The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer

Preoperative radiotherapy (RT) is recommended to many patients with localised rectal cancer, not previously treated with pelvic RT. However, the optimum fractionation, the timing of surgery and the best use of concomitant chemotherapy remains controversial. There are theoretical reasons to believe that radiotherapy given in larger fractions during a shorter period of time might result in more late side effects than giving a conventional, more protracted RT in patients with rectal cancer. In addition, the optimum timing of surgery after RT, with respect to postoperative morbidity, mortality and potential downsizing of the tumour is not known. To address these questions, a prospective randomized multicenter trial was initiated, the Stockholm III trial, in which patients with primarily resectable rectal cancer were randomized to short-course preoperative RT (5x5 Gy) followed by surgery within one week or after 4-8 weeks or long-course preoperative RT(25x2 Gy) followed by surgery after 4-8 weeks.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Biopsy confirmed clinically resectable rectal adenocarcinoma within 15 cm from the anal verge
* Planned for bowel resection with an abdominal procedure.
* Informed consent.

Exclusion Criteria:

* Distant metastases
* Locally advanced unresectable tumors
* Planned for local excision
* Previous radiotherapy to the abdominal or pelvic region
* Severe ischemic heart disease or symptoms of severe arteriosclerosis

• BACKGROUNDPettersson D, Lorinc E, Holm T, Iversen H, Cedermark B, Glimelius B, Martling A. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015 Jul;102(8):972-8; discussion 978. doi: 10.1002/bjs.9811. PMID 26095256
• BACKGROUNDPettersson D, Cedermark B, Holm T, Radu C, Pahlman L, Glimelius B, Martling A. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010 Apr;97(4):580-7. doi: 10.1002/bjs.6914. PMID 20155787
• BACKGROUNDPettersson D, Glimelius B, Iversen H, Johansson H, Holm T, Martling A. Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial. Br J Surg. 2013 Jun;100(7):969-75. doi: 10.1002/bjs.9117. Epub 2013 Apr 2. PMID 23553796
• RESULTErlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallbook O, Syk I, Glimelius B, Martling A. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017 Mar;18(3):336-346. doi: 10.1016/S1470-2045(17)30086-4. Epub 2017 Feb 10. PMID 28190762
• RESULTErlandsson J, Lorinc E, Ahlberg M, Pettersson D, Holm T, Glimelius B, Martling A. Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial. Radiother Oncol. 2019 Jun;135:178-186. doi: 10.1016/j.radonc.2019.03.016. Epub 2019 Apr 1. PMID 31015165
• RESULTErlandsson J, Pettersson D, Glimelius B, Holm T, Martling A. Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. Br J Surg. 2019 Aug;106(9):1248-1256. doi: 10.1002/bjs.11200. Epub 2019 Jun 14. PMID 31197822