title: The role of primary tumor resection in colorectal cancer patients with asymptomatic, synchronous unresectable metastasis: Study protocol for a randomized controlled trial.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01978249 .
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. kcwgkim@gmail.com.
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Gachon University Gil Hospital, Incheon, Republic of Korea. gsbaek@gilhospital.com.
authors.forename: Jeong-Heum
authors.initials: JH
authors.lastname: Baek
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Kyungpook National University Hospital, Daegu, Republic of Korea. kyuschoi@mail.knu.ac.kr.
authors.forename: Gyu-Seog
authors.initials: GS
authors.lastname: Choi
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, Seoul, Republic of Korea. csyu@amc.seoul.kr.
authors.forename: Chang Sik
authors.initials: CS
authors.lastname: Yu
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Seoul National University Bundang Hospital, Bundang, Republic of Korea. kangsb@snubh.org.
authors.forename: Sung Bum
authors.initials: SB
authors.lastname: Kang
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Wonkwang University Hospital, Iksan, Republic of Korea. parkwc@wonkwang.ac.kr.
authors.forename: Won Cheol
authors.initials: WC
authors.lastname: Park
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea. bshlee@hallym.or.kr.
authors.forename: Bong Hwa
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Chonnam National University Hospital, Gwangju, Republic of Korea. drkhr@jnu.ac.kr.
authors.forename: Hyeong Rok
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Center for Colorectal Cancer, National Cancer Center, Ilsan, Republic of Korea. jayoh@ncc.re.kr.
authors.forename: Jae Hwan
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Yeungnam University Hospital, Daegu, Republic of Korea. jhkimgs@ynu.ac.kr.
authors.forename: Jae-Hwang
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. syjeong@snu.ac.kr.
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. vvswm513@yuhs.ac.
authors.forename: Jung Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Section of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul, 135-720, Republic of Korea. whitenoja@yuhs.ac.
authors.forename: Seung Hyuk
authors.initials: SH
authors.lastname: Baik
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002985:Clinical Protocols; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003627:Data Interpretation, Statistical; D005500:Follow-Up Studies; D006801:Humans; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D018401:Sample Size