The impact of change in serum C-reactive protein level on the prediction of effects of molecular targeted therapy in patients with metastatic renal cell carcinoma

BJU Int. 2016 Jun;117(6B):E67-74. doi: 10.1111/bju.13260. Epub 2015 Sep 25.

Abstract

Objectives: To investigate the impact of pretreatment serum C-reactive protein (CRP) level and its change after targeted therapy on the anti-tumour effect of targeted agents in patients with metastatic renal cell carcinoma (mRCC).

Patients and methods: The serum CRP level in 190 cases of molecular targeted therapy for mRCC was measured before starting the prescription of molecular targeted agents and when computed tomography showed the maximum effect. Patients in which the pretreatment CRP level was ≥0.5 mg/dL were classified into a 'higher-CRP' group and others into a 'lower-CRP' group. The higher-CRP group was further classified into two subgroups, i.e. those whose serum CRP level decreased after molecular targeted therapy ('decreased-CRP' subgroup), and those whose level did not decrease after therapy ('non-decreased-CRP' subgroup). All patients were also classified according to their other clinical details and progression-free survival (PFS) rates of each subgroup were compared.

Results: Of the 190 patients, 97 were categorised as lower CRP and 93 as higher CRP, with 50 and 43 patients in the higher-CRP group further categorised as decreased- and non-decreased-CRP subgroups, respectively. For the maximum effects of the targeted therapy, determined based on the Response Evaluation Criteria In Solid Tumors (RECIST) criteria, in the lower-CRP group, significantly more patients had a complete response (CR) and partial response (PR) (P = 0.002) and significantly fewer had progressive disease (PD) (P < 0.001) vs the higher-CRP group. In the higher-CRP group, significantly fewer patients had PD in the decreased-CRP subgroup (P < 0.001) than those in the non-decreased-CRP subgroup. The 2-year PFS rate for the lower-CRP group (39.1%) was significantly better vs the decreased-CRP subgroup (21.2%; P = 0.013) and significantly better vs the non-decreased CRP subgroup (0%; P < 0.001). Multivariate analyses in the higher-CRP group revealed that decreased CRP was an independent predictive factor for PFS (P = 0.002, hazard ratio 2.454, 95% confidence interval 1.404-4.290).

Conclusion: A decrease of CRP and pretreatment CRP levels show promise as a novel predictive factor for anti-tumour effects in patients treated with molecular targeted therapy.

Keywords: C-reactive protein; prognostic factor; progression-free survival; renal cell carcinoma; targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • C-Reactive Protein / metabolism*
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / therapy*
  • Female
  • Humans
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / therapy*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Neoplasm Metastasis
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • C-Reactive Protein