Changes in clinical guidelines for the treatment of colorectal cancer in 2024

Aim. The ensuring that changes to clinical guidelines can be discussed more widely before they are formally introduced into clinical practice.

Materials and methods. A brief review of the literature and rationale for each proposed major change in the treatment section is presented. The refusal to carry out preoperative radiation therapy for cancer of the upper ampullary rectum, the narrowing of indications for preoperative radiation therapy for cancer of the mid-ampullary rectum, as well as the expansion of indications for total non-adjuvant chemotherapy for rectal cancer with damage to the circular resection margin are discussed. Changes to the drug treatment section are discussed.

Results. This article presents planned changes to clinical guidelines for the treatment of non-metastatic colorectal cancer in 2024. The most significant alterations concerned neoadjuvant treatment of rectal cancer and adjuvant treatment of colon cancer. A new algorithm was proposed for choosing rectal cancer neoadjuvant therapy, considering individual treatment decisions.

Conclusion. A consensus was achieved concerning the necessity to expand indications for neoadjuvant rectal cancer chemotherapy, but only in patients with good functional status. The most benefit can be achieved in patients, for whom complete clinical response is the aim of the treatment and in patients with positive circumferential resection margin.

1. Sakamoto T., Shimura M., Kitano S. et al. Extramural depth of tumor invasion at thin-section MR in patients with rectal cancer: results of the MERCURY study. Radiology 2007;243(1):132–9. DOI: 10.1148/radiol.2431051825

2. Engstrom P.F., Arnoletti J.P., Benson A.B. 3rd et al. Rectal cancer. J Natl Compr Canc Netw 2009:7(8):838–81. DOI: 10.6004/jnccn.2009.0057

3. De Caluwé L., Van Nieuwenhove Y., Ceelen W.P. 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

4. Bahadoer R.R., Dijkstra E.A., 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. DOI: 10.1016/S1470-2045(20)30555-6

5. Dijkstra E.A., Nilsson P.J., Hospers G.A.P. et al. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared to long-course chemoradiotherapy and surgery–a five-year follow-up of the RAPIDO trial. Ann Surg 2023;278(4):e766–72. DOI: 10.1097/SLA.0000000000005799

6. Song J.H., Jeong J.U., Lee J.H. et al. Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II–III resectable rectal cancer: a meta-analysis of randomized controlled trials. Radiat Oncol J 2017;35(3): 198–207. DOI: 10.3857/roj.2017.00059

7. Battersby N.J., How P., Moran B. et al. Prospective validation of a low rectal cancer magnetic resonance imaging staging system and development of a local recurrence risk stratification model: the MERCURY II study. Ann Surg 2016;263(4):751–60. DOI: 10.1097/SLA.0000000000001193

8. Marinello F.G., Frasson M., Baguena G. et al. Selective approach for upper rectal cancer treatment: total mesorectal excision and preoperative chemoradiation are seldom necessary. Dis Colon Rectum 2015;58(6):556–65. DOI: 10.1097/DCR.0000000000000349

9. Rosenberg R., Maak M., Schuster T. et al. Does a rectal cancer of the upper third behave more like a colon or a rectal cancer? Dis Colon Rectum 2010;53(5):761–70. DOI: 10.1007/DCR.0b013e3181cdb25a

10. Folkesson J., Birgisson H., Pahlman L. et al. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005;23(24):5644–50. DOI: 10.1200/JCO.2005.08.144

11. Sebag-Montefiore D., Stephens R.J., 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. DOI: 10.1016/S0140-6736(09)60484-0

12. Van Gijn W., Marijnen C.A., Nagtegaal I.D. 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):575–82. DOI: 10.1016/S1470-2045(11)70097-3

13. Morton D., Seymour M., Magill L. et al. Preoperative chemotherapy for operable colon cancer: mature results of an international randomized controlled trial. J Clin Oncol 2023;41(8):1541. DOI: 10.1200/JCO.22.00046

14. Hu H., Huang M., Li Y. et al. Perioperative chemotherapy with mFOLFOX6 or CAPOX for patients with locally advanced colon cancer (OPTICAL): A multicenter, randomized, phase 3 trial. J Clin Oncol 2022;40(16_suppl). DOI: 10.1200/JCO.2022.40.16_suppl.3500

15. Jensen L.H., Kjaer M.L., Holländer N.H., Larsen F.O. Phase III randomized clinical trial comparing the efficacy of neoadjuvant chemotherapy and standard treatment in patients with locally advanced colon cancer: The NeoCol trial. J Clin Oncol 2023;41(17_suppl):LBA3503. DOI: 10.1200/JCO.2023.41.17_suppl.LBA3503

16. Karoui M., Rullier A., Piessen G. et al. Perioperative FOLFOX 4 versus FOLFOX 4 plus cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a phase II multicenter randomized controlled trial (PRODIGE 22). Ann Surg 2020;271(4):637–45. DOI: 10.1097/SLA.0000000000003454

17. Ngan S.Y., Burmeister B., Fisher R.J. 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):3827–33. DOI: 10.1200/JCO.2012.42.9597

18. Cisel 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. Ann Oncol 2019;30(8):1298–303. DOI: 10.1093/annonc/mdz186

19. Dijkstra E.A., Hospers G.A.P., Kranenbarg E.M. et al. Quality of life and late toxicity after short-course radiotherapy followed by chemotherapy or chemoradiotherapy for locally advanced rectal cancer – The RAPIDO trial. Radiother Oncol 2022;171:69–76. DOI: 10.1016/j.radonc.2022.04.013

20. Birgisson H., Påhlman L., Gunnarsson U., Glimelius B. Late adverse effects of radiation therapy for rectal cancer – a systematic overview. Acta Oncol 2007;46(4):504–16. DOI: 10.1080/02841860701348670

21. Grothey A., Sobrero A.F., Shields A.F. et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med 2018;378(13):1177–88. DOI: 10.1056/NEJMoa1713709

22. Schrag D. PROSPECT: A randomized phase III trial of neoadjuvant chemoradiation versus neoadjuvant FOLFOX chemotherapy with selective use of chemoradiation, followed by total mesorectal excision (TME) for treatment of locally advanced rectal cancer (LARC)(Alliance N1048). American Society of Clinical Oncology 2023.

23. Mei W.-J., Wang X.Z., Li Y.F. et al. Neoadjuvant chemotherapy with CAPOX versus Chemoradiation for Locally Advanced Rectal Cancer with Uninvolved Mesorectal Fascia (CONVERT): initial results of a phase III trial. Ann Surg 2023;277(4):557–64. DOI: 10.1097/SLA.0000000000005780

24. Hazen S.-M.J., Sluckin T.C., Intven M.P.W. et al. Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes. JAMA Oncol 2024;10(2):202–11. DOI: 10.1001/jamaoncol.2023.5444

25. Sychev S., Ponomarenko A., Chernyshov S. et al. Total neoadjuvant therapy in rectal cancer: a network meta-analysis of randomized trials. Ann Coloproctol 2023;39(4):289–300. DOI: 10.3393/ac.2022.00920.0131

26. Verheij F.S., Omer D.M., Williams H. et al. Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial. J Clin Oncol 2023:42(5):500–6. DOI: 10.1200/JCO.23.01208

27. Liao C.-K., Kuo Y.T., Lin Y.C. et al. Neoadjuvant short-course radiotherapy followed by consolidation chemotherapy before surgery for treating locally advanced rectal cancer: a systematic review and meta-analysis. Curr Oncol 2022;29(5):3708–27. DOI: 10.3390/curroncol29050297

28. Verheij F.S., Omer D.M.R., Williams H. et al. Sustained organ preservation in patients with rectal cancer treated with total neoadjuvant therapy: Long-term results of the OPRA trial. J Clin Oncol 2023;41(16_suppl). DOI: 10.1200/JCO.2023.41.16_suppl.352

29. Romesser P.B., Park B.K., Nemirovsky D. et al. Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating long-course chemoradiation versus short-course radiation therapy. J Clin Oncol 2023;41(4_suppl). DOI: 10.1200/JCO.2023.41.4_suppl.10

30. Van der Valk M.J., Hilling D.E., 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(10139):2537–45. DOI: 10.1016/S0140-6736(18)31078-X

31. Ellis C.T., Cole A.L., Sanoff H.K. et al. Evaluating surveillance patterns after Chemoradiation-only compared with conventional Management for Older Patients with rectal cancer. J Am Coll Surg 2019;228(5):782–91. DOI: 10.1016/j.jamcollsurg.2019.01.010

32. Giordano P., Efron J., Vernava A.M. 3rd et al. Strategies of followup for colorectal cancer: a survey of the American Society of Colon and Rectal Surgeons. Tech Coloproctol 2006;10(3):199–207. DOI: 10.1007/s10151-006-0280-3

33. Fedyanin M., Glakov O., Gordeev S. et al. Cancer of the colon, rectosigmoid junction and rectum. Zlokachestvennye opukholi = Malignant tumours 2023;13(3s2-1):425–82. (In Russ.). DOI: 10.18027/2224-5057-2023-13-3s2-1-425-482

34. Fedyanin M., Tryakin A.A., Bulanov A.A. et al. On the question of the number of lymph nodes required for study in stage II colon cancer. Onkologicheskaya Koloproktologiya = Colorectal Oncology 2019;9(1):42–50. (In Russ.). DOI: 10.17650/2220-3478-2019-9-1-42-50

35. Jeon J., Shen L., Kim Y. et al. The number of lymph nodes examined as a poor prognosis factor in stage II and stage III colon cancer patients undergoing curative surgery. J Clin Oncol 2023;41(16_suppl). DOI: 10.1200/JCO.2023.41.16_suppl.3612

36. Ahmed F., Selfridge J., Kakishet H. et al. SO-19 The outcome of resected stage II colon cancer patients with deficient mismatch repair T4 tumors: A National Cancer Database analysis. Ann Oncol 2023;34(1_suppl):S170. DOI: 10.1016/j.annonc.2023.04.491

37. Fleming P., Chen Ch., Moore D.F. et al. High-risk MSI-H stage II colon cancer: Treatment patterns and outcomes. J Clin Oncol 2022;40(16_suppl). DOI: 10.1200/JCO.2022.40.16_suppl.e15588

38. Oki E., Kotani D., Nakamura Y. et al. Circulating tumor DNA dynamics as an early predictor of recurrence in patients with radically resected colorectal cancer: Updated results from GALAXY study in the CIRCULATE-Japan. J Clin Oncol 2023;41(16_suppl). DOI: 10.1200/JCO.2023.41.16_suppl.3521

39. Tie J., Cohen J.D., Lahouel K. et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med 2022;386(24):2261–72. DOI: 10.1056/NEJMoa2200075

40. Cohen S.A., Kasi P.M., Aushev V.N., Hanna D. Kinetics of postoperative circulating cell-free DNA and impact on minimal residual disease detection rates in patients with resected stage I–III colorectal cancer. J Clin Oncol 2023;41(4_suppl):5. DOI: 10.1200/JCO.2023.41.4_suppl.5

41. Karoui M., Gallois C., Piessen G. et al. Does neoadjuvant FOLFOX chemotherapy improve the prognosis of high-risk Stage II and III colon cancers? Three years’ follow-up results of the PRODIGE 22 phase II randomized multicentre trial. Colorectal Dis 2021;23(6):1357–69. DOI: 10.1111/codi.15585