Author Contributions
Conceptualization, K.S. and K.M.; methodology, K.S., K.M., and S.M.; software, K.S. and K.M.; validation, S.M. and T.K.; formal analysis, K.S. and K.M.; investigation, K.S. and K.M.; resources, K.S. and K.M.; data curation, N.T., Y.Y., and T.T.; writing—original draft preparation, K.S. and K.M.; writing—review and editing, K.S. and K.M.; visualization, K.S. and K.M.; supervision, R.M., E.K., and M.O.; project administration, K.M.; funding acquisition, K.S. and K.M. All authors have read and agreed to the published version of the manuscript.
Figure 1.
(a) Representative immunohistochemistry (IHC) staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens; pTa low-grade upper tract urothelial carcinoma (UTUC) patients (upper panel) and pT3 high-grade UTUC patients (lower panel). The field scale bar = 200 µm. (b) Heatmap describing the IHC score of FGFR3, p53, CK5/6, and CK20 in UTUC patients (n = 214). Heatmap is divided by pT2 or low (n = 116) and pT3 or high (n = 98). The histoscore (H-score) was calculated by applying the following formula: mean percentage × intensity (range 0–300). (c) Table describing the rate of high expression group in each molecular biomarker. Expression rates were compared between patients who developed intravesical recurrence (IVR) and who did not develop IVR after radical nephroureterectomy (RNU). Chi-squared test was used to assess the significance of differences. (d) K–M curves comparing the IVR free survival rates in UTUC patients compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. (e) A schema describing the molecular characteristics of UTUC that are likely to develop IVR. As the multivariate analysis revealed, CK20 high and CK5/6 low expression tumor specimens were the independent risk factors for developing IVR after radical nephroureterectomy.
Figure 1.
(a) Representative immunohistochemistry (IHC) staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens; pTa low-grade upper tract urothelial carcinoma (UTUC) patients (upper panel) and pT3 high-grade UTUC patients (lower panel). The field scale bar = 200 µm. (b) Heatmap describing the IHC score of FGFR3, p53, CK5/6, and CK20 in UTUC patients (n = 214). Heatmap is divided by pT2 or low (n = 116) and pT3 or high (n = 98). The histoscore (H-score) was calculated by applying the following formula: mean percentage × intensity (range 0–300). (c) Table describing the rate of high expression group in each molecular biomarker. Expression rates were compared between patients who developed intravesical recurrence (IVR) and who did not develop IVR after radical nephroureterectomy (RNU). Chi-squared test was used to assess the significance of differences. (d) K–M curves comparing the IVR free survival rates in UTUC patients compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. (e) A schema describing the molecular characteristics of UTUC that are likely to develop IVR. As the multivariate analysis revealed, CK20 high and CK5/6 low expression tumor specimens were the independent risk factors for developing IVR after radical nephroureterectomy.
Figure 2.
(a) Representative IHC staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens after transurethral resection of bladder tumor (TURBT); pTa low-grade IVR specimen, pT1 high-grade IVR specimen, and pT2 high-grade IVR specimen are shown, respectively. Low-power field scale bar = 500 µm, and high-power field scale bar = 100 µm. (b) Heatmap describing the IHC score of FGFR3, p53, CK5/6, and CK20 in transurethral resection (TUR) specimens after IVR (n = 94). Heatmap is divided by pTa (n = 35), pT1 (n = 41), and pT2 or higher (n = 18). The H-score was calculated by applying the following formula: mean percentage × intensity (range 0–270). (c) Graph showing the transition of four molecular markers’ expressions classified with pathological T stage. P53 and CK5/6 showed significantly higher expressions at muscle-invasive stage (pT2) than that of non-muscle-invasive stage (pTa and/or pT1; p = 0.001, p = 0.035), while CK20 expression decreased as the tumor stage progressed to MIBC (p = 0.072). No significant differences were observed in FGFR3 expression along with tumor stage progression (p = 0.822). (d) K–M curves comparing the bladder cancer progression free survival rates in UTUC patients who developed IVR compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. (e) A schema describing the transition of molecular characteristics of IVR specimen. At the time of bladder tumor recurrence, CK20 high and CK5/6 low expressions (luminal-like) occupy the majority of IVR specimen. In the process of MIBC progression, however, the high CK20 expression rate decreased as it progressed to muscle invasive, whereas the high CK5/6 expression rate increased (basal-like). Schema suggests the concept of “luminal–basal shift” with p53 addition from low stage bladder tumor recurrence to high stage bladder tumor progression.
Figure 2.
(a) Representative IHC staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens after transurethral resection of bladder tumor (TURBT); pTa low-grade IVR specimen, pT1 high-grade IVR specimen, and pT2 high-grade IVR specimen are shown, respectively. Low-power field scale bar = 500 µm, and high-power field scale bar = 100 µm. (b) Heatmap describing the IHC score of FGFR3, p53, CK5/6, and CK20 in transurethral resection (TUR) specimens after IVR (n = 94). Heatmap is divided by pTa (n = 35), pT1 (n = 41), and pT2 or higher (n = 18). The H-score was calculated by applying the following formula: mean percentage × intensity (range 0–270). (c) Graph showing the transition of four molecular markers’ expressions classified with pathological T stage. P53 and CK5/6 showed significantly higher expressions at muscle-invasive stage (pT2) than that of non-muscle-invasive stage (pTa and/or pT1; p = 0.001, p = 0.035), while CK20 expression decreased as the tumor stage progressed to MIBC (p = 0.072). No significant differences were observed in FGFR3 expression along with tumor stage progression (p = 0.822). (d) K–M curves comparing the bladder cancer progression free survival rates in UTUC patients who developed IVR compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. (e) A schema describing the transition of molecular characteristics of IVR specimen. At the time of bladder tumor recurrence, CK20 high and CK5/6 low expressions (luminal-like) occupy the majority of IVR specimen. In the process of MIBC progression, however, the high CK20 expression rate decreased as it progressed to muscle invasive, whereas the high CK5/6 expression rate increased (basal-like). Schema suggests the concept of “luminal–basal shift” with p53 addition from low stage bladder tumor recurrence to high stage bladder tumor progression.
Figure 3.
(a) Representative IHC staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens after radical cystectomy (RC). pT2 UTUC metachronous MIBC and pT2 bladder primary MIBC are shown. Power field scale bar = 200 µm. (b) Heatmap describing the IHC score of each molecular marker in MIBC patients who underwent RC (n = 70). The heatmap of MIBC patients is classified by UTUC metachronous or bladder primary MIBC with information for age, sex, pT stage, grade, pN stage, histological type, and presence of LVI. (c) Chart describing the high/low expressions of all four molecular markers compared between UTUC metachronous and bladder primary MIBC. There were no significances in CK5/6, CK20, and p53 expressions between the two, while significantly higher FGFR3 expression was observed in UTUC metachronous MIBC compared to that of bladder primary MIBC. (d) K–M curves comparing the cancer-specific survival (CSS) rates in MIBC patients after RC compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. High p53 expression groups showed significantly lower CSS rates compared to the counterparts (p = 0.037). In contrast, high FGFR3 expression group showed higher CSS rates compared to the counterparts.
Figure 3.
(a) Representative IHC staining of FGFR3, p53, CK5/6, and CK20 in surgical specimens after radical cystectomy (RC). pT2 UTUC metachronous MIBC and pT2 bladder primary MIBC are shown. Power field scale bar = 200 µm. (b) Heatmap describing the IHC score of each molecular marker in MIBC patients who underwent RC (n = 70). The heatmap of MIBC patients is classified by UTUC metachronous or bladder primary MIBC with information for age, sex, pT stage, grade, pN stage, histological type, and presence of LVI. (c) Chart describing the high/low expressions of all four molecular markers compared between UTUC metachronous and bladder primary MIBC. There were no significances in CK5/6, CK20, and p53 expressions between the two, while significantly higher FGFR3 expression was observed in UTUC metachronous MIBC compared to that of bladder primary MIBC. (d) K–M curves comparing the cancer-specific survival (CSS) rates in MIBC patients after RC compared by low versus high FGFR3 expression, low versus high p53 expression, low versus high CK5/6 expression, and low versus high CK20 expression. Log-rank test was used to assess the significance of differences. High p53 expression groups showed significantly lower CSS rates compared to the counterparts (p = 0.037). In contrast, high FGFR3 expression group showed higher CSS rates compared to the counterparts.
Figure 4.
(a) Heatmap describing the relationships of FGFR3 and p53 expressions from UTUC tumor origin to MIBC progression. Gray bar shows both FGFR3 and p53 low group. Light blue bar shows FGFR3 high but p53 low group. Yellow-green bar shows FGFR3 low but p53 high group. Purple bar shows FGFR3 high p53 high group. Table chart shows the distributions of FGFR3 and p53 expression rates among UTUC tumor origin (n = 214), UTUC tumor origin limited to patients who developed IVR (n = 94), IVR tumor specimen (n = 94), and IVR tumor specimen that progressed to MIBC (n = 18). (b) Heatmap describing the relationships of FGFR3 and p53 expression in UTUC metachronous MIBC (n = 12) and bladder primary MIBC specimens (n = 58). Table chart shows the distributions of FGFR3 and p53 expression rates of the two. (c) K–M curves showing the CSS rates in UTUC patients after RNU (on the left) and MIBC patients after RC (on the right), classified by four groups: FGFR3 low/p53 low (gray line), FGFR3 high/p53 low (blue line), FGFR3 low/p53 high (green line), and FGFR3 high/p53 high (purple line). (d) Schema showing the entire biological characteristics and transitions of four molecular markers in UTUC patients. UTUC patients with luminal-like dependent features are likely to develop IVR, and the molecular characteristics are mostly taken over to IVR specimen. After bladder tumor recurrence, the molecular characteristics shift from luminal-like to basal-like features as the tumor progresses to muscle-invasive status. Although p53 and CK5/6 show higher expression in the MIBC stage, UTUC metachronous MIBC maintains higher FGFR3 expression compared with bladder primary MIBC, which may comprise favorable biological features after RC.
Figure 4.
(a) Heatmap describing the relationships of FGFR3 and p53 expressions from UTUC tumor origin to MIBC progression. Gray bar shows both FGFR3 and p53 low group. Light blue bar shows FGFR3 high but p53 low group. Yellow-green bar shows FGFR3 low but p53 high group. Purple bar shows FGFR3 high p53 high group. Table chart shows the distributions of FGFR3 and p53 expression rates among UTUC tumor origin (n = 214), UTUC tumor origin limited to patients who developed IVR (n = 94), IVR tumor specimen (n = 94), and IVR tumor specimen that progressed to MIBC (n = 18). (b) Heatmap describing the relationships of FGFR3 and p53 expression in UTUC metachronous MIBC (n = 12) and bladder primary MIBC specimens (n = 58). Table chart shows the distributions of FGFR3 and p53 expression rates of the two. (c) K–M curves showing the CSS rates in UTUC patients after RNU (on the left) and MIBC patients after RC (on the right), classified by four groups: FGFR3 low/p53 low (gray line), FGFR3 high/p53 low (blue line), FGFR3 low/p53 high (green line), and FGFR3 high/p53 high (purple line). (d) Schema showing the entire biological characteristics and transitions of four molecular markers in UTUC patients. UTUC patients with luminal-like dependent features are likely to develop IVR, and the molecular characteristics are mostly taken over to IVR specimen. After bladder tumor recurrence, the molecular characteristics shift from luminal-like to basal-like features as the tumor progresses to muscle-invasive status. Although p53 and CK5/6 show higher expression in the MIBC stage, UTUC metachronous MIBC maintains higher FGFR3 expression compared with bladder primary MIBC, which may comprise favorable biological features after RC.
Table 1.
Clinicopathological and molecular characteristics of UTUC patients who underwent radical nephroureterectomy.
Table 1.
Clinicopathological and molecular characteristics of UTUC patients who underwent radical nephroureterectomy.
| Patients Who Underwent RNU | Total | Patients with IVR | Patients without IVR | p Value |
---|
Patient Characteristics | | n = 214 | n = 94, (%) | n = 120, (%) | |
---|
Age | <75 | 107 (50.0) | 53 (49.5) | 54 (50.5) | 0.065 |
| ≥75 | 107 (50.0) | 41 (38.3) | 66 (61.7) | |
Sex | male | 158 (73.8) | 77 (48.7) | 81 (51.3) | 0.012 |
| female | 56 (26.2) | 17 (30.4) | 39 (69.6) | |
Tumor location | pelvis | 118 (55.1) | 50 (42.4) | 68 (57.6) | 0.356 |
| ureter | 96 (44.9) | 44 (46.8) | 52 (53.2) | |
Tumor histology | pure UC | 171 (79.9) | 80 (46.8) | 91 (53.2) | 0.065 |
| UC with histology variants | 43 (20.1) | 14 (32.6) | 29 (67.4) | |
Pathological T stage | ≤ 2 | 116 (54.2) | 64 (55.2) | 52 (44.8) | <0.001 |
| ≥ 3 | 98 (45.8) | 30 (30.6) | 68 (69.4) | |
Pathological N stage | 0 | 49 (22.9) | 23 (46.9) | 26 (53.1) | 0.099 |
| 1,2 | 15 (7.0) | 2 (13.3) | 13 (86.7) | |
| Nx | 150 (70.1) | 69 (46.0) | 81 (54.0) | |
Lymph node dissection | no | 150 (70.1) | 69 (46.0) | 81 (54.0) | 0.216 |
| yes | 64 (29.9) | 25 (39.1) | 39 (60.9) | |
Surgical margin | negative | 189 (88.3) | 87 (46.0) | 102 (54.0) | 0.066 |
| positive | 25 (11.7) | 7 (28.0) | 18 (72.0) | |
Tumor grade | low | 64 (29.9) | 36 (56.3) | 28 (43.7) | 0.013 |
| high | 150 (70.1) | 58 (38.7) | 92 (61.3) | |
LVI | absent | 118 (55.1) | 62 (52.5) | 56 (47.5) | 0.004 |
| present | 96 (44.9) | 32 (33.3) | 64 (66.7) | |
Concomitant CIS | no | 170 (79.4) | 74 (43.5) | 96 (56.5) | 0.475 |
| yes | 44 (20.6) | 20 (45.4) | 24 (54.6) | |
Tumor multifocality | no | 182 (85.0) | 79 (43.4) | 103 (56.6) | 0.430 |
| yes | 32 (15.0) | 15 (46.9) | 17 (53.1) | |
Systemic adjuvant chemotherapy | no | 140 (65.4) | 65 (46.4) | 75 (53.6) | 0.192 |
| yes | 74 (34.6) | 29 (39.2) | 45 (60.8) | |
Previous history of bladder cancer | no | 149 (69.6) | 71 (47.7) | 78 (52.3) | 0.065 |
| yes | 65 (30.4) | 23 (35.4) | 42 (64.6) | |
Exrtravesical tumor recurrence | no | 146 (68.2) | 68 (46.6) | 78 (53.4) | 0.159 |
| yes | 68 (31.8) | 26 (38.2) | 42 (61.8) | |
Cancer specific Death | no | 162 (75.7) | 73 (45.1) | 89 (54.9) | 0.334 |
| yes | 52 (24.3) | 21 (40.4) | 31 (59.6) | |
Table 2.
Uni- and multivariate Cox regression analyses for determining risk factors for IVR development in UTUC patients. Abbreviations: IVR; intravesical recurrence, UTUC; upper tract urothelial carcinoma, HR; hazard ratio, CI; confidence interval, UC; urothelial carcinoma, CIS; carcinoma in situ, LVI; lymphovascular invasion, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
Table 2.
Uni- and multivariate Cox regression analyses for determining risk factors for IVR development in UTUC patients. Abbreviations: IVR; intravesical recurrence, UTUC; upper tract urothelial carcinoma, HR; hazard ratio, CI; confidence interval, UC; urothelial carcinoma, CIS; carcinoma in situ, LVI; lymphovascular invasion, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
| Univariate | Multivariate |
---|
Clinical Indicators | HR | 95% CI | p Value | HR | 95% CI | p Value |
---|
Age (≥ 75 vs. <75) | 0.69 | 0.45–1.06 | 0.086 | | | |
Sex (male vs. female) | 0.64 | 0.37–1.11 | 0.113 | | | |
Tumor location (ureter vs. renal pelvis) | 1.17 | 0.75–1.83 | 0.500 | | | |
Tumor histology (pure UC vs. non-pure UC) | 1.23 | 0.61–2.46 | 0.564 | | | |
Pathological T stage (≤T2 vs. ≥T3) | 1.93 | 1.15–3.22 | 0.013 | 1.94 | 1.20–3.15 | 0.007 |
Pathological N stage (N0 vs. N1,2) | 0.65 | 0.14–3.11 | 0.590 | | | |
Tumor grade (high vs. low) | 1.56 | 0.89–2.75 | 0.121 | 1.61 | 1.04–2.49 | 0.032 |
Concomitant CIS (yes vs. no) | 1.02 | 0.53–1.98 | 0.955 | | | |
Tumor multifocality (yes vs. no) | 1.38 | 0.69–2.77 | 0.365 | | | |
LVI (positive vs. negative) | 0.74 | 0.41–1.35 | 0.326 | | | |
Systemic adjuvant chemotherapy (yes vs. no) | 1.21 | 0.74–2.00 | 0.449 | | | |
Previous history of bladder tumor (yes vs. no) | 0.58 | 0.70–1.90 | 0.581 | | | |
FGFR3 expression (high vs. low) | 1.34 | 0.85–2.13 | 0.210 | | | |
p53 expression (high vs. low) | 0.74 | 0.42–1.29 | 0.287 | | | |
CK5/6 expression (high vs. low) | 0.29 | 0.144–0.590 | 0.001 | 0.26 | 0.14–0.49 | <0.001 |
CK20 expression (high vs. low) | 3.17 | 1.91–5.26 | <0.001 | 3.31 | 2.10–5.23 | <0.001 |
Table 3.
Clinicopathological characteristics of UTUC patients who developed IVR. Abbreviations: UTUC; upper tract urothelial carcinoma, IVR; intravesical recurrence, MIBC; muscle invasive bladder cancer, UC; urothelial carcinoma, LVI; lymphovascular invasion, CIS; carcinoma in situ, BT: bladder tumor.
Table 3.
Clinicopathological characteristics of UTUC patients who developed IVR. Abbreviations: UTUC; upper tract urothelial carcinoma, IVR; intravesical recurrence, MIBC; muscle invasive bladder cancer, UC; urothelial carcinoma, LVI; lymphovascular invasion, CIS; carcinoma in situ, BT: bladder tumor.
| | Total | MIBC Progression | non-MIBC Progression | p Value |
---|
Patient Characteristics | | n = 94, (%) | n = 18, (%) | n = 76, (%) | |
---|
Age | <75 | 41 (43.6) | 10 (24.4) | 31 (75.6) | 0.477 |
| ≥75 | 53 (56.4) | 8 (15.1) | 45 (84.9) | |
Sex | male | 77 (81.9) | 12 (15.6) | 65 (84.4) | 0.143 |
| female | 17 (18.1) | 6 (35.3) | 11 (64.7) | |
Pathological T stage (Initial IVR) | a | 37 (39.4) | 2 (5.4) | 35 (94.6) | 0.005 |
| 1 | 51 (54.3) | 10 (19.6) | 41 (80.4) | |
| 2 | 6 (6.3) | 6 (100.0) | 0 (0.0) | |
Tumor grade (Initial IVR) | low | 48 (51.1) | 5 (10.4) | 43 (89.6) | 0.026 |
| high | 46 (48.9) | 13 (28.3) | 33 (71.7) | |
LVI (Initial IVR) | absent | 73 (77.7) | 8 (11.0) | 65 (89.0) | 0.001 |
| present | 21 (22.3) | 10 (47.6) | 11 (52.4) | |
Concomitant CIS (Initial IVR) | no | 83 (88.3) | 15 (18.1) | 68 (81.9) | 0.352 |
| yes | 11 (11.7) | 3 (27.3) | 8 (72.7) | |
Recurrence times of BT | 1 | 35 (37.2) | 6 (17.1) | 29 (82.9) | <0.001 |
| 2 | 21 (22.3) | 5 (23.8) | 16 (76.2) | |
| 3 | 12 (12.8) | 3 (25.0) | 9 (75.0) | |
| 4 | 24 (25.5) | 4 (16.7) | 20 (83.3) | |
| 5 | 2 (2.1) | 0 (0.0) | 2 (100.0) | |
Intravesical chemotherapy | no | 19 (20.2) | 6 (31.6) | 13 (68.4) | 0.115 |
| yes | 75 (79.8) | 12 (16.0) | 63 (84.0) | |
Table 4.
Uni- and multivariate Cox regression analyses for determining risk factors for MIBC progression after IVR development. Abbreviations: MIBC; muscle invasive bladder cancer, IVR; intravesical recurrence, HR; hazard ratio, CI; confidence interval, UC; urothelial carcinoma, CIS; carcinoma in situ, BT: bladder tumor, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
Table 4.
Uni- and multivariate Cox regression analyses for determining risk factors for MIBC progression after IVR development. Abbreviations: MIBC; muscle invasive bladder cancer, IVR; intravesical recurrence, HR; hazard ratio, CI; confidence interval, UC; urothelial carcinoma, CIS; carcinoma in situ, BT: bladder tumor, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
| Univariate | Multivariate |
---|
Clinical Indicators | HR | 95% CI | p Value | HR | 95% CI | p Value |
---|
Age (≥75 vs. <75) | 0.71 | 0.17–2.93 | 0.636 | | | |
Sex (male vs. female) | 1.19 | 0.29–4.83 | 0.807 | | | |
Pathological T stage (T1 vs. Ta) | 6.62 | 1.04-24.0 | 0.045 | 4.57 | 1.04–20.0 | 0.044 |
Tumor grade (high vs. low) | 2.63 | 1.44–4.78 | 0.020 | 1.95 | 1.27–3.00 | 0.020 |
Concomitant CIS (yes vs. no) | 1.27 | 0.20–8.00 | 0.802 | | | |
Intravesical therapy (yes vs. no) | 0.69 | 0.18–2.68 | 0.591 | | | |
Recurrence times of BT (3 or more vs. 2 or low) | 1.47 | 0.36–6.10 | 0.591 | | | |
FGFR3 expression (high vs. low) | 0.56 | 0.12–4.07 | 0.674 | | | |
p53 expression (high vs. low) | 4.81 | 1.46–15.8 | 0.010 | 5.44 | 1.85–16.0 | 0.002 |
CK5/6 expression (high vs. low) | 5.96 | 1.27–28.0 | 0.024 | 4.56 | 1.31–15.8 | 0.017 |
CK20 expression (high vs. low) | 0.68 | 0.11–4.07 | 0.674 | | | |
Table 5.
Patient and tumor characteristics of MIBC patients who underwent radical cystectomy. Abbreviations: MIBC; muscle invasive bladder cancer, UTUC; upper tract urothelial carcinoma, LVI; lymphovascular invasion.
Table 5.
Patient and tumor characteristics of MIBC patients who underwent radical cystectomy. Abbreviations: MIBC; muscle invasive bladder cancer, UTUC; upper tract urothelial carcinoma, LVI; lymphovascular invasion.
| | Total | UTUC Derived MIBC | Bladder Primary MIBC | |
---|
Patient Characteristics | | n = 70, (%) | n = 12, (%) | n = 58, (%) | p Value |
---|
Age | <75 | 45 (64.3) | 7 (58.3) | 38 (65.5) | 0.744 |
| ≥75 | 25 (35.7) | 5 (41.7) | 20 (34.5) | |
Sex | male | 56 (80.0) | 11 (91.7) | 45 (77.6) | 0.248 |
| female | 14 (20.0) | 1 (8.3) | 13 (22.4) | |
Pathological T stage | <3 | 39 (55.7) | 7 (58.3) | 32 (55.2) | 0.509 |
| 3 or more | 31 (44.3) | 5 (41.7) | 26 (44.8) | |
Pathological N stage | 0 | 41 (58.6) | 6 (50.0) | 35 (60.3) | 0.560 |
| 1,2 | 29 (41.4) | 6 (50.0) | 23 (39.7) | |
Tumor grade | low | 7 (10.0) | 3 (25.0) | 4 (6.9) | 0.092 |
| high | 63 (90.0) | 9 (75.0) | 54 (93.1) | |
LVI | absent | 38 (54.3) | 5 (41.7) | 33 (56.9) | 0.259 |
| present | 32 (45.7) | 7 (58.3) | 25 (43.1) | |
Systemic chemotherapy | no | 19 (27.2) | 4 (33.3) | 15 (25.9) | 0.491 |
| yes | 51 (72.8) | 8 (66.7) | 43 (74.1) | |
Cancer death | no | 38 (54.3) | 10 (83.3) | 28 (48.3) | 0.002 |
| yes | 32 (45.7) | 2 (16.7) | 30 (51.7) | |
Table 6.
Uni- and multivariate analyses evaluating the prognostic factors associated with oncological outcomes in MIBC patients (n = 70). Abbreviations: MIBC; muscle-invasive bladder cancer, HR; hazard ratio, CI; confidence interval, UTUC; upper tract urothelial carcinoma, LVI; lymphovascular invasion, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
Table 6.
Uni- and multivariate analyses evaluating the prognostic factors associated with oncological outcomes in MIBC patients (n = 70). Abbreviations: MIBC; muscle-invasive bladder cancer, HR; hazard ratio, CI; confidence interval, UTUC; upper tract urothelial carcinoma, LVI; lymphovascular invasion, FGFR; fibroblast growth factor receptor, CK; cytokeratin.
| Disease Recurrence | Cancer-Specific Death |
---|
| Univariate | Multivariate | Univariate | Multivariate |
---|
Clinical Indicators | HR | 95% CI | p value | HR | 95% CI | p Value | HR | 95% CI | p Value | HR | 95% CI | p value |
---|
Age (≥75 vs. <75) | 1.62 | 0.66–3.99 | 0.298 | | | | 1.25 | 0.45–3.49 | 0.667 | | | |
Sex (male vs. female) | 1.26 | 0.51–3.11 | 0.614 | | | | 1.04 | 0.43–2.52 | 0.924 | | | |
Systemic chemotherapy (yes vs. no) | 0.38 | 0.12–0.91 | 0.043 | 0.24 | 0.111–0.497 | 0.001 | 1.20 | 0.47–3.09 | 0.699 | | | |
Pathological T stage (≥3 vs. <3) | 2.59 | 0.97–6.94 | 0.059 | 2.47 | 1.05–5.76 | 0.037 | 2.95 | 1.15–7.55 | 0.024 | 2.40 | 1.14-5.06 | 0.021 |
Pathological N stage (1,2 vs. 0) | 3.11 | 1.22–7.97 | 0.614 | 2.86 | 1.40–5.84 | 0.004 | 4.18 | 1.62–10.8 | 0.003 | 3.07 | 1.27-7.41 | 0.013 |
UTUC metachronous MIBC (yes vs. no) | 0.56 | 0.11–2.96 | 0.493 | | | | 0.39 | 0.12–1.21 | 0.103 | 0.14 | 0.02-0.88 | 0.002 |
Tumor grade (high vs. low) | 2.93 | 0.32–2.63 | 0.338 | | | | 2.09 | 0.52–8.54 | 0.301 | | | |
LVI (positive vs. negative) | 2.50 | 0.88–5.52 | 0.084 | | | | 2.73 | 1.00–7.45 | 0.050 | | | |
FGFR3 (high vs. low) | 0.35 | 0.12–0.94 | 0.013 | 0.32 | 0.13–0.79 | 0.013 | 0.47 | 0.20–1.10 | 0.082 | 0.29 | 0.02-1.01 | 0.051 |
p53 (high vs. low) | 1.78 | 0.75–4.25 | 0.194 | | | | 4.29 | 1.73–10.6 | 0.002 | 2.56 | 0.131-0.623 | 0.008 |
CK5/6 (high vs.low) | 1.47 | 0.64–3.03 | 0.371 | | | | 2.15 | 0.94–4.89 | 0.070 | | | |
CK20 (high vs.low) | 0.92 | 0.31–2.68 | 0.873 | | | | 1.07 | 0.44–2.64 | 0.880 | | | |