Current Colorectal Cancer Reports

, Volume 15, Issue 6, pp 157–169 | Cite as

Local Therapy Options for Recurrent Rectal and Anal Cancer: Current Strategies and New Directions

  • Edward Christopher Dee
  • Christine E. Eyler
  • Nina N. Sanford
  • Jennifer Y. WoEmail author
Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer (PP Lee and AC Raldow, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer


Purpose of Review

Although uncommon, locally recurrent rectal cancer (LRRC) and locally recurrent anal cancer (LRAC) after definitive chemoradiation can confer high morbidity and mortality. Although surgery is critical for management, recent studies show promising results with other locally directed and/or systemic treatment approaches. Here we review the literature to examine recent advances in management of this patient population.

Recent Findings

For LRRC, studies demonstrate success with newer surgical approaches and redefine contraindications for surgery. The roles of brachytherapy, repeat external beam irradiation, and induction chemotherapy are under investigation. Advances in LRAC show that surgery remains a core element of treatment after primary chemoradiation failure. Recent reports of overall survival are promising.


Surgery remains the mainstay of treatment for LRRC and LRAC, and overall survival is improving. Benefits of newer surgical, radiotherapeutic, and other treatment approaches are being elucidated. These findings pave the way for further improvements in cancer-specific outcomes and quality of life.


Locally recurrent rectal cancer Locally recurrent anal cancer Oncologic outcomes Rectal cancer Oncologic outcomes Intraoperative radiotherapy 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.PubMedGoogle Scholar
  2. 2.
    Siegel RL, Miller, et al. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.PubMedGoogle Scholar
  3. 3.
    Tawadros PS, Paquette IM, Hanly AM, Mellgren AF, Rothenberger DA, Madoff RD. Adenocarcinoma of the rectum in patients under age 40 is increasing. Dis Colon Rectum. 2015;58:474–8.PubMedGoogle Scholar
  4. 4.
    Valvo F, Ciurlia E, Avuzzi B, Doci R, Ducreux M, Roelofsen F, et al. Cancer of the anal region. Crit Rev Oncol Hematol. 2019;135:115–27.PubMedGoogle Scholar
  5. 5.
    Morton M, Melnitchouk N, Bleday R. Squamous cell carcinoma of the anal canal. Curr Probl Cancer. 2018;42:486–92.PubMedGoogle Scholar
  6. 6.
    Gaertner WB, Kwaan MR, Madoff RD, Melton GB. Rectal cancer: an evidence-based update for primary care providers. World J Gastroenterol. 2015;21:7659–71.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Palmer G, Martling A, Cedermark B, Holm T. A population-based study on the management and outcome in patients with locally recurrent rectal cancer. Ann Surg Oncol. 2007;14:447–54.PubMedGoogle Scholar
  8. 8.
    Lee DJK, Sagar PM, Sadadcharam G, Tan KY. Advances in surgical management for locally recurrent rectal cancer: how far have we come? World J Gastroenterol. 2017;23:4170–80.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Harris CA, Solomon MJ, Heriot AG, Sagar PM, Tekkis PP, Dixon L, et al. The outcomes and patterns of treatment failure after surgery for locally recurrent rectal cancer. Ann Surg. 2016;264:323–9.PubMedGoogle Scholar
  10. 10.
    Camilleri-Brennan J, Steele RJC. The impact of recurrent rectal cancer on quality of life. Eur J Surg Oncol. 2001;27:349–53.PubMedGoogle Scholar
  11. 11.
    Guyot F, Faivre J, Manfredi S, Meny B, Bonithon-Kopp C, Bouvier AM. Time trends in the treatment and survival of recurrences from colorectal cancer. Ann Oncol. 2005;16:756–61.PubMedGoogle Scholar
  12. 12.
    Smith JJ, Strombom P, Chow OS, et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol. 2019. Scholar
  13. 13.
    Habr-Gama A, Sabbaga J, Gama-Rodrigues J, Julião GPS, Proscurshim I, Aguilar PB, 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.PubMedGoogle Scholar
  14. 14••.
    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;391:2537–45 An analysis of over 1000 watch-and-wait patients with rectal cancer, in whom TME was omitted after neoadjuvant therapy, reporting 2-year cumulative incidence of local regrowth of 25.2%. PubMedGoogle Scholar
  15. 15.
    Leichman L, Nigro N, Vaitkevicius VK, et al. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med. 1985;78:211–5.PubMedGoogle Scholar
  16. 16.
    Hatfield P, Cooper R, Sebag-Montefiore D. Involved-field, low-dose chemoradiotherapy for early-stage anal carcinoma. Int J Radiat Oncol Biol Phys. 2008;70:419–24.PubMedGoogle Scholar
  17. 17.
    Glynne-Jones R, Tan D, Hughes R, Hoskin P. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment. Nat Rev Clin Oncol. 2016;13:447–59.PubMedGoogle Scholar
  18. 18.
    Abulafi AM, Williams NS. Local recurrence of colorectal cancer: the problem, mechanisms, management and adjuvant therapy. Br J Surg. 1994;81:7–19.PubMedGoogle Scholar
  19. 19.
    McCall JL, Cox MR, Wattchow DA. Analysis of local recurrence rates after surgery alone for rectal cancer. Int J Color Dis. 1995;10:126–32.Google Scholar
  20. 20.
    Karanjia ND, Schache DJ, North WRS, Heald RJ. “Close shave” in anterior resection. Br J Surg. 1990;77:510–2.PubMedGoogle Scholar
  21. 21.
    Nielsen M, Laurberg S, Holm T. Current management of locally recurrent rectal cancer. Color Dis. 2011;13:732–43.Google Scholar
  22. 22••.
    Westberg K, Palmer G, Hjern F, Johansson H, Holm T, Martling A. Management and prognosis of locally recurrent rectal cancer—a national population-based study. Eur J Surg Oncol. 2018;44:100–7 A large national Swedish study assessing changes over time of LRRC epidemiology and treatment outcomes. PubMedGoogle Scholar
  23. 23.
    De Chaisemartin C, Penna C, Goere D, Benoist S, Beauchet A, Julie C, et al. Presentation and prognosis of local recurrence after total mesorectal excision. Color Dis. 2009;11:60–6.Google Scholar
  24. 24.
    Carpelan A, Karvonen J, Varpe P, Rantala A, Kaljonen A, Grönroos J, et al. Extralevator versus standard abdominoperineal excision in locally advanced rectal cancer: a retrospective study with long-term follow-up. Int J Color Dis. 2018;33:375–81.Google Scholar
  25. 25•.
    Bianco F, Romano G, Tsarkov P, Stanojevic G, Shroyer K, Giuratrabocchetta S, et al. Extralevator with vertical rectus abdominis myocutaneous flap vs. non-extralevator abdominoperineal excision for rectal cancer: the RELAPe randomized controlled trial. Color Dis. 2016. RCT that assesses the value of extralevator abdominoperineal excision (ELAPE) in achieving improved circumferential resection margin in LRRC. PubMedGoogle Scholar
  26. 26.
    Han JG, Wang ZJ, Wei GH, Gao ZG, Yang Y, Zhao BC. Randomized clinical trial of conventional versus cylindrical abdominoperineal resection for locally advanced lower rectal cancer. Am J Surg. 2012;204:274–82.PubMedGoogle Scholar
  27. 27.
    Ortiz H, Ciga MA, Armendariz P, Kreisler E, Codina-Cazador A, Gomez-Barbadillo J, et al. Multicentre propensity score-matched analysis of conventional versus extended abdominoperineal excision for low rectal cancer. Br J Surg. 2014;101:874–82.PubMedGoogle Scholar
  28. 28.
    Prytz M, Angenete E, Ekelund J, Haglind E. Extralevator abdominoperineal excision (ELAPE) for rectal cancer—short-term results from the Swedish Colorectal Cancer Registry. Selective use of ELAPE warranted. Int J Color Dis. 2014;29:981–7.Google Scholar
  29. 29.
    Klein M, Fischer A, Rosenberg J, Gögenur I. ExtraLevatory AbdominoPerineal Excision (ELAPE) does not result in reduced rate of tumor perforation or rate of positive circumferential resection margin: a nationwide database study. Ann Surg. 2015;261:933–8.PubMedGoogle Scholar
  30. 30.
    Bakx R, Visser O, Josso J, Meijer S, Slors JFM, van Lanschot JB. Management of recurrent rectal cancer: a population based study in greater Amsterdam. World J Gastroenterol. 2008;14:6018–23.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, 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.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Tanis PJ, Doeksen A, Van Lanschot JJB. Intentionally curative treatment of locally recurrent rectal cancer: a systematic review. Can J Surg. 2013;56:135–44.PubMedPubMedCentralGoogle Scholar
  33. 33.
    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.PubMedGoogle Scholar
  34. 34.
    Wanebo HJ, Koness RJ, Vezeridis MP, Cohen SI, Wrobleski DE. Pelvic resection of recurrent rectal cancer. Ann Surg. 1994:586–97., PubMedPubMedCentralGoogle Scholar
  35. 35.
    Caricato M, Borzomati D, Ausania F, Valeri S, Rosignoli A, Coppola R. Prognostic factors after surgery for locally recurrent rectal cancer: an overview. Eur J Surg Oncol. 2006;32:126–32.PubMedGoogle Scholar
  36. 36.
    Wong CS, Cummings BJ, Brierley JD, Catton CN, McLean M, Catton P, et al. Treatment of locally recurrent rectal carcinoma—results and prognostic factors. Int J Radiat Oncol Biol Phys. 1998;40:427–35.PubMedGoogle Scholar
  37. 37.
    Mirnezami AH, Sagar PM, Kavanagh D, Witherspoon P, Lee P, Winter D. Clinical algorithms for the surgical management of locally recurrent rectal cancer. Dis Colon Rectum. 2010;53:1248–57.PubMedGoogle Scholar
  38. 38.
    Harji DP, Griffiths B, Mcarthur DR, Sagar PM. Current UK management of locally recurrent rectal cancer. Color Dis. 2012;14:1479–82.Google Scholar
  39. 39.
    Moore HG, Shoup M, Riedel E, Minsky BD, Alektiar KM, Ercolani M, et al. Colorectal cancer pelvic recurrences: determinants of resectability. Dis Colon Rectum. 2004;47:1599–606.PubMedGoogle Scholar
  40. 40.
    Guillem JG, Ruo L (1998) Strategies in operative therapy for locally recurrent rectal cancer. Semin Colon Rectal Surg 9:259–268.Google Scholar
  41. 41.
    Kusters M, Dresen RC, Martijn H, Nieuwenhuijzen GA, van de Velde CJH, van den Berg HA, et al. Radicality of resection and survival after multimodality treatment is influenced by subsite of locally recurrent rectal Cancer. Int J Radiat Oncol Biol Phys. 2009;75:1444–9.PubMedGoogle Scholar
  42. 42.
    Boyle KM, Sagar PM, Chalmers AG, Sebag-Montefiore D, Cairns A, Eardley I. Surgery for locally recurrent rectal cancer. Dis Colon Rectum. 2005;48:929–37.PubMedGoogle Scholar
  43. 43.
    Yamada K, Ishizawa T, Niwa K, Chuman Y, Akiba S, Aikou T. Patterns of pelvic invasion are prognostic in the treatment of locally recurrent rectal cancer. Br J Surg. 2001;88:988–93.PubMedGoogle Scholar
  44. 44•.
    Klose J, Tarantino I, Schmidt T, Bruckner T, Kulu Y, Wagner T, et al. Impact of anatomic location on locally recurrent rectal cancer: superior outcome for intraluminal tumour recurrence. J Gastrointest Surg. 2015;19:1123–31 A description of outcomes based on novel anatomic considerations with key impact on tumor prognosis. PubMedGoogle Scholar
  45. 45.
    Benson AB, Venook AP, Al-Hawary MM, et al. Rectal cancer, version 2.2018 clinical practice guidelines in oncology. JNCCN J Natl Compr Cancer Netw. 2018;16:874–901.Google Scholar
  46. 46.
    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.
  47. 47••.
    Sasikumar A, Bhan C, Jenkins JT, Antoniou A, Murphy J. Systematic review of pelvic exenteration with en bloc sacrectomy for recurrent rectal adenocarcinoma: R0 resection predicts disease-free survival. Dis Colon Rectum. 2017;60:346–52 A thorough review of 220 patients with LRRC that demonstrates feasibility of rectal excision with en bloc sacrectomy in select patients. PubMedGoogle Scholar
  48. 48.
    Alberda WJ, Verhoef C, Schipper MEI, Nuyttens JJ, Rothbarth J, De Wilt JHW, et al. The importance of a minimal tumor-free resection margin in locally recurrent rectal cancer. Dis Colon Rectum. 2015;58:677–85.PubMedGoogle Scholar
  49. 49.
    Heriot AG, Byrne CM, Lee P, Dobbs B, Tilney H, Solomon MJ, et al. Extended radical resection: the choice for locally recurrent rectal cancer. Dis Colon Rectum. 2008;51:284–91.PubMedGoogle Scholar
  50. 50.
    Dresen RC, Gosens MJ, Martijn H, Nieuwenhuijzen GA, Creemers GJ, Daniels-Gooszen AW, et al. Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer. Ann Surg Oncol. 2008;15:1937–47.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Nielsen M, Rasmussen P, Pedersen B, Hagemann-Madsen R, Lindegaard J, Laurberg S. Early and late outcomes of surgery for locally recurrent rectal cancer: a prospective 10-year study in the total mesorectal excision era. Ann Surg Oncol. 2015;22:2677–84.PubMedGoogle Scholar
  52. 52.
    Dozois EJ, Privitera A, Holubar SD, Aldrete JF, Sim FH, Rose PS, et al. High sacrectomy for locally recurrent rectal cancer: can long-term survival be achieved? J Surg Oncol. 2011;103:105–9.PubMedGoogle Scholar
  53. 53••.
    Solomon MJ, Brown KGM, Koh CE, Lee P, Austin KKS, Masya L. Lateral pelvic compartment excision during pelvic exenteration. Br J Surg. 2015;102:1710–7 Important description of the evolution of radical pelvic exenteration techniques for LRRC involving the lateral pelvic compartment. PubMedGoogle Scholar
  54. 54.
    Eng C, Chang GJ, You YN, et al. The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal. Oncotarget. 2015.
  55. 55.
    Yang TX, Morris DL, Chua TC. Pelvic exenteration for rectal cancer: a systematic review. Dis Colon Rectum. 2013;56:519–31.PubMedGoogle Scholar
  56. 56.
    Solomon MJ, Tan KK, Bromilow RG, Al-Mozany N, Lee PJ. Sacrectomy via the abdominal approach during pelvic exenteration. Dis Colon Rectum. 2014;57:272–7.PubMedGoogle Scholar
  57. 57.
    Evans MD, Harji DP, Sagar PM, Wilson J, Koshy A, Timothy J, et al. Partial anterior sacrectomy with nerve preservation to treat locally advanced rectal cancer. Color Dis. 2013. Scholar
  58. 58.
    Milne T, Solomon MJ, Lee P, Young JM, Stalley P, Harrison JD. Assessing the impact of a sacral resection on morbidity and survival after extended radical surgery for locally recurrent rectal cancer. Ann Surg. 2013;258:1007–13.PubMedGoogle Scholar
  59. 59.
    Colibaseanu DT, Mathis KL, Abdelsatter ZM, Larson DW, Haddock MG, Dozois EJ. Is curative resection and long-term survival possible for locally re-recurrent colorectal cancer in the pelvis? Dis Colon Rectum. 2013;56:14–9.PubMedGoogle Scholar
  60. 60.
    Lau YC, Jongerius K, Wakeman C, Heriot AG, Solomon MJ, Sagar PM, et al. Influence of the level of sacrectomy on survival in patients with locally advanced and recurrent rectal cancer. Br J Surg. 2019;106:484–90.PubMedGoogle Scholar
  61. 61.
    Hahnioser D, Nelson H, Gunderson LL, Hassan I, Haddock MG, O’Connell MJ, et al. Curative potential of multimodality therapy for locally recurrent rectal cancer. Ann Surg. 2003;237:502–8.Google Scholar
  62. 62.
    Sagar PM. Ultraradical resection for locally recurrent rectal cancer. Dis Colon Rectum. 2014;57:1–2.PubMedGoogle Scholar
  63. 63.
    Chew MH, Brown WE, Masya L, Harrison JD, Myers E, Solomon MJ. Clinical, MRI, and PET-CT criteria used by surgeons to determine suitability for pelvic exenteration surgery for recurrent rectal cancers: a Delphi study. Dis Colon Rectum. 2013;56:717–25.PubMedGoogle Scholar
  64. 64.
    Senchenkov A, Moran SL, Petty PM, Knoetgen J, Clay RP, Bite U, et al. Predictors of complications and outcomes of external hemipelvectomy wounds: account of 160 consecutive cases. Ann Surg Oncol. 2008;15:355–63.PubMedGoogle Scholar
  65. 65.
    Austin KKS, Solomon MJ. Pelvic exenteration with en bloc iliac vessel resection for lateral pelvic wall involvement. Dis Colon Rectum. 2009;52:1223–33.PubMedGoogle Scholar
  66. 66.
    Akiyoshi T, Nagata J, Nagasaki T, Konishi T, Fujimoto Y, Nagayama S, et al. Laparoscopic salvage lateral pelvic lymph node dissection for locally recurrent rectal cancer. Color Dis. 2015;17:O213–6.Google Scholar
  67. 67.
    Nagasaki T, Akiyoshi T, Ueno M, Fukunaga Y, Nagayama S, Fujimoto Y, et al. Laparoscopic salvage surgery for locally recurrent rectal cancer. J Gastrointest Surg. 2014;18:1319–26.PubMedGoogle Scholar
  68. 68.
    Park SY, Choi GS, Jun SH, Park JS, Kim HJ. Laparoscopic salvage surgery for recurrent and metachronous colorectal cancer: 15 years’ experience in a single center. Surg Endosc. 2011;25:3551–8.PubMedGoogle Scholar
  69. 69.
    Austin KKS, Young JM, Solomon MJ. Quality of life of survivors after pelvic exenteration for rectal cancer. Dis Colon Rectum. 2010;53:1121–6.PubMedGoogle Scholar
  70. 70.
    van Zoggel DMGI, Bosman SJ, Kusters M, Nieuwenhuijzen GAP, Cnossen JS, Creemers GJ, et al. Preliminary results of a cohort study of induction chemotherapy-based treatment for locally recurrent rectal cancer. Br J Surg. 2018;105:447–52 Initial results of study assessing the value of induction chemotherapy as a neoadjuvant option for patients who have already undergone preoperative (chemo)radiotherapy for the primary tumor. PubMedGoogle Scholar
  71. 71.
    De Campos-Lobato LF, Stocchi L, Da Luz MA, Geisler D, Dietz DW, Lavery IC, et al. Pathologic complete response after neoadjuvant treatment for rectal cancer decreases distant recurrence and could eradicate local recurrence. Ann Surg Oncol. 2011;18:1590–8.PubMedGoogle Scholar
  72. 72.
    Valentini V, Morganti AG, Gambacorta MA, et al. Preoperative hyperfractionated chemoradiation for locally recurrent rectal cancer in patients previously irradiated to the pelvis: a multicentric phase II study. Int J Radiat Oncol Biol Phys. 2006;64:1129–39.PubMedGoogle Scholar
  73. 73.
    Bosman SJ, Holman FA, Nieuwenhuijzen GAP, Martijn H, Creemers GJ, Rutten HJT. Feasibility of reirradiation in the treatment of locally recurrent rectal cancer. Br J Surg. 2014;101:1280–9.PubMedGoogle Scholar
  74. 74.
    Glimelius B. Recurrent rectal cancer. The pre-irradiated primary tumour: can more radiotherapy be given? Color Dis. 2003;5:501–3.Google Scholar
  75. 75.
    Van Der Meij W, Rombouts AJM, Rutten H, Bremers AJA, De Wilt JHW. Treatment of locally recurrent rectal carcinoma in previously (chemo)irradiated patients: a review. Dis Colon Rectum. 2016;59:148–56.PubMedGoogle Scholar
  76. 76.
    Mohiuddin M, Marks G, Marks J. Long-term results of reirradiation for patients with recurrent rectal carcinoma. Cancer. 2002;95:1144–50.PubMedGoogle Scholar
  77. 77.
    Yu SKT, Bhangu A, Tait DM, Tekkis P, Wotherspoon A, Brown G. Chemoradiotherapy response in recurrent rectal cancer. Cancer Med. 2014;3:111–7.PubMedGoogle Scholar
  78. 78.
    Hathout L, Williams T, Jabbour SK. The impact of novel radiation treatment techniques on toxicity and clinical outcomes in rectal Cancer. Curr Colorectal Cancer Rep. 2017;13:61–72.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Sun Z, Adam MA, Kim J, Czito B, Mantyh C, Migaly J. Intensity-modulated radiation therapy is not associated with perioperative or survival benefit over 3D-conformal radiotherapy for rectal Cancer. J Gastrointest Surg. 2017;21:106–11.PubMedGoogle Scholar
  80. 80.
    Wiig JN, Poulsen JP, Tveit KM, Olsen DR, Giercksky KE. Intra-operative irradiation (IORT) for primary advanced and recurrent rectal cancera need for randomised studies. Eur J Cancer. 2000;36:868–74.PubMedGoogle Scholar
  81. 81.
    Valentini V, Morganti AG, De Franco A, Coco C, Ratto C, Doglietto GB, et al. Chemoradiation with or without intraoperative radiation therapy in patients with locally recurrent rectal carcinoma: prognostic factors and long term outcome. Cancer. 1999;86:2612–24.PubMedGoogle Scholar
  82. 82.
    Hashiguchi Y, Sekine T, Sakamoto H, Tanaka Y, Kazumoto T, Kato S, et al. Intraoperative irradiation after surgery for locally recurrent rectal cancer. Dis Colon Rectum. 2005;42:886–93.Google Scholar
  83. 83.
    Haddock MG, Gunderson LL, Nelson H, Cha SS, Devine RM, Dozois RR, et al. Intraoperative irradiation for locally recurrent colorectal cancer in previously irradiated patients. Int J Radiat Oncol Biol Phys. 2001:1;49(5):1267–74. Google Scholar
  84. 84.
    Haddock MG, Miller RC, Nelson H, Pemberton JH, Dozois EJ, Alberts SR, et al. Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. Int J Radiat Oncol Biol Phys. 2011;79:143–50.Google Scholar
  85. 85.
    Suzuki K, Dozois RR, Devine RM, Nelson H, Weaver AL, Gunderson LL, et al. Curative reoperations for locally recurrent rectal cancer. Dis Colon Rectum. 1996:39(7):730–6. Google Scholar
  86. 86.
    Allee PE, Tepper JE, Gunderson LL, Munzenrider JE. Postoperative radiation therapy for incompletely resected colorectal carcinoma. Int J Radiat Oncol Biol Phys. 1989;17:1171–6.PubMedGoogle Scholar
  87. 87.
    Kishan AU, Voog JC, Wiseman J, et al. Standard fractionation external beam radiotherapy with and without intraoperative radiotherapy for locally recurrent rectal cancer: the role of local therapy in patients with a high competing risk of death from distant disease. Br J Radiol. 2017. Scholar
  88. 88.
    Suzuki K, Gunderson LL, Devine RM, Weaver AL, Dozois RR, Ilstrup DM, et al. Intraoperative irradiation after palliative surgery for locally recurrent rectal cancer. Cancer. 1995;75:939–52.PubMedGoogle Scholar
  89. 89.
    Guo S, Reddy CA, Kolar M, Woody N, Mahadevan A, Deibel FC, et al. Intraoperative radiation therapy with the photon radiosurgery system in locally advanced and recurrent rectal cancer: retrospective review of the Cleveland clinic experience. Radiat Oncol. 2012;7:1–8. Scholar
  90. 90.
    Colaco RJ, Nichols RC, Huh S, Getman N, Ho MW, Li Z, et al. Protons offer reduced bone marrow, small bowel, and urinary bladder exposure for patients receiving neoadjuvant radiotherapy for resectable rectal cancer. J Gastrointest Oncol. 2014;5:3–8.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Palmer M, Mok H, Ciura K, Georges R, Nguyen B, Crawford C, et al. Dose reduction to small bowel and other relevant structures in rectal carcinoma with proton therapy. Int J Radiat Oncol. 2012;84:S846.Google Scholar
  92. 92.
    Wolff HA, Wagner DM, Conradi LC, Hennies S, Ghadimi M, Hess CF, et al. Irradiation with protons for the individualized treatment of patients with locally advanced rectal cancer: a planning study with clinical implications. Radiother Oncol. 2012;102:30–7.PubMedGoogle Scholar
  93. 93.
    Ie M, Yamaguchi T, Kinugasa Y, Sato S, Yamakawa Y, Kagawa H, et al. Complete response of locally recurrent anorectal cancer to proton beam therapy alone—a case report. Gan To Kagaku Ryoho. 2014;41:2623–5.PubMedGoogle Scholar
  94. 94.
    Berman AT, Both S, Sharkoski T, Goldrath K, Tochner Z, Apisarnthanarax S, et al. Proton reirradiation of recurrent rectal cancer: dosimetric comparison, toxicities, and preliminary outcomes. Int J Part Ther. 2014;1:2–13.Google Scholar
  95. 95.
    Goes RN, Beart RW, Simons AJ, Gunderson LL, Grado G, Streeter O. Use of brachytherapy in management of locally recurrent rectal cancer. Dis Colon Rectum. 1997;40:1177–9.PubMedGoogle Scholar
  96. 96.
    Bishop AJ, Gupta S, Cunningham MG, Tao R, Berner PA, Korpela SG, et al. Interstitial brachytherapy for the treatment of locally recurrent anorectal cancer. Ann Surg Oncol. 2015;22:596–602 A key study exploring the benefit of brachytherapy in LRRC and LRAC. Google Scholar
  97. 97.
    Wang JJ, Yuan HS, Li JN, Jiang YL, Tian SQ, Yang RJ. CT-guided radioactive seed implantation for recurrent rectal carcinoma after multiple therapy. Med Oncol. 2010;27:421–9.PubMedGoogle Scholar
  98. 98.
    Wang ZM, Huang G, Chen KM, Lu J, Gong J, Zheng YF, et al. Clinical application of CT-guided 125 I seed interstitial implantation for recurrent rectum carcinoma. J Interv Radiol. 2009;18:681–4.Google Scholar
  99. 99.
    Hildebrandt B, Wust P, Gellermann J, Nicolaou A, Trappe RU, Felix R, et al. Treatment of locally recurrent rectal cancer with special focus on regional pelvic hyperthermia. Onkologie. 2004;27:506–11.PubMedGoogle Scholar
  100. 100.
    De Haas-Kock DFM, Buijsen J, Pijls-Johannesma M, Lutgens L, Lammering G, Van Mastrigt GAPG, et al. Concomitant hyperthermia and radiation therapy for treating locally advanced rectal cancer. Cochrane Database Syst Rev. 2009.
  101. 101.
    Ohno S, Sumiyoshi Y, Mori M, Sugimachi K. Hyperthermia for rectal cancer. Surgery. 2002;131:S121–7.PubMedGoogle Scholar
  102. 102.
    Kim SW, Yea JW, Kim JH, Gu MJ, Kang MK. Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Clin Oncol. 2018;23:287–97.PubMedGoogle Scholar
  103. 103.
    González DG (1996) Thermoradiotherapy for Tumors of the Lower Gastrointestinal Tract. In: Thermoradiotherapy and Thermochemotherapy. Medical Radiology (Diagnostic Imaging and Radiation Oncology). Springer, Berlin, Heidelberg. Google Scholar
  104. 104.
    Milani V, Pazos M, Issels RD, Buecklein V, Rahman S, Tschoep K, et al. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer. Strahlenther Onkol. 2008;184:163–8.PubMedGoogle Scholar
  105. 105.
    Chu W, Staruch RM, Pichardo S, Tillander M, Köhler MO, Huang Y, et al. Magnetic resonance-guided high-intensity focused ultrasound hyperthermia for recurrent rectal cancer: MR thermometry evaluation and preclinical validation. Int J Radiat Oncol Biol Phys. 2016;95:1259–67.PubMedGoogle Scholar
  106. 106.
    Fraunholz I, Rabeneck D, Weiß C, Rödel C. Combined-modality treatment for anal cancer: current strategies and future directions. Strahlenther Onkol. 2010;186:361–6.PubMedGoogle Scholar
  107. 107.
    Sebag-Montefiore D, Adams R, Bell S, et al. The development of an umbrella trial (PLATO) to address radiation therapy dose questions in the locoregional management of squamous cell carcinoma of the anus. Int J Radiat Oncol. 2016;96:E164–5.Google Scholar
  108. 108.
    Nigro ND. Multidisciplinary management of cancer of the anus. World J Surg. 1987;11:446–51.PubMedGoogle Scholar
  109. 109.
    Cummings BJ. Concomitant radiotherapy and chemotherapy for anal cancer. SeminOncol. 1992;19:102–8.Google Scholar
  110. 110.
    Mackowski A, Levitt M, Makin G, Salama P, Tan P, Penter C, et al. Anal squamous cell carcinoma: are we improving outcomes? ANZ J Surg. 2018;88:1013–6.PubMedGoogle Scholar
  111. 111.
    Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB, Thomas CR, et al. Prognostic factors derived from a prospective database dictate clinical biology of anal cancer: the intergroup trial (RTOG 98-11). Cancer. 2010;116:4007–13.PubMedGoogle Scholar
  112. 112.
    Harris DA, Williamson J, Davies M, Evans MD, Drew P, Beynon J. Outcome of salvage surgery for anal squamous cell carcinoma. Color Dis. 2013;15:968–73.Google Scholar
  113. 113.
    Gunderson LL, Moughan J, Ajani JA, et al. Anal carcinoma: impact of TN category of disease on survival, disease relapse, and colostomy failure in US gastrointestinal intergroup RTOG 98-11 phase 3 trial. Int J Radiat Oncol Biol Phys. 2013;87:638–45.PubMedPubMedCentralGoogle Scholar
  114. 114.
    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.PubMedGoogle Scholar
  115. 115.
    Hong JC, Cui Y, Patel BN, et al. Association of interim FDG-PET imaging during chemoradiation for squamous anal canal carcinoma with recurrence. Int J Radiat Oncol Biol Phys. 2018;102:1046–51.PubMedGoogle Scholar
  116. 116.
    Renehan AG, Saunders MP, Schofield PF, O’Dwyer ST. Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer. Br J Surg. 2005;92:605–14.PubMedGoogle Scholar
  117. 117.
    Renehan AG, O’Dwyer ST. Management of local disease relapse. Color Dis. 2011;13:44–52.Google Scholar
  118. 118.
    Bignell M, Chave H, Branagan G. Outcome of surgery for recurrent anal cancer: results from a tertiary referral centre. Color Dis. 2018;20:771–7.Google Scholar
  119. 119.
    Pesi B, Scaringi S, Di Martino C, Batignani G, Giudici F, Bisogni D, et al. Results of surgical salvage treatment for anal canal cancer: a retrospective analysis with overview of the literature. Dig Surg. 2017;34:380–6.PubMedGoogle Scholar
  120. 120.
    Singh M, Kinsley S, Huang A, Ricci JA, Clancy TE, Irani J, et al. Gracilis flap reconstruction of the perineum: an outcomes analysis. J Am Coll Surg. 2016;223:602–10.PubMedGoogle Scholar
  121. 121.
    Chessin DB, Hartley J, Cohen AM, et al. Rectus flap reconstruction decreases perineal wound complications after pelvic chemoradiation and surgery: a cohort study. Ann Surg Oncol. 2005;12:104–10.PubMedGoogle Scholar
  122. 122.
    Longo WE, Vernava AM, Wade TP, Coplin MA, Virgo KS, Johnson FE. Recurrent squamous cell carcinoma of the anal canal: predictors of initial treatment failure and results of salvage therapy. Ann Surg. 1994;220:40–9.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Akbari RP, Paty PB, Guillem JG, Weiser MR, Temple LK, Minsky BD, et al. Oncologic outcomes of salvage surgery for epidermoid carcinoma of the anus initially managed with combined modality therapy. Dis Colon Rectum. 2004;47:1136–44.PubMedGoogle Scholar
  124. 124.
    Schiller DE, Cummings BJ, Rai S, Le LW, Last L, Davey P, et al. Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol. 2007;14:2780–9.PubMedGoogle Scholar
  125. 125.
    Mullen JT, Rodriguez-Bigas MA, Chang GJ, Barcenas CH, Crane CH, Skibber JM, et al. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol. 2007;14:478–83.PubMedGoogle Scholar
  126. 126.
    Hannes S, Reinisch A, Bechstein WO, Habbe N. Salvage abdominoperineal excisions in recurrent anal cancer—impact of different reconstruction techniques on outcome, morbidity, and complication rates. Int J Color Dis. 2016;31:653–9.Google Scholar
  127. 127.
    Ellenhorn JDI, Enker WE, Quan SHQ. Salvage abdominoperineal resection following combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus. Ann Surg Oncol. 1994;1:105–10.PubMedGoogle Scholar
  128. 128.
    Van Der Wal BCH, Cleffken BI, Gulec B, Kaufman HS, Choti MA. Results of salvage abdominoperineal resection for recurrent anal carcinoma following combined chemoradiation therapy. J Gastrointest Surg. 2001;5:383–7.PubMedGoogle Scholar
  129. 129.
    Nilsson PJ, Svensson C, Goldman S, Glimelius B. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg. 2002;89:1425–9.PubMedGoogle Scholar
  130. 130.
    Alamri Y, Buchwald P, Dixon L, Dobbs B, Eglinton T, McCormick J, et al. Salvage surgery in patients with recurrent or residual squamous cell carcinoma of the anus. Eur J Surg Oncol. 2016;42:1687–92.PubMedGoogle Scholar
  131. 131.
    Hagemans JAW, Blinde SE, Nuyttens JJ, Morshuis WG, Mureau MAM, Rothbarth J, et al. Salvage abdominoperineal resection for squamous cell anal cancer: a 30-year single-institution experience. Ann Surg Oncol. 2018;25:1970–9 A recent single-center report of APR for LRAC, updating our data on outcomes for this relatively rare condition.PubMedPubMedCentralGoogle Scholar
  132. 132.
    Shridhar R, Shibata D, Chan E, Thomas CR. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin. 2015;65:139–62.PubMedGoogle Scholar
  133. 133.
    Pia Sormani M. The Will Rogers phenomenon: the effect of different diagnostic criteria. J Neurol Sci. 2009. Scholar
  134. 134.
    Severino NP, Chadi SA, Rosen L, Coiro S, Choman E, Berho M, et al. Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival? Color Dis. 2016;18:959–66.Google Scholar
  135. 135.
    Yao J-N, Zhang X-X, Zhou H-N, Li Y-L, Xu H-R, Wang C-F, et al. Human papillomavirus related anal squamous cell carcinoma survival: a systematic review and meta-analysis. Transl Cancer Res. 2017;6:463–73.Google Scholar
  136. 136.
    NCCN. Anal carcinoma (version.2018).Google Scholar
  137. 137.
    Sclafani F, Morano F, Cunningham D, Baratelli C, Kalaitzaki E, Watkins D, et al. Platinum-fluoropyrimidine and paclitaxel-based chemotherapy in the treatment of advanced anal cancer patients. Oncologist. 2017;22:402–8.PubMedPubMedCentralGoogle Scholar
  138. 138.
    Rao S, Sclafani F, Eng C, et al. InterAACT: a multicentre open label randomised phase II advanced anal cancer trial of cisplatin (CDDP) plus 5-fluorouracil (5-FU) vs carboplatin (C) plus weekly paclitaxel (P) in patients (pts) with inoperable locally recurrent (ILR) or metastatic treatments. Ann Oncol. 2018;29:viii715–6.Google Scholar
  139. 139••.
    Kim S, François E, André T, et al. Docetaxel, cisplatin, and fluorouracil chemotherapy for metastatic or unresectable locally recurrent anal squamous cell carcinoma (Epitopes-HPV02): a multicentre, single-arm, phase 2 study. Lancet Oncol. 2018;19:1094–106 A phase II study attempting to establish a new standard of chemotherapeutic care for LRAC. PubMedGoogle Scholar
  140. 140.
    Strauss J, Gatti-Mays ME, Redman J, et al. Safety and activity of M7824, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with HPV associated cancers. J Clin Oncol. 2018;36:3007.Google Scholar
  141. 141.
    Ott PA, Piha-Paul SA, Munster P, et al. Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ann Oncol Off J Eur Soc Med Oncol. 2017;28:1036–41.Google Scholar
  142. 142.
    Osborne EM, Eng C, Skibber JM, et al. Hyperfractionated accelerated reirradiation for patients with recurrent anal cancer previously treated with definitive chemoradiation. Am J Clin Oncol Cancer Clin Trials. 2018;41:632–7.Google Scholar
  143. 143.
    Hallemeier CL, You YN, Larson DW, Dozois EJ, Nelson H, Klein KA, et al. Multimodality therapy including salvage surgical resection and intraoperative radiotherapy for patients with squamous-cell carcinoma of the anus with residual or recurrent disease after primary chemoradiotherapy. Dis Colon Rectum. 2014:57(4):442–8. Google Scholar
  144. 144.
    Wright JL, Gollub MJ, Weiser MR, Saltz LB, Wong WD, Paty PB, et al. Surgery and high-dose-rate intraoperative radiation therapy for recurrent squamous-cell carcinoma of the anal canal. Dis Colon Rectum. 2011;54:1090–7.PubMedGoogle Scholar
  145. 145.
    Detering R, Karthaus E, Borstlap W, Marijnen C, van de Velde C, Bemelman W, et al. Treatment and survival of locally recurrent rectal cancer: a cross-sectional population study 15 years after the Dutch TME trial. Eur J Surg Oncol. 2019. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Edward Christopher Dee
    • 1
  • Christine E. Eyler
    • 2
  • Nina N. Sanford
    • 3
  • Jennifer Y. Wo
    • 2
    Email author
  1. 1.Harvard Medical SchoolBostonUSA
  2. 2.Department of Radiation OncologyMassachusetts General HospitalBostonUSA
  3. 3.Department of Radiation OncologyUniversity of Texas SouthwesternDallasUSA

Personalised recommendations