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| Prognostic role of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with non-metastatic and metastatic prostate cancer: A meta-analysis and systematic review |
Stefano Salcicciaa,Marco Frisendaa,*( ),Giulio Bevilacquaa,Pietro Viscusoa,Paolo Casaleb,Ettore De Berardinisa,Giovanni Battista Di Pierroa,Susanna Cattarinoa,Gloria Giorginoa,Davide Rosatia,Francesco Del Giudicea,Alessandro Sciarraa,Gianna Mariottia,Alessandro Gentiluccia
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aDepartment of Urology, Sapienza Rome University, Policlinico Umberto I, 00161 Rome, Italy
bDepartment of Urology, Humanitas, 20089 Rozzano, MI, Italy |
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Abstract Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03-0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16-0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78-1.88) and between high and low PLR was 1.47 (95% CI: 0.91-2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44-2.13) and between high and low PLR was 1.05 (95% CI: 0.87-1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.
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Received: 08 May 2022
Available online: 20 April 2024
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Corresponding Authors:
* E-mail address: marco.frisenda@uniroma1.it (M. Frisenda).
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Flow chart for meta-analysis.
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| Study | Cut-off groups | Treatment | HR (95% CI) for BPH vs. PCa | Cases on the basis of T stage, n (%) | OR (95% CI) for PCa diagnosis | Cases on the basis of N stage, n (%) | HR or OR (95% CI) for N+ disease | Cases on the basis of ISUP, n (%) | HR (95% CI) for ISUP 4-5 | HR (95% CI) for progression after treatment | HR (95% CI) for OM or CSM | | Sun et al. [11] | ? NLR<2.31
? NLR≥2.31 | Initial biopsy | NA | NA | NA | NA | NA | ? NLR<2.31
o-
1: 33 (30.8)
o-
2-5: 74 (69.2)
? NLR ≥ 2.31
o-
1: 22 (18.5)
o-
2-5: 97 (81.5) | NA | NA | ? CSM: 2.0 (1.0-3.8)
? OM: 2.0 (0.8-5.4) | | Zanaty et al. [8] | ? NLR<3
? NLR≥3 | RP | NA | NA | NA | NA | NA | NA | NA | 0.9 (0.721-1.384) | NA | | Shelton et al. [12] | ? Low NLR: 2.00 (SD 0.67)
? High NLR: 5.15 (SD 2.62) | Active surveillance | NA | NA | NA | NA | NA | ? Low NLR
o-
1: 66 (89.2)
o-
2: 8 (10.8)
? High NLR
o-
1: 23 (95.8)
o-
2: 1 (4.2) | NA | NA | NA | | Vidal et al. [13] | ? No cut-off | RP | NA | NA | NA | NA | NA | NA | NA | 1.06 (0.97-1.17) | ? CSM: 1.15 (0.81-1.65)
? OM: 1.04 (0.91-1.17) | | Cao et al. [14] | ? NLR<2
? NLR≥2 | RP | NA | ? NLR<2
o-
pT2: 362 (69.9)
o-
pT3: 148 (28.6)
o-
pT4: 8 (1.5)
? NLR≥2
o-
pT2: 298 (67.7)
o-
pT3: 126 (28.6)
o-
pT4: 16 (3.6) | NA | ? NLR<2
o-
N0: 395 (92.3)
o-
N1: 33 (7.7)
? NLR≥2
o-
N0: 326 (93.1)
o-
N1: 24 (6.9) | NA | ? NLR<2
o-
1: 99 (19.6)
o-
2: 185 (36.6)
o-
3: 95 (18.8)
o-
4-5: 126 (25.0)
? NLR≥2
o-
1: 81 (18.6)
o-
2: 145 (33.3)
o-
3: 75 (17.2)
o-
4-5: 134 (30.8) | NA | 0.600 (0.413-0.871) | ? OM: 1.466 (0.607-3.542) | | Nkengurutse et al. [15] | ? NLR<2
? NLR≥2 | RP | NA | NA | NA | NA | NA | NA | NA | 1.131 (0.633-2.021) | NA | | Taussky et al. [16] | ? NLR>3
? NLR≤3 | Brachytherapy | NA | NA | NA | NA | NA | NA | NA | 0.37 (0.15-0.92) | NA | | Langsenlehner et al. [17] | ? NLR≥5
? NLR<5 | Radiotherapy | NA | NA | NA | NA | NA | NA | NA | 3.09 (1.64-5.82) | ? OM: 2.16 (1.17-3.99) | | Lee et al. [18] | ? NLR<2.5
? NLR≥2.5 | RP | NA | ? NLR<2.5
o-
pT2: 836 (69.2)
o-
pT3a: 252 (20.9)
o-
≥pT3b: 120 (9.9)
? NLR≥2.5
o-
pT2: 78 (49.4)
o-
pT3a: 47 (29.7)
o-
≥pT3b: 33 (20.9) | NA | NA | HR: 0.819 (0.303-2.216) | ? NLR<2.5
o-
1: 616 (51.0)
o-
2-3: 429 (35.5)
o-
4-5: 163 (13.5)
? NLR≥2.5
o-
1: 63 (39.9)
o-
2-3: 48 (30.4)
o-
4-5: 47 (29.7) | 1.750 (0.960-3.189) | 1.358 (1.008-1.829) | NA | | Jang et al. [19] | ? NLR<1.76
? NLR≥1.76 | RP | NA | ? NLR<1.76
o-
pT2: 484 (47.3)
o-
pT3: 540 (52.7)
? NLR≥1.76
o-
pT2: 476 (45.6)
o-
pT3: 567 (54.4) | NA | NA | NA | ? NLR<1.76
o-
1-3: 812 (79.3)
o-
4-5: 212 (20.7)
? NLR≥1.76
o-
1-3: 802 (76.9)
o-
4-5: 241 (23.1) | NA | 1.099 (0.944-1.278) | ? CSM: 2.012 (1.222-3.310)
? OM: 1.650 (1.127-2.416) | | Jang et al. [20] | ? NLR<3.5
? NLR≥3.5 | RP | NA | ? NLR<3.5
o-
pT2: 708 (44.8)
o-
pT3: 871 (55.2)
? NLR≥3.5
o-
pT2: 227 (50.1)
o-
pT3: 226 (49.9) | NA | NA | NA | ? NLR<3.5
o-
1-3: 483 (30.6)
o-
4-5: 1096 (69.4)
? NLR≥3.5
o-
1-3: 138 (30.5)
o-
4-5: 315 (69.5) | NA | 1.270 (1.066-1.514) | NA | | Zhang et al. [21] | ? NLR<2.36
? NLR≥2.36 | RP | NA | ? NLR<2.36
o-
pT2: 127 (78.9)
o-
pT3-4: 34 (21.1)
? NLR≥2.36
o-
pT2: 43 (56.6)
o-
pT3-4: 33 (43.4) | NA | ? NLR<2.36
o-
N0: 152 (94.4)
o-
N1: 9 (5.6)
? NLR≥2.36
o-
N1: 15 (19.7)
o-
N0: 61 (80.3) | NA | ? NLR<2.36
o-
1: 34 (21.1)
o-
2-3: 75 (46.6)
o-
4-5: 52 (32.3)
? NLR≥2.36
o-
1: 13 (17.1)
o-
2-3: 31 (40.8)
o-
4-5: 32 (42.1) | NA | 1.388 (0.909-2.118) | NA | | ?zsoy et al. [22] | ? NLR≥3
? NLR<3 | RP | NA | ? NLR≥3
o-
cT1: 1565 (91.7)
o-
cT2: 114 (6.7)
o-
cT3: 1 (0.1)
? NLR<3
o-
cT1: 5320 (93.0)
o-
cT2: 302 (5.3)
o-
cT3: 2 (0.1) | 1.60 (1.30-1.95) | NA | OR: 1.43 (1.20-1.72) | ? NLR≥3
o-
1: 344 (20.2)
o-
2-3: 1116 (65.4)
o-
4-5: 247 (14.5)
? NLR<3
o-
ISUP 1: 1888 (33.0)
o-
ISUP 2-3: 3487 (61.0)
o-
ISUP 4-5: 339 (5.9) | 2.32 (1.90-2.83) | NA | NA | | Adhyatma et al. [23] | ? NLR≥3.08
? NLR<3.08 | Initial biopsy | 2.856 (1.734 -4.702) | NA | NA | NA | NA | NA | NA | NA | NA | | Masuda et al. [24] | ? NLR≤1.92
? NLR>1.92 | Biopsy | 2.44 (1.19-5.17) | NA | NA | NA | NA | NA | NA | NA | NA | | Huang et al. [25] | ? NLR<2.44
? NLR≥2.44 | Initial biopsy | 1.640 (1.045-2.573) | NA | NA | NA | NA | ? NLR<2.44
o-
1-2: 47 (33.1)
o-
3-4: 95 (66.9)
? NLR≥2.44
o-
1-2: 61 (34.9)
o-
3-5: 114 (65.1) | NA | NA | NA | | Oh et al. [26] | ? No cut-off | Initial biopsy | 1.372 (1.017-1.850) | NA | NA | NA | NA | NA | NA | NA | NA | | Hashimoto et al. [27] | ? No cut-off | Biopsy | 1.29 (0.874-1.9) | NA | NA | NA | NA | NA | NA | NA | NA |
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Clinical trials on non-metastatic PC included in the analysis: results on the basis of NLR groups.
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| Study | Cut-off groups | Treatment | HR (95% CI) for pretreatment vs. posttreatment | Cases on the basis of ISUP, n (%) | Cases on the basis of progression after treatment, n (%) | HR (95% CI) for progression after treatment | HR (95% CI) for OM | | Lolli et al. [28] | ? NLR<3
? NLR≥3 | Abiraterone | NA | NA | NA | NA | ? Low-High (<3-≥3): 1.49 (0.84-2.63)
? High-Low (≥3-<3): 3.22 (1.89-5.49) | | Onal et al. [29] | ? NLR<3.1
? NLR≥3.1 | Abiraterone | ? Low-high: 1.55 (0.64-3.74)
? High-low: 3.96 (1.26-12.47) | ? 1-3:
o-
NLR<3.1: 25 (54.3)
o-
NLR≥3.1: 21 (45.7)
? 4-5:
o-
NLR<3.1: 25 (44.6)
o-
NLR≥3.1: 31 (55.4) | NA | ? 2.25 (1.44-3.51) | ? 3.13 (1.67-5.88) | | Bauckneht et al. [30] | ? NLR<4.8
? NLR≥4.8 | Radium-223 | NA | NA | NA | NA | ? 1.09 (1.00-1.20) | | Bauckneht et al. [31] | ? NLR<3.1
? NLR≥3.1 | Radium-223 | NA | NA | NA | NA | ? 2.70 (2.06-3.56) | | Pei et al. [32] | ? NLR≤3.3
? NLR>3.3 | Docetaxel | NA | NA | NA | ? 1.831 (1.087-3.085) | ? 2.056 (1.007-4.200) | | Sonpavde et al. [33] | ? NLR<2.5
? NLR 2.5 to <5
? NLR≥5 | Sunitinib | NA | NA | NA | NA | ? 1.55 (1.32-1.83) | | Buttigliero et al. [34] | ? NLR≤3
? NLR>3 | Docetaxel | NA | NA | ? NLR≤3: 39/46 (84.8)
? NLR>3: 57/64 (89.1) | ? 1.57 (0.84-2.92) | ? 3.16 (1.50-6.65) | | Kawahara et al. [35] | ? NLR>3.02
? NLR≤3.02 | Abiraterone and/or enzalutamide | NA | NA | NA | NA | ? 2.115 (1.540-2.906) | | Chong et al. [36] | ? NLR<2.65
? NLR≥2.65 | ARTA and docetaxel | NA | NA | ? NLR<2.65: 14/21 (66.7)
? NLR≥2.65: 31/42 (73.8) | ? 1.65 (0.87-3.12) | ? 3.27 (1.11-9.63) | | Lorente et al. [37] | ? NLR>3
? NLR<3 | Mitoxantrone and cabazitaxel | NA | NA | NA | ? BCP: 1.35 (1.12-1.62)
? RCP: 1.42 (1.15-1.76) | ? 1.55 (1.30-1.84) | | Uemura et al. [38] | ? NLR<3.83
? NLR≥3.83 | Cabazitaxel | NA | NA | NA | NA | ? 3.01 (1.06-8.49) | | Templeton et al. [39] | ? NLR<3
? NLR>3 | Docetaxel | NA | NA | NA | NA | ? 1.89 (1.27-2.82) | | Boegemann et al. [40] | ? NLR<5
? NLR>5 | Abiraterone | NA | ? 4-5:
o-
NLR<5: 46 (60.5)
o-
NLR>5: 9 (56.3) | NA | ? 3.4 (0.8-15.2) | ? 1.6 (0.5-5.6) | | Conteduca et al. [41] | ? NLR<3
? NLR≥3 | Abiraterone and/or enzalutamide | NA | NA | NA | ? 1.98 (1.54-2.56) | ? 2.04 (1.54-2.70) | | Yasui et al. [42] | ? NLR<3.76
? NLR≥3.76 | Abiraterone | NA | ? NLR<3.76:
o-
1: 1 (2.0)
o-
2-3: 7 (14.0)
o-
4-5: 42 (84.0)
? NLR≥3.76:
o-
1: 0 (0)
o-
2-3: 6 (20.0)
o-
4-5: 24 (80.0) | NA | NA | ? 2.506 (1.106-5.68) | | Fan et al. [43] | ? NLR≥3
? NLR<3 | Abiraterone and docetaxel | NA | ? NLR≥3:
o-
1-3: 25 (40.3)
o-
4-5: 37 (59.7)
? NLR<3:
o-
1-3: 23 (54.8)
o-
4-5: 19 (45.2) | NA | NA | NA |
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Clinical trials on metastatic CRPC included in the analysis: results on the basis of NLR groups.
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| Study | Cut-off groups | Treatment | HR (95% CI) for BPH vs. PCa | HR (95% CI) for pretreatment vs. posttreatment | Cases on the basis of T stage, % | Cases on the basis of ISUP, % | Cases on the basis of treatment, n (%) | HR (95% CI) for progression after treatment | HR (95% CI) for OM or CSM | | Sun et al. [11] | ? Low PLR<134
? High PLR≥134 | Initial biopsy | NA | NA | NA | ? Low PLR
o-
1: 31.6
o-
2-5: 68.4
? High PLR
o-
1: 16.5
o-
2-5: 83.5 | NA | NA | ? CSM: 1.30 (0.60-2.80)
? OM: 2.10 (0.80-4.90) | | Zanaty et al. [8] | ? Low PLR<190
? High PLR≥190 | RP | NA | NA | NA | NA | NA | BCP: 0.997 (0.988-1.006) | NA | | Shelton et al. [12] | | Active surveillance | NA | NA | NA | ? Low PLR
o-
1: 90.0
o-
2: 10.0
? High PLR
o-
1: 92.0
o-
2: 8.0 | NA | NA | NA | | Ferro et al. [44] | ? Low PLR<118
? High PLR≥118 | RP and active surveillance | NA | NA | NA | ? 2-5
o-
PLR<118: 29.9
o-
PLR≥118: 44.2 | NA | NA | NA | | Vidal et al. [13] | NA | RP | NA | NA | NA | NA | NA | NA | ? CSM: 1.00 (0.99-1.01)
? OM: 1.00 (0.98-1.03) | | Shu et al. [45] | ? Low PLR<100.7
? High PLR≥100.7 | RP | NA | NA | NA | NA | ? BCP:
o-
Low PLR: 184/380 (48.4)
o-
High PLR: 196/380 (51.6) | NA | NA | | Nkengurutse et al. [15] | ? Low PLR<120.4
? High PLR≥120.4 | RP | NA | NA | NA | NA | NA | BCP: 1.020 (0.575-1.811) | NA | | Lee at al. [46] | NA | Initial biopsy | 0.094 (0.003-2.900) | NA | NA | NA | NA | | NA | | Wang et al. [47] | ? Low PLR<117.58
? High PLR≥117.58 | ADT | NA | NA | NA | ? Low PLR<117.58
o-
≤7: 52.0
o-
>7: 48.0
? High PLR≥117.58
o-
≤7: 47.0
o-
>7: 53.0 | NA | RCP: 1.581 (1.100-2.272) | ? CSM: 1.768 (1.036-3.015)
? OM: 1.650 (1.013-2.687) | | Li et al. [48] | ? Low PLR<150
? High PLR ≥150 | Initial biopsy | NA | 2.67 (1.73-4.92) | ? PCa: T3
o-
Low PLR: 41.8
o-
High PLR: 75.0 | ? 4-5
o-
Low PLR: 53.7
o-
High PLR: 58.3 | NA | NA | NA | | Langsenlehner et al. [49] | ? Low PLR<190
? High PLR≥190 | Radiotherapy | NA | NA | NA | NA | NA | NA | ? CSM: 3.99 (1.19-13.4)
? OM: 1.87 (1.02-3.42) | | Adhyatma et al. [50] | ? Low PLR<143
? High PLR≥143 | Initial biopsy | 1.152 (0.648-2.049) | NA | NA | NA | NA | NA | NA | | Masuda et al. [24] | ? Low PLR<101.3
? High PLR≥101.3 | Initial biopsy | 1.710 (0.810-3.630) | NA | NA | NA | NA | NA | NA |
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Clinical trials on non-metastatic PCa included in the analysis: results on the basis of PLR groups.
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| Study | Cut-off groups | Treatment | HR (95% CI) for pretreatment vs. posttreatment | Cases on the basis of ISUP, % | Cases on the basis of progression after treatment, n (%) | HR (95% CI) for progression after treatment | HR (95% CI) for OM | | Onal et al. [29] | ? Low PLR<163
? High PLR≥163 | ARTA (abiraterone) | ? Low-high: 0.90 (0.38-2.13)
? High-low: 1.39 (0.49-3.92) | ? PLR<163
o-
≤7: 59
o-
>7: 41
? PLR≥163- ≤7: 41- >7: 59 | NA | 0.88 (0.56-1.37) | ? 1.02 (0.56-1.87) | | Shi et al. [51] | ? Low PLR<104.275
? High PLR≥104.275 | Chemotherapy (docetaxel) | NA | NA | NA | NA | ? Poor vs. favorable: 28.606 (9.390-87.144)
? Poor vs. intermediate: 7.412 (2.406-22.808) | | Bauckneht et al. [30] | ? Low PLR<241
? High PLR≥241 | Radium-223 | NA | NA | NA | NA | ? 1.03 (0.90-1.18) | | Chong et al. [36] | ? Low PLR<155.54
? High PLR≥155.54 | ARTA and chemotherapy | NA | NA | ? Low PLR<155.54: 14/23 (60.9%)
? High PLR≥155.54: 31/40 (77.5%) | 1.72 (0.91-3.24) | ? 2.38 (0.88-6.43) | | Lolli et al. [28] | ? Low PLR<210
? High PLR≥210 | ARTA (abiraterone) | NA | NA | NA | NA | ? Low-high (<210-≥210): 1.54 (0.71-3.33)
? High-low (≥210-<210): 1.46 (0.91-2.36) |
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Clinical trials on metastatic CRPC included in the analysis: results on the basis of PLR groups.
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Forrest plot assessing risk differences with 95% CI for non-organ confined PCa (T stage), lymph node involvement (N stage), ISUP grading 4-5, PR (biochemical and clinical) between high and low NLR or PLR groups. (A) NLR in non-metastatic PCa; (B) NLR in metastatic PCa; (C) PLR in non-metastatic PCa; (D) PLR in metastatic PCa. I2 for heterogeneity and test of group differences are reported. ISUP, International Society of Urological Pathology; PR, progression; CI, confidence interval; PLR, platelet-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; REML, residual maximum likelihood; PCa, prostate cancer.
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Forrest plot assessing pooled HR with 95% CI for BCP, CSM, and OM between high and low NLR or PLR groups. (A) NLR in non-metastatic PCa; (B) NLR in metastatic PCa; (C) PLR in non-metastatic PCa; (D) PLR in metastatic PCa. I2 for heterogeneity and test of group differences are reported. CI, confidence interval; NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; BCP, biochemical progression; CSM, cancer-specific mortality; OM, overall mortality; PCa, prostate cancer; REML, residual maximum likelihood.
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