Skip to main content

Advertisement

Log in

Locally Advanced Rectal Cancer: What We Learned in the Last Two Decades and the Future Perspectives

  • Review Article
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

The advancement in surgical techniques, optimization of systemic chemoradiotherapy, and development of refined diagnostic and imaging modalities have brought a phenomenal shift in the treatment of the locally advanced rectal cancer. Although each therapeutic option has shown substantial progress in their field, it is finding their ideal amalgamation which has baffled the clinician and researchers alike. In the effort to identifying the perfect salutary treatment plan, we have even shifted our attention from the trimodal approach to non-operative “watchful waiting” to more recent individualized care. In this article, we acknowledge the scientific progress in the management of locally advanced rectal cancer and compare the opportunities as well as the obstacles while implementing them clinically. We also explore the current challenges and controversies surrounding the multidisciplinary approach and highlight the new trends and recent advances with an ultimate goal to improve the patients’ quality of life.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fry RD, Mahmoud NN, Maron DJ, Bleier J. Colon and rectum. In C. M. Townsend, R. D. Beauchamp, B. M. Evers, & K. L. Mattox (Eds.), Sabiston Textbook of Surgery. Philadelphia, PA: Saunders Elsevier. 2008.

  2. Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg. 1982;69(10):613–6.

    Article  CAS  PubMed  Google Scholar 

  3. Birgisson H, Talbäck M, Gunnarsson U, et al. Improved survival in cancer of the colon and rectum in Sweden. Eur J Surg Oncol. 2005;31(8):845–53.

    Article  CAS  PubMed  Google Scholar 

  4. Basu S, Srivastava V, Shukla VK. Recent advances in the management of carcinoma of the rectum. Clin Exp Gastroenterol. 2009;2:49–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maurer CA, Renzulli P, Kull C, et al. The impact of the introduction of total mesorectal excision on local recurrence rate and survival in rectal cancer: long-term results. Ann Surg Oncol. 2011;18(7):1899–906.

    Article  CAS  PubMed  Google Scholar 

  6. Nicholls J. No more “standard” abdominoperineal excision. Colorectal Dis. 2013;15(11):1329–30.

    Article  PubMed  Google Scholar 

  7. Tekkis PP, Heriot AG, Smith J, et al. Association of Coloproctology of Great Britain and Ireland. Comparison of circumferential margin involvement between restorative and nonrestorative resections for rectal cancer. Colorectal Dis. 2005;7(4):369–74.

  8. Holm T, Ljung A, Häggmark T, et al. Extended abdominoperineal resection with gluteus maximus flap reconstruction of the pelvic floor for rectal cancer. Br J Surg. 2007;94(2):232–8.

    Article  CAS  PubMed  Google Scholar 

  9. Huang A, Zhao H, Ling T, et al. Oncological superiority of extralevator abdominoperineal resection over conventional abdominoperineal resection: a meta-analysis. Int J Colorectal Dis. 2014;29(3):321–7.

    Article  PubMed  Google Scholar 

  10. Gunderson LL, Sosin H. Areas of failure found at reoperation (second or symptomatic look) following “curative surgery” for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy. Cancer. 1974;34:1278–92.

    Article  CAS  PubMed  Google Scholar 

  11. Cass AW, Million RR, Pfaff WW. Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer. 1976;37:2861–5.

    Article  CAS  PubMed  Google Scholar 

  12. Gilbertsen VA, Nelms JM. The prevention of invasive cancer of the rectum. Cancer. 1978;41:1137–9.

    Article  CAS  PubMed  Google Scholar 

  13. Douglass HO Jr, Moertel CG, Mayer RJ, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med. 1986;315:1294–5.

    Article  PubMed  Google Scholar 

  14. KrookJE MCG, Gunderson LL, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324:709–15.

    Article  Google Scholar 

  15. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA. 1990;264:1444–50.

    Article  Google Scholar 

  16. Sauer R, Becker H, Hohenberger W, et al. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. Roh MS, Colangelo LH, O’Connell MJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Reyngold M, Niland J, ter Veer A, et al. Neoadjuvant radiotherapy use in locally advanced rectal cancer at NCCN member institutions. J Natl ComprCanc Netw. 2014;12:235–43.

    Article  Google Scholar 

  20. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336(14):980–7.

    Article  Google Scholar 

  21. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345(9):638–46.

  22. van Gijn W, Marijnen CA, Nagtegaal ID, et al. Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12(6):575–82.

  23. Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811–20.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Peeters KC, Marijnen CA, Nagtegaal ID, et al. Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007;246:693–701.

  25. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93:1215–23.

    Article  CAS  PubMed  Google Scholar 

  26. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004;72:15–24.

  27. Ngan SY, Burmeister B, Fisher RJ, et al. 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. 2004;30:3827–33.

  28. Erlandsson J, Holm T, Pettersson D, et al. The Stockholm III Trial on optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer – a randomised controlled trial. Lancet Oncol. 2017;18:336–46.

    Article  PubMed  Google Scholar 

  29. Pietrzak L, Bujko K, Nowacki MP, et al. Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiother Oncol. 2007;84:217–25.

    Article  PubMed  Google Scholar 

  30. Ngan S, Fisher R, Burmeister B, et al. Long-term quality of life in patients treated in TROG 01.04: a randomized trial comparing short course and long course preoperative radiation therapy for rectal cancer. Int J Radiat Oncol. 2012;84:s143–4.

  31. Guckenberger M, Saur G, Wehner D, et al. Long-term quality-of-life after neoadjuvant short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer. Radiother Oncol. 2013;108:326–30.

    Article  PubMed  Google Scholar 

  32. Brændengen M, Tveit KM, Bruheim K, et al. Late patient-reported toxicity after preoperative radiotherapy or chemoradiotherapy in nonresectable rectal cancer: results from a randomized phase III study. Int J Radiat Oncol Biol Phys. 2011;81:1017–24.

    Article  PubMed  Google Scholar 

  33. Kollmorgen CF, Meagher AP, Wolff BG, et al. The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg. 1994;220:676–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sebag-Montefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–20.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Quirke P, Steele R, Monson J, et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. 2009;373:821–8.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Taylor FG, Quirke P, Heald RJ, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol. 2014;32:34–43.

    Article  PubMed  Google Scholar 

  37. Ishii Y, Hasegawa H, Endo T, et al. Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Oncol. 2010;36:1061–5.

    Article  CAS  PubMed  Google Scholar 

  38. Uehara K, Hiramatsu K, Maeda A, et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 phase II trial. Jpn J Clin Oncol. 2013;43:964–71.

    Article  PubMed  Google Scholar 

  39. Hasegawa J, Nishimura J, Mizushima T, et al. Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer. Cancer Chemother Pharmacol. 2014;73:1079–87.

    Article  CAS  PubMed  Google Scholar 

  40. Cercek A, Weiser MR, Goodman KA, et al. Complete pathologic response in the primary of rectal or colon cancer treated with FOLFOX without radiation. J Clin Oncol. 2010;28:abstr 3649.

  41. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Glynne-Jones R, Hall M. R, Lopes A, et al. BACCHUS: a randomised non-comparative phase II study of neoadjuvant chemotherapy (NACT) in patients with locally advanced rectal cancer (LARC). Heliyon. 2018;4(9), e00804.

  43. Deng Y, Chi P, Lan P, et al. Neoadjuvant modified FOLFOX6 with or without radiation versus fluorouracil plus radiation for locally advanced rectal cancer: final results of the Chinese FOWARC trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;37(34):3223–33.

    Article  CAS  PubMed  Google Scholar 

  44. Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.

    Article  CAS  PubMed  Google Scholar 

  45. Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.

    Article  CAS  PubMed  Google Scholar 

  46. Fernández-Martos C, Pericay C, Aparicio J, et al. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study. J Clin Oncol. 2010;28:859–65.

    Article  PubMed  Google Scholar 

  47. Fernandez-Martos C, Pericay C, Aparicio J, et al. Chemoradiation (CRT) followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant CRT and surgery for locally advanced rectal cancer: results of the Spanish GCR-3 randomized phase II trial after a median follow-up of 5 years. J Clin Oncol. 2014;32:abstr 383.

  48. Perez K, Safran H, Sikov W, et al. Complete neoadjuvant treatment for rectal cancer: the Brown University Oncology Group CONTRE Study. Am J Clin Oncol. 2017;40(3):283–7.

    Article  CAS  PubMed  Google Scholar 

  49. Schou JV, Larsen FO, Rasch L, et al. Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer. Ann Oncol. 2012;23:2627–33.

    Article  CAS  PubMed  Google Scholar 

  50. Maréchal R, Vos B, Polus M, et al. Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study. Ann Oncol. 2012;23:1525–30.

    Article  PubMed  Google Scholar 

  51. Koeberle D, Burkhard R, von Moos R, et al. Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer. Br J Cancer. 2008;98:1204–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Dewdney A, Cunningham D, Tabernero J, et al. Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol. 2012;30:1620–7.

    Article  CAS  PubMed  Google Scholar 

  53. Sclafani F, Gonzalez D, Cunningham D, et al. RAS mutations in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab (C) in MRI-defined, high-risk rectal cancer (RC). J Clin Oncol. 2014;32: abstr 489.

  54. Nogué M, Salud A, Vicente P, et al. Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study. Oncologist. 2011;16:614–20.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Simon G, David S-M, Richard A, et al. A phase II single arm feasibility trial of neoadjuvant chemotherapy (NAC) with oxaliplatin/fluorouracil (OxMdG) then short-course preoperative radiotherapy (SCPRT) then immediate surgery in operable rectal cancer (ORC): COPERNICUS (NCT01263171). J Clin Oncol. 2015;33:3609–3609.

    Article  Google Scholar 

  56. Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702–15.

    Article  CAS  PubMed  Google Scholar 

  57. 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.

    Article  PubMed  Google Scholar 

  58. Lee KH, Song MS, Park JB, et al. A phase II study of additional four-week chemotherapy with capecitabine during the resting periods after six-week neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Ann Coloproctol. 2013;29:192–7.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Zhu J, Gu W, Lian P, et al. A phase II trial of neoadjuvant IMRT-based chemoradiotherapy followed by one cycle of capecitabine for stage II/III rectal adenocarcinoma. Radiat Oncol. 2013;8:130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. Gao YH, Zhang X, An X, et al. Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer. Strahlenther Onkol. 2014;190:158–64.

    Article  PubMed  Google Scholar 

  62. van Dijk TH, Tamas K, Beukema JC, et al. Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol. 2013;24:1762–9.

    Article  PubMed  Google Scholar 

  63. Garcia-Aguilar J, Marcet J, Coutsoftides T, et al. Impact of neoadjuvant chemotherapy following chemoradiation on tumor response, adverse events, and surgical complications in patients with advanced rectal cancer treated with TME. J Clin Oncol. 2011;29:abstr 3514.

  64. Bujko K, Wyrwicz L, Rutkowski A, et al. Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Annals of oncology: official journal of the European Society for Medical Oncology. 2016;27(5):834–42.

    Article  CAS  PubMed  Google Scholar 

  65. Ciseł B, Pietrzak L, Michalski W, et al. Long-course preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Annals of oncology : official journal of the European Society for Medical Oncology. 2019;30(8):1298–303.

    Article  PubMed  Google Scholar 

  66. Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29–42.

    Article  CAS  PubMed  Google Scholar 

  67. Khrizman P, Niland JC, ter Veer A, et al. Postoperative adjuvant chemotherapy use in patients with stage II/III rectal cancer treated with neoadjuvant therapy: a national comprehensive cancer network analysis. J Clin Oncol. 2013;31:30–8.

    Article  PubMed  Google Scholar 

  68. Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.

    Article  CAS  PubMed  Google Scholar 

  69. Collette L, Bosset JF, den Dulk M, et al. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol. 2007;25:4379–86.

    Article  CAS  PubMed  Google Scholar 

  70. Bosset JF, Calais G, Mineur L, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.

    Article  CAS  PubMed  Google Scholar 

  71. Willett CG, Duda DG, di Tomaso E, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009;27:3020–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Resch G, De Vries A, Öfner D, et al. Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer–a two stage phase II clinical trial. Radiother Oncol. 2012;102:10–3.

    Article  CAS  PubMed  Google Scholar 

  73. Spigel DR, Bendell JC, McCleod M, et al. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. 2012;11:45–52.

    Article  CAS  PubMed  Google Scholar 

  74. Crane CH, Eng C, Feig BW, et al. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2010;76:824–30.

    Article  CAS  PubMed  Google Scholar 

  75. Glynne-Jones R, Mawdsley S, Harrison M. Cetuximab and chemoradiation for rectal cancer–is the water getting muddy? Acta Oncol. 2010;49:278–86.

    Article  CAS  PubMed  Google Scholar 

  76. Kachnic LA, Winter K, Myerson RJ, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86:27–33.

    Article  CAS  PubMed  Google Scholar 

  77. Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Phys. 2002;53:1111–6.

    Article  PubMed  Google Scholar 

  78. Mundt AJ, Lujan AE, Rotmensch J, et al. Intensity-modulated whole pelvic radiotherapy in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys. 2002;52:1330–7.

    Article  PubMed  Google Scholar 

  79. Robertson JM, Lockman D, Yan D, et al. The dose-volume relationship of small bowel irradiation and acute grade 3 diarrhea during chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2008;70:413–8.

    Article  CAS  PubMed  Google Scholar 

  80. Engels B, De Ridder M, Tournel K, et al. Preoperative helical tomotherapy and megavoltage computed tomography for rectal cancer: impact on the irradiated volume of small bowel. Int J Radiat Oncol Biol Phys. 2009;74:1476–80.

    Article  PubMed  Google Scholar 

  81. Kim JY, Kim DY, Kim TH, et al. Intensity-modulated radiotherapy with a belly board for rectal cancer. Int J Colorectal Dis. 2007;22:373–9.

    Article  PubMed  Google Scholar 

  82. Hong TS, Moughan J, Garofalo MC, et al. NRG Oncology Radiation Therapy Oncology Group 0822: a phase 2 study of preoperative chemoradiation therapy using intensity modulated radiation therapy in combination with capecitabine and oxaliplatin for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2015;93(1):29–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Samuelian JM, Callister MD, Ashman JB, et al. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2012;82:1981–7.

    Article  PubMed  Google Scholar 

  84. Parekh A, Truong MT, Pashtan I, et al. Acute gastrointestinal toxicity and tumor response with preoperative intensity modulated radiation therapy for rectal cancer. Gastrointest Cancer Res. 2013;6:137–43.

    PubMed  PubMed Central  Google Scholar 

  85. 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.

    Article  PubMed  Google Scholar 

  86. Guillem JG, Chessin DB, Shia J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol. 2005;23:3475–9.

    Article  PubMed  Google Scholar 

  87. Maretto I, Pomerri F, Pucciarelli S, et al. The potential of restaging in the prediction of pathologic response after preoperative chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2007;14:455–61.

    Article  PubMed  Google Scholar 

  88. Pastor C, Subtil JC, Sola J, et al. Accuracy of endoscopic ultrasound to assess tumor response after neoadjuvant treatment in rectal cancer: can we trust the findings? Dis Colon Rectum. 2011;54:1141–6.

    Article  PubMed  Google Scholar 

  89. Guillem JG, Ruby JA, Leibold T, et al. Neither FDG-PET nor CT can distinguish between a pathological complete response and an incomplete response after neoadjuvant chemoradiation in locally advanced rectal cancer: a prospective study. Ann Surg. 2013;258:289–95.

    Article  PubMed  Google Scholar 

  90. van der Paardt MP, Zagers MB, Beets-Tan RG, et al. Patients who undergo preoperative chemoradiotherapy for locally advanced rectal cancer restaged by using diagnostic MR imaging: a systematic review and meta-analysis. Radiology. 2013;269:101–12.

    Article  PubMed  Google Scholar 

  91. Gollub MJ, Gultekin DH, Akin O, et al. Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer. Eur Radiol. 2012;22:821–31.

    Article  CAS  PubMed  Google Scholar 

  92. Kluza E, Rozeboom ED, Maas M, et al. T2 weighted signal intensity evolution may predict pathological complete response after treatment for rectal cancer. Eur Radiol. 2013;23:253–61.

    Article  PubMed  Google Scholar 

  93. Lambregts DM, Beets GL, Maas M, et al. Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer. Ann Surg. 2011;253:539–45.

    Article  PubMed  Google Scholar 

  94. 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.

    Article  PubMed  Google Scholar 

  95. Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29:4633–40.

    Article  PubMed  Google Scholar 

  96. 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;263(3):458–64.

    Article  PubMed  Google Scholar 

  97. Habr-Gama A, Perez RO, Proscurshim I, et al. Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome? Int J Radiat Oncol Biol Phys. 2008;71:1181–8.

    Article  PubMed  Google Scholar 

  98. 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 717–8.

  99. Habr-Gama A, Perez RO, Nadalin W, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005;9:90–9; discussion 99–101.

  100. Habr-Gama A, Perez RO, Proscurshim I, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10:1319–28; discussion 1328–9.

  101. Habr-Gama A. Assessment and management of the complete clinical response of rectal cancer to chemoradiotherapy. Colorectal Dis;8 Suppl. 2006;3:21–4.

  102. Habr-Gama A, Perez RO, São Julião GP, et al. Nonoperative approaches to rectal cancer: a critical evaluation. Semin Radiat Oncol. 2011;21:234–9.

    Article  PubMed  Google Scholar 

  103. Smith JD, Ruby JA, Goodman KA, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256:965–72.

    Article  PubMed  Google Scholar 

  104. Coleman MG, Hanna GB, M Kennedy R. National Training Programme Lapco. The national training programme for laparoscopic colorectal surgery in England: a new training paradigm. Colorectal Dis. 2011;13(6):614–6.

  105. Morino M, Parini U, Giraudo G, et al. Laparoscopic total mesorectal excision: a consecutive series of 100 patients. Ann Surg. 2003;237(3):335–42.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Guillou PJ, Quirke P, Thorpe H, et al. Short-term endpoints of conventional versus laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet. 2005;365(9472):1718–26.

    Article  PubMed  Google Scholar 

  107. Hasegawa H, Ishii Y, Nishibori H, et al. Short- and midterm outcomes of laparoscopic surgery compared for 131 patients with rectal and rectosigmoid cancer. SurgEndosc. 2007;21(6):920–4.

    CAS  Google Scholar 

  108. Jayne DG, Guillou PJ, Thorpe H, et al. Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group. J Clin Oncol. 2007;25(21):3061–8.

    Article  PubMed  Google Scholar 

  109. Miyajima N, Fukunaga M, Hasegawa H, et al. Japan Society of Laparoscopic Colorectal Surgery. Results of a multicenter study of 1,057 cases of rectal cancer treated by laparoscopic surgery. Surg Endosc. 2009;23(1):113–8.

  110. Jayne DG, Thorpe HC, Copeland J, et al. Five-year follow-up of the Medical Research Council CLASICC trial of laparoscopically assisted versus open surgery for colorectal cancer. Br J Surg. 2010;97(11):1638–45.

    Article  CAS  PubMed  Google Scholar 

  111. Kang SB, Park JW, Jeong SY, et al. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial. Lancet Oncol. 2010;11(7):637–45.

    Article  PubMed  Google Scholar 

  112. Green BL, Marshall HC, Collinson F, et al. Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg. 2013;100(1):75–82.

    Article  CAS  PubMed  Google Scholar 

  113. Van der Pas MH, Haglind E, Cuesta MA, et al. Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol. 2013;14(3):210–8.

    Article  PubMed  Google Scholar 

  114. D’Annibale A, Pernazza G, Monsellato I, et al. Total mesorectal excision: a comparison of oncological and functional outcomes between robotic andv laparoscopic surgery for rectal cancer. SurgEndosc. 2013;27(6):1887–95.

    Google Scholar 

  115. Trastulli S, Farinella E, Cirocchi R, et al. Robotic resection compared with laparoscopic rectal resection for cancer: systematic review and meta-analysis of short-term outcome. Colorectal Dis. 2012;14(4):e134–56.

    Article  CAS  PubMed  Google Scholar 

  116. Jayne D, Pigazzi A, Marshall H, et al. Effect of robotic-assisted vs conventional laparoscopic surgery on risk of conversion to open laparotomy among patients undergoing resection for rectal cancer: the ROLARR randomized clinical trial. JAMA. 2017;318(16):1569–80.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Mohan HM, Evans MD, Larkin JO, et al. Multivisceral resection in colorectal cancer: a systematic review. Ann Surg Oncol. 2013;20(9):2929–36.

    Article  CAS  PubMed  Google Scholar 

  118. Beyond TME. Collaborative. Consensus statement on the multidisciplinary management of patients with recurrent and primary rectal cancer beyond total mesorectal excision planes. Br J Surg. 2013;100(8):1009–14

  119. Emhoff IA, Lee GC, Sylla P. Transanal colorectal resection using natural orifice translumenal endoscopic surgery (NOTES). Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2014;26(Suppl 1):29–42. https://doi.org/10.1111/den.12157.

    Article  PubMed  Google Scholar 

  120. de Lacy AM, Rattner DW, Adelsdorfer C, Tasende MM, Fernández M, Delgado S, Sylla P, Martínez-Palli G. Transanal natural orifice transluminal endoscopic surgery (NOTES) rectal resection: “down-to-up” total mesorectal excision (TME)–short-term outcomes in the first 20 cases. Surg Endosc. 2013;27(9):3165–72. https://doi.org/10.1007/s00464-013-2872-0.

    Article  PubMed  Google Scholar 

  121. Zhang H, Zhang YS, Jin XW, Li MZ, Fan JS, Yang ZH. Transanal single-port laparoscopic total mesorectal excision in the treatment of rectal cancer. Tech Coloproctol. 2013;17(1):117–23. https://doi.org/10.1007/s10151-012-0882-x.

    Article  CAS  PubMed  Google Scholar 

  122. Atallah S, Drake J, Martin-Perez B, Kang C, Larach S. Robotic transanal total mesorectal excision with intersphincteric dissection for extreme distal rectal cancer: a video demonstration. Tech Coloproctol. 2015;19(7):435. https://doi.org/10.1007/s10151-015-1304-7.

    Article  CAS  PubMed  Google Scholar 

  123. Verheijen, P. M., Consten, E. C., & Broeders, I. A. Robotic transanal total mesorectal excision for rectal cancer: experience with a first case. The international journal of medical robotics + computer assisted surgery : MRCAS. 2014;10(4), 423–426. https://doi.org/10.1002/rcs.1594

  124. Marks J, Ng S, Mak T. Robotic transanal surgery (RTAS) with utilization of a next-generation single-port system: a cadaveric feasibility study. Tech Coloproctol. 2017;21(7):541–5. https://doi.org/10.1007/s10151-017-1655-3.

    Article  CAS  PubMed  Google Scholar 

  125. Kuo LJ, Ngu JC, Tong YS, Chen CC. Combined robotic transanal total mesorectal excision (R-taTME) and single-site plus one-port (R-SSPO) technique for ultra-low rectal surgery-initial experience with a new operation approach. Int J Colorectal Dis. 2017;32(2):249–54. https://doi.org/10.1007/s00384-016-2686-3.

    Article  PubMed  Google Scholar 

  126. Huscher CG, Bretagnol F, Ponzano C. Robotic-assisted transanal total mesorectal excision: the key against the Achilles’ heel of rectal cancer? Ann Surg. 2015;261(5):e120–1. https://doi.org/10.1097/SLA.0000000000001089.

    Article  PubMed  Google Scholar 

  127. Deijen CL, Velthuis S, Tsai A, Mavroveli S, de Lange-de Klerk ES, Sietses C, Tuynman JB, Lacy AM, Hanna GB, Bonjer HJ. COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer. Surg Endosc. 2016;30(8):3210–5. https://doi.org/10.1007/s00464-015-4615-x.

    Article  PubMed  Google Scholar 

  128. Hendren SK, O’Connor BI, Liu M, Asano T, Cohen Z, Swallow CJ, Macrae HM, Gryfe R, McLeod RS. Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg. 2005;242(2):212–23. https://doi.org/10.1097/01.sla.0000171299.43954.ce.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Rombouts, A., Al-Najami, I., Abbott, N. L., Appelt, A., Baatrup, G., Bach, S., Bhangu, A., Garm Spindler, K. L., Gray, R., Handley, K., Kaur, M., Kerkhof, E., Kronborg, C. J., Magill, L., Marijnen, C., Nagtegaal, I. D., Nyvang, L., Peters, F. P., Pfeiffer, P., Punt, C., … for STAR-TREC Collaborative Group. Can we Save the rectum by watchful waiting or TransAnal microsurgery following (chemo) Radiotherapy versus Total mesorectal excision for early REctal Cancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study. BMJ Open. 2017;7(12): e019474. https://doi.org/10.1136/bmjopen-2017-019474.

    Article  Google Scholar 

  130. Peters FP, Teo M, Appelt AL, Bach S, Baatrup G, de Wilt J, Jensenius Kronborg C, Garm Spindler KL, Marijnen C, Sebag-Montefiore D. Mesorectal radiotherapy for early stage rectal cancer: a novel target volume. Clinical and translational radiation oncology. 2020;21:104–11. https://doi.org/10.1016/j.ctro.2020.02.001.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Network NCC, Rectal Cancer. Clinical practice guidelines in oncology: National Comprehensive Cancer Network. 2015;1. Accessed 2014 Sept 17.

  132. Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., Martus, P., Tschmelitsch, J., Hager, E., Hess, C. F., Karstens, J. H., Liersch, T., Schmidberger, H., Raab, R., & German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40. https://doi.org/10.1056/NEJMoa040694.

    Article  Google Scholar 

  133. Schiessel R, Karner-Hanusch J, Herbst F, Teleky B, Wunderlich M. Intersphincteric resection for low rectal tumours. Br J Surg. 1994;81(9):1376–8. https://doi.org/10.1002/bjs.1800810944.

    Article  CAS  PubMed  Google Scholar 

  134. Portier G, Ghouti L, Kirzin S, Guimbaud R, Rives M, Lazorthes F. Oncological outcome of ultra-low coloanal anastomosis with and without intersphincteric resection for low rectal adenocarcinoma. Br J Surg. 2007;94(3):341–5. https://doi.org/10.1002/bjs.5621.

    Article  CAS  PubMed  Google Scholar 

  135. Saito N, Ito M, Kobayashi A, Nishizawa Y, Kojima M, Nishizawa Y, Sugito M. Long-term outcomes after intersphincteric resection for low-lying rectal cancer. Ann Surg Oncol. 2014;21(11):3608–15. https://doi.org/10.1245/s10434-014-3762-y.

    Article  PubMed  Google Scholar 

  136. Williams NS, Murphy J. The APPEAR technique: a new concept in ultralow sphincter-saving resection. Dis Colon Rectum. 2008;51(3):369–71. https://doi.org/10.1007/s10350-007-9156-5.

    Article  PubMed  Google Scholar 

  137. Bosset JF, Calais G, Mineur L, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15(2):184–90.

    Article  CAS  PubMed  Google Scholar 

  138. Fernández-Martos C, Pericay C, Losa F, et al. Effect of aflibercept plus modified folfox6 induction chemotherapy before standard chemoradiotherapy and surgery in patients with high-risk rectal adenocarcinoma: the GEMCAD 1402 randomized clinical trial. JAMA Oncol. 2019;5(11):1566–73.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Fokas E, Allgäuer M, Polat B, et al. Randomized phase II Trial of Chemoradiotherapy Plus Induction or Consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2019;37(34):3212–22.

    Article  CAS  PubMed  Google Scholar 

  140. Zhu J, Liu A, Sun X, et al. Multicenter, randomized, phase III trial of neoadjuvant chemoradiation with capecitabine and irinotecan guided by UGT1A1 status in patients with locally advanced rectal cancer. J Clin Oncol. 2020;38(36):4231–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Wen Z, Haitao Z, Jun J, et al. Neoadjuvant chemotherapy with modified FOLFOXIRI for locally advanced rectal cancer: a single center phase II trial. J Clin Oncol. 2021;39:69–69.

    Article  Google Scholar 

  142. Rahma OE, Yothers G, Hong TS, et al. Use of total neoadjuvant therapy for locally advanced rectal cancer: initial results from the pembrolizumab arm of a phase 2 randomized clinical trial. JAMA Oncol. 2021;7(8):1225–30.

    Article  PubMed  Google Scholar 

  143. Management of locally advanced rectal cancer. ClinicalTrials.gov. 2021. Retrieved August 29, 2021, from https://clinicaltrials.gov/ct2/results?cond=locally+advanced+rectal+cancer&term=management&type=&rslt=&age_v=&gndr=&intr=&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&rsub=&strd_s=1%2F1%2F2015&strd_e=12%2F31%2F2021&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Somprakas Basu.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

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

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srivastava, V., Goswami, A.G., Basu, S. et al. Locally Advanced Rectal Cancer: What We Learned in the Last Two Decades and the Future Perspectives. J Gastrointest Canc 54, 188–203 (2023). https://doi.org/10.1007/s12029-021-00794-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-021-00794-9

Keywords

Navigation