Table 4 Summary of included studies for predictive/prognostic biomarkers

Ando et al. [44]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

PSA

Docetaxel

Median OS: 13.51 months

Median TTN: 5.14 months

Houede et al. [65]

PSA

Abiracetone acetate

PSA response > 3 months: p = 0.00025

Median OS: 14.6 months

Follow-up: 36.3 months

Kuo et al. [56]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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