Introduction
Patients and methods
Study population
Study endpoints
Statistical analysis
Results
Baseline characteristics
Patients (n = 836) | |
---|---|
Sex | |
Male | 613 (73) |
Female | 223 (27) |
Age, years (y) | |
Median | 71 |
Range | 26 − 95 |
Interquartile ranges: | |
26–63 | 189 |
64–70 | 229 |
71–76 | 214 |
77–95 | 204 |
ECOG Performance Status | |
0 | 268 (32) |
1 | 425 (51) |
2 | 132 (16) |
3 | 11 (1) |
Current or former smokers | 549(66) |
Primary tumor location | |
Upper urinary tract | 220 (26) |
Lower urinary tract | 616 (74) |
Tumor histology | |
Pure urothelial carcinoma | 702 (84) |
Variants | 134 (16) |
Metastatic disease | |
Synchronous | 254 (30) |
Metachronous | 582 (70) |
Common sites of metastasis | |
Lymph nodes | 586 (70) |
Lung | 280 (33) |
Bone | 243 (29) |
Liver | 152 (18) |
Brain | 15 (2) |
Visceral metastases | |
Yes | 555 (66) |
No | 281 (34) |
Patients progressed during first-line platinum-based chemotherapy (cohort A) | 544 (65) |
Patients relapsed within < 1y since the completion of neoadjuvant/adjuvant chemotherapy (cohort B) | 292 (35) |
Successive therapies (cohort A) | |
Paclitaxel | 46 (6) |
Vinflunine | 30 (4) |
Carboplatin and Gemcitabine | 6 (1) |
Enfortumab vedotin | 6 (1) |
Clinical trials | 6 (1) |
Carboplitn and paclitaxel | 5 (1) |
Docetaxel | 4 (< 1) |
Gemcitabine | 3 (< 1) |
Carboplatin | 1 (< 1) |
MVAC | 1 (< 1) |
Successive therapies (cohort B) | |
Vinflunine | 14 (2) |
Paclitaxel | 12 (1) |
Carboplatin and Gemcitabine | 10 (1) |
Clinical trials | 7 (1) |
Enfortumab vedotin | 4 (< 1) |
Gemcitabine and Palitaxel | 4 (< 1) |
MVAC | 2 (< 1) |
Cyclphosphamide | 2 (< 1) |
Carboplitn and paclitaxel | 1 (< 1) |
Gemcitabine | 1 (< 1) |
Carboplatin | 1 (< 1) |
Survival analysis
Response to therapy
Role of prognostic factors
Overall survival | Univariate Cox regression | Multivariate Cox regression | ||
---|---|---|---|---|
HR (95%CI) | p-value | HR (95%CI) | p-value | |
Gender (females vs males) | 1.23(1.01 − 1.50) | 0.046 | 1.21 (0.98 − 1.50) | 0.080 |
Age (≥ 65y vs < 65y) | 1.06 (0.86 − 1.31) | 0.581 | ||
Smokers vs non-smokers | 0.82 (0.67 − 0.99) | 0.037 | 0.87 (0.71 − 1.06) | 0.166 |
ECOG-PS (≥ 2 vs 0–1) | 2.71 (2.18 − 3.38) | < 0.001 | 2.56(2.04 − 3.20) | < 0.001 |
Histology (mixed vs pure UC) | 1.08 (0.86 − 1.36) | 0.511 | ||
Upper vs Lower urinary tract | 1.12 (0.91 − 1.37) | 0.287 | ||
Synchronous metastatic disease (yes vs no) | 1.36 (1.12 − 1.66) | 0.002 | 1.15 (0.94 − 1.41) | 0.173 |
Lymph node (Y vs N) | 0.87 (0.71 − 1.07) | 0.183 | ||
Lung metastases (Y vs N) | 1.20 (0.99–1.45) | 0.069 | ||
Liver metastases (Y vs N) | 1.49 (1.19 − 1.86) | < 0.001 | 1.45 (1.14 − 1.85) | 0.003 |
Bone metastases (Y vs N) | 1.59 (1.30 − 1.93) | < 0.001 | 1.32 (1.06 − 1.67) | 0.014 |
Patients progressed during first-line therapy vs recurred within < 1y from adjuvant/neoadjuvant therapy | 1.47 (1.20 − 1.80) | < 0.001 | 1.42 (1.15 − 1.75) | < 0.001 |
Progression-free survival | Univariate Cox regression | Multivariate Cox regression | ||
---|---|---|---|---|
HR (95%CI) | p-value | HR (95%CI) | p-value | |
Gender (females vs males) | 0.99 (0.81 − 1.20) | 0.923 | ||
Age (≥ 65y vs < 65y) | 0.93 (0.77 − 1.12) | 0.440 | ||
Smokers vs non-smokers | 0.93 (0.78 − 1.12) | 0.442 | ||
ECOG-PS (≥ 2 vs 0–1) | 2.02 (1.63 − 2.51) | < 0.001 | 1.93 (1.55 − 2.40) | < 0.001 |
Histology (mixed vs pure UC) | 1.04 (0.84 − 1.29) | 0.737 | ||
Upper vs Lower urinary tract | 1.06 (0.87 − 1.28) | 0.576 | ||
Synchronous metastatic disease (yes vs no) | 1.26 (1.05 − 1.51) | 0.014 | 1.13 (0.94 − 1.36) | 0.210 |
Lymph node metastases (Y vs N) | 0.89 (0.74 − 1.07) | 0.222 | ||
Lung metastases (Y vs N) | 1.14 (0.96 − 1.37) | 0.138 | ||
Liver metastases (Y vs N) | 1.52 (1.24 − 1.88) | < 0.001 | 1.43 (1.15 − 1.79) | 0.002 |
Bone metastases (Y vs N) | 1.52 (1.27 − 1.83) | < 0.001 | 1.27 (1.03 − 1.62) | 0.028 |
Patients progressed during first-line therapy vs recurred within < 1y from adjuvant/neoadjuvant therapy | 1.40 (1.15 − 1.69) | < 0.001 | 1.33 (1.10 − 1.62) | 0.003 |