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Table 4 Summary of included studies for predictive/prognostic biomarkers

From: Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review

Article Year Biomarker Intervention Significant outcomes
Ando et al. [44] 2019 Testosterone Docetaxel Median OS: 35.8 months
Median OS (TST > 13 ng/dl vs < 13 ng/dl): 19.2 vs 76.9 months
Median PFS (TST > 13 ng/dl vs < 13 ng/dl): 5.1 vs 7.1 months
Median follow-up: 21.6 months
Hashimoto et al. [45] 2019 Testosterone Abiraterone or enzalutamide Median follow-up: 26 months
Median PFS (< 5 ng/dl vs 5 ng/dl): 12.2 vs 4.5 months
Shiota et al. [46] 2018 Testosterone Enzalutamide, abiraterone, docetaxel, cabazitaxel PFS (T < 0.05 vs > 0.05): p = 0.047
OS (T < 0.05 vs > 0.05): p = 0.18
Wang et al. [47] 2017 Testosterone ADT Median time to CRPC (T < 25 ng/dl vs > 25 ng/dl): 19.1 vs 14.6 months
Median follow-up: 14 months
Yasouka et al. [48] 2019 PSA Cabazitaxel Median follow-up: 13.2 (IQR) = 6.9–21.5 months
45.5%
Median PFS: 4.3 months
Median OS: 20.7 months
PSA (> 100 ng/ml):HR = 3.65, 95% CI 1.39–10.60, p = 0.0085
Lin et al. [53] 2018 PSA ADT nPSA > 0.2 ng/ml: HR, 2.665, 95% CI 1.495–4.750, p < 0.001
Median follow-up: HR: 0.262, 95% CI 0.161–0.426
Median PFS: 14.0 months
Median PSA: 14.7 months
Median TTN: 8.10 months
Kosaka et al. [49] 2018 PSA Cabazitaxel Median OS: 16.1 months
PSA ≥ 100 ng/ml prior to cabazitaxel: HR = 4.375; 95% CI 1.755–10.91, p = 0.002
Pei et al. [51] 2019 PSA Docetaxel TTN ≥ 15 weeks: HR 0.093, 95% CI 0.044–0.188, p < 0.001
PSA nadir < 4.55 ng/ml: HR 4.002, 95% CI 1.890–8.856, p = 0.001
PSA decline > 50%: HR 0.573, 95% CI 0.428–0.756, p < 0.001
Sathekge et al. [60] 2019 PSA 225Ac-PSMA-617 Median OS: 18 months
Median PFS: 15.2 months
PSA decline > 50%: p < 0.001
Median follow-up: 9 months
Alvim et al. [63] 2019 PSA Abiraterone acetate Median OS (PSAr): HR: 0.19; 95% CI 0.10–0.38; p < 0.001
Median PFS (PSAr): HR: 0.24; 95% CI 0.14–0.41; p < 0.001
Median OS (PSA): 11.5 months
29.3 vs 9.7
17 vs 5.3
Armstrong et al. [70] 2018 PSA Enzalutamide Median OS: 23.1 months
Median time to PSA (no-decline or decline < 30% group): 3.7 month
Median time to PSA progression: 13.8 months (95% CI 11.3–14.0)
Hamano et al. [57] 2019 PSA Docetaxel, AA and ENZ PSA nadir > 0.64 ng/ml and TTN < 7 months: HR, 3.34; 95% CI 1.99–5.61; p < 0.001
Median OS: (PSA nadir > 0.64 ng/ml and TTN < 7 months): HR: 2.98; 95% CI 1.77–5.02; p < 0.001
Median follow-up: 35 months
Yang et al. [52] 2015 PSA Docetaxel Median OS: 13.51 months
Median TTN: 5.14 months
Houede et al. [65] 2015 PSA Abiracetone acetate PSA response > 3 months: p = 0.00025
Median OS: 14.6 months
Follow-up: 36.3 months
Kuo et al. [56] 2015 PSA ADT Median time to PSA rise: 4.5 months
Median time to PSA rises after first T > 50 ng/dl: 1.0 months
Median times from primary treatment to CRPC: 9.7 years
Schiff et al. [64] 2019 PSA Abiraterone ≥ 30% PSA at 4, 8, 12 weeks OS: range: 35.2 months to 40.0 months
≥ 50% PSA at 4, 8, 12 weeks OS: range: 37.3 months to 41.1 months
Rahbar et al. [61] 2017 PSA 177Lu-PSMA-617 Median OS: 56.0 weeks
Median OS (PSA decline > 50% vs < 50%): 66 weeks vs 47 weeks
Ahmadzadehfar et al. [62] 2017 PSA 177Lu-PSMA-617 PSA decline ≥ 14 OS vs < 14: 88 weeks vs 29 weeks
PSA decline ≥ 50% vs < 50%: HR: 70; 95% CI 39.5–100.5 vs HR: 49; 95% CI 30.2–67.8
Time to CRPC progression: 38 months
Ji et al. [54] 2017 PSA ADT PSA nadir: HR 1.185, 95% CI 1.080–1.301, p = 0.001
Velocity of PSA decline > 11 ng/ml/month: HR 2.124, 95% CI 1.195–3.750, p = 0.001
Time to PSA nadir: 9 months
Median time to progression to CRPC: 38 months
He et al. [55] 2017 PSA ADT Mean time to CRPC: 23 months
Time to reach minimal PSA (> 1-year vs < 1 year): 8.5 months vs 3.9 months
Belderbos et al. [50] 2019 PSA Cabazitaxel Median OS: 13.3 months
Haemoglobin: OR 1.48, 95% CI 1.05–2.07, p = 0.024
Lower AP: OR 0.61, 95% CI 0.39–0.96, p = 0.034
Chang et al. [66] 2019 PSA Abiraterone, enzalutamide Median follow-up (AA vs Enza): 18.2 vs 14.5 months
Median PFS: 7.3 months vs 9.5 months
PSA nadir: HR = 1.000, 95% CI 1.000–1.001, p = 0.010
Median time to CRPC (AA vs Enza): 31.5 vs 24.9 months
Fan et al. [67] 2018 PSA Abiraterone + prednisone vs prednisone Median follow-up: 14 months (range 7.0–18.5 months
Median PSA PFS:10.3 vs 3.0 months
Median PSA rPFS: 13.9 vs 3.9 months
Median OS: 23.3 vs 17.5 months
Time to castration resistance < 18 months: HR, 12.8, 95% CI 2.0–83.1, p = 0.007
Fukuoka et al. [58] 2019 PSA FGA therapy Time to CRPC p = 0.007
Median PSA PFS: HR: 2.39, p = 0.020
Median PSA nadir > 1 ng/ml: HR: 2.40, p = 0.034
Time from starting PADT to PSA nadir ≤ 1 year: HR: 1.85. p = 0.047
Kodama et al. [87] 2019 PSA ADT Median follow-up: 31 months
Median time to CRPC: 13 months
CRPC survival (PSA < 100 vs > 100): 31 vs 18 months,
Median OS (PSA < 100 vs > 100): 85 vs 78 months, p = 0.509
Papazoglou et al. [69] 2016 PSA Enzalutamide Median survival time from diagnosis of CRPC: 41.1 months
Median PFS: 3.0 months
Median OS: 6.3 months
Miyake et al. [68] 2017 PSA Enzalutamide, abiraterone Median time to PSA progression (TTN < 19 weeks vs TTN > 19 weeks) in Abiraterone acetate: 8.4 vs 11.1 months
Median time to PSA progression (< 14 weeks vs > 14 weeks) in Enzalutamide: 11 vs 9.9 weeks
Kobayashi et al. [71] 2019 LDH/ALP ADT Median follow-up: 48.1 months
Median PFS: 24 months
Median OS: 67.4 months
LDH PFS: HR: 1.42; 95% CI 1.15–1.74; p = 0.0004
LDH OS: HR = 1.46, 95% CI 1.13–1.82; p = 0.0014
ALP OS: HR = 1.04; 95% CI 1.00–1.07; p = 0.015
Hiew et al. [72] 2018 LDH Docetaxel Serum LDH > 450 U/l: SD:0.054; 95% CI 0.650–0.864, p < 0.001
LDH PFS: HR: 1.876, 95% CI 1.289–2.7300
LDH OS: HR: 1.630, 95% CI 1.127–2.357
Gravis et al. [73] 2015 ALP ADT ALP OS: 62.1 vs 23.2%
ALP C-index: 0.64 95% CI 0.52–0.66
Median follow-up: 58.3 months
Mori et al. [74] 2017 LDH Abiracetone, enzalutamide LDH (< 210 IU/l: 17 months) vs LDH ≥ 210 IU/l: 8 months
PFS: HR: 0.39 (0.15–1.03) 0.056
OS: HR: 0.79 (0.31–2.02) 0.63
Song et al. [42] 2016 Tyrosine Phosphatase Docetaxel PSA response (ERG+ vs ERG−): 15.4% vs 62.1%, p = 0.004
OS (ERG+ vs ERG−): 10.8 months vs 21.4 months, p < 0.001
C/R PFS (ERG+ vs ERG−): 3.8 months vs 9.0 months, p < 0.001
Mean follow-up: 52.9 ± 27.2 months
Berg et al. [43] 2015 Tyrosine Phosphatase ADT Median follow-up: 6.8 years (IQR: 4.9–7.3)
Median time to CRPC (ERG+ vs ERG−): 3.9 years vs 4.5 years
Median OS: 5.6 months
  1. PFS progression free survival, OS overall survival, ADT Androgen deprivation therapy