Baseline characteristics of included patients
According to the inclusion and exclusion criteria, 191 patients including 166 (86.9%) males and 25 (13.1%) females with BC who received radical cystectomy were finally included in the study. The median follow-up time was 43.23 months (interquartile range, 27.03 to 74.77 months) of whole cohort. A total of 191 patients were then divided into the training cohort (n = 135) and the validation cohort (n = 56) randomly. The median age was 71 years and 69 years in the training cohort and the validation cohort. The clinicopathological characteristics of patients in the study are listed in Table 1. For the results acquired from X-tile software, the optimal cutoff values were 3.1, 202.2, 3.4 and 46.5 for NLR, PLR, LMR and PNI (Fig. 2).
Table 1
Clinicopathological characteristics of patients
Variable | Training cohort (n = 135) | Validation cohort (n = 56) |
---|
| No. of patients (%) | No. of patients (%) |
Gender | | |
Male | 116 (85.9) | 50 (89.3) |
Female | 19 (14.1) | 6 (10.7) |
Age | | |
Median | 71 | 69 |
Range | 38–85 | 37–85 |
ASA | | |
≤ 2 | 119 (88.1) | 9 (16.1) |
> 2 | 16 (11.9) | 47 (83.9) |
Hydronephrosis | | |
Yes | 33 (24.4) | 22 (39.3) |
No | 102 (75.6) | 34 (60.7) |
Grade | | |
High | 119 (88.1) | 48 (85.7) |
Low | 16 (11.9) | 8 (14.3) |
History of smoking | 21 (15.6) | 14 (25.0) |
hypertension | 51 (37.8) | 30 (53.6) |
diabetes | 23 (17.0) | 15 (26.8) |
Multiplicity | | |
Yes | 84 (62.2) | 32 (57.1) |
No | 51 (37.8) | 24 (42.9) |
Stage_T | | |
T1/a/is | 70 (51.9) | 27 (48.2) |
T2 | 37 (27.4) | 16 (28.6) |
T3 | 17 (12.6) | 10 (17.9) |
T4 | 11 (8.1) | 3 (5.3) |
Stage_N | | |
Positive | 20 (14.8) | 14 (25.0) |
Negative | 115 (85.2) | 42 (75.0) |
EGFR | | |
Positive | 54 (40.0) | 19 (33.9) |
Negative | 81 (60.0) | 37 (66.1) |
LVI | | |
Yes | 41 (30.4) | 19 (33.9) |
No | 94 (69.6) | 37 (66.1) |
Abbreviations: ASA, American society of anesthesiologists; EGFR, epidermal growth factor receptor; LVI, lymphovascular invasion. |
Tumor recurrence and OS in the training cohort
In the training cohort, the median OS time was 63.5 months, and postoperative 1-, 3-, 5-year OS rates were 87.7%, 63.9% and 55.8%. The median DFS was 63.3 months, and the 1-, 3-, and 5-year DFS rates were 84.6%, 64.3%, and 58.7%, respectively. Univariate analysis showed that preoperative hydronephrosis, Stage_T, Stage_N, PNI, EGFR, tumor size, LVI, NLR, PLR and LMR were associated with OS. Meanwhile, hydronephrosis, Stage_T, Stage_N, ASA, EGFR, LVI, PNI, diabetes were associated with DFS (Table 2).
Table 2
Univariate analysis of variables for OS and DFS in the training cohort
Variable | OS | DFS |
---|
| HR | 95%CI | P value | HR | 95% | P value |
Gender (male vs female ) | 0.740 | 0.248–2.203 | 0.588 | 2.382 | 0.851–6.667 | 0.098 |
Age (> 65 vs ≤ 65 years) | 1.037 | 0.991–1.085 | 0.116 | 1.015 | 0.760–1.358 | 0.916 |
ASA (> 2 vs ≤ 2) | 2.207 | 0.873–5.581 | 0.094 | 2.108 | 1.014–4.379 | 0.046 |
Hydronephrosis (yes vs no) | 4.767 | 2.007–11.323 | < 0.001 | 2.578 | 1.395–4.765 | 0.003 |
Grade (high vs low) | 6.500 | 0.873–48.388 | 0.068 | 2.081 | 0.645–6.716 | 0.220 |
Multiplicity (yes vs no) | 0.678 | 0.305–1.508 | 0.341 | 0.883 | 0.488–1.597 | 0.680 |
Size (> 3 vs ≤ 3) | 3.137 | 1.380–7.133 | 0.006 | 1.408 | 0.781–2.537 | 0.255 |
Smoke (yes vs no) | 0.316 | 0.094–1.063 | 0.063 | 0.702 | 0.297–1.658 | 0.419 |
Hypertension (yes vs no) | 0.950 | 0.431–2.094 | 0.899 | 0.618 | 0.328–1.166 | 0.138 |
Diabetes (yes vs no) | 0.913 | 0.379–2.197 | 0.839 | 2.169 | 1.117–4.204 | 0.022 |
Stage_T (2 ≥ vs < 2) | 2.826 | 1.848–4.322 | < 0.001 | 2.301 | 1.740–3.042 | < 0.001 |
Stage_N (positive vs negative) | 7.792 | 3.410−17.806 | < 0.001 | 6.599 | 3.509–12.410 | < 0.001 |
EGFR (positive vs negative) | 2.679 | 1.215–5.910 | 0.015 | 2.586 | 1.423–4.701 | 0.002 |
LVI (yes vs no) | 27.269 | 7.838–94.876 | < 0.001 | 5.643 | 3.071–10.370 | < 0.001 |
PNI (high vs low) | 0.040 | 0.005–0.299 | 0.002 | 0.133 | 0.056–0.314 | < 0.001 |
NLR (high vs low) | 2.541 | 1.156–5.587 | 0.020 | 1.322 | 0.701–2.492 | 0.389 |
PLR (high vs low) | 3.142 | 1.378–7.163 | 0.006 | 1.854 | 0.984–3.491 | 0.056 |
LMR (high vs low) | 0.368 | 0.166–0.815 | 0.014 | 0.699 | 0.389–1.256 | 0.231 |
ALB (high vs low) | 0.688 | 0.302–1.568 | 0.374 | 0.602 | 0.329–1.103 | 0.101 |
LDH (high vs low) | 2.059 | 0.748–5.670 | 0.162 | 0.741 | 0.312–1.760 | 0.497 |
Independent prognostic factors of survival in the training cohort
In multivariate analysis (Table 3), the results revealed that hydronephrosis, Stage_T, Stage_N, PNI and EGFR were independent risk factors for OS. While Stage_T, Stage_N, PNI and EGFR were significantly associated with DFS. The OS of patients was shown in Fig. 3.
Table 3
Multivariate analysis of variables for OS and DFS in the training cohort
| OS | DFS |
---|
Variable | HR | 95%CI | P value | HR | 95% | P value |
Hydronephrosis (yes vs no) | 1.708 | 1.005–2.903 | 0.048 | - | - | - |
Stage_T T1/is/a | Reference | | | Reference | | |
T2 | 2.420 | 1.100−5.325 | 0.028 | 2.795 | 1.270–6.150 | 0.011 |
T3 | 3.923 | 1.734–8.877 | 0.001 | 2.514 | 1.029–6.140 | 0.043 |
T4 | 4.391 | 1.470−13.117 | 0.008 | 4.290 | 1.605–11.468 | 0.004 |
Stage_N (positive vs negative) | 2.681 | 1.564–4.594 | 0.003 | 3.358 | 1.523–7.402 | 0.003 |
EGFR (positive vs negative) | 1.947 | 1.072–3.534 | 0.029 | 2.381 | 1.261–4.497 | 0.007 |
PNI (high vs low) | 0.310 | 0.136–0.707 | 0.011 | 0.242 | 0.098–0.599 | 0.002 |
Development of a prognostic nomogram
The prognostic nomogram of OS and DFS that included all significant independent factors in the training cohort were shown in Fig. 4. The C-index for OS and DFS prediction value was 0.834 (95% CI: 0.785–0.833), and 0.823 (95% CI: 0.772–0.873), respectively. A calibration plot of survival rate at 3 or 5 years after surgery showed a great agreement between prediction and actual observation (Fig. 5A-D).
Validation of a prognostic nomogram
In the validation cohort, the median OS time was 54.23 months and the postoperative 1-, 3-, 5-year OS rates were 79.3%, 56.1% and 47.8%, respectively. The median DFS was 54.23 months, and the 1-, 3-, and 5-year DFS rates were 75.4%, 58.3%, and 47.7%, respectively. The C-index of the nomogram for predicting OS and DFS was 0.834 (95% CI: 0.796–0.926) and 0.856 (95% CI: 0.787–0.925), Which showed a superiority compared to the AJCC staging system (0.812; 95% CI: 0.724-0.900 and 0.811; 95% CI: 0.727–0.895). The calibration curve showed a good accordance between prediction and observation in the probability of 5-year survival of OS and DFS (Fig. 5E-F).