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

Results

During the study period, 79 CRPC patients received docetaxel-based chemotherapy at our institution. The patients' characteristics at diagnosis and at the start of chemotherapy are shown in Table 1. The median age was 72 years (range: 52–86 years). ECOG PS was <1 in 52 (65.8 %) patients and ≥1 in 27 (34.2 %) patients. Most patients had one or more metastases when they were diagnosed with prostate cancer. Overall, 9 (11.4 %) and 17 (21.5 %) patients underwent radical prostatectomy and radiation therapy, respectively. The median androgen deprivation therapy administration period was 31.4 months (range: 2.8–152.6 months). The median serum PSA level at chemotherapy initiation was 43.2 ng/mL (range: 2.7–3133.7 ng/mL). 54 patients (68.4 %) simultaneously received estramustine. Oral estramustine (560 mg) was administered on days 1 to 5 and days 8 to 12. However, adverse events associated with estramustine, such as thromboembolic events, did not develop.

The median number of chemotherapy cycles was 6 (range: 1–43). 20 patients (25.3 %) required dose reduction due to treatment intolerance or side effects. A total of 71 patients (89.9 %) discontinued docetaxel treatment because of disease progression (N = 39, 54.9 %), adverse events (N = 24, 33.8 %), patient's refusal (N = 3, 4.2 %), and other reasons (N = 5, 7.0 %), respectively. The remaining 8 patients (10.1 %) were still undergoing docetaxel treatment during the course of the study. The median number of chemotherapy cycles in patients who discontinued treatment because of adverse events was 2.5 (range: 1–14).

Waterfall plots of the PSA response are shown in Fig. 1. PSA responses ≥0 %, ≥30 %, and ≥50 % were observed in 69 (87.3 %), 64 (81.0 %), and 55 (69.6 %) of the total patients, respectively.

Figure 1.

Waterfall plot of PSA response. PSA responses of ≥0 %, ≥30 %, and ≥50 % are seen in 69 (87.3 %), 64 (81.0 %), and 55 (69.6 %) patients, respectively

During the observation period (median 15.1 months, range: 1.8–53.4 months), 36 of all 79 patients (53.2 %) died of prostate cancer, and 6 (7.6 %) died of another cause. The median OS was 22.5 months, and the 1-year OS rate was 78.8 %.

Univariate and multivariate Cox proportional hazards regression models were used to investigate pre-treatment predictors of OS (Table 2). Among several predictors, age ≥ 72 years, ECOG PS ≥ 1, serum PSA level at the start of chemotherapy ≥ 40 ng/mL, duration from initiation of androgen deprivation therapy ≥ 30 months, Hb ≥ 12.0 g/dL, ALP ≥ 300 IU/L, and LDH ≥ 230 IU/L were identified as significant predictors for OS on univariate analysis. Furthermore, significant clinical pain, NLR ≥ 3, CRP-to-albumin ratio ≥ 7, and combination use of estramustine were not significant, but were considered possible predictors for OS. Of these factors, age ≥ 72 years and serum PSA level at the start of chemotherapy ≥ 40 ng/mL were independent unfavorable predictors of OS and Hb ≥ 12.0 g/dL was an independent favorable predictor of OS on multivariate analysis. ECOG PS ≥ 1 and CRP-to-albumin ratio ≥ 7 were not significant, but they were considered possible unfavorable predictors for OS.

To develop a risk classification model to help in the appropriate selection of docetaxel chemotherapy in patients with CRPC, five pre-treatment factors, including advanced age (age ≥ 72 years), poor PS (ECOG PS ≥ 1), high serum PSA level at the start of chemotherapy (PSA ≥ 40 ng/mL), anemia (Hb < 12 g/dL), and high CRP-to-albumin ratio (CRP-to albumin ratio ≥ 7) were used, and the cohort was classified into three groups according to the presence of these five risk factors. Patients with 0–1, 2–3, and 4–5 risk factors were classified as low (N = 21), intermediate (N = 37), and high (N = 21) risk groups, respectively. This model effectively stratified patients in terms of OS according to risk group (p < 0.001), as shown in Fig. 2.

Figure 2.

Kaplan-Meier curves for overall survival (OS) according to risk group classification

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