Journal of Gastrointestinal Cancer

, Volume 50, Issue 1, pp 98–108 | Cite as

Is It Possible a Conservative Approach After Radiochemotherapy in Locally Advanced Rectal Cancer (LARC)? A Systematic Review of the Literature and Meta-analysis

  • Francesco FioricaEmail author
  • Marco Trovò
  • Gabriele Anania
  • Daniele Marcello
  • Fabrizio Di Benedetto
  • Marina Marzola
  • Fabrizio D’Acapito
  • Guglielmo Nasti
  • Massimiliano Berretta
Original Research



Locally advanced rectal cancer is usually treated with a preoperative approach with radiochemotherapy followed by surgery. Patients obtaining a pathologic complete response have a very favorable long-term prognosis. This study was intended to assess whether major surgery can reduce tumor recurrences and prolong survival of patients with a complete response after radiochemotherapy.


Computerized literature search was performed to identify relevant articles. Comparative studies reporting the outcomes of non-operative and operative management in patients after neoadjuvant treatment were reviewed. Data synthesis was performed using Review Manager 5.0 software.


Twelve non-randomized comparative studies with a total of 1812 patients were suitable for analysis. There was no significant difference in overall survival at 3 and 5 years (odds ratio [OR] 1.31; 95% CI 0.64–2.69; p = 0.46 and 1.48; 95% CI 1.00–2.20; p = 0.50) and in disease-free survival at 3 and 5 years (odds ratio [OR] 1.20; 95% CI 0.68–2.14; p = 0.53 and 1.22; 95% CI 0.86–1.74; p = 0.26, respectively) between locally advanced rectal cancer patients treated with and without operative approach.


Major surgery does not seem to improve prognosis in patients obtaining a complete response after radiochemotherapy. Clinical trials, using clear criteria to identify complete response patients, are needed to recommend non-operative approach.


Rectal cancer conservative approach Conservative approach Radiochemotherapy 



Programma di ricerca Regione-Università, Regione Emilia-Romagna, bando Giovani Ricercatori “Alessandro Liberati” 2012 supported the idea.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Fiorica F, Cartei F, Licata A, Enea M, Ursino S, Colosimo C, et al. Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data. Cancer Treat Rev. 2010;36(7):539–49. Scholar
  2. 2.
    Capirci C, Valentini V, Cionini L, De Paoli A, Rodel C, Glynne-Jones R, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72(1):99–107. Scholar
  3. 3.
    Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo L-J, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44. Scholar
  4. 4.
    De Divitiis C, Nasti G, Montano M, Fisichella R, Iaffaioli RV, Berretta M. Prognostic and predictive response factors in colorectal cancer patients: between hope and reality. World J Gastroenterol. 2014;20(41):15049–59. Scholar
  5. 5.
    Marijnen CAM, Kapiteijn E, van de Velde CJH, Martijn H, Steup WH, Wiggers T, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol Off J Am Soc Clin Oncol. 2002;20(3):817–25. Scholar
  6. 6.
    Rutten HJT, den Dulk M, Lemmens VEPP, van de Velde CJH, Marijnen CAM. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol. 2008;9(5):494–501. Scholar
  7. 7.
    Berretta M, Di Francia R, Tirelli U. Editorial—The new oncologic challenges in the 3RD millennium. WCRJ. 2014;1:e133.Google Scholar
  8. 8.
    Fiorica F, Cartei F, Carau B, Berretta S, Spartà D, Tirelli U, et al. Adjuvant radiotherapy on older and oldest elderly rectal cancer patients. Arch Gerontol Geriatr. 2009;49(1):54–9. Scholar
  9. 9.
    Berretta M, Di Benedetto F, Di Francia R, Lo Menzo E, Palmeri S, De Paoli P, et al. Colorectal cancer in elderly patients: from best supportive care to cure. Anti Cancer Agents Med Chem. 2013;13(9):1332–43. Scholar
  10. 10.
    Fiorica F, Stefanelli A, Fisichella R, Tirelli U, Berretta M. Comorbidity assessment and radiotherapy in elderly cancer patients. Eur Rev Med Pharmacol Sci. 2012;16(11):1605–6.Google Scholar
  11. 11.
    Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12. Scholar
  12. 12.
    Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712–6. Scholar
  13. 13.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88. Scholar
  14. 14.
    Caricato M, Borzomati D, Ausania F, Tonini G, Rabitti C, Valeri S, et al. Complementary use of local excision and transanal endoscopic microsurgery for rectal cancer after neoadjuvant chemoradiation. Surg Endosc. 2006;20(8):1203–7. Scholar
  15. 15.
    Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Silva e Sousa AH, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Trans Meet Am Surg Assoc. 2004;CXXII:309–16. Scholar
  16. 16.
    Kundel Y, Brenner R, Purim O, Peled N, Idelevich E, Fenig E, et al. Is local excision after complete pathological response to neoadjuvant chemoradiation for rectal cancer an acceptable treatment option? Dis Colon rectum. 2010;53(12):1624–31. CrossRefGoogle Scholar
  17. 17.
    Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256(6):965–72. Scholar
  18. 18.
    Ayloor Seshadri R, Kondaveeti SS, Jayanand SB, John A, Rajendranath R, Arumugam V, et al. Complete clinical response to neoadjuvant chemoradiation in rectal cancers: can surgery be avoided? Hepato-Gastroenterology. 2013;60(123):410–4. Google Scholar
  19. 19.
    Maas M, Beets-Tan RGH, Lambregts DMJ, Lammering G, Nelemans PJ, Engelen SME, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40. Scholar
  20. 20.
    Habr-Gama A, Sabbaga J, Gama-Rodrigues J, São Julião GP, Proscurshim I, Bailão Aguilar P, et al. Watch and wait approach following extended neoadjuvant chemoradiation for distal rectal cancer: are we getting closer to anal cancer management? Dis Colon rectum. 2013;56(10):1109–17. Scholar
  21. 21.
    Callender GG, Das P, Rodriguez-Bigas MA, Skibber JM, Crane CH, Krishnan S, et al. Local excision after preoperative chemoradiation results in an equivalent outcome to total mesorectal excision in selected patients with T3 rectal cancer. Ann Surg Oncol. 2010;17(2):441–7. Scholar
  22. 22.
    Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, et al. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016;17(2):174–83. Scholar
  23. 23.
    Araujo ROC, Valadão M, Borges D, Linhares E, de Jesus JP, Ferreira CG, et al. Nonoperative management of rectal cancer after chemoradiation opposed to resection after complete clinical response. A comparative study. Eur J Surg Oncol EJSO. 2015;41(11):1456–63. Scholar
  24. 24.
    Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. J Clin Oncol [Internet]. 2016. Available from
  25. 25.
    Bonnen M, Crane C, Vauthey J-N, Skibber J, Delclos ME, Rodriguez-Bigas M, et al. Long-term results using local excision after preoperative chemoradiation among selected T3 rectal cancer patients. Int J Radiat Oncol. 2004;60(4):1098–105. Scholar
  26. 26.
    Nappi A, Nasti G, Romano C, Cassata A, Silvestro L, Ottaiano A, Casaretti R, Iaffaioli RV. Multimodal treatment of recurrent colorectal cancer. WORLD CANCER Res J [Internet]. 2016 [cited 2017 Jun 24]; 3. Available from
  27. 27.
    Read TE, Andujar JE, Caushaj PF, Johnston DR, Dietz DW, Myerson RJ, et al. Neoadjuvant therapy for rectal cancer: histologic response of the primary tumor predicts nodal status. Dis Colon rectum. 2004;47(6):825–31. Scholar
  28. 28.
    Borschitz T, Wachtlin D, Möhler M, Schmidberger H, Junginger T. Neoadjuvant chemoradiation and local excision for T2-3 rectal cancer. Ann Surg Oncol. 2008;15(3):712–20. Scholar
  29. 29.
    Abraham NS, Byrne CJ, Young JM, Solomon MJ. Meta-analysis of well-designed nonrandomized comparative studies of surgical procedures is as good as randomized controlled trials. J Clin Epidemiol. 2010;63(3):238–45. Scholar
  30. 30.
    Ryan JE, Warrier SK, Lynch AC, Heriot AG. Assessing pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis. 2015;17(10):849–61. Scholar
  31. 31.
    Abrams MJ, Koffer PP, Leonard KL. The emerging non-operative management of non-metastatic rectal cancer: a population analysis. Anticancer Res. 2016;36(4):1699–702.Google Scholar
  32. 32.
    Cappellani A, Di Vita M, Zanghi A, Veroux P, Cavallaro A, Lo Menzo E, et al. Biological and clinical markers in colorectal cancer: state of the art. Front Biosci Sch Ed. 2010;2:422–31.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Francesco Fiorica
    • 1
    Email author
  • Marco Trovò
    • 2
  • Gabriele Anania
    • 1
  • Daniele Marcello
    • 1
  • Fabrizio Di Benedetto
    • 3
  • Marina Marzola
    • 1
  • Fabrizio D’Acapito
    • 4
  • Guglielmo Nasti
    • 5
  • Massimiliano Berretta
    • 6
  1. 1.Gastrointestinal Cancer Unit, Departments of Radiation Oncology, Medical Oncology and SurgeryUniversity Hospital FerraraFerraraItaly
  2. 2.Department of Radiation OncologyUdine General HospitalUdineItaly
  3. 3.Department of Liver and Multivisceral Transplant Center, Liver SurgeryUniversity Hospital ModenaModenaItaly
  4. 4.Department of Surgery and Advanced Oncological TherapiesState Hospital ForlìForlìItaly
  5. 5.Department of Abdominal Oncology, Istituto Nazionale per lo Studio e la Cura dei TumoriFondazione “G. Pascale”-IRCCSNaplesItaly
  6. 6.Division of Medical Oncology ANational Cancer Institute, IRCCSAvianoItaly

Personalised recommendations