Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer

Abstract

In colorectal cancer (CRC), 20–50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II–IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32–11.69); 3.72 (1.99–6.95); 2.58 (1.18–5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64–5.73); 3.41 (1.55–7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38–7.04) and OS, HR 3.20 (1.39–7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0–53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.

Preoperative C‐reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer

“…In contrast, ALB has a half‐life of 21 days and a steady‐state level of 100 days, limiting its clinical utility and value 28 . Moreover, weight loss is another typical feature of malnutrition in patients with cancers and is negatively correlated with prealbumin but not with ALB 13 . Thus, several scholars believe that prealbumin is more sensitive to malnutrition than ALB.…”

“…28 Moreover, weight loss is another typical feature of malnutrition in patients with cancers and is negatively correlated with prealbumin but not with ALB. 13 Thus, several scholars believe that prealbumin is more sensitive to malnutrition than ALB. However, other scholars disagree because prealbumin only reflects the recent dietary intake of patients, rather than their overall nutritional status.…”

“…CRP is an acute‐phase reactant that is regulated by a variety of proinflammatory cytokines, such as tumor necrosis factor‐α, interleukin‐1, and interleukin‐6 12 . CRP is the most sensitive biomarker of systemic inflammatory response and has shown significant predictive value for the prognosis of a series of malignancies, including CRC 13 . Moreover, prealbumin is an important biomarker for nutritional status and is more sensitive to malnutrition than ALB 14 .…”

“…12 CRP is the most sensitive biomarker of systemic inflammatory response and has shown significant predictive value for the prognosis of a series of malignancies, including CRC. 13 Moreover, prealbumin is an important biomarker for nutritional status and is more sensitive to malnutrition than ALB. 14 Thus, the combination of CRP and prealbumin in the CRP to prealbumin ratio (CPAR) can play a prognostic role in various cancers, and CPAR is superior to other inflammatory-based prognostic scores in terms of predictive performance.…”

Circulating cell‐free circRNA panel predicted tumorigenesis and development of colorectal cancer

“…Similarly, imaging examination is difficult to be used for early diagnosis of colorectal cancer due to its poor identification. In terms of diagnostic markers, carcinoembryonic antigen and CA19‐9 has been widely applied in the diagnosis of tumor, but previous studies show that CEA is more suitable for being used in the detection of for tumor recurrence and metastasis; in addition, the CEA levels in intestinal inflammation and adenoma has increased in the tumor, for early colorectal cancer its poor sensitivity and specific degree, CA19‐9 is a good predictor of tumor metastasis 18 …”