Ann Surg Treat Res.  2019 Jun;96(6):296-304. 10.4174/astr.2019.96.6.296.

Impact of tumor sidedness on survival and recurrence patterns in colon cancer patients

• Lee JM
• Han YD
• Cho MS
• Hur H
• Min BS
• Lee KY
• Kim NK

• KMID: 2447954
• DOI: http://doi.org/10.4174/astr.2019.96.6.296

Abstract

PURPOSE
Previous studies have reported conflicting results regarding the prognostic value of tumor sidedness in colon cancer. We investigated the oncologic impact of tumor location and examined whether recurrence patterns were related to tumor sidedness in colon cancer patients.
METHODS
We identified stage I-III colon adenocarcinoma patients from a prospective colorectal cancer registry at Severance Hospital, Seoul, Korea, who underwent complete mesocolic excision between 2005 and 2012. Adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for predictors of cancer-specific survival (CSS), recurrence-free survival (RFS), and cumulative recurrence at specific anatomic sites were examined using Cox proportional hazard regression analysis.
RESULTS
Overall, 1,912 patients, 1,077 (56.3%) with left-sided colon cancer (LCC), and 835 (43.7%) with right-sided colon cancer (RCC), at a median follow-up of 59 months, were eligible and included in the study. In univariate analysis, similar 5-year CSS and RFS were observed for LCC and RCC in the total patient population, and when stratified by stage for stage I and II patients. For stage III patients, an adjusted Cox regression analysis indicated that RCC patients had a higher risk of cancer-specific mortality (HR, 1.75; 95% CI, 1.07-2.86; P = 0.024) and recurrence (HR, 1.78; 95% CI, 1.22-2.60; P = 0.003). Furthermore, RCC was an independent predictor of peritoneal recurrence (HR, 1.86; 95% CI, 1.05-3.29; P = 0.031) in stage III patients.
CONCLUSION
RCC correlated with worse CSS and RFS than LCC. In stage III patients, RCC correlated with increased risk of peritoneal recurrence. The reasons for these differences remain to be investigated.

Keyword

Colonic neoplasm; Right; Left; Neoplasm recurrence, local; Survival; Treatment outcome

MeSH Terms

Adenocarcinoma
Colon*
Colonic Neoplasms*
Colorectal Neoplasms
Follow-Up Studies
Humans
Korea
Mortality
Prospective Studies
Recurrence*
Seoul
Treatment Outcome

Figure

• 

  Fig. 1 Kaplan-Meier curves for survival analysis within stage III colon cancer patients. Cancer specific survival (CSS) (A), recurrence-free survival (RFS) (B), peritoneal recurrence (PR) (C), CSS from recurrence to death (CSS2) according to presence of peritoneal recurrence (D), and CSS2 in patients with peritoneal recurrence (E). LCC, left-sided colon cancer; RCC, right-sided colon cancer.

Reference

1. Meguid RA, Slidell MB, Wolfgang CL, Chang DC, Ahuja N. Is there a difference in survival between right-versus left-sided colon cancers? Ann Surg Oncol. 2008; 15:2388–2394.

2. Weiss JM, Pfau PR, O'Connor ES, King J, LoConte N, Kennedy G, et al. Mortality by stage for right-versus left-sided colon cancer: analysis of surveillance, epidemiology, and end results--Medicare data. J Clin Oncol. 2011; 29:4401–4409.

3. Warschkow R, Sulz MC, Marti L, Tarantino I, Schmied BM, Cerny T, et al. Better survival in right-sided versus left-sided stage I - III colon cancer patients. BMC Cancer. 2016; 16:554.

4. Benedix F, Kube R, Meyer F, Schmidt U, Gastinger I, Lippert H, et al. Comparison of 17,641 patients with right- and left-sided colon cancer: differences in epidemiology, perioperative course, histology, and survival. Dis Colon Rectum. 2010; 53:57–64.

5. Lim DR, Kuk JK, Kim T, Shin EJ. Comparison of oncological outcomes of right-sided colon cancer versus left-sided colon cancer after curative resection: Which side is better outcome? Medicine (Baltimore). 2017; 96:e8241.

6. Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, et al. Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol. 2014; 25:1995–2001.

7. Nawa T, Kato J, Kawamoto H, Okada H, Yamamoto H, Kohno H, et al. Differences between right- and left-sided colon cancer in patient characteristics, cancer morphology and histology. J Gastroenterol Hepatol. 2008; 23:418–423.

8. Yang SY, Cho MS, Kim NK. Difference between right-sided and left-sided colorectal cancers: from embryology to molecular subtype. Expert Rev Anticancer Ther. 2018; 18:351–358.

9. Moritani K, Hasegawa H, Okabayashi K, Ishii Y, Endo T, Kitagawa Y. Difference in the recurrence rate between right- and left-sided colon cancer: a 17-year experience at a single institution. Surg Today. 2014; 44:1685–1691.

10. Ishihara S, Murono K, Sasaki K, Yasuda K, Otani K, Nishikawa T, et al. Impact of primary tumor location on postoperative recurrence and subsequent prognosis in nonmetastatic colon cancers: a multicenter retrospective study using a propensity score analysis. Ann Surg. 2018; 267:917–921.

11. Cho MS, Baek SJ, Hur H, Soh Min B, Baik SH, Kyu Kim N. Modified complete mesocolic excision with central vascular ligation for the treatment of right-sided colon cancer: long-term outcomes and prognostic factors. Ann Surg. 2015; 261:708–715.

12. Noh GT, Han J, Cho MS, Hur H, Min BS, Lee KY, et al. Impact of the prognostic nutritional index on the recovery and long-term oncologic outcome of patients with colorectal cancer. J Cancer Res Clin Oncol. 2017; 143:1235–1242.

13. Tokunaga R, Sakamoto Y, Nakagawa S, Miyamoto Y, Yoshida N, Oki E, et al. Prognostic nutritional index predicts severe complications, recurrence, and poor prognosis in patients with colorectal cancer undergoing primary tumor resection. Dis Colon Rectum. 2015; 58:1048–1057.

14. Kontovounisios C, Kinross J, Tan E, Brown G, Rasheed S, Tekkis P. Complete mesocolic excision in colorectal cancer: a systematic review. Colorectal Dis. 2015; 17:7–16.

15. Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Kawai K, et al. Prognostic impact of tumor location in stage IV colon cancer: a propensity score analysis in a multicenter study. Int J Surg. 2014; 12:925–930.

16. Dawson LE, Russell AH, Tong D, Wisbeck WM. Adenocarcinoma of the sigmoid colon: sites of initial dissemination and clinical patterns of recurrence following surgery alone. J Surg Oncol. 1983; 22:95–99.

17. Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A. Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2012; 99:699–705.

18. Nitsche U, Stogbauer F, Späth C, Haller B, Wilhelm D, Friess H, et al. Right sided colon cancer as a distinct histopathological subtype with reduced prognosis. Dig Surg. 2016; 33:157–163.

19. Sinicrope FA, Mahoney MR, Yoon HH, Smyrk TC, Thibodeau SN, Goldberg RM, et al. Analysis of molecular markers by anatomic tumor site in stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance). Clin Cancer Res. 2015; 21:5294–5304.

20. Tran B, Kopetz S, Tie J, Gibbs P, Jiang ZQ, Lieu CH, et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011; 117:4623–4632.

21. Kim CG, Ahn JB, Jung M, Beom SH, Kim C, Kim JH, et al. Effects of microsatellite instability on recurrence patterns and outcomes in colorectal cancers. Br J Cancer. 2016; 115:25–33.

22. Arakawa K, Kawai K, Ishihara S, Hata K, Nozawa H, Oba K, et al. Prognostic significance of peritoneal metastasis in stage IV colorectal cancer patients with R0 resection: a multicenter, retrospective study. Dis Colon Rectum. 2017; 60:1041–1049.

23. Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, et al. Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol. 2016; 17:1709–1719.

24. Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017; 28:1713–1729.