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)

Conclusions

Age, serum PSA level at the start of chemotherapy, and Hb were identified as independent prognostic factors of OS, and ECOG PS and the CRP-to-albumin ratio were not significant but were considered as possible predictors for OS in Japanese CRPC patients treated with docetaxel. Risk stratification based on these factors could be helpful for estimating OS.

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Abbreviations
ALP: alkaline phosphatase; ARC: Armstrong risk classification; CRP: C-reactive protein; CRPC: castration-resistant prostate cancer; EAU: European Association of Urology; ECOG: Eastern Cooperative Oncology Group; GPS: Glasgow Prognostic Score; Hb: hemoglobin; LDH: lactate dehydrogenase; NCCN: National Comprehensive Cancer Network; NLR: neutrophil-to-lymphocyte ratio; OS: overall survival; PNI: Prognostic Nutritional Index; PS: performance status; PSA: prostate specific antigen; PSADT: PSA doubling time.

Acknowledgements
None.

Table 1. Patient characteristics
	n = 79
Median age (range), years	72 (52–86)
ECOG performance status, n (%)
0	52 (65.8)
1	15 (19.0)
> = 2	12 (15.2)
Significant pain, n (%)	32 (40.5)
Median PSA at prostate cancer dianosis (range), ng/mL	125.2 (6.8–18778.0)
Gleason score, n (%)
> =8	43 (54.4)
< =7	36 (45.6)
Metastatic site, n (%)
bone	41 (51.9)
Lymph nodes	35 (44.3)
Lung	2 (2.5)
Liver	2 (2.5)
Prior treatment, n (%)
Prostatectomy	9 (11.4)
Radiotherapy	17 (21.5)
Combined androgen blockade	79 (100)
Combination treatment, n (%)
Bisphosphonate	23 (29.1)
Estramustine	54 (68.4)
Median PSA at docetaxel initiation (range), ng/mL	43.2 (2.7–3133.7)
Median androgen deprivation therapy administration period (range), months	31.4 (2.8–152.6)
Median serum markers at the start of docetaxel therapy (range)
Hemoglobin, g/dL	11.9 (6.6–14.9)
NLR	2.9 (0.8–18.6)
Cre, mg/dL	0.8 (0.5–2.1)
ALP, IU/L	277 (1.9–4151.0)
LDH, IU/L	231 (123–594)
CRP-to-Albumin-Ratio	7.3 (0.5–225.3)

Abbreviations: ECOG eastern cooperative oncology group, PSA prostate-specific antigen, NLR neutrophil-to-lymphocyte ratio, Cre creatinine, ALP alkaline phosphatase, LDH lactate dehydrogenase

Table 2. Univariate and multivariate analyses of associations between various pre-treatment parameters and overall survival
Variabl	Univariate analysis			Multivariate analysis
Variabl	HR	95 % CI	P value	HR	95 % CI	P value
Age > = 72 years	2.38	1.23–4.60	0.01	4.07	1.68–9.90	<0.01
ECOG PS > =1	2.92	1.59–5.51	<0.01	2.18	1.00–4.77	0.05
Significant pain	1.72	0.94–3.15	0.08	1.37	0.63–2.96	0.43
PSA at prostate cancer diagnosis > = 125 ng/mL	1.06	0.58–1.95	0.85
Gleason score > = 8	0.7	0.38–5.78	0.26
Metastatic site
Bone	1.49	0.80–2.77	0.21
Lymph node	1.05	0.57–1.93	0.89
Prior treatment
Prostatectomy	0.81	0.32–2.07	0.66
Radiotherapy	1.14	0.57–2.27	0.72
Combination therapy
Bisphosphonate	1.02	0.52–1.99	0.96
Estramustine	2.52	0.99–6.47	0.05	1.35	0.49–3.68	0.56
PSA at docetaxel initiation	3.45	1.76–6.77	<0.01	2.36	1.02–5.45	<0.05
Androgen deprivation therapy administration period > = 30 months	0.46	0.25–0.85	0.01	0.76	0.37–1.54	0.44
Serum markers at the start of docetaxel therapy
Hemoglobin > = 12 g/dL	0.24	0.12–0.48	<0.01	0.24	0.10–0.59	<0.01
NLR > = 3	1.71	0.93–3.15	0.09	1.33	0.62–2.85	0.46
Cre > = 0.8 mg/dL	0.68	0.37–1.26	0.22
ALP > =300 IU/L	3.27	1.70–6.30	<0.01	0.87	0.34–2.22	0.76
LDH > =230 IU/L	1.88	1.02–3.49	<0.05	1.24	0.62–2.46	0.55
CRP-to-Albumin-Ratio > =7	1.7	0.92–3.12	0.09	2.34	0.91–6.05	0.08

Abbreviations: ECOG Eastern Cooperative Oncology Group, PSA prostate-specific antigen, NLR Neutrophil-to-Lymphocyte Ratio, Cre creatinine, ALP alkaline phosphatase, LDH lactate dehydrogenase

Table 3. The prognostic factors for CRPC patients reported in previous studies
	Patient characteristics							Prognostic factor
	Number of patients	PSA at DTX median	Age median	% bone meta	% visceral meta	% PSA >50 % reduction	OS median	Age	PS	Hb (Anemia)	CRP	PSA	PSA DT	PSA >50 % reduction	Pain	Bone scan progression	ALP	Visceral meta	Duration from initial ADT
Armstrong et al.	656	110	69	91	23	45–48	17.8–19.2	×	×	○		×	×		○	○		○
Nakano et al.	78	19.7	70	54	5	23		×	×	×		×	○		○ 1	○ 1		○ 1	×
Shiota et al.	97	81.3	70	83.5	15.5	44.3	20.8	×	×	×		×	×		×	×	○	○	○
Bamias et al.	94	84	71	87		54	16.2	×	×	×		○			○				×
Matsuyama et al.	279	35.2	71	60.5	7.9	57.5	26	×		×	○	○		○			○	×
Ito et al.	80						14.5	×	×	○	○	×			×		×	×
Nuhn et al.	238	91.2–112.9	68.3	90.3	16.5		14.4–18.3	×	×	○		○			×		×
Present study	79	43.2	72	51.9	5	69.6	22.5	○	×	○	○ ?dctmLink chronic_id='' object_id='' edit_widget_type=graphic??dctmEditor selectedObject=''?2	○			×		×		×

Abbreviations: PSA prostate-specific antigen, DTX docetaxel, OS overall survival, PS performance status, Hb haemoglibin, CRP C-reactive protein, PSA DT prostate-specific antigen doubling time, ALP alkaline phosphatase, ADT androgen deprivation therapy
○: Significant
×: Not significant
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