The role of radiation therapy in rectal cancer

Česká verzia

Authors: P. Pospíšil ^1,2; P. Šlampa ^1,2
Authors place of work: Klinika radiační onkologie MOÚ Brno ¹; Klinika radiační onkologie LF MU, Brno ²
Published in the journal: Klin Onkol 2020; 33(Suppl 1): 38-47
Category: Review
doi: https://doi.org/10.14735/amko2020S38

Summary

Background: Currently, surgery is still the only reliable curative procedure at all stages of rectal cancer. Its early stage involving the submucosa may be most effectively managed by local and gentle surgical procedures, without oncology therapy. However, most patients have deeper invading tumors that require radical transabdominal surgery. A large part of these tumors are locally advanced; they need a comprehensive solution consisting of a combination of surgery, radiotherapy and chemotherapy. The surgical and oncology treatment of these patients depends on the stage and location of the rectal tumor. The main goal of radiotherapy is to reduce the risk of local recurrences. Despite evident advances in the treatment, several issues remain unclear. The main subject of discussion is currently the best method of radiotherapy, the sequence of treatment modalities, as well as surgical approach to patients who achieve a clinical complete response after neoadjuvant treatment. The quality of life is considered to be a significant factor in assessing the therapeutic success in addition to the oncological outcome. Radiotherapy does not have the same benefit for all patients with advanced rectal cancer; in addition, it is necessary to take account of its adverse effects, especially late ones. According to current recommendations, radiotherapy may be omitted in some cases, particularly in upper rectal tumors. The tumors in the lower third of the rectum are a difficult issue. This is the main therapeutic challenge in terms of local control and preservation of the anal sphincter.

Purpose: The aim of this paper is to summarize the basic knowledge about radiotherapy of rectal cancer and relevant results of clinical trials and to highlight some controversial or unresolved issues.

Keywords:

radiotherapy – rectal cancer – Chemoradiotherapy – non-surgical – watch and wait – local recurrence

Zdroje

1. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001; 358 (9290): 1291–304. doi: 10.1016/S0140-6736 (01) 06409-1.

2. Sauer R, Becker H, Hohenberger W et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351 (17): 1731–1740. doi: 10.1056/NEJMoa040694.

3. Salerno G, Sinnatamby C, Branagan G et al. Defining the rectum: surgically, radiologically and anatomically. Colorectal Dis 2006; Suppl 3: 5–9. doi: 10.1111/j.1463-1318.2006.01062.x.

4. Mulcahy MF. Radiotherapy for cancer of the rectum: which patients stand to benefit? Gastrointest Cancer Res 2009; 3 (2): 81–83.

5. Joshi N, Woody NM, Abdel-Wahab M. Pre-operative chemoradiation for rectosigmoid cancers: Where do we draw the line? [online]. Available from: https: //appliedradiationoncology.com/articles/pre-operative-chemoradiation-for-rectosigmoid-cancers-where-do-we-draw-the-line.

6. Shin R, Jeong SY, Yoo HY et al. Depth of mesorectal extension has prognostic significance in patients with T3 rectal cancer. Dis Colon Rectum 2012; 55 (12): 1220–1228. doi: 10.1097/DCR.0b013e31826fea6a.

7. Merkel S, Mansmann U, Siassi M et al. The prognostic inhomogeneity in pT3 rectal carcinomas. Int J Colorectal Dis 2001; 16 (5): 298–304. doi: 10.1007/s00384-001-0376-1.

8. Amin MB, Edge S, Greene F et al. AJCC Cancer Staging Manual. Springer International Publishing: American Joint Commission on Cancer 2017.

9. Beets-Tan RG, Beets GL, Vliegen RF et al. Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery. Lancet 2001; 357 (9255): 497–504. doi: 10.1016/s0140-6736 (00) 04040-x.

10. Glimelius B, Tiret E, Cervantes A et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; Suppl 6: vi81–vi88. doi: 10.1093/annonc/mdt240.

11. Goodman KA, Patton CE, Fisher GA et al. Appropriate customization of radiation therapy for stage II and III rectal cancer: Executive summary of an ASTRO Clinical Practice Statement using the RAND/UCLA Appropriateness Method. Pract Radiat Oncol 2016; 6 (3): 166–175. doi: 10.1016/j.prro.2015.11.014.

12. Zhou ZR, Liu SX, Zhang TS et al. Short-course preoperative radiotherapy with immediate surgery versus long-course chemoradiation with delayed surgery in the treatment of rectal cancer: a systematic review and meta-analysis. Surg Oncol 2014; 23 (4): 211–221. doi: 10.1016/j.suronc.2014.10.003.

13. Wang X, Zheng B, Lu X et al. Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data. PLoS One 2018; 13 (7): e0200142. doi: 10.1371/journal.pone.0200142.

14. Cedermark B, Dahlberg M, Glimelius B et al. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997; 336 (14): 980–987. doi: 10.1056/NEJM199704033361402.

15. 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 (5): 693–701. doi: 10.1097/01.sla.0000257358.56863.ce.

16. 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 (6): 575–582. doi: 10.1016/S1470-2045 (11) 70097-3.

17. Peeters KC, van de Velde CJ, Leer JW et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients – a Dutch colorectal cancer group study. J Clin Oncol 2005; 23 (25): 6199–6206. doi: 10.1200/JCO.2005.14.779.

18. 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 (10): 1215–1223. doi: 10.1002/bjs.5506.

19. 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 2012; 30 (31): 3827–3833. doi: 10.1200/JCO.2012.42.9597.

20. Ansari N, Solomon MJ, Fisher RJ et al. Acute adverse events and postoperative complications in a randomized trial of preoperative short-course radiotherapy versus long-course chemoradiotherapy for T3 adenocarcinoma of the rectum: Trans-Tasman Radiation Oncology Group trial (TROG 01.04). Ann Surg 2017; 265 (5): 882–888. doi: 10.1097/SLA.0000000000001987.

21. Latkauskas T, Pauzas H, Gineikiene I et al. Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery. Colorectal Dis 2012; 14 (3): 294–298. doi: 10.1111/j.1463-1318.2011.02815.x.

22. 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. Ann Oncol 2016; 27 (5): 834–842. doi: 10.1093/annonc/mdw062.

23. McCarthy K, Pearson K, Fulton R et al. Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer. Cochrane Database Syst Rev 2012; 12: CD008368. doi: 10.1002/14651858.CD008368.pub2.

24. De Caluwé L, Van Nieuwenhove Y, Ceelen WP. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev 2013; (2): CD006041. doi: 10.1002/14651858.CD006041.pub3.

25. 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 (31): 5124–5130. doi: 10.1200/JCO.2009.22.0467.

26. Park JH, Yoon SM, Yu CS et al. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer 2011; 117 (16): 3703–3712. doi: 10.1002/cncr.25943.

27. Fan WH, Wang FL, Lu ZH et al. Surgery with versus without preoperative concurrent chemoradiotherapy for mid/low rectal cancer: an interim analysis of a prospective, randomized trial. Chin J Cancer 2015; 34 (9): 394–403. doi: 10.1186/s40880-015-0024-8.

28. Rödel C, Liersch T, Becker H et al. 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 2012; 13 (7): 679–687. doi: 10.1016/S1470-2045 (12) 70187-0.

29. Yang YJ, Cao L, Li ZW et al. Fluorouracil-based neoadjuvant chemoradiotherapy with or without oxaliplatin for treatment of locally advanced rectal cancer: An updated systematic review and meta-analysis. Oncotarget 2016; 7 (29): 45513–45524. doi: 10.18632/oncotarget.9995.

30. Alliance for Clinical Trials in Oncology. Chemotherapy alone or chemotherapy plus radiation therapy in treating patients with locally advanced rectal cancer undergoing surgery. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT01515787.

31. 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 (9): 835–844. doi: 10.1016/S1470-2045 (10) 70172-8.

32. Smith FM, Wiland H, Mace A et al. Clinical criteria underestimate complete pathological response in rectal cancer treated with neoadjuvant chemoradiotherapy. Dis Colon Rectum 2014; 57 (3): 311–315. doi: 10.1097/DCR.0b013e3182a84eba.

33. Li J, Li L, Yang L et al. Wait-and-see treatment strategies for rectal cancer patients with clinical complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis. Oncotarget 2016; 7 (28): 44857–44870. doi: 10.18632/oncotarget.8622.

34. 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 (8): 919–927. doi: 10.1016/S1470-2045 (15) 00120-5.

35. 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 (2): 174–183. doi: 10.1016/S1470-2045 (15) 00467-2.

36. Lai CL, Lai MJ, Wu CC et al. Rectal cancer with complete clinical response after neoadjuvant chemoradiotherapy, surgery, or „watch and wait“. Int J Colorectal Dis 2016; 31 (2): 413–419. doi: 10.1007/s00384-015-2460-y.

37. 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 (10): 1319–1329. doi: 10.1016/j.gassur.2006.09.005.

38. 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 (9): 1211–1218. doi: 10.1002/bjs.8821.

39. Petrelli F, Sgroi G, Sarti E et al. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies. Ann Surg 2016; 263 (3): 458–464. doi: 10.1097/SLA.0000000000000368.

40. Francois Y, Nemoz CJ, Baulieux J et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 1999; 17 (8): 2396. doi: 10.1200/JCO.1999.17.8.2396.

41. Lefevre JH, Mineur L, Kotti S et al. Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: A multicenter, randomized, controlled trial (GRECCAR-6). J Clin Oncol 2016; 34 (31): 3773–3780. doi: 10.1200/JCO.2016.67.6049.

42. Evans J, Bhoday J, Sizer B et al. Results of a prospective randomised control 6 vs 12 trial: Is greater tumour downstaging observed on post treatment MRI if surgery is delayed to 12-weeks versus 6-weeks after completion of neoadjuvant chemoradiotherapy? Ann Oncol 2016; 27 (suppl 6): VI149. doi: 10.1093/annonc/mdw370.01.

43. Huntington CR, Boselli D, Symanowski J et al. Optimal timing of surgical resection after radiation in locally advanced rectal adenocarcinoma: an analysis of the national cancer database. Ann Surg Oncol 2016; 23 (3): 877–887. doi: 10.1245/s10434-015-4927-z.

44. Pettersson D, Lörinc E, Holm T et al. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg 2015; 102 (8): 972–978. doi: 10.1002/bjs.9811.

45. Kocáková I, Špelda S, Kocák I et al. Předoperační chemoradioterapie s kapecitabinem v léčbě lokálně pokročilého adenokarcinomu rekta. Klin Onkol 2003; 16 (2): 60–67.