Supplement 1. Patient Characteristics of the Eligible Studies

Supplements

Supplement 1. Patient characteristics of the eligible studies

Study / No. of patients / Median age,
range (years) / Gender (male/female) / Upper limit of PLND / Neoadjuvant chemotherapy / Adjuvant chemotherapy / Median follow-up,
range (months)
Kassouf [1] / 108 / 69, 45-85 / 92/16 / NA / 0 / 76 / NA
Stepheson [5] / 134 / 68, 59-75 / 102/32 / Bifurcation of CIA (127),
Aortic bifurcation (7) / NA / 90 / 23, 10-36
Jeong [15] / 112 / 61.8 (mean),
37-79 / 99/13 / Bifurcation of CIA (112),
Aortic bifurcation (14) / 0 / 73 / 23, 2-146
Seiler [16] / 162 / 67, 35-89 / 132/30 / Crossing of the ureter
with CIA / 0 / NA / 7.1 yr, 0.1-19.9 yr
Jensen [17] / 43 / 63, 39-80 / 126/41 / Inferior mesenteric artery / 0 / 0 / NA
Nakagawa [18] / 46 / 66, 46-83 / 37/9 / Bifurcation of CIA (36),
Aortic bifurcation (7),
Inferior mesenteric artery (3) / 0 / 18 / 32, 3-272
Masson-Lecome [19] / 75 / 65, 31-85 / 64/11 / Bifurcation of CIA / NA / 46 / 40.6, 3-127
Fajkovic [20] / 748 / 66.9 / 609-139 / NA / 0 / 423 / 27
Fritsche [21] / 158 / 69, 61.8-76 (IQR) / 121/47 / Bifurcation of CIA / 0 / 0 / 20, 11-38 (IQR)
Clifton [22] / 307 / 68.6, 32.9-87 / 252/55 / NA / 13 / 111 / 8.7 yr, 5.9-15.7 yr (IQR)

PLND: pelvic lymph node dissection, NA: not available,CIA: common iliac artery, IQR: interquartile range.

Supplement 2. Pathologic characteristics of the eligible studies

Study / Tumor grade
(G1/G2/G3) / Pathologic T stage
(pT0/is/a/1/2/3/4) / Pathologic
N stage
(pN1/2/3) / Median no. of
LNs removed,
range / Median no. of
positive LNs,
range / Non-UC / Variant
Form / LVI / Concomitant
CIS / Positive surgical margin
Kassouf [1] / NA / 3/0/1/3/14/53/34 / 25/38/23 / 12, 1-58 / 2, 1-10 / 0 / NA / 58 / 37 / 11
Stepheson [5] / NA / 27(≤T2)/107(T3/4) / 62/72(N2/3) / 14, 9-20 (IQR) / 2, 1-3 (IQR) / 0 / NA / 87 / NA / 23
Jeong [15] / 0/5/107 / 24(≤T2)/88(T3/4) / 37/74/1 / 16, 3-94 / 3, 1-37 / 0 / NA / NA / NA / 13
Seiler [16] / NA / 0/0/0/23(T1/2)/97/42 / 52/110/0 / 27, 10-56 / 3, 1-46 / 0 / NA / NA / NA / NA
Jensen [17] / NA / 0/2(Tis/a)/32/68/48/17 / 16/9/18 / NA / NA / 5 / NA / NA / NA / NA
Nakagawa [18] / 0/0/46 / 0/0/0/0/6/26/14 / 16/25/5 / 12.5, 4-36 / 2, 1-17 / 0 / 8 / NA / NA / NA
Masson-Lecome [19] / NA / 0/0/0/2/15/39/19 / 10/10/6 / 18, 3-49 / 3, 1-35 / 2 / NA / 40 / NA / 19
Fajkovic [20] / 18/113/616 / 44(≤T1)/121/377/206 / NA / 15 / 2 / 0 / NA / 457 / 287 / 110
Fritsche [21] / 0/0/158 / 31(≤T1)/31/73/54 / 49/107/2 / 14, 9-19 (IQR) / 2, 1-5 (IQR) / 0 / NA / 153 / NA / 42
Clifton [22] / 2/86/207 / 25(≤T1)/61/221(T3/4) / 136/171(N2/3) / 12, 7-19 (IQR) / 2, 1-3 (IQR) / 43 / 58 / NA / NA / 18

LV: lymph node, UC: urothelial carcinoma, LVI: lymphovascular invasion, CIS: carcinoma in situ, NA: not available, IQR: interquartile range.

Supplement 3. Extracapsular extension according to pathological features

Study / No. (%) of positive ECE
pT stage / Tumor grade / pN stage
Total / ≤T2 / ≥T3 / G1 / G2 / G3 / pN1 / pN2 / pN3
Kassouf [1] / 44/108 (40.7) / NA / NA / NA / NA / NA / NA / NA / NA
Stepheson [5] / 67/134 (50.0) / NA / NA / NA / NA / NA / NA / NA / NA
Jeong [15] / 41/112 (36.6) / 5/24 (20.8) / 36/88 (40.9) / 0/0 (0.0) / 1/5 (20.0) / 40/107 (37.4) / 6/37 (16.2) / 34/74 (45.9) / 1/1 (100.0)
Seiler [16] / 82/162 (50.6) / 4/22 (18.2) / 78/170 (45.9) / NA / NA / NA / 14/53 (26.4) / 68/109 (62.4) / 0/0 (0.0)
Jensen [17] / 25/43 (58.1) / NA / NA / NA / NA / NA / NA / NA / NA
Nakagawa [18] / 19/46 (41.3) / NA / NA / NA / NA / NA / NA / NA / NA
Masson-Lecome [19] / 31/75 (41.3) / NA / NA / NA / NA / NA / NA / NA / NA
Fajkovic [20] / 375/748 (50.1) / 54/165 (32.7) / 321/583 (55.1) / 10/18 / 54/114 (47.4) / 311/616 (50.5) / NA / NA / NA
Fritsche [21] / 83/158 (52.5) / NA / NA / NA / NA / NA / NA / NA / NA
Clifton [22] / 103/307 (33.6) / NA / NA / NA / NA / NA / NA / NA / NA
Total / 870/1893 (46.0) / 63/211 (29.9) / 435/841 (51.7) / 10/18 (55.6) / 55/119 (46.2) / 351/723 (48.5) / 20/90 (22.2) / 102/183 (55.7) / 1/1 (100.0)

ECE: extracapsular extension, NA: not available.

Supplement 4. Estimation of the hazard ratios

Study / Survival analysis / HR estimation / Co-factors / Analysis results
Kassouf [1] / CSS / P value, event no. (univariate) / - / Not significant
Stepheson [5] / OS / HR, 95% CI / pT stage, aggregate LN metastasis diameter, LVI, positive surgical margin, Charlson comorbidity index, LN density / Not significant
Jeong [15] / RFS / HR, 95% CI / pT stage, pN stage, no. of positive LNs, No. of LNs removed, LN density, adjuvant chemotherapy / Not significant
CSS / HR, 95% CI / pT stage, pN stage, no. of positive LNs, No. of LNs removed, LN density, adjuvant chemotherapy / Not significant
Seiler [16] / RFS / HR, 95% CI / pT stage / Significant
CSS / HR, 95% CI / pT stage / Significant
OS / HR, 95% CI / pT stage / Significant
Jensen [17] / RFS / HR, 95% CI / Gender, age, pT stage, pN stage, metastasis above the aortic bifurcation, LN density, volume-dependent LN density, diameter of largest metastatic LN, volume of metastatic LNs / Not significant
CSS / HR, 95% CI / Gender, age, pT stage, pN stage, metastasis above the aortic bifurcation, LN density, volume-dependent LN density, diameter of largest metastatic LN, volume of metastatic LNs / Not significant
Nakagawa [18] / RFS / P value, event no.(univariate) / - / Not significant
CSS / HR, 95% CI / No. of positive LNs, diameter of largest metastatic LN / Significant
Masson-Lecome [19] / RFS / HR, 95% CI / pT stage, LVI, LN density, adjuvant therapy / Significant
Fajkovic [20] / RFS / HR, 95% CI / pT stage, tumor grade, gender, age, LVI, adjuvant chemotherapy, positive surgical margin, LN density, no. of LNs removed, no. of positive LNs / Significant
CSS / HR, 95% CI / pT stage, tumor grade, gender, age, LVI, adjuvant chemotherapy, positive surgical margin, LN density, no. of LNs removed, no. of positive LNs / Significant
Fritsche [21] / CSS / HR, 95% CI / Age, gender, pT stage, pN stage, perinodal LVI, diameter of largest metastatic LN / Not significant
Clifton [22] / CSS / HR, 95% CI / Age, Charlson comorbidity index, pT stage, pN stage, LVI, no. of LNs removed, no. of positive LNs, adjuvant chemotherapy / Significant

HR: hazard ratio, CSS: cancer-specific survival, OS: overall survival, LN: lymph node, LVI: lymphovascular invasion, RFS: recurrence-free survival, CI: confidence interval.

Supplement 5. Subgroup analysis for recurrence-free survival

No. of included articles / No. of cases / Pooled HR (95% CI) / Chi2 (p value) / I2 / Ph*
HR estimation / 0.242
Univariate / 2 / 154 / 1.27 (0.77-2.09) / 2.45 (0.12) / 59%
Multivariate / 5 / 1140 / 1.75 (1.42-2.16) / 4.89 (0.30) / 18%
Region* / <0.0001
USA / 1 / 108 / 1.07 (0.99-1.16) / NA / NA
Europe / 3 / 280 / 1.91 (1.37-2.66) / 0.56 (0.76) / 0%
Asia / 2 / 158 / 1.34 (0.78-2.32) / 1.65 (0.20) / 39%
No. of patients / 0.221
<100 / 3 / 164 / 2.03 (1.30-3.17) / 0.41 (0.81) / 0%
≥100 / 4 / 1130 / 1.41 (0.96-2.06) / 31.80 (0.00001) / 91%
Median follow-up** / 0.4352
<30 months / 2 / 860 / 1.49 (0.85-2.60) / 4.14 (0.04) / 76%
≥30 months / 3 / 283 / 1.92 (1.41-2.63) / 0.50 (0.78) / 0%
Analysis results / <0.0001
Not significant / 4 / 309 / 1.09 (0.98-1.22) / 3.10 (0.38) / 3%
Significant / 3 / 985 / 1.90 (1.60-2.26) / 0.51 (0.78) / 0%
Quality scale / 0.8712
≤3 / 4 / 974 / 1.60 (1.01-2.52) / 31.88 (<0.00001) / 91%
3 / 3 / 320 / 1.52 (1.06-2.18) / 2.85 (0.24) / 30%

HR: hazard ratio, CI: confidence interval, NA: not applicable.

Ph* for heterogeneity between subgroups with meta-regression analysis.

*One study was excluded because the region was multination (Fajkovic [8]).

**Two studies were excluded because the duration of follow-up was not available (Kassouf [1] and Jensen [5]).