The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial

Chang Woo Kim, Jeong-Heum Baek, Gyu-Seog Choi, Chang Sik Yu, Sung Bum Kang, Won Cheol Park, Bong Hwa Lee, Hyeong Rok Kim, Jae Hwan Oh, Jae-Hwang Kim, Seung-Yong Jeong, Jung Bae Ahn, Seung Hyuk Baik, Chang Woo Kim, Jeong-Heum Baek, Gyu-Seog Choi, Chang Sik Yu, Sung Bum Kang, Won Cheol Park, Bong Hwa Lee, Hyeong Rok Kim, Jae Hwan Oh, Jae-Hwang Kim, Seung-Yong Jeong, Jung Bae Ahn, Seung Hyuk Baik

Abstract

Background: Approximately 20 % of all patients with colorectal cancer are diagnosed as having Stage IV cancer; 80 % of these present with unresectable metastatic lesions. It is controversial whether chemotherapy with or without primary tumor resection (PTR) is effective for the treatment of patients with colorectal cancer with unresectable metastasis. Primary tumor resection could prevent tumor-related complications such as intestinal obstruction, perforation, bleeding, or fistula. Moreover, it may be associated with an increase in overall survival. However, surgery delays the use of systemic chemotherapy and affects the systemic spread of malignancy.

Methods/design: Patients with colon and upper rectal cancer patients with asymptomatic, synchronous, unresectable metastasis will be included after screening. They will be randomized and assigned to receive chemotherapy with or without PTR. The primary endpoint measure is 2-year overall survival rate and the secondary endpoint measures are primary tumor-related complications, quality of life, surgery-related morbidity and mortality, interventions with curative intent, chemotherapy-related toxicity, and total cost until death or study closing day. The authors hypothesize that the group receiving PTR following chemotherapy would show a 10 % improvement in 2-year overall survival, compared with the group receiving chemotherapy alone. The accrual period is 3 years and the follow-up period is 2 years. Based on the inequality design, a two-sided log-rank test with α-error of 0.05 and a power of 80 % was conducted. Allowing for a drop-out rate of 10 %, 480 patients (240 per group) will need to be recruited. Patients will be followed up at every 3 months for 3 years and then every 6 months for 2 years after the last patient has been randomized.

Discussion: This randomized controlled trial aims to investigate whether PTR with chemotherapy shows better overall survival than chemotherapy alone for patients with asymptomatic, synchronous unresectable metastasis. This trial is expected to provide evidence so support clear treatment guidelines for patients with colorectal cancer with asymptomatic, synchronous unresectable metastasis.

Trial registration: Clinicaltrials.gov NCT01978249 .

Figures

Fig. 1
Fig. 1
Flow diagram of the trial. ASA, American Society of Anesthesiologists; ECOG, Eastern Cooperative Oncology Group; PTR, primary tumor resection
Fig. 2
Fig. 2
Chemotherapy regimens. FOLFIRI, 5-fluorouracil-based combination therapy with irinotecan; FOLFOX, 5-fluorouracil with oxaliplatin; XELOX, xeloda with oxaliplatin
Fig. 3
Fig. 3
Data collection and management

References

    1. Poston GJ, Adam R, Alberts S, Curley S, Figueras J, Haller D, et al. OncoSurge: a strategy for improving resectability with curative intent in metastatic colorectal cancer. J Clin Oncol. 2005;23:7125–34. doi: 10.1200/JCO.2005.08.722.
    1. 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;12:637–45. doi: 10.1245/ASO.2005.06.012.
    1. National Comprehensive Cancer Network. NCCN guidelines. Colon cancer (Version 3. 2013). . Accessed 6 June 2015.
    1. Scoggins CR, Meszoely IM, Blanke CD, Beauchamp RD, Leach SD. Nonoperative management of primary colorectal cancer in patients with stage IV disease. Ann Surg Oncol. 1999;6:651–7. doi: 10.1007/s10434-999-0651-x.
    1. Tebbutt NC, Norman AR, Cunningham D, Hill ME, Tait D, Oates J, et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 2003;52:568–73. doi: 10.1136/gut.52.4.568.
    1. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25:4779–86. doi: 10.1200/JCO.2007.11.3357.
    1. Saltz LB, 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;26:2013–9. doi: 10.1200/JCO.2007.14.9930.
    1. Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370:143–52. doi: 10.1016/S0140-6736(07)61087-3.
    1. Benoist S, Pautrat K, Mitry E, Rougier P, Penna C, Nordlinger B. Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases. Br J Surg. 2005;92:1155–60. doi: 10.1002/bjs.5060.
    1. Muratore A, Zorzi D, Bouzari H, Amisano M, Massucco P, Sperti E, et al. Asymptomatic colorectal cancer with un-resectable liver metastases: immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol. 2007;14:766–70. doi: 10.1245/s10434-006-9146-1.
    1. 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;27:3379–84. doi: 10.1200/JCO.2008.20.9817.
    1. Bajwa A, Blunt N, Vyas S, Suliman I, Bridgewater J, Hochhauser D, et al. Primary tumour resection and survival in the palliative management of metastatic colorectal cancer. Eur J Surg Oncol. 2009;35:164–7. doi: 10.1016/j.ejso.2008.06.005.
    1. Ferrand F, Malka D, Bourredjem A, Allonier C, Bouche O, Louafi S, et al. Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Federation Francophone de Cancerologie Digestive 9601. Eur J Cancer. 2013;49:90–7. doi: 10.1016/j.ejca.2012.07.006.
    1. 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;143:352–8. doi: 10.1001/archsurg.143.4.352.
    1. Joffe J, Gordon PH. Palliative resection for colorectal carcinoma. Dis Colon Rectum. 1981;24:355–60. doi: 10.1007/BF02603417.
    1. 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;54:930–8. doi: 10.1097/DCR.0b013e31821cced0.
    1. Makela J, Haukipuro K, Laitinen S, Kairaluoma MI. Palliative operations for colorectal cancer. Dis Colon Rectum. 1990;33:846–50. doi: 10.1007/BF02051920.
    1. 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;196:722–8. doi: 10.1016/S1072-7515(03)00136-4.
    1. Tanoue Y, Tanaka N, Nomura Y. Primary site resection is superior for incurable metastatic colorectal cancer. World J Gastroenterol. 2010;16:3561–6. doi: 10.3748/wjg.v16.i28.3561.
    1. Kim MS, Chung M, Ahn JB, Kim CW, Cho MS, Shin SJ, et al. Clinical significance of primary tumor resection in colorectal cancer patients with synchronous unresectable metastasis. J Surg Oncol. 2014;110:214–21. doi: 10.1002/jso.23607.
    1. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13. doi: 10.1097/.
    1. National Cancer Institute. Common Terminology Criteria for Adverse Events version 4.03. NCI, NIH, DHHS. May 29, 2009. NIH publication # 09-7473.
    1. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics. 1975;31:103–15. doi: 10.2307/2529712.
    1. van Hooft JE, Fockens P, Marinelli AW, Timmer R, van Berkel AM, Bossuyt PM, et al. Early closure of a multicenter randomized clinical trial of endoscopic stenting versus surgery for stage IV left-sided colorectal cancer. Endoscopy. 2008;40:184–91. doi: 10.1055/s-2007-995426.
    1. Johnson WR, McDermott FT, Pihl E, Milne BJ, Price AB, Hughes ES. Palliative operative management in rectal carcinoma. Dis Colon Rectum. 1981;24:606–9. doi: 10.1007/BF02605756.
    1. Liu SK, Church JM, Lavery IC, Fazio VW. Operation in patients with incurable colon cancer – is it worthwhile? Dis Colon Rectum. 1997;40:11–4. doi: 10.1007/BF02055675.

Source: PubMed

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