Abstract
Optimizing the Cost/benefit ratio of treatment: Evidence Based The aim of a cancer treatment is always to achieve the maximum of cure rate with a minimum of toxicity and best quality of life at an acceptable cost for the society. It is always a multifactorial challenge depending on the patient, the tumor, the doctor, and the society cultural and financial backgrounds. The goal is to find the best cost/benefit ratio between all possible strategies in agreement with a well-informed patient. In rectal cancer (M0) surgery is the cornerstone of treatment. Combined modality therapies aim at optimizing the cost/benefit ratio of possible strategies and only randomized trials can bring strong evidence regarding their results and recommendations. Lessons from randomized trials: quite modest During the past decades many phase III trials have shown that: (1) neoadjuvant treatment even with “TME” surgery was better than adjuvant, (2) chemoradiotherapy (CRT) was better than RT alone, (3) long course CRT was probably more efficient (in terms of ypCR) than short course (25/5), and (4) capecitabine was as efficient as 5 FU but oxaliplatin was not adding benefit. Overall, the gains of nCRT remain modest and it is mainly a reduction in local relapse not exceeding 5 %, but no benefit in survival and neither in sphincter saving surgery has been proven. The way forwards organ preservation in case of CCR. Local control: can probably be improved for T4 tumors by RT dose escalation. Survival: can be increased by innovative medical treatment either before or after surgery. Toxicity: may be reduced by a less aggressive treatment in elderly. Conservative treatment: A new field of clinical research is to achieve “organ preservation” (and not only sphincter saving). To modify the surgical approach and preserve the whole rectum, neoadjuvant treatment must achieve safely a clinical complete response. As rectal adenocarcinoma is a relatively radioresistant tumor endocavitary irradiation (contact X-Ray) is a promising safe approach and this hypothesis will be addressed by the OPERA randomized trial.
Conflict of interest: JP Gérard is the medical advisor of the Ariane Medical Systems company
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References
Appelt AL et al (2013) Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys 85(1):74–80
Aschele C et al (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29(20):2773–2780
Bosset JF et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355(11):1114–1123
Bosset JF et al (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol 15(2):184–190
Braendengen M et al (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26(22):3687–3694
Braendengen M et al (2011) 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 81(4):1017–1024
Bujko K et al (2006) Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiother Oncol 80(1):4–12
Conference NC (1990) Adjuvant therapy for patients with colon and rectal cancer. JAMA 264:1444–1450
Chua YJ et al (2010) Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol 11(3):241–248
Crane CH et al (2003) Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 97(2):517–524
Dewdney A et al (2012) 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 30(14):1620–1627
Fernandez-Martos C et al (2010) 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 28(5):859–865
Folkesson J et al (2005) Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 23(24):5644–5650
Francois Y et al (1999) Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 17(8):2396
Francois E et al (2014) Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: tolerance and efficacy. Radiother Oncol (2014)
Frykholm GJ, Glimelius B, Pahlman L (1993) Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum 36(6):564–572
Garcia-Aguilar J, Shi Q, Thomas CR, Jr., et al (2012) A phase II trial of neoadjuvant chemoradiation and local excision for T2N0 rectal cancer : preliminary results of the ACOSOG Z6041 trial. Ann Surg Oncol 19:384--391
Gérard JP, Romestaing P, Chapet O (2003) Radiotherapy alone in the curative treatment of rectal carcinoma. Lancet Oncol 4(3):158–166
Gerard JP et al (2004) Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial. J Clin Oncol 22(12):2404–2409
Gerard JP et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24(28):4620–4625
Gerard JP et al (2010) Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28(10):1638–1644
Gerard JP et al (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol 30(36):4558–4565
Gerard JP et al (2012) Can we increase the chance of sphincter saving surgery in rectal cancer with neoadjuvant treatments: lessons from a systematic review of recent randomized trials. Crit Rev Oncol Hematol 81(1):21–28
Glehen O et al (2003) Long-term results of the Lyons R90-01 randomized trial of preoperative radiotherapy with delayed surgery and its effect on sphincter-saving surgery in rectal cancer. Br J Surg 90(8):996–998
Habr-Gama A et al (2009) 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 52(12):1927–1934
Habr-Gama A et al (2014) 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 88:822–828
Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1(8496):1479–1482
Jakobsen A et al (2006) Preoperative chemoradiation of locally advanced T3 rectal cancer combined with an endorectal boost. Int J Radiat Oncol Biol Phys 64(2):461–465
Jakobsen A et al (2012) Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses. Int J Radiat Oncol Biol Phys 84(4):949–954
Kapiteijn E et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345(9):638–646
Krook JE et al (1991) Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324(11):709–715
Lezoche E et al (2012) Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg 99(9):1211–1218
Maas M et al (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29(35):4633–4640
Machiels JP et al (2007) Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. Ann Oncol 18(4):738–744
Marsh PJ, James RD, Schofield PF (1994) Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial. Dis Colon Rectum 37(12):1205–1214
Methy N et al (2010) Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial. Ann Oncol 21(3):518–524
Nougaret S et al (2013) The use of MR imaging in treatment planning for patients with rectal carcinoma: have you checked the “DISTANCE”? Radiology 268(2):330–344
O’Connell MJ et al (1994) Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331(8):502–507
Ortholan C et al (2006) Role of radiotherapy with surgery for T3 and resectable T4 rectal cancer: evidence from randomized trials. Dis Colon Rectum 49(3):302–310
Ortholan C et al (2012) Correlation in rectal cancer between clinical tumor response after neoadjuvant radiotherapy and sphincter or organ preservation: 10-year results of the Lyon R 96-02 randomized trial. Int J Radiat Oncol Biol Phys 83(2):e165–e171
Pahlman L, Glimelius B (1990) Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 211(2):187–195
Pahlman L et al (2013) Altering the therapeutic paradigm towards a distal bowel margin of < 1 cm in patients with low-lying rectal cancer: a systematic review and commentary. Colorectal Dis 15(4):e166–e174
Park JH et al (2011) Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer 117(16):3703–3712
Patel UB et al (2011) Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol 29(28):3753–3760
Panis Y et al (2011) Mortality after colorectal cancer surgery: a French survey of more than 84,000 patients. Ann Surg 254(5):738–743 (discussion 743–744)
Pettersson D et al (2010) Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg 97(4):580–587
Pettersson D et al (2012) Preoperative short-course radiotherapy with delayed surgery in primary rectal cancer. Br J Surg 99(4):577–583
Perez RO et al (2013) Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another word of caution. Dis Colon Rectum 56(1):6–13
Rodel C et al (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13(7):679–687
Rutten HJ et al (2008) Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol 9(5):494–501
Roh MS et al. (2011) The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP 5-04. J Clin Oncol 29(221s): p. suppl 15; abstr 3503
Rullier E et al (2013) Low rectal cancer: classification and standardization of surgery. Dis Colon Rectum 56(5):560–567
Sauer R et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351(17):1731–1740
Sauer R et al (2012) 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 30(16):1926–1933
Schrag D et al (2014) Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol 32(6):513–518
Sebag-Montefiore D, Stephens RJ, Steele R et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016) : a multicentre, randomised trial. Lancet 373:811--820
Sloothaak DA et al (2013) Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg 100(7):933–939
Schmoll HJ, Haustermans K et al (2013) Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: first results of the PETACC-6 randomized phase III trial; ASCO, Abstract, p 3531
Taylor FG et al (2011) Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter European study. Ann Surg 253(4):711–719
Thariat J et al (2013) Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 10(1):52–60
Tunio MA et al (2010) High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers. World J Gastroenterol 16(35):4436–4442
van Gijn W et al (2011) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12(6):575–582
Vuong T, Devic S, Podgorsak E (2007) High dose rate endorectal brachytherapy as a neoadjuvant treatment for patients with resectable rectal cancer. Clin Oncol (R Coll Radiol) 19(9):701–705
Wang Y et al (2005) Primary radical external beam radiotherapy of rectal adenocarcinoma: long term outcome of 271 patients. Radiother Oncol 77(2):126–132
Wiltshire KL et al (2006) Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival. Int J Radiat Oncol Biol Phys 64(3):709–716
Willett CG et al (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27(18):3020–3026
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Gerard, J.P., Benezery, K., Doyen, J., Francois, E. (2014). Aims of Combined Modality Therapy in Rectal Cancer (M0). In: Otto, F., Lutz, M. (eds) Early Gastrointestinal Cancers II: Rectal Cancer. Recent Results in Cancer Research, vol 203. Springer, Cham. https://doi.org/10.1007/978-3-319-08060-4_11
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