Factors Influencing Survival in Stage IV Colorectal Cancer: The Influence of DNA Ploidy

Objective. To evaluate the prognostic significance of microscopically assessed DNA ploidy and other clinical and laboratory parameters in stage IV colorectal cancer (CRC). Methods. 541 patients with histologically proven stage IV CRC treated with palliative chemotherapy at our institution were included in this retrospective analysis, and 9 variables (gender, age, performance status, carcinoembryonic antigen, cancer antigen 19-9, C-Reactive Protein (CRP), anaemia, hypoalbuminaemia, and ploidy (DNA Index)) were assessed for their potential relationship to survival. Results. Mean survival time was 12.8 months (95% confidence interval (CI) 12.0–13.5). Multivariate analysis revealed that DNA indexes of 2.2–3.6 and >3.6 were associated with 2.94 and 4.98 times higher probability of death, respectively, compared to DNA index <2.2. CRP levels of >15？mg/dL and 5–15？mg/dL were associated with 2.52 and 1.72 times higher risk of death, respectively. Hazard ratios ranged from 1.29 in patients mild anaemia (Hb 12–13.5？g/dL) to 1.88 in patients with severe anaemia (Hb < 8.5？g/dL). Similarly, the presence of hypoalbuminaemia (albumin < 5？g/dL) was found to confer 1.41 times inferior survival capability. Conclusions. Our findings suggest that patients with stage IV CRC with low ploidy score and CRP levels, absent or mild anaemia, and normal albumin levels might derive greatest benefit from palliative chemotherapy. 1. Introduction More than 1 million individuals worldwide will be diagnosed with colorectal cancer (CRC) every year [1, 2]. Approximately 35% of CRC patients present with stage IV metastatic disease at the time of diagnosis, and 20%–50% with stage II or III disease will progress to stage IV at some point during the course of their disease [3–5]. Stage IV CRC carries an unfavourable outcome as the 5-year survival rate is less than 10% [4, 5] with a median survival time of about 6–12 months [6, 7]. In metastatic CRC, surgery and/or chemotherapy are used mainly with palliative intent. However, as treatment modalities in stage IV CRC are associated with significant complications and increased costs, there is a need to identify prognostic factors which may determine treatment response and survival. It is anticipated that such an approach could refine palliative management according to the likelihood of clinical benefit [8]. As part of our systematic search for prognostic factors in CRC, this study expanded our previous work [9] by evaluating the prognostic significance of DNA ploidy in addition to other clinicopathological factors in a cohort of patients with stage