1Department of Urology, Urologic Cancer, Research Institute and Hospital of National Cancer Center, Goyang, Korea
2Department of Pathology, Hospital of National Cancer Center, Goyang, Korea
3Biostatistics Collaboration Unit, Research Institute of National Cancer Center, Goyang, Korea
Copyright © 2020 by the Korean Cancer Association
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Cut-point | No. (n=162) | Event (%) |
Univariable |
Multivariable |
|||
---|---|---|---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | ||||
IVRFSa) (n=162, event=58) | |||||||
C-erb | |||||||
Low | 0 | 141 | 52 (36.9) | 1 (reference) | 1 (reference) | ||
High | > 0 | 21 | 6 (28.6) | 0.74 (0.32-1.72) | 0.483 | 2.59 (1.05-6.39) | 0.039 |
C-myc | |||||||
Low | ≤ 30 | 82 | 35 (42.7) | 1 (reference) | 1 (reference) | ||
High | > 30 | 80 | 23 (28.8) | 0.56 (0.33-0.95) | 0.031 | 0.88 (0.52-1.51) | 0.650 |
E-cadherin | |||||||
Low | ≤ 270 | 119 | 45 (37.8) | 1 (reference) | 1 (reference) | ||
High | > 270 | 43 | 13 (30.2) | 0.69 (0.37-1.27) | 0.231 | 0.49 (0.26-0.91) | 0.025 |
ERCC1 | |||||||
Low | ≤ 130 | 63 | 31 (49.2) | 1 (reference) | 1 (reference) | ||
High | > 130 | 99 | 27 (27.3) | 0.5 (0.3-0.83) | 0.008 | 1.06 (0.63-1.8) | 0.818 |
Rb loss | |||||||
Low | ≤ 20 | 66 | 22 (33.3) | 1 (reference) | 1 (reference) | ||
High | > 20 | 96 | 36 (37.5) | 1.21 (0.71-2.06) | 0.478 | 1.85 (1.07-3.19) | 0.028 |
VEGF | |||||||
Low | ≤ 170 | 75 | 35 (46.7) | 1 (reference) | 1 (reference) | ||
High | > 170 | 87 | 23 (26.4) | 0.45 (0.27-0.77) | 0.003 | 0.66 (0.39-1.13) | 0.132 |
DFSb) (n=162, event=48) | |||||||
COX2 | |||||||
Low | < 300 | 110 | 27 (24.6) | 1 (reference) | 1 (reference) | ||
High | ≥ 300 | 52 | 21 (40.4) | 1.9 (1.08-3.37) | 0.027 | 1.55 (0.87-2.75) | 0.137 |
Cyclin D1 | |||||||
Low | ≤ 40 | 81 | 17 (21.0) | 1 (reference) | 1 (reference) | ||
High | > 40 | 81 | 31 (38.3) | 2.07 (1.15-3.75) | 0.016 | 2.16 (1.19-3.94) | 0.011 |
HMWCK | |||||||
Low | ≤ 130 | 88 | 34 (38.6) | 1 (reference) | 1 (reference) | ||
High | > 130 | 74 | 14 (18.9) | 0.39 (0.21-0.72) | 0.003 | 0.42 (0.22-0.79) | 0.007 |
PD-L1 | |||||||
Low | 0 | 157 | 45 (28.7) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 4.05 (1.25-13.16) | 0.020 | 2.26 (0.69-7.37) | 0.178 |
OSc) (n=162, event=19) | |||||||
E-cadherin | |||||||
Low | < 150 | 85 | 14 (16.5) | 1 (reference) | 1 (reference) | ||
High | > 150 | 77 | 5 (6.5) | 0.37 (0.13-1.02) | 0.055 | 0.34 (0.12-0.94) | 0.038 |
PD-L1 | |||||||
Low | 0 | 157 | 16 (10.2) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 17.2 (4.68-63.18) | < 0.001 | 13.42 (3.64-49.43) | < 0.001 |
IVRFS, intravescial recurrence-free survival; DFS, disease-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval; ERCC1, ERCC excision repair 1; Rb, retinoblastoma; VEGF, vascular endothelial growth factor; COX2, cytochrome coxidase II; HMWCK, high-molecular-weight heparin; PD-L1, programmed cell death 1 ligand.
a) Adjusted for intravesical instillation in multivariable bladder recurrence-free survival model,
b) Adjusted for intravesical instillation and pTstage in multivariable progression-free survival model,
c) Adjusted for pTstage in multivariable OS model.
Cut-point | No. (n=111) | Event (%) |
Univariable |
Multivariable |
|||
---|---|---|---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | ||||
BRFSa) (n=111, event=36) | |||||||
C-erb | |||||||
Low | 0 | 95 | 30 (31.6) | 1 (reference) | 1 (reference) | ||
High | > 0 | 16 | 6 (37.5) | 1.24 (0.52-2.99) | 0.629 | 2.55 (1.01-6.41) | 0.047 |
C-myc | |||||||
Low | ≤ 30 | 58 | 23 (39.7) | 1 (reference) | 1 (reference) | ||
High | > 30 | 53 | 13 (24.5) | 0.54 (0.27-1.06) | 0.072 | 1.02 (0.50-2.05) | 0.964 |
E-cadherin | |||||||
Low | ≤ 270 | 84 | 27 (32.1) | 1 (reference) | 1 (reference) | ||
High | > 270 | 27 | 9 (33.3) | 1.07 (0.50-2.27) | 0.867 | 1.28 (0.60-2.76) | 0.522 |
ERCC1 | |||||||
Low | ≤ 130 | 42 | 17 (40.5) | 1 (reference) | 1 (reference) | ||
High | > 130 | 69 | 19 (27.5) | 0.61 (0.32-1.17) | 0.138 | 1.23 (0.62-2.42) | 0.554 |
Rb | |||||||
Low | ≤ 20 | 43 | 12 (27.9) | 1 (reference) | 1 (reference) | ||
High | > 20 | 68 | 24 (35.3) | 1.37 (0.68-2.75) | 0.375 | 1.74 (0.85-3.54) | 0.129 |
VEGF | |||||||
Low | ≤ 170 | 47 | 19 (40.4) | 1 (reference) | 1 (reference) | ||
High | > 170 | 64 | 17 (26.6) | 0.57 (0.30-1.11) | 0.097 | 0.97 (0.50-1.89) | 0.925 |
DPFSb) (n=111, event=34) | |||||||
COX2 | |||||||
Low | < 300 | 71 | 18 (25.4) | 1 (reference) | 1 (reference) | ||
High | 300 | 40 | 16 (40.0) | 1.85 (0.94-3.63) | 0.074 | 1.53 (0.77-3.01) | 0.223 |
Cyclin D1 | |||||||
Low | ≤ 40 | 53 | 12 (22.6) | 1 (reference) | 1 (reference) | ||
High | > 40 | 58 | 22 (37.9) | 2.04 (1.01-4.14) | 0.048 | 2.33 (1.14-4.75) | 0.020 |
HMWCK | |||||||
Low | ≤ 130 | 59 | 22 (37.3) | 1 (reference) | 1 (reference) | ||
High | > 130 | 52 | 12 (23.1) | 0.50 (0.25-1.02) | 0.057 | 0.48 (0.24-0.99) | 0.047 |
PD-L1 | |||||||
Low | 0 | 106 | 31 (29.3) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 4.05 (1.22-13.48) | 0.023 | 2.32 (0.69-7.74) | 0.173 |
OSc) (n=111, event=17) | |||||||
E-cadherin | |||||||
Low | ≤ 150 | 57 | 12 (21.1) | 1 (reference) | 1 (reference) | ||
High | > 150 | 54 | 5 (9.3) | 0.41 (0.14-1.15) | 0.090 | 0.35 (0.12-0.99) | 0.048 |
PD-L1 | |||||||
Low | 0 | 106 | 14 (13.2) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 13.82 (3.64-52.49) | < 0.001 | 10.8 (2.83-41.25) | 0.001 |
BRFS, bladder recurrence-free survival; DPFS, disease progression-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval; C-erb, epidermal growth factor receptor; ERCC1, ERCC excision repair 1; Rb, retinoblastoma; VEGF, vascular endothelial growth factor; COX2, cytochrome c oxidase II; HMWCK, high-molecular-weight heparin; PD-L1, programmed cell death 1 ligand.
a) Adjusted for intravesical instillation in multivariable BRFS model,
b) Adjusted for age, intravesical instillation and pTstage in multivariable progression-free survival model,
c) Adjusted for pTstage in multivariable OS model.
Characteristic | No. (%) (n=162) |
---|---|
Follow-up duration, median (range, mo) | 53.4 (3.6-176.5) |
Age, mean±SD (yr) | 66.5±10.4 |
Body mass index, mean±SD (kg/m2) | 24.0±3.4 |
Sex | |
Male | 119 (73.5) |
Female | 43 (26.5) |
Hypertension | 74 (45.7) |
Diabetes | 22 (13.6) |
Other | 63 (38.9) |
ASA score | |
1 | 34 (22.4) |
2 | 105 (69.1) |
3 | 13 (8.5) |
Nephroureterectomy method | |
Open | 90 (55.6) |
Laparoscopy | 72 (44.4) |
Previous history | |
No | 111 (68.5) |
Previous bladder tumor history | 46 (28.4) |
Concomitant bladder tumor history | 5 (3.1) |
Intravesical instillation | 59 (36.4) |
Tumor location | |
Renal pelvis | 65 (40.4) |
Proximal | 7 (4.4) |
Mid | 18 (11.2) |
Distal | 38 (23.6) |
More than two sites | 33 (20.5) |
Tumor grade | |
I | 5 (3.3) |
II | 55 (36.2) |
III | 92 (60.5) |
ISUP | |
Low | 32 (21.1) |
High | 120 (78.9) |
Pathologic T category | |
Ta | 8 (5.0) |
T1 | 25 (15.7) |
T2 | 40 (25.2) |
T3 | 76 (47.8) |
T4 | 8 (5.0) |
CIS only | 2 (1.3) |
Pathologic N category | |
Nx | 96 (59.3) |
N0 | 53 (32.7) |
N1 | 10 (6.2) |
N2 | 3 (1.9) |
Tumor size (cm) | |
0-1.5 | 13 (8.1) |
1.5-2.5 | 27 (16.9) |
> 2.5 | 120 (75.0) |
Adjuvant chemotherapy | 72 (44.4) |
Bladder recurrence | 58 (35.8) |
Disease progression | 48 (29.6) |
Cause-specific death | |
Upper tract | 4 (21.1) |
Bladder | 2 (10.5) |
Others | 13 (68.4) |
Cut-point | No. (n=162) | Event (%) | Univariable |
Multivariable |
|||
---|---|---|---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | ||||
IVRFS |
|||||||
C-erb | |||||||
Low | 0 | 141 | 52 (36.9) | 1 (reference) | 1 (reference) | ||
High | > 0 | 21 | 6 (28.6) | 0.74 (0.32-1.72) | 0.483 | 2.59 (1.05-6.39) | 0.039 |
C-myc | |||||||
Low | ≤ 30 | 82 | 35 (42.7) | 1 (reference) | 1 (reference) | ||
High | > 30 | 80 | 23 (28.8) | 0.56 (0.33-0.95) | 0.031 | 0.88 (0.52-1.51) | 0.650 |
E-cadherin | |||||||
Low | ≤ 270 | 119 | 45 (37.8) | 1 (reference) | 1 (reference) | ||
High | > 270 | 43 | 13 (30.2) | 0.69 (0.37-1.27) | 0.231 | 0.49 (0.26-0.91) | 0.025 |
ERCC1 | |||||||
Low | ≤ 130 | 63 | 31 (49.2) | 1 (reference) | 1 (reference) | ||
High | > 130 | 99 | 27 (27.3) | 0.5 (0.3-0.83) | 0.008 | 1.06 (0.63-1.8) | 0.818 |
Rb loss | |||||||
Low | ≤ 20 | 66 | 22 (33.3) | 1 (reference) | 1 (reference) | ||
High | > 20 | 96 | 36 (37.5) | 1.21 (0.71-2.06) | 0.478 | 1.85 (1.07-3.19) | 0.028 |
VEGF | |||||||
Low | ≤ 170 | 75 | 35 (46.7) | 1 (reference) | 1 (reference) | ||
High | > 170 | 87 | 23 (26.4) | 0.45 (0.27-0.77) | 0.003 | 0.66 (0.39-1.13) | 0.132 |
DFS |
|||||||
COX2 | |||||||
Low | < 300 | 110 | 27 (24.6) | 1 (reference) | 1 (reference) | ||
High | ≥ 300 | 52 | 21 (40.4) | 1.9 (1.08-3.37) | 0.027 | 1.55 (0.87-2.75) | 0.137 |
Cyclin D1 | |||||||
Low | ≤ 40 | 81 | 17 (21.0) | 1 (reference) | 1 (reference) | ||
High | > 40 | 81 | 31 (38.3) | 2.07 (1.15-3.75) | 0.016 | 2.16 (1.19-3.94) | 0.011 |
HMWCK | |||||||
Low | ≤ 130 | 88 | 34 (38.6) | 1 (reference) | 1 (reference) | ||
High | > 130 | 74 | 14 (18.9) | 0.39 (0.21-0.72) | 0.003 | 0.42 (0.22-0.79) | 0.007 |
PD-L1 | |||||||
Low | 0 | 157 | 45 (28.7) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 4.05 (1.25-13.16) | 0.020 | 2.26 (0.69-7.37) | 0.178 |
OS |
|||||||
E-cadherin | |||||||
Low | < 150 | 85 | 14 (16.5) | 1 (reference) | 1 (reference) | ||
High | > 150 | 77 | 5 (6.5) | 0.37 (0.13-1.02) | 0.055 | 0.34 (0.12-0.94) | 0.038 |
PD-L1 | |||||||
Low | 0 | 157 | 16 (10.2) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 17.2 (4.68-63.18) | < 0.001 | 13.42 (3.64-49.43) | < 0.001 |
Cut-point | No. (n=111) | Event (%) | Univariable |
Multivariable |
|||
---|---|---|---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | ||||
BRFS |
|||||||
C-erb | |||||||
Low | 0 | 95 | 30 (31.6) | 1 (reference) | 1 (reference) | ||
High | > 0 | 16 | 6 (37.5) | 1.24 (0.52-2.99) | 0.629 | 2.55 (1.01-6.41) | 0.047 |
C-myc | |||||||
Low | ≤ 30 | 58 | 23 (39.7) | 1 (reference) | 1 (reference) | ||
High | > 30 | 53 | 13 (24.5) | 0.54 (0.27-1.06) | 0.072 | 1.02 (0.50-2.05) | 0.964 |
E-cadherin | |||||||
Low | ≤ 270 | 84 | 27 (32.1) | 1 (reference) | 1 (reference) | ||
High | > 270 | 27 | 9 (33.3) | 1.07 (0.50-2.27) | 0.867 | 1.28 (0.60-2.76) | 0.522 |
ERCC1 | |||||||
Low | ≤ 130 | 42 | 17 (40.5) | 1 (reference) | 1 (reference) | ||
High | > 130 | 69 | 19 (27.5) | 0.61 (0.32-1.17) | 0.138 | 1.23 (0.62-2.42) | 0.554 |
Rb | |||||||
Low | ≤ 20 | 43 | 12 (27.9) | 1 (reference) | 1 (reference) | ||
High | > 20 | 68 | 24 (35.3) | 1.37 (0.68-2.75) | 0.375 | 1.74 (0.85-3.54) | 0.129 |
VEGF | |||||||
Low | ≤ 170 | 47 | 19 (40.4) | 1 (reference) | 1 (reference) | ||
High | > 170 | 64 | 17 (26.6) | 0.57 (0.30-1.11) | 0.097 | 0.97 (0.50-1.89) | 0.925 |
DPFS |
|||||||
COX2 | |||||||
Low | < 300 | 71 | 18 (25.4) | 1 (reference) | 1 (reference) | ||
High | 300 | 40 | 16 (40.0) | 1.85 (0.94-3.63) | 0.074 | 1.53 (0.77-3.01) | 0.223 |
Cyclin D1 | |||||||
Low | ≤ 40 | 53 | 12 (22.6) | 1 (reference) | 1 (reference) | ||
High | > 40 | 58 | 22 (37.9) | 2.04 (1.01-4.14) | 0.048 | 2.33 (1.14-4.75) | 0.020 |
HMWCK | |||||||
Low | ≤ 130 | 59 | 22 (37.3) | 1 (reference) | 1 (reference) | ||
High | > 130 | 52 | 12 (23.1) | 0.50 (0.25-1.02) | 0.057 | 0.48 (0.24-0.99) | 0.047 |
PD-L1 | |||||||
Low | 0 | 106 | 31 (29.3) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 4.05 (1.22-13.48) | 0.023 | 2.32 (0.69-7.74) | 0.173 |
OS |
|||||||
E-cadherin | |||||||
Low | ≤ 150 | 57 | 12 (21.1) | 1 (reference) | 1 (reference) | ||
High | > 150 | 54 | 5 (9.3) | 0.41 (0.14-1.15) | 0.090 | 0.35 (0.12-0.99) | 0.048 |
PD-L1 | |||||||
Low | 0 | 106 | 14 (13.2) | 1 (reference) | 1 (reference) | ||
High | > 0 | 5 | 3 (60.0) | 13.82 (3.64-52.49) | < 0.001 | 10.8 (2.83-41.25) | 0.001 |
SD, standard deviation; ASA, American Society of Anesthesiologists; ISUP, International Society of Urologic Pathologists; CIS, carcinoma
IVRFS, intravescial recurrence-free survival; DFS, disease-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval; ERCC1, ERCC excision repair 1; Rb, retinoblastoma; VEGF, vascular endothelial growth factor; COX2, cytochrome coxidase II; HMWCK, high-molecular-weight heparin; PD-L1, programmed cell death 1 ligand. Adjusted for intravesical instillation in multivariable bladder recurrence-free survival model, Adjusted for intravesical instillation and pTstage in multivariable progression-free survival model, Adjusted for pTstage in multivariable OS model.
BRFS, bladder recurrence-free survival; DPFS, disease progression-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval; C-erb, epidermal growth factor receptor; ERCC1, ERCC excision repair 1; Rb, retinoblastoma; VEGF, vascular endothelial growth factor; COX2, cytochrome c oxidase II; HMWCK, high-molecular-weight heparin; PD-L1, programmed cell death 1 ligand. Adjusted for intravesical instillation in multivariable BRFS model, Adjusted for age, intravesical instillation and pTstage in multivariable progression-free survival model, Adjusted for pTstage in multivariable OS model.