Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis

Figures & data

Figure 1 Flowchart of study selection.

Table 1 Basic characteristics of 27 studies included in meta-analysis

First author(y)	Conutry	Index	Patients	Material	Assay	Staining pattern	Cut-off	Number	PD-L1(+/-) TC, NO.	Positive(%)	survival analysis method	HR estimation	Quality assessment(score)
1Bellmunt, J.	USA	Protein	Bladder cancer.	TMA	IHC	Membrane	Percentage (≥5%)	160	32/128	20	MA	Reported	8
2Huang, Y.	China	Gene	Bladder cancer.	datasets	Datasets IHC	NA	Median PD-L1 expression levels	165	40/125	24.2	MA	Reported	7
3Boorjian, S. A.	USA	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥5%)	314	39/275	12.4	MA	Reported	8
4 Wang, Y.	China	Protein	Bladder cancer.	TMA	IHC	Membrane/ cytoplasm	Percentage (≥10%)	50	36/14	72	MA	Reported	8
5Le Goux, C.	France	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥1%)	108	55/53	50.9	NA	NA	7
6Wu, C. T.	Taiwan	Protein	Bladder cancer.	TMA	IHC	NA	IRS scoring grade ≥2	120	58/62	48.3	UA	Calculated	8
7Inman, B. A.	USA	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥1%)	280	77/203	27.5	NA	NA	6
8Wang, Y. H.	China	Protein	Bladder cancer.	TMA	IHC	Membrane	Percentage (≥10%)	60	43/17	71.7	NA	NA	6
9Erlmeier.F	Germany	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥10%)	64	19/45	29.7	UA	Calculated	6
10Faraj, S. F.	USA	Protein	Bladder cancer.	TMA	IHC	Membrane	Percentage (≥5%)	56	10/46	17.9	NA	NA	8
11Liu, Z. H.	China	Protein	Bladder cancer.	FFPE	IHC	Membrane/ cytoplasm	Percentage (≥10%)	55	31/24	56.4	NA	NA	6
12Noro, D.	Japan	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥5%)	102	38/64	37.3	UA	Calculated	8
13Xylinas, E.	USA	Protein	Bladder cancer.	TMA	IHC	Membrane	Percentage (≥5%)	302	76/226	25	MA	Reported	8
14Powles, T.	NA	Protein	Bladder cancer.	FFPE	IHC	NA	Percentage (≥5%)	205	22/183	11	NA	NA	8
15Zhang, B.	China	Protein	UTUC	FFPE	IHC	Membrane	Percentage (≥5%)	162	20/142	12.3	MA	Reported	8
16Rosenberg, J. E.	NA	Protein	Bladder, Renal pelvis, Ureter Urethra.	FFPE	IHC	Membrane	Percentage (≥5%)	310	100/210	32.3	UA	Calculated	8
17Plimack, E. R.	USA and Israel	Protein	Bladder, Renal pelvis, Ureter, Urethra.	FFPE	IHC	Membrane	Percentage (≥1%)	115	61/54	53	NA	NA	8
18Balar, A. V.	NA	Protein	Bladder, Renal pelvis, Ureter, Urethra.	FFPE	IHC	Membrane	Percentage (≥5%)	119	32/87	26.9	NA	Calculated	8
19Apolo, A. B.	NA	Protein	Bladder, Renal pelvis, Ureter, Urethra.	FFPE	IHC	Membrane	Percentage (≥5%) Percentage	37	13/24	35.1	NA	Calculated	8
20Sharma, P.	NA	Protein	Bladder, Renal pelvis, Ureter, Urethra.	FFPE	IHC	Membrane	(≥1%)	265	122/143	46	NA	Calculated	8
21Sharma, P.	NA	Protein	Bladder, Renal pelvis.	FFPE	IHC	Membrane	Percentage (≥1%)	67	25/42	37.3	NA	NA	7
22Massard, C.	NA	Protein	Bladder cancer.	FFPE	IHC	Membrane	Percentage (≥25%)	61	40/21	65.6	NA	NA	8
23Powles, T.	NA	Protein	Urothelial carcinoma	FFPE	IHC	Membrane	Percentage (≥25%)	177	98/79	55.3	NA	Calculated	8
24Krabbe, L.M.	NA	Protein	UTUC.	TMA		Membrane/ cytoplasm	Percentage (≥1%)	423	111/312	26.2	MA	Reported	8
25Skala, S.L.	USA	Protein	UTUC.	TMA	IHC	Membrane	Percentage (≥5%)	149	35/114	23.5	MA	Reported	8
26Tretiakova, M.	USA	Protein	Urothelial carcinoma	TMA	IHC	Membrane	Composite score	101	21/80	20.8	UA	Reported	7
27Pichler, R.	Austria	Protein	Urothelial carcinoma	FFPE	IHC	Membrane	Percentage (≥5%)	61	16/61	26.2	UA	Reported	7

Abbreviations: IHC, immunohistochemistry; FFPE, formalin-fixed paraffin-embedded; TMA, tissue microarray; UA, univariate analysis; MA, multivariate analysis; NA, not available; TC, tumor cell; UTUC, urothelial carcinoma of the upper urinary tract.

Figure 2 Association between PD-L1 expression and (A1) tumor stage; (B1) tumor stage; (C) intravesical therapy of BCG; (D1) tumor grade; (E1) sex; (F1) smoking history; (G1) prior use of chemotherapy; (H1) lymph node metastases; and (I1) distant metastases in bladder cancer. Association between PD-L1 expression and (A2) tumor stage; (B2) tumor stage; (D2) tumor grade; (E2) sex; (F2) smoking history; (G2) prior use of chemotherapy; (H2) lymph node metastases; (I2) distant metastases; (J) recurrence; (K) death due to UTUC for patients with UTUC. Figure 2(A, C–K) expression of PD-L1 was defined by tumor cells. Figure 2(B) expression of PD-L1 was defined by tumor-infiltrating immune cells.

Abbreviations: PD-L1, programmed cell death-1; BCG, bacilli Calmette-Guerin; UTUC, upper urinary tract urothelial carcinoma; OR, odds ratio.

Figure 3 Forest plot to assess effect of PD-L1 tumor cell expression on (A1) OS for BC; (A2) OS for organ-confined BC, and (B1) CSS for BC; (B2) CSS for UTUC; (B3) CSS for organ-confined BC.

Abbreviations: PD-L1, programmed cell death ligand 1; OS, overall survival; BC, bladder cancer; CSS, cancer specific survival; UTUC, upper urinary tact urothelial carcinoma.

Figure 4 Forest plot of the combined overall survival (OS) for (A1) bladder cancer patients; (A2) patients with organ-confined BC; analyzed with multivariate analysis, with PD-L1 status defined by TCs and OS (B1) without and (B2) with anti-PD-1/PD-L1 treatment in urothelial carcinoma patients with PD-L1 status stratified by ICs.

Abbreviations: OS, overall survival; BC, bladder cancer; TCs, tumor cells; PD-L1, programmed cell death ligand 1; ICs, tumor-infiltrating immune cells.

Figure 5 Forest plot of the combined overall response rate (ORR) of anti-PD-1/PD-L1 antibody treatment for UC with PD-L1 status defined by 1) TCs; 2) ICs; 3) CPS.

Abbreviations: ORR, overall response rate; PD-1/PD-L1, programmed cell death-1/programmed cell death ligand 1; UC, urothelial carcinoma; TCs, tumor cells; ICs, tumor-infiltrating immune cells; CPS, combined positive score.

Figure 6 Funnel plot evaluating possible publication bias for (A) tumor stage; (B) sex; (C) OS; (D) ORR.

Abbreviations: OS, overall survival; ORR, objective response rate.