Role of Primary Tumour Resection and Addition of Bevacizumab to Chemotherapy in the Management of Advanced Colorectal Cancer with Inoperable Metastasis: A Retrospective Analysis


  • Javier Garde Noguera Servicio Oncología Médica, Hospital Arnau de Vilanova de Valencia, Spain
  • Elena Evgenyeva Servicio de Anatomía Patológica, Hospital Marinasalud de Denia, Spain
  • Mireia Gil Raga Servicio Oncología Médica, Hospital de Sagunto, Spain
  • Asunción Juárez Marroquí Servicio Oncología Médica, Hospital de Elda, Spain
  • Juan Manuel Gasent Blesa Servicio Oncología Médica, Hospital Marinasalud de Denia Spain
  • Juan Laforga Servicio de Anatomía Patológica, Hospital Marinasalud de Denia, Spain
  • Laia Bernet Servicio de Anatomía Patológica y Oncología Diagnóstica, Hospital Lluís Alcanyís, Xativa, Spain
  • Mónica Clemente Císcar Centro de Gestión de la Calidad y el Cambio, Universitat Politécnica de Valencia, Spain
  • Carlos Camps Herrero Servicio de Oncología Médica, Consorcio Hospital General Universitario de Valencia, Spain
  • Antonio Llombart Cussac Servicio Oncología Médica, Hospital Arnau de Vilanova de Valencia, Spain



Primary Tumour Resection, Advanced Colorectal Cancer, Metastases, Survival, Bevacizumab.


 Purpose:To analyze the impact of primary tumour resection on treatment outcomes in patients with advanced colorectal cancer (CRC) and inoperable metastases at diagnosis in combination with optimal systemic therapy.

Methods:A retrospective study was carried out in four hospitals in Valencia (Spain) including all consecutive patients diagnosed between 1/2009 and 12/2010 of advanced CRC with inoperable metastasis and treated with a fluoropyrimidine and oxaliplatin combination chemotherapy regimens with or without bevacizumab (B). Treatment outcomes were compared between patients undergoing or not primary tumour resection.

Results:A total of 112 patients met inclusion criteria: 62 patients underwent resection of the primary tumour (Group 1) and 50 were treated with exclusive chemotherapy (Group 2). Globally, patients in group 2 presented more disfavorable characteristics. Forty-five (72%) and 31 (62%) patients received chemotherapy with bevacizumab respectively. Overallresponse rate(ORR) were 67% in Group 1 and 56% in Group 2. There were no statistically significant differences between the two groups in progression free survival (PFS) (12 vs. 10 months; p =0.11) and overall survival (OS) (27 vs. 22 months; p 0.1). B regimens increased ORR (73% vs. 42%; p = 0.003) and PFS (12 vs. 11 months; p = 0.019) but not OS. Complications were higher in the group of patients without primary tumour resection, particularly when associated to B regimens.

Conclusions:Primary tumour resection offers no survival gain for patients with advanced CRC and inoperable metastases. Benefits of adding Bevacizumab to standard chemotherapy were similar in both groups, but it increases the risk of complications in non-resected patients.


Surveillance, Epidemiology and End Results (SEER) Program ( SEER*Stat Database: Incidence - SEER 17 Regs Limited-Use, Nov 2006 Sub (1973-2004 varying), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2007, based on the November 2006 submission. Accessed May 2013.

Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, Eds. AJCC cancer staging manual (7th ed). New York, NY: Springer 2010; p. 143.

Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin 2012; 62(1): 10-29.

Bleiberg H. Role of chemotherapy for advanced colorrectal cancer. New oportunities. Semin Oncol 1996; 23(1 Suppl 3): 42-50.

De Gramont A, Vignoud J, Tournigand C, Louvet C, André T, Varette C, et al. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hours continuous infusion in preatreated metastático colorrectal cancer. Eur J Cancer 1997; 33(2): 214-9.

Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol 2001; 280(6): C1358-66.

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9(6): 669-76.

Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987-9.

Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S. Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 2005; 23(16): 3706-12.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(23): 2335-42.

Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25(12): 1539-44.

Saltz L, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26(12): 2013-9.

Shah SA, Haddad R, Al-Sukhni W, Kim RD, Greig PD, Grant DR, et al. Surgical resection of hepatic and pulmonary metastases from colorectal carcinoma. J Am Coll Surg 2006; 202(3): 468-75.

Galizia G, Lieto E, Orditura M, Castellano P, Imperatore V, Pinto M, et al. First-line chemotherapy vs bowel tumor resection plus chemotherapy for patients with unresectable synchronous colorectal hepatic metastases. Arch Surg 2008; 143(4): 352-8.

Cook AD, Single R, McCahill LE. Surgical resection of primary tumors in patients who present with stage IV colorectal cancer: an analysis of surveillance, epidemiology, and end results data, 1988 to 2000. Ann Surg Oncol 2005; 12(8): 637-45.

Konyalian VR, Rosing DK, Haukoos JS, Dixon MR, Sinow R, Bhaheetharan S, et al. The role of primary tumour resection in patients with stage IV colorectal cancer. Colorectal Dis 2007; 9(5): 430-7.

Karoui M, Roudot-Thoraval F, Mesli F, Mitry E, Aparicio T, Des Guetz G, et al. Primary colectomy in patients with stage IV colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study. Dis Colon Rectum 2011; 54(8): 930-8.

Scoggins CR, Meszoely IM, Blanke CD, Beauchamp RD, Leach SD, et al. Nonoperative management of primary colorectal cancer in patients with stage IV disease. Ann Surg Oncol 1999; 6(7): 651-7.

Stelzner S, Hellmich G, Koch R, Ludwig K. Factors predicting survival in stage IV colorectal carcinoma patients after palliative treatment: a multivariate analysis. J Surg Oncol 2005; 89(4): 211-7.

Karoui M, Koubaa W, Delbaldo C, Charachon A, Laurent A, Piedbois P, et al. Chemotherapy has also an effect on primary tumor in colon carcinoma. Ann Surg Oncol 2008; 15(12): 3440-6.

McCahill L, Yothers GA, Sharif S, Petrelli NJ, Lai LL, Bechar N, et al. Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically unresectable metastático colon cancer and an intact asymptomatic colon cancer: definitive análisis of NSABP trial C-10. J Clin Oncol 2012; 30(26): 3223-8.

Venderbosch S, Wilt JH, Teerenstra S, Loosveld OJ, van Bochove A, Sinnige HA, et al. Prognostic value of resection of primary tumor in patients with stage IV colorectal cancer: retrospective análisis of two randomized Studies and a review of the literature. Ann Surg Oncol 2011; 18(12): 3252-60.

Faron M, Bourredjem A, Pignon JP, Bouche O, Douillard JY, Adenis A, et al. Impact on survival of primary tumor resection in patients with colorrectal cancer and unresectable metastasis: pooled análisis of individual patients´ data from four randomized trials. J Clin Oncol 2012; 30(15suppl): Abstract 3507.

Poultsides GA, Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, 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(20): 3379-84.

Cirocchi R, Trastulli S, Abraha I, Vettoretto N, Boselli C, Montedori A, et al. Non-resection versus resection for an asyptomatic primary tumour in patients with unresectable stage IV colorectal cancer. Cochrane Database Syst Rev 2012; 8: CD008997.

Scheer MG, Sloots CE, van der Wilt GJ, Ruers TJ. Management of patients with asymptomatic colorectal cancer and synchronous irresectable metastases. Ann Oncol 2008; 19(11): 1829-35.

Kozloff M, Yood MU, Berlin H, Flynn PJ, Kabbinavar FF, Purdie DM, et al. Clinical Outcomes associated with bevacizumab-containing treatment of metastático colorectal cancer: The BRITE Observational Cohort Study. Oncologist 2009; 14(9): 862-70.

Ruo L, Gougoutas C, Paty PB, Guillem JG, Cohen AM, Wong WD. Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients. J Am Coll Surg 2003; 196(5): 722-8.




How to Cite

Javier Garde Noguera, Elena Evgenyeva, Mireia Gil Raga, Asunción Juárez Marroquí, Juan Manuel Gasent Blesa, Juan Laforga, Laia Bernet, Mónica Clemente Císcar, Carlos Camps Herrero, & Antonio Llombart Cussac. (2013). Role of Primary Tumour Resection and Addition of Bevacizumab to Chemotherapy in the Management of Advanced Colorectal Cancer with Inoperable Metastasis: A Retrospective Analysis. Journal of Analytical Oncology, 2(4),  209–217.