High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Cohort
2.2. Serum PD-L1 and MMP-7 Analyses
2.3. Statistical Analysis
3. Results
3.1. Clinical Background
3.2. Correlations of PD-L1 Concentrations with Clinicopathological Parameters
3.3. Correlation of Pretreatment sPD-L1 Levels with Patients’ Prognosis
3.4. Changes in sPD-L1 Levels during and after Therapy
3.5. Correlation between sPD-L1 and sMMP-7 Levels
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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RNU | CTX | ICI | ||||||
---|---|---|---|---|---|---|---|---|
General data | n | median (range) | p | n | median (range) | p | n | median (range) |
Age at baseline, median (range) | 34 | 68.9 (46.0–90.0) | - | 25 | 72.0 (46.0–84.0) | - | 6 | 64.5 (50.0–76.0) |
Follow-up in months, median (range) | 34 | 24.2 (1.1–81.9) | - | 25 | 17.6 (1.1–67.7) | - | 6 | 20.4 (2.6–28.3) |
Number of patients died | 11 | - | - | 13 | - | - | 2 | - |
Parameters/sPD-L1 concentrations | n | sPD-L1 cc. | p | n | sPD-L1 cc. | p | n | sPD-L1 cc. |
Total No. of patients, median (range) | 34 | 84.0 (49.9–172.3) | 0.347 | 25 | 96.1 (53.1–152.9) | - | 6 | 78.3 (42.17–192.1) |
Non-malignant * | 3 | 68.4 (65.6–83.2) | ||||||
Age ≤ 65 | 10 | 77.3 (49.9–162.4) | 0.183 | 5 | 78.6 (53.1–139.5) | 0.408 | 3 | 94.8 (61.9–122.9) |
Age > 65 | 24 | 91.4 (59.3–172.3) | 20 | 99.4 (65.0–152.9) | 3 | 57.2 (42.2–192.1) | ||
Sex male | 21 | 93.7 (49.9–172.3) | 0.600 | 21 | 102.7 (53.1–152.9) | 0.452 | 5 | 94.8 (57.2–192.1) |
female | 13 | 80.7 (57.9–166.1) | 4 | 93.9 (65.0–106.8) | 1 | 42.2 | ||
ECOG PS 0 | 19 | 80.6 (50.1–166.1) | - | 11 | 89.0 (53.1–128.8) | - | 5 | 61.9 (42.2–192.1) |
1 | 10 | 89.8 (49.9–162.4) | - | 10 | 103.9 (65.0–139.5) | - | 0 | - |
2 | 4 | 98.4 (73.1–172.3) | - | 4 | 107.7 (105.6–152.9) | - | 0 | - |
3 | 1 | 119.6 | - | 0 | - | - | 1 | 122.9 |
ECOG PS 0–1 | 29 | 80.7 (49.9–166.1) | 0.149 | 21 | 91.8 (53.1–139.5) | 0.132 | 5 | 61.9 (42.2–192.1) |
ECOG PS 2–3 | 5 | 106.7 (73.1–172.3) | 4 | 107.7 (105.6–152.9) | 1 | 122.9 | ||
Localization Ureter | 17 | 70.2 (50.1–166.1) | 0.088 | 13 | 90.82 (53.1–152.9) | 0.298 | 2 | 68.5 (42.2–94.8) |
Pyelon | 10 | 90.9 (61.7–172.3) | 12 | 106.2 (65.0–139.5) | 3 | 122.9 (61.9–192.1) | ||
Both | 7 | 97.4 (49.9–155.3) | 0 | 1 | 57.2 | |||
RNU data | ||||||||
pT0 | 3 | 68.4 (65.6–83.2) | - | - | - | - | - | - |
pTa | 7 | 70.2 (50.1–111.7) | - | 0 | - | - | - | - |
CIS | 1 | 57.9 | - | 0 | - | - | 1 | 57.2 |
pT1 | 9 | 68.9 (49.9–113.3) | - | 1 | 135.3 | - | 1 | 122.9 |
pT2 | 2 | 110.0 (64.1–155.3) | - | 6 | 80.0 (68.3–128.8) | - | 1 | 94.78 |
pT3 | 14 | 102.0 (72.7–172.3) | - | 14 | 99.4 (53.1–152.9) | - | 3 | 61.9 (42.2–192.1) |
pT4 | 1 | 126.8 | - | 2 | 92.5 (89.02–96.1) | - | 0 | - |
n.a. | 0 | 2 | 0 | |||||
pTa-pT1-CIS (non-invasive) | 17 | 69.4 (49.9–113.3) | <0.001 | 1 | 135.3 | - | 2 | 90 (57.2–122.9) |
pT2-pT4 (invasive) | 17 | 106.7 (64.6–172.3) | 22 | 93.9 (53.1–152.9) | 4 | 78.3 (42.2–192.1) | ||
G1 | 7 | 62.5 (49.9–85.9) | - | 0 | - | - | 0 | - |
G2 | 12 | 87.3 (59.3–117.3) | - | 5 | 96.1 (68.3–135.3) | 0.951 | 3 | 94.8 (61.9–122.9) |
G3 | 15 | 97.4 (57.9–172.3) | - | 16 | 99.4 (53.1–152.9) | - | 2 | 124.6 (57.2–192.1) |
n.a. | 0 | 4 | 1 | |||||
G1–G2 | 19 | 80.6 (49.9–117.3) | 0.019 | - | - | 3 | 94.8 (61.9–122.9) | |
G3 | 15 | 97.4 (57.9–172.3) | - | - | 2 | 124.6 (57.2–192.1) | ||
R0 | 26 | 81.3 (49.9–166.1) | 0.368 | 14 | 104.2 (65.0–139.5) | 0.305 | 4 | 76.0 (42.2–192.1) |
R+ | 8 | 91.9 (64.6–172.3) | 9 | 89.0 (53.1–152.9) | 1 | 61.9 | ||
n.a. | 0 | 2 | 1 | 122.9 | ||||
Metastatic status at RNU | ||||||||
N0/M0 | 25 | 76.8 (49.9–155.3) | 0.002 | 14 | 86.0 (53.1–134.5) | 0.096 | 2 | 76.0 (57.2–94.8) |
N+ or M+ | 9 | 119.6 (73.1–172.3) | 9 | 102.7 (78.6–152.9) | 3 | 61.9 (42.2–192.1) | ||
n.a. | 0 | 2 | 1 | |||||
Metastatic status at CTX baseline | ||||||||
M0 | - | - | - | 10 | 76.2 (53.1–134.5) | <0.001 | - | - |
M+ | - | - | - | 14 | 110.2 (78.6–152.9) | - | - | |
n.a. | - | - | - | 1 | - | - | - | |
CTX regimen | ||||||||
Gem/Cis | - | - | - | 14 | 89.9 (53.1–125.9) | 0.013 | - | - |
Gem/Carbo | - | - | - | 11 | 111.8 (78.6–152.9) | - | - |
Pat. 1 | Pat. 2 | Pat. 3 | Pat. 4 | Pat. 5 | Pat. 6 | |
---|---|---|---|---|---|---|
Age | 76 | 64 | 64 | 75 | 65 | 50 |
Sex | Female | Male | Male | Male | Male | Male |
Clinicopath. parameters at RNU | ||||||
Stage (pT) | 3 | 2 | 3 | CIS | 3 | 1 |
Grade (G) | - | 2 | 2 | 3 | 3 | 2 |
N+ | yes | no | yes | no | Yes | no |
M+ | no | no | no | no | No | unknown |
Pre-ICI CTX treatment | Gem/Car | Gem/Cis | Gem/Car | n.a. | Gem/Car | Gem/Cis |
Clinicopath. parameters at ICI baseline | ||||||
ICI-treatment | Atezo | Atezo | Atezo | Atezo | Atezo | Pembro |
N+ | yes | yes | yes | no | Yes | unknown |
M+ | yes | yes | no | no | Yes | yes |
sPD-L1 at baseline (pg/mL) | 42.2 | 94.8 | 61.9 | 57.2 | 192.1 | 122.9 |
sPD-L1 at 3 months (pg/mL) | 1903 | 1939 | 1993 | Unknown | 1972 | n.a. |
OS (months) | 14.4 | 30.2 | 28.4 | 28.0 | 9.9 | 2.6 |
status | alive | alive | alive | alive | dead | dead |
Objective response | PD | PD | PD | PD | PD | unknown |
RNU | CTX | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OS | PFS | OS | PFS | |||||||||||
n | HR | 95% CI | p | HR | 95% CI | p | n | HR | 95% CI | p | HR | 95% CI | p | |
Pretreatment sPD-L1 | ||||||||||||||
median cut-off * | 17 | ref. | ref. | 11 | ref. | ref. | ||||||||
median cut-off * | 17 | 4.023 | 1.060–15.269 | 0.041 | 2.793 | 1.011–7.716 | 0.048 | 14 | 6.956 | 1.461–33.110 | 0.015 | 1.584 | 0.560–4.478 | 0.386 |
ROC cut-off ** | 27 | ref. | ref. | 11 | ref. | ref. | ||||||||
ROC cut-off ** | 7 | 12.114 | 2.990–49.082 | <0.001 | 6.667 | 2.140–20.764 | 0.001 | 14 | 6.956 | 1.461–33.110 | 0.015 | 1.584 | 0.560–4.478 | 0.386 |
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Széles, Á.; Kovács, P.T.; Csizmarik, A.; Váradi, M.; Riesz, P.; Fazekas, T.; Váncsa, S.; Hegyi, P.; Oláh, C.; Tschirdewahn, S.; et al. High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma. Biomedicines 2022, 10, 2560. https://doi.org/10.3390/biomedicines10102560
Széles Á, Kovács PT, Csizmarik A, Váradi M, Riesz P, Fazekas T, Váncsa S, Hegyi P, Oláh C, Tschirdewahn S, et al. High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma. Biomedicines. 2022; 10(10):2560. https://doi.org/10.3390/biomedicines10102560
Chicago/Turabian StyleSzéles, Ádám, Petra Terézia Kovács, Anita Csizmarik, Melinda Váradi, Péter Riesz, Tamás Fazekas, Szilárd Váncsa, Péter Hegyi, Csilla Oláh, Stephan Tschirdewahn, and et al. 2022. "High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma" Biomedicines 10, no. 10: 2560. https://doi.org/10.3390/biomedicines10102560