Table 2.
Cox proportional hazards model for time to recurrence (TTR) in relation to clinicopathological factors and investigated immune cell markers and PD-L1TC.
| Unadjusted | Adjusted | ||||
|---|---|---|---|---|---|
| n(events) | HR (95% CI) | p-value | HR (95% CI) | p-value | |
| Age (continuous) | 145(57) | 1.04 (1.00–1.07) | 0.028 | 0.99 (0.95–1.04) | 0.723 |
| Sex | |||||
| Female | 30 (10) | 1.00 | 1.00 | ||
| Male | 115 (47) | 1.22 (0.62–2.42) | 0.564 | 2.42 (0.85–6.84) | 0.097 |
| Postoperative T-stage | |||||
| T0, Ta, CIS only | 44 (12) | 1.00 | 1.00 | ||
| T1 | 13 (3) | 0.81 (0.23–2.86) | 0.741 | 1.57 (0.14–17.57) | 0.713 |
| T2 | 29 (10) | 1.27 (0.55–2.93) | 0.583 | 2.74 (0.33–22.51) | 0.347 |
| T3 | 43 (21) | 2.25 (1.11–4.58) | 0.025 | 2.83 (0.36–22.19) | 0.321 |
| T4 | 16 (11) | 4.09 (1.80–9.31) | 0.001 | 3.46 (0.39–31.07) | 0.267 |
| N-stage | |||||
| N0 | 103 (30) | 1.00 | 1.00 | ||
| N1 | 16 (8) | 1.87 (0.86–4.08) | 0.117 | 3.88 (1.44–10.50) | 0.007 |
| N2 | 13 (9) | 4.56 (2.15–9.66) | <0.001 | 4.54 (1.64–12.58) | 0.004 |
| N3 | 13 (10) | 6.08 (2.93–12.60) | <0.001 | 12.11 (3.68–39.80) | <0.001 |
| M-stage | |||||
| M0 | 132 (49) | 1.00 | 1.00 | ||
| M1 | 3 (1) | 0.71 (0.10–5.13) | 0.733 | 1.20 (0.14–10.15) | 0.867 |
| LVI in cystectomy specimens | |||||
| No | 95 (40) | 1.00 | 1.00 | ||
| Yes | 7 (5) | 2.14 (0.84–5.42) | 0.110 | 1.87 (0.56–6.22) | 0.306 |
| Neoadjuvant chemotherapy | |||||
| No | 80 (40) | 1.00 | 1.00 | ||
| Yes | 65 (17) | 0.42 (0.24–0.74) | 0.003 | 0.32 (0.10–0.99) | 0.047 |
| Adjuvant chemotherapy | |||||
| No | 133 (51) | 1.00 | 1.00 | ||
| Yes | 12 (6) | 1.36 (0.58–3.16) | 0.481 | 0.25 (0.08–0.80) | 0.020 |
| TURB specimens (median cut off) | |||||
| CD8 | |||||
| Low | 85 (41) | 1.00 | 1.00 | ||
| High | 55 (15) | 0.48 (0.26–0.86) | 0.014 | 0.56 (0.30–1.07)* | 0.080 |
| FoxP3 | |||||
| Low | 74 (30) | 1.00 | 1.00 | ||
| High | 69 (26) | 0.88 (0.52–1.49) | 0.631 | 1.03 (0.60–1.78)* | 0.907 |
| CD20 | |||||
| Low | 77 (35) | 1.00 | 1.00 | ||
| High | 65 (21) | 0.65 (0.38–1.11) | 0.112 | 0.76 (0.43–1.37)* | 0.364 |
| PD-1 | |||||
| Low | 76 (36) | 1.00 | 1.00 | ||
| High | 68 (20) | 0.58 (0.33–1.00) | 0.049 | 0.62 (0.35–1.11)* | 0.105 |
| PD-L1IC | |||||
| Low | 77 (37) | 1.00 | 1.00 | ||
| High | 62 (19) | 0.58 (0.34–1.01) | 0.055 | 0.71 (0.39–1.27)* | 0.244 |
| PD-L1TC | |||||
| Low | 75 (35) | 1.00 | 1.00 | ||
| High | 64 (21) | 0.64 (0.37–1.10) | 0.108 | 1.21 (0.65–2.23)* | 0.548 |
| Cystectomy specimens (median cut off) | |||||
| CD8 | |||||
| Low | 50 (30) | 1.00 | 1.00 | ||
| High | 39 (12) | 0.39 (0.20–0.77) | 0.006 | 0.28 (0.13–0.60)* | 0.001 |
| FoxP3 | |||||
| Low | 47 (25) | 1.00 | 1.00 | ||
| High | 46 (19) | 0.63 (0.35–1.15) | 0.133 | 0.43 (0.22–0.84)* | 0.013 |
| CD20 | |||||
| Low | 47 (27) | 1.00 | 1.00 | ||
| High | 47 (16) | 0.52 (0.28–0.96) | 0.036 | 0.69 (0.34–1.37)* | 0.286 |
| PD-1 | |||||
| Low | 53 (33) | 1.00 | 1.00 | ||
| High | 42 (12) | 0.35 (0.18–0.68) | 0.002 | 0.34 (0.17–0.70)* | 0.003 |
| PD-L1IC | |||||
| Low | 41 (26) | 1.00 | 1.00 | ||
| High | 40 (15) | 0.52 (0.27–0.98) | 0.042 | 0.47 (0.23–0.95)* | 0.036 |
| PD-L1TC | |||||
| Low | 42 (26) | 1.00 | 1.00 | ||
| High | 39 (15) | 0.50 (0.27–0.95) | 0.034 | 0.59 (0.30–1.17)* | 0.130 |
| TURB specimens (CRT-derived cut off) | |||||
| CD8 | |||||
| Low | 109 (52) | 1.00 | 1.00 | ||
| High | 31 (4) | 0.21 (0.08–0.58) | 0.003 | 0.27 (0.09–0.76)* | 0.014 |
| FoxP3 | |||||
| Low | 23 (14) | 1.00 | 1.00 | ||
| High | 120 (42) | 0.50 (0.27–0.91) | 0.023 | 0.77 (0.39–1.52)* | 0.448 |
| CD20 | |||||
| Low | 136 (56) | 1.00 | - | ||
| High | 6 (0) | 0.05 (0.00–8.60) | 0.248 | - | - |
| PD-1 | |||||
| Low | 128 (56) | 1.00 | - | ||
| High | 16 (0) | 0.04 (0.00–1.10) | 0.057 | - | - |
| PD-L1IC | |||||
| Low | 80 (40) | 1.00 | 1.00 | ||
| High | 59 (16) | 0.48 (0.27–0.86) | 0.013 | 0.57 (0.31–1.06)* | 0.075 |
| PD-L1TC | |||||
| Low | 130 (56) | 1.00 | - | ||
| High | 9 (0) | 0.04 (0.00–2.68) | 0.136 | - | - |
| Cystectomy specimens (CRT-derived cut off) | |||||
| CD8 | |||||
| Low | 42 (29) | 1.00 | 1.00 | ||
| High | 47 (13) | 0.27 (0.14–0.52) | <0.001 | 0.17 (0.08–0.35)* | <0.001 |
| FoxP3 | |||||
| Low | 30 (20) | 1.00 | 1.00 | ||
| High | 63 (24) | 0.41 (0.22–0.74) | 0.003 | 0.35 (0.18–0.69)* | 0.002 |
| CD20 | |||||
| Low | 15 (12) | 1.00 | 1.00 | ||
| High | 79 (31) | 0.26 (0.13–0.50) | <0.001 | 0.25 (0.12–0.55)* | 0.001 |
| PD-1 | |||||
| Low | 64 (38) | 1.00 | 1.00 | ||
| High | 31 (7) | 0.29 (0.13–0.65) | 0.003 | 0.23 (0.10–0.54)* | 0.001 |
| PD-L1IC | |||||
| Low | 61 (36) | 1.00 | 1.00 | ||
| High | 20 (5) | 0.35 (0.14–0.89) | 0.027 | 0.30 (0.11–0.82)* | 0.018 |
| PD-L1TC | |||||
| Low | 70 (40) | 1.00 | 1.00 | ||
| High | 11 (1) | 0.11 (0.02–0.80) | 0.029 | 0.15 (0.02–1.15)* | 0.068 |
LVI = Lymphovascular invasion. * Hazard ratios from multivariable analysis adjusted for age (continuous), postoperative T-stage, N-stage, neoadjuvant and adjuvant chemotherapy. Bold text indicates significant hazard ratios (p < 0.05). ”-” = statistical analyses could not be performed, due to no denoted recurrent disease after radical cystectomy in patients with high density (based on CRT-derived cut off values) of CD20+ and PD-1+ immune cells and PD-L1+ tumor cells in TURB specimens.