Prognostic Factors and Risk Stratification in Patients With Castration-Resistant Prostate Cancer Receiving Docetaxel-based Chemotherapy

Shimpei Yamashita; Yasuo Kohjimoto; Takashi Iguchi; Hiroyuki Koike; Hiroki Kusumoto; Akinori Iba; Kazuro Kikkawa; Yoshiki Kodama; Nagahide Matsumura; Isao Hara

Disclosures

BMC Urol. 2016;16(13) 

In This Article

Background

Prostate cancer is currently the most common malignancy in men from Western countries, and its occurrence has recently been increasing in Japan.

Because most prostate cancers grow in an androgen-dependent manner, androgen-deprivation therapy has been the initial treatment for recurrent or metastatic prostate cancer.[1,2] However, under prolonged androgen deprivation, prostate cancer finally becomes refractory to hormonal manipulation and is then defined as castration-resistant prostate cancer (CRPC).[3,4]

Recently, possible therapeutic strategies for CRPC have been increasing.[5–8] Novel therapies including enzalutamide, abiraterone acetate, cabazitaxel, sipuleucel-T, and radium 223 have been approved for therapy of CRPC patients. Enzalutamide and abiraterone acetate have shown their efficacy in not only the post-docetaxel setting but also the pre-docetaxel setting.[9,10] In patients with no visceral metastasis, enzalutamide and abiraterone are recommended as well as docetaxel in the NCCN guideline. Moreover, in patients with visceral metastasis, these novel agents have been approved by FDA in the pre-chemotherapy setting. However, it was in 2014 that these agents were approved in Japan. In addition, the efficacy of novel therapies is still limited, and the prognoses of CRPC patients still remain poor.

To date, docetaxel, a natural taxane from Taxus baccata, has been established as effective and has been widely used in CRPC treatment.[11,12] While novel drugs have been developed, docetaxel remains one of the standard initial systemic therapies for CRPC patients. In the EAU guideline 2014, docetaxel is still recommended as the first-line chemotherapeutic agent, especially in patients with evidence of progressive disease. Docetaxel is also recommended as the first-line drug in the NCCN guideline 2015. Despite of the excellent anti-tumor effect of docetaxel, its severe adverse effects, including myelosuppression, sometimes distress patients. Therefore, it would be helpful to predict the efficacy of docetaxel before treatment. Since novel agents such as enzalutamide and abiraterone acetate are now available, appropriate selection of CRPC patients using prognostic factors is crucial when choosing first-line therapy.

A predictive factor is a measurement that is associated with response or lack of response to a particular therapy. In contrast, a prognostic factor is a measurement that is associated with patient's prognoses with or without treatment. Several prognostic factors in CRPC patients have been reported, and some nomograms or risk classifications have been developed. However, the magnitude of the benefit provided by each factor has varied among studies.

We previously reported that visceral metastases, including lung, liver and lymph nodes and excluding bone, and pretreatment anemia (hemoglobin < 11.3 g/dL) were two independent factors predicting overall survival in patients who received docetaxel chemotherapy for prostate cancer.[13] In a previous study, we collected the data from not only our hospital but also our related hospitals. Thus, the cohort in that study was rather heterogeneous regarding the indications, chemotherapy regimens, and amount of missing data. In the present study, patients only from our institute were targeted, and more variables, such as the neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP)-to-albumin ratio, were evaluated as predictors of overall survival.

The aims of this study were to evaluate the potential value of patient characteristics in predicting overall survival (OS) and to develop a risk classification for CRPC patients treated with docetaxel-based chemotherapy.

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