Can we S ave the rectum by watchful waiting or T rans A nal microsurgery following (chemo) R adiotherapy versus T otal mesorectal excision for early RE ctal C ancer (STAR-TREC study)?: protocol for a multicentre, randomised feasibility study

Anouk J M Rombouts, Issam Al-Najami, Natalie L Abbott, Ane Appelt, Gunnar Baatrup, Simon Bach, Aneel Bhangu, Karen-Lise Garm Spindler, Richard Gray, Kelly Handley, Manjinder Kaur, Ellen Kerkhof, Camilla Jensenius Kronborg, Laura Magill, Corrie A M Marijnen, Iris D Nagtegaal, Lars Nyvang, Femke P Peters, Per Pfeiffer, Cornelis Punt, Philip Quirke, David Sebag-Montefiore, Mark Teo, Nick West, Johannes H W de Wilt, for STAR-TREC Collaborative Group, Anouk J M Rombouts, Issam Al-Najami, Natalie L Abbott, Ane Appelt, Gunnar Baatrup, Simon Bach, Aneel Bhangu, Karen-Lise Garm Spindler, Richard Gray, Kelly Handley, Manjinder Kaur, Ellen Kerkhof, Camilla Jensenius Kronborg, Laura Magill, Corrie A M Marijnen, Iris D Nagtegaal, Lars Nyvang, Femke P Peters, Per Pfeiffer, Cornelis Punt, Philip Quirke, David Sebag-Montefiore, Mark Teo, Nick West, Johannes H W de Wilt, for STAR-TREC Collaborative Group

Abstract

Introduction: Total mesorectal excision (TME) is the highly effective standard treatment for rectal cancer but is associated with significant morbidity and may be overtreatment for low-risk cancers. This study is designed to determine the feasibility of international recruitment in a study comparing organ-saving approaches versus standard TME surgery.

Methods and analysis: STAR-TREC trial is a multicentre international randomised, three-arm parallel, phase II feasibility study in patients with biopsy-proven adenocarcinoma of the rectum. The trial is coordinated from Birmingham, UK with national hubs in Radboudumc (the Netherlands) and Odense University Hospital Svendborg UMC (Denmark). Patients with rectal cancer, staged by CT and MRI as ≤cT3b (up to 5 mm of extramural spread) N0 M0 can be included. Patients will be randomised to either standard TME surgery (control), organ-saving treatment using long-course concurrent chemoradiation or organ-saving treatment using short-course radiotherapy. For patients treated with an organ-saving strategy, clinical response to (chemo)radiotherapy determines the next treatment step. An active surveillance regime will be performed in the case of a complete clinical regression. In the case of incomplete clinical regression, patients will proceed to local excision using an optimised platform such as transanal endoscopic microsurgery or other transanal techniques (eg, transanal endoscopic operation or transanal minimally invasive surgery). The primary endpoint of this phase II study is to demonstrate sufficient international recruitment in order to sustain a phase III study incorporating pelvic failure as the primary endpoint. Success in phase II is defined as randomisation of at least four cases per month internationally in year 1, rising to at least six cases per month internationally during year 2.

Ethics and dissemination: The medical ethical committees of all the participating countries have approved the study protocol. Results of the primary and secondary endpoints will be submitted for publication in peer-reviewed journals.

Trial registration number: ISRCTN14240288, 20 October 2016. NCT02945566; Pre-results, October 2016.

Keywords: TEM; chemoradiation; radiotherapy; rectal cancer; watchful waiting.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Flow chart of the inclusion, randomisation and management of the study subjects in STAR-TREC trial. APE, anterior perianal excision; CRT, chemoradiation therapy; LAR, low anterior resection; SCRT, short-course radiation therapy; TEM, transanal endoscopic microsurgery; TME, total mesorectal excision.

References

    1. Atkin WS, Cook CF, Cuzick J, et al. . Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet 2002;359:1291–300. 10.1016/S0140-6736(02)08268-5
    1. UK Colorectal Cancer Screening Pilot Group. Results of the first round of a demonstration pilot of screening for colorectal cancer in the United Kingdom. BMJ 2004;329:133 10.1136/bmj.38153.491887.7C
    1. Bentrem DJ, Okabe S, Wong WD, et al. . T1 adenocarcinoma of the rectum: transanal excision or radical surgery? Ann Surg 2005;242:472–9.
    1. Peeters KC, Marijnen CA, Nagtegaal ID, et al. . 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. 10.1097/01.sla.0000257358.56863.ce
    1. Endreseth BH, Myrvold HE, Romundstad P, et al. . Transanal excision vs. major surgery for T1 rectal cancer. Dis Colon Rectum 2005;48:1380–8. 10.1007/s10350-005-0044-6
    1. Bökkerink GM, de Graaf EJ, Punt CJ, et al. . The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery. BMC Surg 2011;11:34 10.1186/1471-2482-11-34
    1. Homan J, Bökkerink GM, Aarts MJ, et al. . Variation in circumferential resection margin: Reporting and involvement in the South-Netherlands. Eur J Surg Oncol 2015;41:1485–92. 10.1016/j.ejso.2015.07.015
    1. Anderin K, Gustafsson UO, Thorell A, et al. . The effect of diverting stoma on long-term morbidity and risk for permanent stoma after low anterior resection for rectal cancer. Eur J Surg Oncol 2016;42:788–93. 10.1016/j.ejso.2016.04.001
    1. Kim MJ, Kim YS, Park SC, et al. . Risk factors for permanent stoma after rectal cancer surgery with temporary ileostomy. Surgery 2016;159:721–7. 10.1016/j.surg.2015.09.011
    1. Hendren SK, O’Connor BI, Liu M, et al. . Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer. Ann Surg 2005;242:212–23. 10.1097/01.sla.0000171299.43954.ce
    1. Wallner C, Lange MM, Bonsing BA, et al. . Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the Cooperative Clinical Investigators of the Dutch total mesorectal excision trial. J Clin Oncol 2008;26:4466–72. 10.1200/JCO.2008.17.3062
    1. Engel J, Kerr J, Schlesinger-Raab A, et al. . Quality of life in rectal cancer patients: a four-year prospective study. Ann Surg 2003;238:203–13. 10.1097/01.sla.0000080823.38569.b0
    1. Temple LK, Bacik J, Savatta SG, et al. . The development of a validated instrument to evaluate bowel function after sphincter-preserving surgery for rectal cancer. Dis Colon Rectum 2005;48:1353–65. 10.1007/s10350-004-0942-z
    1. Lange MM, Marijnen CA, Maas CP, et al. . Risk factors for sexual dysfunction after rectal cancer treatment. Eur J Cancer 2009;45:1578–88. 10.1016/j.ejca.2008.12.014
    1. Marijnen CA, Kapiteijn E, van de Velde CJ, et al. . Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002;20:817–25. 10.1200/JCO.2002.20.3.817
    1. Grumann MM, Noack EM, Hoffmann IA, et al. . Comparison of quality of life in patients undergoing abdominoperineal extirpation or anterior resection for rectal cancer. Ann Surg 2001;233:149–56. 10.1097/00000658-200102000-00001
    1. Wilson TR, Alexander DJ. Clinical and non-clinical factors influencing postoperative health-related quality of life in patients with colorectal cancer. Br J Surg 2008;95:1408–15. 10.1002/bjs.6376
    1. Stephens RJ, Thompson LC, Quirke P, et al. . Impact of short-course preoperative radiotherapy for rectal cancer on patients' quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol 2010;28:4233–9. 10.1200/JCO.2009.26.5264
    1. Wiltink LM, Marijnen CA, Meershoek-Klein Kranenbarg E, et al. . A comprehensive longitudinal overview of health-related quality of life and symptoms after treatment for rectal cancer in the TME trial. Acta Oncol 2016;55:502–8. 10.3109/0284186X.2015.1088171
    1. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. . Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–46. 10.1056/NEJMoa010580
    1. Tekkis PP, Poloniecki JD, Thompson MR, et al. . Operative mortality in colorectal cancer: prospective national study. BMJ 2003;327:1196–201. 10.1136/bmj.327.7425.1196
    1. Bos AC, van Erning FN, Elferink MA, et al. . No Difference in Overall Survival Between Hospital Volumes for Patients With Colorectal Cancer in The Netherlands. Dis Colon Rectum 2016;59:943–52. 10.1097/DCR.0000000000000660
    1. Habr-Gama A, Gama-Rodrigues J, São Julião 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. 10.1016/j.ijrobp.2013.12.012
    1. Habr-Gama A, Perez RO, Nadalin W, et al. . Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Trans Meet Am Surg Assoc Am Surg Assoc 2004;CXXII:309–16. 10.1097/01.sla.0000141194.27992.32
    1. 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. 10.1200/JCO.2011.37.7176
    1. Appelt AL, Pløen 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. 10.1016/S1470-2045(15)00120-5
    1. Glynne-Jones R, Wallace M, Livingstone JI, et al. . Complete clinical response after preoperative chemoradiation in rectal cancer: is a "wait and see" policy justified? Dis Colon Rectum 2008;51:10–20. 10.1007/s10350-007-9080-8
    1. Renehan AG, Malcomson L, Emsley R, et al. . Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol 2016;17:174–83. 10.1016/S1470-2045(15)00467-2
    1. 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. 10.1016/S1470-2045(15)00004-2
    1. Bach SP, Hill J, Monson JR, et al. . A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg 2009;96:280–90. 10.1002/bjs.6456
    1. Cataldo PA, O’Brien S, Osler T. Transanal endoscopic microsurgery: a prospective evaluation of functional results. Dis Colon Rectum 2005;48:1366–71. 10.1007/s10350-005-0031-y
    1. Restivo A, Zorcolo L, D’Alia G, et al. . Risk of complications and long-term functional alterations after local excision of rectal tumors with transanal endoscopic microsurgery (TEM). Int J Colorectal Dis 2016;31:257–66. 10.1007/s00384-015-2371-y
    1. Kumar AS, Coralic J, Kelleher DC, et al. . Complications of transanal endoscopic microsurgery are rare and minor: a single institution’s analysis and comparison to existing data. Dis Colon Rectum 2013;56:295–300. 10.1097/DCR.0b013e31827163f7
    1. You YN, Baxter NN, Stewart A, et al. . Is the increasing rate of local excision for stage I rectal cancer in the United States justified?: a nationwide cohort study from the National Cancer Database. Ann Surg 2007;245:726–33. 10.1097/01.sla.0000252590.95116.4f
    1. Garcia-Aguilar J, Mellgren A, Sirivongs P, et al. . Local excision of rectal cancer without adjuvant therapy: a word of caution. Ann Surg 2000;231:345–51.
    1. Ricciardi R, Madoff RD, Rothenberger DA, et al. . Population-based analyses of lymph node metastases in colorectal cancer. Clin Gastroenterol Hepatol 2006;4:1522–7. 10.1016/j.cgh.2006.07.016
    1. Martens MH, Maas M, Heijnen LA, et al. . Long-term Outcome of an Organ Preservation Program After Neoadjuvant Treatment for Rectal Cancer. J Natl Cancer Inst 2016;108:djw171 10.1093/jnci/djw171
    1. van Gijn W, Marijnen CA, Nagtegaal ID, et al. . 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;12:575–82. 10.1016/S1470-2045(11)70097-3
    1. Lezoche E, Baldarelli M, Lezoche G, et al. . Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg 2012;99:1211–8. 10.1002/bjs.8821
    1. 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. 10.1016/j.radonc.2012.12.005
    1. Verseveld M, de Graaf EJ, Verhoef C, et al. . Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg 2015;102:853–60. 10.1002/bjs.9809
    1. Smart CJ, Korsgen S, Hill J, et al. . Multicentre study of short-course radiotherapy and transanal endoscopic microsurgery for early rectal cancer. Br J Surg 2016;103:1069–75. 10.1002/bjs.10171
    1. Garcia-Aguilar J, Renfro LA, Chow OS, et al. . Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol 2015;16:1537–46. 10.1016/S1470-2045(15)00215-6
    1. Marijnen CA. Organ preservation in rectal cancer: have all questions been answered? Lancet Oncol 2015;16:e13–e22. 10.1016/S1470-2045(14)70398-5
    1. Valentini V, Gambacorta MA, Barbaro B, et al. . International consensus guidelines on Clinical Target Volume delineation in rectal cancer. Radiother Oncol 2016;120:195–201. 10.1016/j.radonc.2016.07.017
    1. Leibold T, Shia J, Ruo L, et al. . Prognostic implications of the distribution of lymph node metastases in rectal cancer after neoadjuvant chemoradiotherapy. J Clin Oncol 2008;26:2106–11. 10.1200/JCO.2007.12.7704

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