Impact of C‐reactive protein kinetics on survival of patients with advanced urothelial carcinoma treated by second‐line chemotherapy with gemcitabine, etoposide and cisplatin
Authors: Saito Kazutaka , Urakami Shinji , Komai Yoshinobu , Yasuda Yosuke , Kubo Yuichi , Kitsukawa Shinichi , Okubo Yuhei , Yamamoto Shinya , Yonese Junji , Fukui Iwao 
Published: April 2012

Study Type – Prognosis (cohort)

Level of Evidence 2a

What's known on the subject? and What does the study add?

C‐reactive protein (CRP) level has been shown to be a significant prognostic factor for various malignancies, including urothelial carcinoma treated surgically. Apart from CRP level, several prognostic factors have been identified for advanced urothelial carcinoma patients receiving a second‐line chemotherapy.

CRP could also be a significant prognostic factor for advanced urothelial carcinoma patients receiving a second‐line chemotherapy. CRP kinetics, the dynamic change of CRP concentration, has a strong impact on survival. Adding to the baseline CRP status at the start of treatment, the normalization of CRP during treatment is significantly associated with prognosis. The period with normalized CRP level was strongly correlated with survival period. Therefore, CRP could be a potential biomarker for advanced urothelial carcinoma patients.

OBJECTIVE

To assess the impact of C‐reactive protein (CRP) kinetics, the effect of dynamic changes of CRP concentration on the survival of patients with locally advanced or metastatic urothelial carcinoma (UC) treated by single chemotherapeutic regimen including cisplatin was examined.

PATIENTS AND METHODS

Eighty patients with advanced UC, who failed treatment of advanced UC with the first‐line chemotherapy or who received perioperative treatment of neoadjuvant or adjuvant settings, were treated with gemcitabine, etoposide and cisplatin (GEP) as second‐line chemotherapy.

Patients were divided into three groups according to CRP kinetics based on baseline and nadir CRP concentrations. Patients whose baseline CRP levels were <5 mg/L, patients whose baseline CRP levels were ≥5 mg/L and normalized (<5 mg/L), and patients whose baseline CRP levels were ≥5 mg/L and never normalized were assigned to non‐elevated, normalized and non‐normalized CRP groups, respectively.

The prognostic impact of CRP kinetics and the correlation between normalized CRP period and overall survival period were determined.

RESULTS

In 46 (57%) of the 80 patients, CRP levels were elevated at the diagnosis of advanced UC. During treatment, after a median follow‐up period of 12 months CRP levels were normalized in 24 (71%) of 34 patients, whereas CRP levels remained elevated in the remaining 10 patients.

Overall survival rates were significantly different between the non‐elevated, normalized, and non‐normalized CRP groups (P < 0.001), with 1‐year survival rates of 72, 51 and 14%, respectively. On multivariate analysis including Eastern Cooperative Oncology Group performance status, visceral metastasis, number of metastatic sites, previous definitive surgery, anaemia, baseline and nadir CRP levels (mg/L), and CRP kinetics status, CRP kinetics was an independent and significant factor for overall survival.

The normalized CRP period was significantly correlated with the overall survival period in 52 patients who died.

CONCLUSIONS

CRP kinetics is significantly associated with the prognosis and survival period of patients with advanced UC treated by chemotherapy.

Although larger confirmatory studies are warranted to validate our results, CRP can potentially be a useful biomarker for patients with advanced UC.