Predictive Biomarkers of Bacillus Calmette-Guérin Immunotherapy Response in Bladder Cancer: Where Are We Now?

Table 2

Urinary markers predicting BCG treatment outcome. The markers are ordered from the most studied to the less, and, within each marker, the studies are ordered by quality score.

Marker	Author	Quality	n	Treatment scheme	Impact	Outcome
						Rec(P)	RFS; (P/HR (95% CI))	Prog(P)	PFS; (P/HR (95% CI))
IL-8	Sagnak et al., [54]	6/8	41	iBCG	−	X	0.006/2.98 (1.02–8.72)a	X	X
	Kumar et al., [57]	5/8	26	iBCG	+	0.001	X	X	X
	Sanchez-Carbayo et al., [58]	5/8	15	iBCG	None	NS	X	X	X
	Jackson et al., [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	Rabinowitzir et al., [62]	5/8	46	iBCG	None	NS	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	+	<0.05	0.013/NS^*	X	X
	Thalmann et al., [59]	4/8	17	iBCG	+	0.0209	X	X	X
	Thalmann et al., [61]	4/8	20	iBCG	+	0.0002	X	X	X
IL2	Saint et al., [64]	5/8	37	iBCG	+	X	0.0009	X	NS
	Sanchez-Carbayo et al., [58]	5/8	15	iBCG	+	0.041	X	X	X
	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	De Reijke et al., [66]	5/8	23	iBCG	+	0.003	X	X	X
	Saint et al., [63]	4/8	39	mBCG	+	X	0.01	X	0.01
	Watanabe et al., [56]	4/8	20	iBCG	+	<0.01	0.0003/0.37 (0.03–0.895)^*	X	X
	Saint et al., [65]	4/8	19	iBCG + iBCG	None/+	NS/; <0.05	X	X	X
IFN-γ	Saint et al., [64]	5/8	37	iBCG	None	X	NS	X	NS
	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	None	NS	NS/NS^*	X	X
	Saint et al., [65]	4/8	19	iBCG + iBCG	+/None	<0.05/; NS	X	X	X
TNF-α	Sanchez-Carbayo et al., [58]	5/8	15	iBCG	None	NS	X	X	X
	Jackson, [60]	5/8	34	iBCG	+	NS/; <0.05^*	X	X	X
	De Reijke et al., [66]	5/8	23	iBCG	+	0.025	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	+	<0.05	0.012/NS^*	X	X
IL-10	Saint et al., [64]	5/8	37	iBCG	None	X	NS	X	NS
	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	Saint et al., [63]	4/8	39	mBCG	None	X	NS	X	NS
	Watanabe et al., [56]	4/8	20	iBCG	+	<0.01	0.009/NS^*	X	X
	Saint et al., [65]	4/8	19	iBCG + iBCG	None	NS	X	X	X
IL-6	Sanchez-Carbayo et al., [58]	5/8	15	iBCG	None	NS	X	X	X
	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	De Reijke et al., [66]	5/8	23	iBCG	+	0.04	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	+	<0.05	0.023/NS^*	X	X
Urovysion (FISH)	Whitson et al., [100]	6/8	48	mBCG	−	X	<0.01/6.7 (2.1–22.1)^*	X	X
+posttreat	Savic et al., [101]	5/8	68	iBCG	−	X	<0.001/5.6 (2.5–12.2)^*	X	X
	Mengual, [102]	5/8	65	iBCG	−	X	0.015/2.7(1.18–6.15)^*	X	X
+pretreat	Kipp et al., [103]	5/8	37	iBCG	−	X	NS/3.3(1.3–8.5)^*	X	NS/NS^*
+posttreat					−	X	<0.001/4.6 (1.9–11.1)	X	0.001/9.4 (1.9–45.3)
IL-12	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	None	NS	NS/NS^*	X	X
IL-1β	De Reijke et al., [66]	5/8	23	iBCG	None	NS	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
	Watanabe et al., [56]	4/8	20	iBCG	None	NS	NS/NS^*	X	X
GM-CSF	Jackson, [60]	5/8	34	iBCG	−	<0.05/; <0.05^*	X	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
WBC	Saint et al., [104]	5/8	72	mBCG	+	X	0.009	X	X
	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
G-CSF	Shintani et al., [55]	4/8	20	iBCG	None	NS	X	X	X
FN	Danişman et al., [69]	5/8	38	iBCG	None	NS	X	X	X
IL-4	Jackson, [60]	5/8	34	iBCG	None	NS/NS^*	X	X	X
sICAM-1	Jackson, [60]	5/8	34	iBCG	+	NS/; <0.05^*	X	X	X
sCD14	Jackson, [60]	5/8	34	iBCG	−	NS/; <0.05^*	X	X	X
Survivin	Hausladen, [68]	4/8	23	iBCG	−	<0.05	X	X	X
IL-18	Thalmann et al., [59]	4/8	17	iBCG	+	0.0464	X	X	X

iBCG: induction BCG scheme only.
mBCG: maintenance BCG scheme.
−: negative impact, marker associated with a poor BCG response.
+: positive impact, marker associated to a better BCG response.
Rec: recurrence; P value for recurrence.
RFS: recurrence-free survival; P value for log-rank test/HR: hazard ratio from Cox regression; (95% Cl): 95% confidence interval.
Prog: progression; P value for progression.
PFS: progression-free survival; P value for log-rank test/HR: hazard ratio from Cox regression; (95% Cl): 95% confidence interval.
NS: no statistical significance.
X: not evaluated.
^*all analysed variables (indepent prognostic factor).
aadjusted for BCG-related complications, tumour stage, and grade.