Advertisement

Complete Clinical Response in Rectal Cancer After Neoadjuvant Therapy: Organ Preservation Strategies and the Role of Surgery

  • Laura Melina Fernandez
  • Guilherme Pagin São Julião
  • Bruna Borba Vailati
  • Angelita Habr-Gama
  • Rodrigo O. Perez
Chapter

Abstract

The traditional concept of rectal cancer management has changed significantly over the last few years. Although surgical resection is still the main pillar in the management of distal rectal cancer by proctectomy and total mesorectal excision (TME), organ preservation strategies have gained popularity. Neoadjuvant chemoradiation (nCRT) may result in significant tumor regression and may lead to complete pathological response in up to 42% of patients. In an attempt to avoid considerable morbidity and functional consequences of proctectomy and TME, selected patients that develop complete clinical response to neoadjuvant chemoradiation have been offered organ-preserving strategies including transanal local excision or even no immediate surgery and strict follow-up (watch and wait (WW)) with acceptable oncological outcomes and minimal functional consequences. Transanal local excisions may be an attractive organ-preserving strategy in this setting by providing definitive confirmation of complete primary tumor regression after nCRT. However, specific issues in tumor regression patterns, wound healing, postoperative function, and surveillance may constitute significant disadvantages of this approach over watch and wait.

Keywords

Rectal cancer Organ preservation Watch and wait Local excision Neoadjuvant chemoradiation 

Notes

Conflicts of Interest

The authors have no conflicts of interest to declare.

References

  1. 1.
    Smith FM, Rao C, Oliva Perez R, et al. Avoiding radical surgery improves early survival in elderly patients with rectal cancer, demonstrating complete clinical response after neoadjuvant therapy: results of a decision-analytic model. Dis Colon Rectum. 2015;58:159–71.CrossRefGoogle Scholar
  2. 2.
    Denost Q, Laurent C, Capdepont M, et al. Risk factors for fecal incontinence after intersphincteric resection for rectal cancer. Dis Colon Rectum. 2011;54:963–8.CrossRefGoogle Scholar
  3. 3.
    Didailler R, Denost Q, Loughlin P, et al. Antegrade Enema after total mesorectal excision for rectal cancer: the last chance to avoid definitive colostomy for refractory low anterior resection syndrome and fecal incontinence. Dis Colon Rectum. 2018;61:667–72.PubMedGoogle Scholar
  4. 4.
    Celerier B, Denost Q, Van Geluwe B, et al. The risk of definitive stoma formation at 10 years after low and ultralow anterior resection for rectal cancer. Color Dis. 2016;18:59–66.CrossRefGoogle Scholar
  5. 5.
    Chen L, Glimelius I, Neovius M, et al. Risk of disability pension in patients following rectal cancer treatment and surgery. Br J Surg. 2015;102:1426–32.CrossRefGoogle Scholar
  6. 6.
    Smith FM, Waldron D, Winter DC. Rectum-conserving surgery in the era of chemoradiotherapy. Br J Surg. 2010;97:1752–64.CrossRefGoogle Scholar
  7. 7.
    Habr-Gama A, Perez RO, Wynn G, et al. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010;53:1692–8.CrossRefGoogle Scholar
  8. 8.
    Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–7. discussion 7-8.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefGoogle Scholar
  10. 10.
    Sauer R, Liersch T, Merkel S, 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;30:1926–33.CrossRefGoogle Scholar
  11. 11.
    Taylor FG, Quirke P, Heald RJ, et al. Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, European study. Ann Surg. 2011;253:711–9.CrossRefGoogle Scholar
  12. 12.
    Peeters KC, van de Velde CJ, Leer JW, et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study. J Clin Oncol. 2005;23:6199–206.CrossRefGoogle Scholar
  13. 13.
    Loos M, Quentmeier P, Schuster T, et al. Effect of preoperative radio(chemo)therapy on long-term functional outcome in rectal cancer patients: a systematic review and meta-analysis. Ann Surg Oncol. 2013;20:1816–28.CrossRefGoogle Scholar
  14. 14.
    Perez RO, Habr-Gama A, Sao Juliao GP, et al. Predicting complete response to neoadjuvant CRT for distal rectal cancer using sequential PET/CT imaging. Tech Coloproctol. 2014;18:699–708.CrossRefGoogle Scholar
  15. 15.
    Garcia-Aguilar J, Shi Q, Thomas CR Jr, et al. A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer: preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol. 2012;19:384–91.CrossRefGoogle Scholar
  16. 16.
    Habr-Gama A, Sao Juliao GP, Gama-Rodrigues J, et al. Baseline T classification predicts early tumor regrowth after nonoperative management in distal rectal cancer after extended neoadjuvant chemoradiation and initial complete clinical response. Dis Colon Rectum. 2017;60:586–94.CrossRefGoogle Scholar
  17. 17.
    Habr-Gama A, Gama-Rodrigues J, Perez RO. Is tailoring treatment of rectal cancer the only true benefit of long-course neoadjuvant chemoradiation? Dis Colon Rectum. 2013;56:264–6.CrossRefGoogle Scholar
  18. 18.
    Radu C, Berglund A, Pahlman L, et al. Short-course preoperative radiotherapy with delayed surgery in rectal cancer - a retrospective study. Radiother Oncol. 2008;87:343–9.CrossRefGoogle Scholar
  19. 19.
    Appelt AL, Ploen J, Vogelius IR, et al. Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:74–80.CrossRefGoogle Scholar
  20. 20.
    Appelt AL, Ploen J, Harling H, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16:919–27.CrossRefGoogle Scholar
  21. 21.
    Vuong T, Devic S. High-dose-rate pre-operative endorectal brachytherapy for patients with rectal cancer. J Contemp Brachytherapy. 2015;7:183–8.CrossRefGoogle Scholar
  22. 22.
    Gerard JP, Benezery K, Doyen J, et al. Aims of combined modality therapy in rectal cancer (M0). Recent results. Cancer Res. 2014;203:153–69.Google Scholar
  23. 23.
    Sun Myint A, Smith FM, Gollins S, et al. Dose escalation using contact x-ray brachytherapy after external beam radiotherapy as nonsurgical treatment option for rectal cancer: outcomes from a single-center experience. Int J Radiat Oncol Biol Phys. 2018;100(3):565–73.Google Scholar
  24. 24.
    Habr-Gama A, Perez RO, Sabbaga J, et al. Increasing the rates of complete response to neoadjuvant chemoradiotherapy for distal rectal cancer: results of a prospective study using additional chemotherapy during the resting period. Dis Colon Rectum. 2009;52:1927–34.CrossRefGoogle Scholar
  25. 25.
    Habr-Gama A, Sabbaga J, Gama-Rodrigues J, 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;56:1109–17.CrossRefGoogle Scholar
  26. 26.
    Fu XL, Fang Z, Shu LH, et al. Meta-analysis of oxaliplatin-based versus fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy for locally advanced rectal cancer. Oncotarget. 2017;8(21):34340–51.Google Scholar
  27. 27.
    Hupkens BJP, Martens MH, Stoot JH, et al. Quality of life in rectal cancer patients after chemoradiation: watch-and-wait policy versus standard resection - a matched-controlled study. Dis Colon Rectum. 2017;60:1032–40.CrossRefGoogle Scholar
  28. 28.
    Vailati BB, Habr-Gama A, Mattacheo AE, et al. Quality of life in patients with rectal cancer after chemoradiation: watch-and-wait policy versus standard resection-are we comparing apples to oranges? Dis Colon Rectum. 2018;61:e21.CrossRefGoogle Scholar
  29. 29.
    Schrag D, Weiser MR, Goodman KA, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32:513–8.CrossRefGoogle Scholar
  30. 30.
    Fornaro L, Caparello C, Vivaldi C, et al. Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: a systematic review. World J Gastroenterol. 2014;20:6081–91.CrossRefGoogle Scholar
  31. 31.
    Borg C, Andre T, Mantion G, et al. Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. Ann Oncol. 2014;25:2205–10.CrossRefGoogle Scholar
  32. 32.
    Dellas K, Buller J, Gortz GJ, et al. Analysis of bevacizumab-based preoperative radiochemotherapy in patients with locally advanced rectal cancer on surgery-associated spectrum of complications. Ann Surg Oncol. 2014;21:1352–60.CrossRefGoogle Scholar
  33. 33.
    Patel UB, Brown G, Rutten H, et al. Comparison of magnetic resonance imaging and histopathological response to chemoradiotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2012;19:2842–52.CrossRefGoogle Scholar
  34. 34.
    Francois Y, Nemoz CJ, Baulieux J, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999;17:2396.CrossRefGoogle Scholar
  35. 35.
    Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250:582–9.PubMedGoogle Scholar
  36. 36.
    Garcia-Aguilar J, Smith DD, Avila K, et al. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011;254:97–102.CrossRefGoogle Scholar
  37. 37.
    Garcia-Aguilar J, Chow OS, Smith DD, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16:957–66.CrossRefGoogle Scholar
  38. 38.
    Rullier E, Rouanet P, Tuech JJ, et al. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet. 2017;390:469.CrossRefGoogle Scholar
  39. 39.
    Hupkens BJP, Maas M, Martens MH, et al. Organ preservation in rectal cancer after chemoradiation: should we extend the observation period in patients with a clinical near-complete response? Ann Surg Oncol. 2018;25(1):197–203.Google Scholar
  40. 40.
    Perez RO, Habr-Gama A, Sao Juliao GP, et al. Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks? Int J Radiat Oncol Biol Phys. 2012;84:1159–65.CrossRefGoogle Scholar
  41. 41.
    Perez RO, Habr-Gama A, Pereira GV, et al. Role of biopsies in patients with residual rectal cancer following neoadjuvant chemoradiation after downsizing: can they rule out persisting cancer? Color Dis. 2012;14:714–20.CrossRefGoogle Scholar
  42. 42.
    Duldulao MP, Lee W, Streja L, et al. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer. Dis Colon Rectum. 2013;56:142–9.CrossRefGoogle Scholar
  43. 43.
    Lambregts DM, Maas M, Bakers FC, et al. Long-term follow-up features on rectal MRI during a wait-and-see approach after a clinical complete response in patients with rectal cancer treated with chemoradiotherapy. Dis Colon Rectum. 2011;54:1521–8.CrossRefGoogle Scholar
  44. 44.
    Patel UB, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011;29:3753–60.CrossRefGoogle Scholar
  45. 45.
    Lambregts DM, van Heeswijk MM, Delli Pizzi A, et al. Diffusion-weighted MRI to assess response to chemoradiotherapy in rectal cancer: main interpretation pitfalls and their use for teaching. Eur Radiol. 2017;27:4445.CrossRefGoogle Scholar
  46. 46.
    Curvo-Semedo L, Lambregts DM, Maas M, et al. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy--conventional MR volumetry versus diffusion-weighted MR imaging. Radiology. 2011;260:734–43.CrossRefGoogle Scholar
  47. 47.
    Dos Anjos DA, Perez RO, Habr-Gama A, et al. Semiquantitative volumetry by sequential PET/CT may improve prediction of complete response to neoadjuvant chemoradiation in patients with distal rectal cancer. Dis Colon Rectum. 2016;59:805–12.CrossRefGoogle Scholar
  48. 48.
    Maas M, Lambregts DM, Nelemans PJ, et al. Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI: selection for organ-saving treatment. Ann Surg Oncol. 2015;22:3873–80.CrossRefGoogle Scholar
  49. 49.
    Smith FM, Ahad A, Perez RO, et al. Local excision techniques for rectal cancer after neoadjuvant chemoradiotherapy: what are we doing? Dis Colon Rectum. 2017;60:228–39.CrossRefGoogle Scholar
  50. 50.
    Clancy C, Burke JP, Albert MR, et al. Transanal endoscopic microsurgery versus standard transanal excision for the removal of rectal neoplasms: a systematic review and meta-analysis. Dis Colon Rectum. 2015;58:254–61.CrossRefGoogle Scholar
  51. 51.
    Perez RO, Habr-Gama A, Sao Juliao GP, et al. Transanal endoscopic microsurgery for residual rectal cancer after neoadjuvant chemoradiation therapy is associated with significant immediate pain and hospital readmission rates. Dis Colon Rectum. 2011;54:545–51.CrossRefGoogle Scholar
  52. 52.
    Sao Juliao GP, Ortega CD, Vailati BB, et al. Magnetic resonance imaging following neoadjuvant chemoradiation and transanal endoscopic microsurgery for rectal cancer. Color Dis. 2017;19:O196–203.CrossRefGoogle Scholar
  53. 53.
    Habr-Gama A, Lynn PB, Jorge JM, et al. Impact of organ-preserving strategies on anorectal function in patients with distal rectal cancer following neoadjuvant chemoradiation. Dis Colon Rectum. 2016;59:264–9.CrossRefGoogle Scholar
  54. 54.
    Bujko K, Richter P, Smith FM, et al. Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders: a prospective multicentre study. Radiother Oncol. 2013;106:198–205.CrossRefGoogle Scholar
  55. 55.
    Morino M, Allaix ME, Arolfo S, et al. Previous transanal endoscopic microsurgery for rectal cancer represents a risk factor for an increased abdominoperineal resection rate. Surg Endosc. 2013;27:3315–21.CrossRefGoogle Scholar
  56. 56.
    Hompes R, McDonald R, Buskens C, et al. Completion surgery following transanal endoscopic microsurgery: assessment of quality and short- and long-term outcome. Color Dis. 2013;15:e576–81.CrossRefGoogle Scholar
  57. 57.
    Doornebosch PG, Ferenschild FT, de Wilt JH, et al. Treatment of recurrence after transanal endoscopic microsurgery (TEM) for T1 rectal cancer. Dis Colon Rectum. 2010;53:1234–9.CrossRefGoogle Scholar
  58. 58.
    Perez RO, Habr-Gama A, Sao Juliao GP, et al. Transanal endoscopic microsurgery (TEM) following neoadjuvant chemoradiation for rectal cancer: outcomes of salvage resection for local recurrence. Ann Surg Oncol. 2016;23:1143–8.CrossRefGoogle Scholar
  59. 59.
    Koedam TWA, Veltcamp Helbach M, Penna M, et al. Short-term outcomes of transanal completion total mesorectal excision (cTaTME) for rectal cancer: a case-matched analysis. Surg Endosc. 2018;33:103–9.CrossRefGoogle Scholar
  60. 60.
    Habr-Gama A, Sao Juliao GP, Perez RO. Nonoperative management of rectal cancer: identifying the ideal patients. Hematol Oncol Clin North Am. 2015;29:135–51.CrossRefGoogle Scholar
  61. 61.
    Hallam S, Messenger DE, Thomas MG. A systematic review of local excision after neoadjuvant therapy for rectal cancer: are ypT0 tumors the limit? Dis Colon Rectum. 2016;59:984–97.CrossRefGoogle Scholar
  62. 62.
    Dossa F, Chesney TR, Acuna SA, et al. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:501.CrossRefGoogle Scholar
  63. 63.
    Dattani M, Heald RJ, Goussous G, et al. Oncological and survival outcomes in watch and wait patients with a clinical complete response after neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and pooled analysis. Ann Surg. 2018;268:955.CrossRefGoogle Scholar
  64. 64.
    Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88:822–8.CrossRefGoogle Scholar
  65. 65.
    Kong JC, Guerra GR, Warrier SK, et al. Outcome and salvage surgery following “watch and wait” for rectal cancer after neoadjuvant therapy: a systematic review. Dis Colon Rectum. 2017;60:335–45.PubMedGoogle Scholar
  66. 66.
    Maas M, Nelemans PJ, Valentini V, 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;11:835–44.CrossRefGoogle Scholar
  67. 67.
    van der Valk MJM, Hilling DE, Bastiaannet E, et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018;391(10139):2537–45.Google Scholar
  68. 68.
    Perez RO, Habr-Gama A, Sao Juliao GP, et al. Should we give up the search for a clinically useful gene signature for the prediction of response of rectal cancer to neoadjuvant chemoradiation? Dis Colon Rectum. 2016;59:895–7.CrossRefGoogle Scholar
  69. 69.
    Bettoni F, Masotti C, Habr-Gama A, et al. Intratumoral genetic heterogeneity in rectal cancer: are single biopsies representative of the entirety of the tumor? Ann Surg. 2017;265:e4–6.CrossRefGoogle Scholar
  70. 70.
    Lopes-Ramos C, Koyama FC, Habr-Gama A, et al. Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer. Cancer Genet. 2015;208:319–26.CrossRefGoogle Scholar
  71. 71.
    Carpinetti P, Donnard E, Bettoni F, et al. The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation. Oncotarget. 2015;6:38360–71.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Laura Melina Fernandez
    • 1
  • Guilherme Pagin São Julião
    • 1
  • Bruna Borba Vailati
    • 1
  • Angelita Habr-Gama
    • 1
    • 2
  • Rodrigo O. Perez
    • 1
    • 2
    • 3
  1. 1.Angelita & Joaquim Gama InstituteSao PauloBrazil
  2. 2.Colorectal Surgery DivisionUniversity of São Paulo School of MedicineSao PauloBrazil
  3. 3.Ludwig Institute for Cancer Research São Paulo BranchSao PauloBrazil

Personalised recommendations