteristics. Clin Colorectal Cancer 17(4):e699–e709.

    Article  PubMed  PubMed Central  Google Scholar 

  20. García-Aguilar J, Hernandez de Anda E, Sirivongs P, Lee S-H, Madoff RD, Rothenberger DA (2003) A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 46(3):298–304.

    Article  PubMed  Google Scholar 

  21. McCawley N, Clancy C, O'Neill BD, Deasy J, McNamara DA, Burke JP (2016) Mucinous rectal adenocarcinoma is associated with a poor response to neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Dis Colon Rectum 59(12):1200–1208.

    Article  PubMed  Google Scholar 

  22. Oberholzer K, Menig M, Pohlmann A, Junginger T, Heintz A, Kreft A, Hansen T, Schneider A, Lollert A, Schmidberger H, Christoph D (2013) Rectal cancer: assessment of response to neoadjuvant chemoradiation by dynamic contrast-enhanced MRI. J Magn Reson Imaging 38(1):119–126.

    Article  PubMed  Google Scholar 

  23. Jayanand SB, Seshadri RA, Tapkire R (2011) Signet ring cell histology and non-circumferential tumors predict pathological complete response following neoadjuvant chemoradiation in rectal cancers. Int J Color Dis 26(1):23–27.

    Article  Google Scholar 

  24. Yun SO, Cho YB, Lee WY, Kim HC, Yun SH, Park YA, Huh JW (2017) Clinical significance of signet-ring-cell colorectal cancer as a prognostic factor. Ann Coloproctol 33(6):232–238.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Belli S, Aytac HO, Karagulle E, Yabanoglu H, Kayaselcuk F, Yildirim S (2014) Outcomes of surgical treatment of primary signet ring cell carcinoma of the colon and rectum: 22 cases reviewed with literature. Int Surg 99(6):691–698.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Baqar AR, Wilkins S, Staples M, Angus Lee CH, Oliva K, McMurrick P (2019) The role of preoperative CEA in the management of colorectal cancer: a cohort study from two cancer centres. Int J Surg 64:10–15.

    Article  PubMed  Google Scholar 

  27. Takagawa R, Fujii S, Ohta M, Nagano Y, Kunisaki C, Yamagishi S, Osada S, Ichikawa Y, Shimada H (2008) Preoperative serum carcinoembryonic antigen level as a predictive factor of recurrence after curative resection of colorectal cancer. Ann Surg Oncol 15(12):3433–3439.

    Article  PubMed  Google Scholar 

  28. Wiratkapun S, Kraemer M, Seow-Choen F, Ho YH, Eu KW (2001) High preoperative serum carcinoembryonic antigen predicts metastatic recurrence in potentially curative colonic cancer: results of a five-year study. Dis Colon Rectum 44(2):231–235.

    CAS  Article  PubMed  Google Scholar 

  29. Duffy MJ, van Dalen A, Haglund C, Hansson L, Klapdor R, Lamerz R, Nilsson O, Sturgeon C, Topolcan O (2003) Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines. Eur J Cancer 39(6):718–727.

    CAS  Article  PubMed  Google Scholar 

  30. Restivo A, Zorcolo L, Cocco IM, Manunza R, Margiani C, Marongiu L, Casula G (2013) Elevated CEA levels and low distance of the tumor from the anal verge are predictors of incomplete response to chemoradiation in patients with rectal cancer. Ann Surg Oncol 20(3):864–871.

    Article  PubMed  Google Scholar 

  31. Park YA, Sohn SK, Seong J, Baik SH, Lee KY, Kim NK, Cho CW (2006) Serum CEA as a predictor for the response to preoperative chemoradiation in rectal cancer. J Surg Oncol 93(2):145–150.

    Article  PubMed  Google Scholar 

  32. Probst CP, Becerra AZ, Aquina CT, Tejani MA, Hensley BJ, Gonzalez MG, Noyes K, Monson JR, Fleming FJ (2016) Watch and wait?--Elevated pretreatment CEA is associated with decreased pathological complete response in rectal cancer. J Gastrointest Surg 20(1):43–52; discussion 52.

    Article  PubMed  Google Scholar 

  33. Nicholls RJ, Mason AY, Morson BC, Dixon AK, Fry IK (1982) The clinical staging of rectal cancer. Br J Surg 69(7):404–409.

    CAS  Article  PubMed  Google Scholar 

  34. Wilkins S, Haydon A, Porter I, Oliva K, Staples M, Carne P, McMurrick P, Bell S (2016) Complete pathological response after neoadjuvant long-course chemoradiotherapy for rectal cancer and its relationship to the degree of T3 mesorectal invasion. Dis Colon Rectum 59(5):361–368.

    Article  PubMed  Google Scholar 

  35. Nicholls RJ, Galloway DJ, Mason AY, Boyle P (1985) Clinical local staging of rectal cancer. Br J Surg 72(Suppl):S51–S52

    Article  Google Scholar 

  36. Freedman LS, Macaskill P, Smith AN (1984) Multivariate analysis of prognostic factors for operable rectal cancer. Lancet. 2(8405):733–736

    CAS  Article  Google Scholar 

  37. De Caluwe L, Van Nieuwenhove Y, Ceelen WP (2013) Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev (2):CD006041.

  38. Liu SX, Zhou ZR, Chen LX, Yang YJ, Hu ZD, Zhang TS (2015) Short-course versus long-course preoperative radiotherapy plus delayed surgery in the treatment of rectal cancer: a meta-analysis. Asian Pac J Cancer Prev 16(14):5755–5762

    Article  Google Scholar 

  39. Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J (2012) Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol 30(31):3827–3833.

    Article  PubMed  Google Scholar 

  40. Ruo L, Tickoo S, Klimstra DS, Minsky BD, Saltz L, Mazumdar M, Paty PB, Wong WD, Larson SM, Cohen AM, Guillem JG (2002) Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 236(1):75–81

    Article  Google Scholar 

  41. Garland ML, Vather R, Bunkley N, Pearse M, Bissett IP (2014) Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Color Dis 29(3):301–307.

    Article  Google Scholar 

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We thank the colorectal surgeons at Cabrini Hospital, Alfred Hospital and the Avenue Hospital for their contributions to this study.


These studies are funded in part by the “Let’s Beat Bowel Cancer” (, a benevolent fund raising and public awareness foundation, and the Collie Foundation.

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Authors and Affiliations



RME, KO, CK, RY and PJM participated in the conceptualization and study design; KO performed the data collection; RME performed the data analysis; RME, KO, CK and PJM participated in writing—original draft; RME, KO, CK, RY and PJM participated in writing—review and editing. All authors approved the final version of the manuscript.

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Correspondence to Rebekah M. Engel.

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The authors declare that they have no conflict of interest.

Ethical approval

Ethics approval for this study was granted by the Cabrini Human Research Ethics Committee (Reference #02-10-04-06 and #09-29-10-18).

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Informed consent was obtained for all individual patients included on the database.

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Engel, R.M., Oliva, K., Koulis, C. et al. Predictive factors of complete pathological response in patients with locally advanced rectal cancer. Int J Colorectal Dis 35, 1759–1767 (2020).

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  • Rectal adenocarcinoma
  • Neoadjuvant therapy
  • Chemoradiotherapy
  • Pathological response