Journal of Gastrointestinal Surgery

, Volume 19, Issue 9, pp 1676–1683 | Cite as

The Impact of Preoperative Radiation Therapy on Locoregional Recurrence in Patients with Stage IV Rectal Cancer Treated with Definitive Surgical Resection and Contemporary Chemotherapy

  • Bindu V. Manyam
  • Ismail H. Mallick
  • May M. Abdel-Wahab
  • Chandana A. Reddy
  • Feza H. Remzi
  • Matthew F. Kalady
  • Ian Lavery
  • Shlomo A. Koyfman
Original Article

Abstract

Purpose

Definitive resection of primary rectal cancers is frequently incorporated, with or without preoperative radiotherapy and perioperative chemotherapy, in the management of selected patients with metastatic rectal adenocarcinoma. This study reviews the impact of preoperative radiotherapy and perioperative chemotherapy on locoregional recurrence and overall survival in these patients.

Methods and Materials

This retrospective study with an Institutional Review Board (IRB) waiver included 109 patients with metastatic rectal adenocarcinoma who underwent definitive primary resection between 1998 and 2011. In addition to resection, 64 patients were treated with preoperative radiotherapy and perioperative chemotherapy and 45 patients were treated with perioperative chemotherapy alone. Radiotherapy dose was typically 50.4 Gy. Baseline variables were compared using chi-square and unpaired t tests. Overall survival was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression.

Results

There were no significant baseline differences between the two groups. There was no significant difference in locoregional recurrence (10.9 vs. 11.1 %; p = 0.90) or overall survival (34.5 vs. 34.8 months; p = 0.89) for patients treated with preoperative radiotherapy compared to those treated with perioperative chemotherapy alone, respectively. Patients who underwent radiotherapy were less likely to have a positive margin (10.9 vs. 20.0 %; p = 0.19), lymphovascular invasion (32.8 vs. 53.3 %; p = 0.03), and pathologic stage N2 disease (25.0 vs. 42.2 %; p = 0.02). Grade 2 postoperative complications were more common in the preoperative radiotherapy group (32.8 vs. 15.6 %; p = 0.04). Multivariate analysis demonstrated that patients with poorly differentiated tumors (HR 2.19; p = 0.009) and those that did not undergo liver-directed therapy (HR 2.20; p = 0.005) had inferior survival.

Conclusions

Locoregional recurrence is modest in patients with metastatic rectal adenocarcinoma receiving definitive primary resection, irrespective of the use of radiotherapy. Preoperative radiotherapy may enhance pathologic downstaging at the expense of increased grade 2 postoperative complications. Its use should be reserved for patients at high risk for locoregional recurrence.

Keywords

Oligometastatic rectal cancer Radical primary resection Locoregional recurrence Radiotherapy 

References

  1. 1.
    National Comprehensive Cancer Network: Practice guidelines in oncology. Rectal cancer. www.nccn.org, v.4, 2013.
  2. 2.
    Venderbosch S, deWilt JH, Teerenstra S, et al. Prognostic value of resection of primary tumor in patients with stage IV colorectal cancer: retrospective analysis of two randomized studies and a review of the literature. Ann Surg Oncol 2011; 18:3253-3260.Google Scholar
  3. 3.
    Martin R, Paty P, Fong Y, et al. Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 2003; 197:233-242.CrossRefPubMedGoogle Scholar
  4. 4.
    Millikian KW, Staren ED, Doolas A. Invasive therapy of metastatic colorectal cancer to the liver. Surg Clin North Am 1997; 77:27-48.CrossRefGoogle Scholar
  5. 5.
    An HJ, Yu CS, Yun SC, et al. Adjuvant chemotherapy with or without pelvic radiotherapy after simultaneous surgical resection of rectal cancer with liver metastases: analysis of prognosis and patterns of recurrence. Int J Radiation Oncol Biol Phys 2012; 84:73-80.CrossRefGoogle Scholar
  6. 6.
    Koopman M, Antonini NF, Douma J, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxliplatin in advanced colorectal cancer (CAIRO): a phase III randomized controlled trial. Lancet 2007; 370:135-142.CrossRefPubMedGoogle Scholar
  7. 7.
    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 Oncol 2013; 30:1926-1933.CrossRefGoogle Scholar
  8. 8.
    Frykholm GJ, Glimelius B, Pahlman L. 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 1993; 36:564-672.CrossRefPubMedGoogle Scholar
  9. 9.
    Butte JM, Gonen M, Ding P, et al. Patterns of failure in patients with early onset (synchronous) resectable liver metastases from rectal cancer. Cancer 2012; 118:5414-5423.CrossRefPubMedGoogle Scholar
  10. 10.
    Poultsides GA, Servais EL, Saltz LB, et al. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol 2009; 27:3379-3384.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Cellini C, Hunt SR, Fleshman JW, et al. Stage IV rectal cancer with liver metastases: is there a benefit to resection of the primary tumor? World J Surg 2010; 34:1102-1108.CrossRefPubMedGoogle Scholar
  12. 12.
    Rees M, Tekkis P, Welsh F, et al. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg 2008; 247:125-135.CrossRefPubMedGoogle Scholar
  13. 13.
    Abdalla EK, Vauthey JN, Ellis LM, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 2004; 239:818-827.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Manfredi S, Lepage C, Hatem C, et al. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 2006; 244:254-259.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Chang CY, Kim HC, Park YS, et al. The effect of postoperative pelvic irradiation after complete resection of metastatic rectal cancer. J Surg Oncol 2012; 105:244-248.CrossRefPubMedGoogle Scholar
  16. 16.
    Kim JW, Kim YB, Kim N, et al. The role of adjuvant pelvic radiotherapy in rectal cancer with synchronous liver metastasis: a retrospective study. Radiat Oncol 2010; 5:75-81.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 1998; 13:245-252.CrossRefGoogle Scholar
  18. 18.
    Mohiuddin M, Winter K, Mitchell E, et al. Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol 2006; 4:650-655.CrossRefGoogle Scholar
  19. 19.
    Minsky BD, Cohen AM, Kemeny N, et al. Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach. J Clin Oncol 1992; 10:1218-1224.PubMedGoogle Scholar
  20. 20.
    Turner II, Russell GB, Blackstock AW, et al. Impact of neoadjuvant therapy on postoperative complications in patients undergoing resection for rectal adenocarcinoma. Am Surg 2004; 70:1045-1049.PubMedGoogle Scholar
  21. 21.
    Schiffman L, Wedermann N, Gock N, et al. Intensified neoadjuvant radiochemotherapy for rectal cancer enhances surgical complications. BMC Surg 2013; 13:43-48.CrossRefGoogle Scholar
  22. 22.
    Law WL, Chu KW. Outcomes of resection of stage IV rectal cancer with mesorectal excision. Outcomes of resection of stage IV rectal cancer with mesorectal excision. J Surg Onc 2006; 93:523-538.CrossRefGoogle Scholar
  23. 23.
    Assumpcoa L, Choti MA, Gleismer AL, et al. Patterns of recurrence following liver resection for colorectal metastases: effect of primary rectal tumor site. Arch Surg 2008; 143:743-749.CrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2015

Authors and Affiliations

  • Bindu V. Manyam
    • 1
  • Ismail H. Mallick
    • 2
  • May M. Abdel-Wahab
    • 1
  • Chandana A. Reddy
    • 1
  • Feza H. Remzi
    • 2
  • Matthew F. Kalady
    • 2
  • Ian Lavery
    • 2
  • Shlomo A. Koyfman
    • 1
  1. 1.Department of Radiation OncologyCleveland ClinicClevelandUSA
  2. 2.Department of Colorectal SurgeryCleveland ClinicClevelandUSA

Personalised recommendations