Comprehensive treatment of rectal cancer patients with synchronous distant metastases

Objective: to analyze short-term and long-term outcomes of surgical, combination, and comprehensive treatment in patients with metastatic rectal cancer.

Materials and methods. We performed a retrospective analysis of prospectively collected data on the outcomes of rectal cancer patients receiving surgical, combination (surgery + chemotherapy), or comprehensive (chemoradiotherapy + surgery + chemotherapy) treatment in the Department of Proctology at the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, between 1999 and 2015. We assessed overall survival, frequency of postoperative complications, postoperative death rates and frequency of complications associated with chemoradiotherapy.

Results. The study included 366patients that were divided into 3 groups according to the treatment strategy. The 2-year survival rate was 83 % in group 3 (comprehensive treatment) vs 40 % in groups 1 and 2. Median survival was 43 months in group 3 compared to 18 and 14 months in groups 2 and 1 respectively. The number of postoperative complications was 19 %, 13.4 %, and 15.1 % in groups 1, 2 and 3 respectively. There was one postoperative death (1.1 %) in group 3.

Conclusion. Comprehensive treatment significantly improves overall survival of rectal cancer patients without increasing the risk of postoperative complications.

1. Heidelberger C., Chaudhuri N.K., Danneberg D. et al. Fluorinated pyrimidines, a new class of tumor-inhibitory com-pounds. Nature 1957;179(4561):663—6. PMID: 13418758.

2. Cooray P., McKendrick J., Wong S.W. et al. Synchronised chemoradiation and systemic chemotherapy for patients presenting with simultaneously primary and metastatic rectal cancer. Eur J Cancer 2013;49(2):S506.

3. Van Dijk T.H., Tamas K., Beukema J.C. et al. Evaluation of short-course radio-therapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol 2013;24(7):1762—9. PMID: 23524865. DOI: 10.1093/annonc/mdt124.

4. Lavnikova G.A. Some mechanisms of radiation pathomorphosis of human tumors and their practical use. Bulletin of the USSR Academy of medical Sciences 1976;6:13-9. (In Russ.).

5. Dworak O., Keilholz L., Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12(1):19-23. PMID: 9112145.

6. Siegel R., Desantis C., Jemal A. Colorectal cancer statistics. CA Cancer J Clin 2014;64(2):104—17. PMID: 24639052. DOI: 10.3322/caac.21220.

7. McMillan D.C., McArdle C.S. Epidemiology of colorectal liver metastases. Surg Oncol 2007;16(1):3— 5. PMID: 17493802. DOI: 10.1016/j.suronc.2007.04.008.

8. Julien L.A., Thorson A.G. Current neoadjuvant strategies in rectal cancer. J Surg Oncol 2010;101(4):321—6. PMID: 20187066. DOI: 10.1002/jso.21480.

9. 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. PMID: 16110023. DOI: 10.1200/JCO.2005.08.144.

10. Sauer R., Liersch T., Merkel S. et al. 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 On-col 2012;30(16):1926—33. PMID: 22529255. DOI: 10.1200/JCO.2011.40.1836.

11. 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. PMID: 23008301. DOI: 10.1200/JCO.2012.42.9597.

12. Wang Z.M., Chen Y.Y., Chen F.F. et al. Perioperative chemotherapy for patients with resectable colorectal hepatic metastasis: a meta-analysis. Eur J Surg Oncol 2015;41(9):1197—203. DOI: 10.1016/j.ejso.2015.05.020.

13. Ciliberto D., Prati U., Roveda L. et al. Role of systemic chemotherapy in the management of resected or resectable colorectal Oncol Rep 2012;27(6):1849—56. PMID: 22446591. DOI: 10.3892/or.2012.1740.

14. Lee K.C., Ou Y.C., Hu W.H. et al. Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection. Onco Targets Ther 2016;9:7059—69. PMID: 27895498. DOI: 10.2147/OTT.S112965.

15. Snijders H.S., Wouters M.W., van Leersum N.J. et al. Meta-analysis of the risk for anastomotic leakage, the postoperative mortality caused by leakage in relation to the overall postoperative mortality. Eur J Surg Oncol 2012;38(11):1013—9. PMID: 22954525. DOI: 10.1016/j.ejso.2012.07.111.

16. Scheer M.G., Sloots C.E., van der Wilt G.J., Ruers T.J. Management of patients with asymptomatic colorectal cancer and synchronous irresectable metastases. Ann Oncol 2008;19(11):1829—35. PMID: 18662955. DOI: 10.1093/annonc/mdn398.

17. Ng S.C., Stupart D., Bartolo D., Watters D. Anastomotic leaks in stage IV colorectal cancer. ANZ J Surg 2018;88(9):E649—53. PMID: 29895100. DOI: 10.1111/ans.14494.

18. Vigano L., Karoui M., Ferrero A. et al. Locally advanced mid/low rectal cancer with synchronous liver metastases. World J Surg 2011;35(12):2788—95. PMID: 21947493. DOI: 10.1007/s00268-011-1272-7.

19. Manceau G., Brouquet A., Bachet J.B. et al. Response of liver metastases to pre-operative radiochemotherapy in patients with locally advanced rectal cancer and resectable synchronous liver metastases. Surgery 2013;154(3):528—35. PMID: 23601902. DOI: 10.1016/j.surg.2013.02.010.

20. Agas R.A.F., Co L.B.A., Jacinto J.C.K.M. et al. Neoadjuvant radiotherapy versus no radiotherapy for stage iv rectal cancer: a systematic review and meta-analysis. J Gastrointest Cancer 2018;49(4):389— 401. PMID: 30043227. DOI: 10.1007/s12029-018-0141-0.

21. Zabelin M.V., Gordeev S.S., Petrov L.O. et al. The role of antiangiogenic drugs in the treatment of metastatic colorectal cancer patients. Onkologicheskaya Koloproktologiya = Colorectal Oncology 2018;(1):11–9. (In Russ.).