Main characteristics of included studies in the meta-analysis
| Study cohort | Year | Study region | Research time | Follow-up (month) | Treatment | M/F (n) | Age (years) | Tumour type | Distal metastasis (n) |
|---|---|---|---|---|---|---|---|---|---|
| De Martino et al16 | 2013 | USA | 1995–2012 | Mean:49; IQR: (15–71) | Radical and partial nephrectomy | 202/79 | Mean: 63; IQR: (54–72) | Non-clear cell RCC | 0 |
| Ohno et al17 | 2012 | Japan | 1990–2008 | Mean±SD: (75±54) | Radical and partial nephrectomy | 186/64 | Mean±SD: (61±12) | Clear cell RCC | 0 |
| Ohno et al12 | 2014 | Japan | 1990–2008 | Mean (range): 20.6 (1–114) | Cytoreductive nephrectomy: Yes 48; No 25 | 61/12 | Cytoreductive nephrectomy (median (range)): yes: 63 (38–79); No: 65 (34–88) | mRCC | 73 |
| Dirican et al18 | 2013 | Turkey | 2006–2011 | Median:13.43; range: (1.97–40.91) | Nephrectomy, INF-α, sunitinib | 17/6 | Median (range): 59 (43–76) | Clear cell RCC:18; non-clear cell RCC: 5 | 23 |
| Keizman et al19 | 2014 | USA, Israel | 2004–2013 | NA | Sunitinib | 186/92 | Median: 63 | mRCC | 278 |
| Santoni et al20 | 2013 | Italy | 2005–2013 | Median:46.9; 95% CI (39.9 to 53.9) | Past nephrectomy: 91; second-line everolimus: 65; third-line everolimus: 32 | 70/27 | Median:64; 95% CI (44 to 82) | mRCC | 97 |
| Cetin et al21 | 2013 | Turkey | 2008–2011 | Median:15; range: (1–53) | First-line therapy with IFN-α; second-line therapy with VEGF targeted TKIs | 76/24 | Median (range): 58 (24–80) | mRCC: clear cell 73; non-clear cell 24; unknown 3 | 100: liver 17; bone 24; lung 65 |
| Forget et al22 | 2013 | Belgium | 1993–2005 | Median:74.5; IQR: (31–112) | Radical nephrectomy | 71/156 | Mean±SD: (63±12) | Clear cell 166; tubulopapillary 29; chromophobe 4; others 28 | 0 |
| Pichler et al23 | 2013 | Austria | 2000–2010 | Mean (range): 44 (0–130) | Curative radical or partial nephrectomy | Total: 678 | Mean±SD: (63.7±11.9) | Clear cell RCC | 0 |
| Kobayashi et al24 | 2013 | Japan | 2008–2012 | Median:12; range: (1.1–48.9) | Radical nephrectomy, cytokine therapy and sorafenib, sunitinib or mTORi | 44/14 | Median (range): 64 (53–81) | mRCC | 26 |
| Templeton et al25 | 2014 | Canada | NA | NA | Targeted therapy | Total: 859 | NA | RCC | NA |
| Fox et al26 | 2013 | Australia | 2002–2005 | NA | As in EGF20001 | 268/94 | Median (range): 62 (19–84) | mRCC | 362 |
| Huang et al27 | 2011 | USA | 2004–2011 | Median: 35 | Sunitinib | Total: 109 | NA | mRCC | 109 |
| Hatakeyama et al28 | 2013 | Japan | 1995–2013 | Surgery: 26; immunotherapy or IFN-α: 5 | Radical nephrectomy with thrombectomy, immunotherapy or IFN-α | 55/30 | Mean±SD: (62±12) | RCC with tumour thrombus | 14 |
| Study cohort | NLR value | Cut-off | Elevated NLR (n) | Survival analysis | HR | Adjustment variables | NOS score |
|---|---|---|---|---|---|---|---|
| De Martino et al16 | Median (IQR): 2.6 (1.9–3.6) | 3.6 | NA | RFS (DFS) | R (M) | Age, gender, ECOG performance score, pT stage, TNM group, grade, MVI, subtype, ANC, ALC | 7 |
| Ohno et al17 | Mean±SD: 2.62±1.44 | 2.7 | 84 | RFS | R (M) | Age, presentation, nephrectomy, tumour size, pT, grade, MVI, eastern Cooperative Oncology Group, neutrophil, lymphocytes | 8 |
| Ohno et al12 | Mean±SD: 3.98±2.27 | 4 | NA | OS | R (M) | Age, presentation mode, T stage, ECOG PS, Charlson comorbidity index, haemoglobin, LDH, corrected calcium, CRP, neutrophils, lymphocytes | 5 |
| Dirican et al18 | NA | 3 | NA | OS, PFS | E (U) | / | 4 |
| Keizman et al19 | NA | 3 | NA | OS, PFS | R (M) | Unclear | 5 |
| Santoni et al20 | Median: 2.2 | 3 | 38 | OS, PFS | R (M) | Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia | 6 |
| Cetin et al21 | Median: 3.04 | 3.04 | 50 | OS, PFS | R (U) | Age, tumour history, sex, haemoglobin level, red cell distribution width, albumin level, alkaline phosphatase level, PFS, site and number of metastatic organs, MSKCC score, dose reduction, second-line mTOR inhibitors | 5 |
| Forget et al22 | Median (IQR): 3.01 (1.97–4.49) | 5 | 52 | OS, RFS | R (U) | Age, sex, node status, histological grade, stage | 8 |
| Pichler et al23 | Mean±SD: 3.51±2.49 | 3.3 | 398 | OS,RFS (MFS), CSS | R (M) | Age, gender, T stage, tumour grade, presence of tumour necrosis | 7 |
| Kobayashi et al24 | Mean±SD: sorafenib: 4.25±3.01; sunitinib: 4.50±3.43; mTORi: 4.26±2.87 | 4.41 | Sorafenib: 8; sunitinib: 23; mTORi: 16 | OS, PFS | R (M) in OS, E (U) in PFS | Karnofsky PS, metastasis at presentation, number of metastases, prior nephrectomy, prior cytokine therapy, initial targeted agent, Heng’s risk classification, pretreatment level of haemoglobin, platelet count, albumin, CRP, corrected calcium | 5 |
| Templeton et al25 | Mean: 4.98; Median (95% CI) 3.51 (1.42 to 14.0) | 2.5 | 622 | OS | R (M), E (U) | 6 international metastatic renal cell carcinoma database consortium (IMDC) | / |
| Fox et al26 | NA | 3 | 188 | OS | R (M) | MSKCC and systemic inflammation markers | 7 |
| Huang et al27 | NA | 3 | 57 | OS, PFS | R (U) | / | / |
| Hatakeyama et al28 | Mean±SD: 3.1±1.5 | NA | NA | OS | R (U, M) | Age, ECOG-performance status, gender, thrombus level, distant metastasis, underwent surgery, haemoglobin, serum albumin, eGFR, cholinesterase, serum sodium, correlated calcium, LDH, CRP, Charison comorbidity index, molecular targeted agents | 5 |
HR obtained by reporting in text (R), or estimating (E).
ANC, absolute neutrophil count; ALC, absolute lymphocyte count; CSS; CRP, C reactive protein;
CSS, cancer-specific survival; DFS, disease free survival; ECOG, Eastern Cooperative Oncology Group; PS, ; EGF, epidermal growth factor; eGFR, estimated glomerular filtration rate; IFN-α, interferon α; LDH, lactate dehydrogenase; M/F, male, female; (M), the HR comes from multivariate analysis; MFS, metastasis free survival; mRCC, metastatic renal cell carcinoma; MSKCC, Memorial Sloan Kettering Cancer Center; mTORi, inhibitor of the mammalian target of rapamycin; MVI, microvascular invasion; NA, not available; NLR, neutrophil–lymphocyte ratio; NOS, Newcastle-Ottawa Quality Scale; OS, overall survival; PFS, progress-free survival; PS, performance status; pT, primary tumour; RCC, renal cell carcinoma; RFS, recurrence-free survival; TNM, tumour, node, metastasis; TKIs, tyrosine-kinase inhibitor; (U), the HR comes from univariate analysis; VEGF, vascular endothelial growth factor.