Factors Affecting Prognosis in Metastatic Colorectal Cancer Patients

  • Eker, Baki (Department of Internal Medicine, Kayseri Training and Research Hospital) ;
  • Ozaslan, Ersin (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Karaca, Halit (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Berk, Veli (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Bozkurt, Oktay (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Inanc, Mevlude (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Duran, Ayse Ocak (Department of Medical Oncology, Erciyes University Faculty of Medicine) ;
  • Ozkan, Metin (Department of Medical Oncology, Erciyes University Faculty of Medicine)
  • Published : 2015.04.14


Background: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Patients and Methods: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. Findings: Median age was 56 (32-82) years and the male/female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. Conclusions: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.


Colorectal cancer;prognostic factors;survival;stage at diagnosis


  1. Bokemeyer C, Van Cutsem E, Rougier P, et al (2012). A metaanalysis of the CRYSTAL and OPUS studies combining cetuximab with chemotherapy as 1st-line treatment for patients with metastatic colorectal cancer: results according to KRAS and BRAF mutation status. Eur J Cancer, 48, 1466-75.
  2. Bozkurt O, Inanc M, Turkmen E, et al (2014). Clinicopathological characteristics and prognosis of patients according to recurrence time after curative resection for colorectal cancer. Asian Pac J Cancer Prev, 15, 9277-81.
  3. Chapuis PH, Dent OF, Fisher R, et al (1985). A multivariate analysis of clinical and pathological variables in prognosis after resection of large bowel cancer. Br J Surg, 72, 698-702.
  4. Chew MH, Teo JY, Kabir T, et al (2012). Stage IV colorectal cancers: an analysis of factors predicting outcome and survival in 728 cases. J Gastrointest Surg, 16, 603-12.
  5. Christos S, Karapetis, ShirinKhambata-Ford, et al (2008). K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med, 359, 1757-65.
  6. Cokmert S, Ellidokuz H, Demir L, et al (2014). Survival outcomes of liver metastasectomy in colorectal cancer cases: a single-center analysis in Turkey. Asian Pac J Cancer Prev, 15, 5195-200.
  7. Compton CC, Fielding LP, Burqart LJ, et al (2000). Prognostic factors in colorectal cancer. college of American Pathologists consensus statement 1999. Arch Pathol Lab Med, 124, 979-94.
  8. Cvetanovic A, Vrbic S, Filipovic S, et al (2014). Clinical benefit of cetuximab and prognostic value of cetuximab-related skin toxicity in metastatic colorectal cancer: a single in stitution analysis. J BUON, 19, 83-90.
  9. Dixon MR, Haukoos JS, Udani SM, et al (2003). Carcino embryonic antigen and albumin predict survival in patients with advanced colon and rectal cancer. Arch Surg, 138, 962-6.
  10. Dong H, Tong J, Li LH, et al (2013). Serum carbonhydrate antigen 19-9 as an indicator of liver metastasis in colorectal carcinoma cases. Asian Pac J Cancer Prev, 14, 909-13.
  11. Edge SB, CC Compton (2010). The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol, 17, 1471-4.
  12. Filella X, Molina R, Grau JJ, et al (1992). Prognostic value of CA 19-9 levels in colorectal cancer. Ann Surg, 216, 55-9.
  13. Giantonio BJ, Catalano PJ, Meropol NJ, et al (2007). 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, 25, 1539-44.
  14. Gonsalves WI, Wolpert J, Tashi T, et al (2012). Assessment of prognostic factors after primary tumor resection in metastatic colon cancer patients: a veteran's affairs central cancer registry (VACCR) analysis, 1995-2008. J Surg Oncol, 106, 486-90.
  15. He WZ, Jiang C, Yin CX, et al (2014). Prognostic model built on blood-based biomarkers in patients with metastatic colorectal cancer. Asian Pac J Cancer Prev, 15, 7327-31.
  16. Hurwitz H, Fehrenbacher L, Novotny W, et al (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med, 350, 2335-42.
  17. Inoue M, Ohta M, Iuchi K, et al (2004). Benefits of surgery for patients with pulmonary metastases from colorectal carcinoma. Ann Thorac Surg, 78, 238-44.
  18. Karagkounis G, Torbenson MS, Daniel HD, et al (2013). Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer, 119, 4137-44.
  19. Khattak MA, Martin HL, Beeke C, et al (2012). Survival differences in patients with metastatic colorectal cancer and with single site metastatic disease at initial presentation: results from South Australian clinical registry for advanced colorectal cancer. Clin Colorectal Cancer, 11, 247-54.
  20. Kim G, Jung EJ, Ryu CG, et al (2013). Usefulness of carcino embryonic antigen for monitoring tumor progression during palliative chemotherapy in metastatic colorectal cancer. Yonsei Med J, 54, 116-22.
  21. Kiss I, Bortlicek Z, Melichar B, et al (2014). Efficacy and toxicity of bevacizumab on combination with chemotherapy in different lines of treatment for metastatic colorectal carcinoma. Anticancer Res, 34, 949-54.
  22. Maughan T, Adams RA, Smith CG, et al (2009). Addition of cetuximab to oxaliplatin-based combination chemotherapy in patients with KRAS wild-type advanced colorectal cancer: a randomised superiority trial (MRC COIN). Eur J Cancer, 7, 6LBA (abstr).
  23. Michelassi F, Ayala JJ, Balestracci T, et al (1991). Verification of a new clinico pathologic staging system for colorectal adeno carcinoma. Ann Surg, 214, 11-8.
  24. Mourtzikou A, Stamouli M, Kroupis C, et al (2012). Evaluation of carcino embryonic antigen (CEA), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule EpCAM (GA733-2), and carbonhydrate antigen 19-9 (CA 19-9) levels in colorectal cancer patients and correlation with clinicopathological characteristics. Clin Lab, 58, 441-8.
  25. Nordlinger B, Van Cutsem E, Gruenberger T, et al (2009). Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol, 20, 985-92.
  26. Padman S, Padbury R, Beeke C, et al (2013). Liver only metastatic disease in patients with metastatic colorectal cancer: impact of surgery and chemotherapy. Acta Oncol, 52, 1699-706.
  27. Park IJ, Choi GS, Lim KH, et al (2009). Serum carcino embryonic antigen monitoring after curative resection for colorectal cancer: clinical significance of the preoperative level. Ann Surg Oncol, 16, 3087-93.
  28. Patanaphan V, Salazar OM (1993). Colorectal cancer; metastatic patterns and prognosis. South Med J, 86, 38-41.
  29. Pulitano C, Bodingbauer M, Aldrighetti L, et al (2011). Liver resection for colorectal metastases in presence of extrahepatic disease: results from an international multiinstitutional analysis. Ann Surg Oncol, 18, 1380-8.
  30. Saltz LB, Clarke S, az-Rubio E, et al (2008). Bevacizumab in combination with oxaliplatin-based chemotherapy as firstline therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol, 26, 2013-19.
  31. Samowitz WS, Slattery ML, Sweeney C, et al (2007). APC mutations and other genetic and epigenetic changes in colon cancer. Mol Cancer Res, 5, 165-70.
  32. Schule S, Dittmar Y, Knosel T, et al (2013). Long-term results and prognostic factors after resection of hepatic and pulmonary metastases of colorectal cancer. Int J Colorectal Dis, 28, 537-45.
  33. Sisik A, Kaya M, Bas G, et al (2013). CEA and CA 19-9 are still valuable markers for the prognosis of colorectal and gastric cancer patients. Asian Pac J Cancer Prev, 14, 4289-94.
  34. Sun LC, Chu KS, Cheng SC, et al (2009). Preoperative serum carcino embryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients under going surgical treatment. BMC Cancer, 9, 288.
  35. Tournigand C, Andre T, Achille E, et al (2004). FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol, 22, 229-37.
  36. Van Cutsem E, Kohne CH, Hitre E, et al (2009). Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med, 360, 1408-17.
  37. Von Kleist S (1986). The clinical value of the tumor markers CA 19.9 and carcino embryonic antigen (CEA) in colorectal carcinomas: a critical comparison. Int J Biol Markers, 1, 3-8.
  38. Wang WS, Lin JK, Chiou TJ, et al (2002). CA19-9 as the most significant prognostic indicator of metastatic colorectal cancer. Hepatogastroenterology, 49, 160-4.
  39. Wang JY, Lu CY, Chu KS, et al (2007). Prognostic significance of pre- and postoperative serum carcinoembryonic antigen levels in patients with colorectal cancer. Eur Surg Res, 39, 245-50.
  40. Washington K (2010). 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol, 17, 3077-9.
  41. Yoon YS, Kim CW, Lim SB, et al (2014). Palliative surgery in patients with unresectable colorectal liver metastases: a propensity score matching analysis. J Surg Oncol, 109, 239-44.

Cited by

  1. ) Gene Variations and Susceptibility of Colorectal Cancer vol.19, pp.12, 2015,
  2. Long-term outcomes and recurrence pattern of 18F-FDG PET-CT complete metabolic response in the first-line treatment of metastatic colorectal cancer: a lesion-based and patient-based analysis vol.18, pp.1, 2018,
  3. Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer vol.9, pp.1, 2019,