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384 Miyake et al. | Journal of Clinical and Translational Research 2023; 9(6): 381-391
2.4. Follow-up and endpoints with UTUC, while 56% of bladder cancer received three cycles of
NAC. According to the pathological response to NAC, 14 (15%),
A standard protocol was generally used for the follow-up after 39 (41%), and 42 (44%) patients were categorized into down-
RC or RNU: Cystoscopy only for patients undergoing RNU, staged ≥ypT2, no-changed ≥ypT2, and up-staged ≥ypT2 groups,
urinary cytology if needed, and abdominopelvic and chest CT or respectively. The patterns of pathological response to NAC are
MRI are performed every 3 months for 2 years, every 6 months shown in Figure 1B. The two most common patterns were cTany
until 5 years, and then yearly [1,9]. This study evaluated three cN0 to ypTany ypN+ in 26 patients (up-staged group) and cT3N0
endpoints: Extra-urinary tract recurrence-free survival (EUTRFS), to ypT3 ypN0 in 14 patients (no-changed group).
CSS, and overall survival (OS). Extra-urinary tract recurrence To investigate possible factors associated with pathological
was defined as any recurrence, excluding bladder, upper urinary response to NAC, we compared patient characteristics among
tract, and urethral recurrences. While urinary tract recurrence is down-staged ≥ypT2, no-changed ≥ypT2, and up-staged
generally considered non-life-threatening, EUTR includes life-
threatening events, such as local recurrence in soft tissue, regional ≥ypT2 groups (Table 2). Sex, clinical T category, and clinical
lymph node, or distant organs. Patients who were alive without N category were found to be different among groups. More
events were censored at the date of the last follow-up, including the than half of male patients were categorized into the up-staged
last imaging examination for EUTR and the last visit for cancer- ypT2≤ group, while more than half of female patients were the
specific death. no-changed ypT2≤ group. Majority of the patients with clinical
N- tumor were categorized into the up-staged ≥ypT2 group.
2.5. Statistical analysis The regimen and cycles of NAC were not different among three
groups.
Data visualization and statistical analyses were performed
using PRISM software version 9 (GraphPad Software, Inc., San 3.2. Association between response to NAC and survival outcomes
Diego, CA, USA). Event-free survival curves from the day of
radical surgery were obtained using the Kaplan–Meier method There was no significant difference in EUTRFS, CSS, and OS
and compared by log-rank test for trend. Variables that potentially among the three groups (Figure 1C). We performed univariate
affected prognosis (P < 0.05) in univariate analysis were included and multivariate analyses using the Cox proportional hazards
in a step-wise Cox proportional hazards regression model. regression model to found prognostic factors for EUTRFS,
Regression model. Hazard ratio (HR) with 95% confidence CSS, and OS in patients with ypT2 and/or ypN+ UC after NAC
interval (CI) was calculated to identify independent prognostic (Table 3). The univariate analysis of EUTRFS showed advanced
variables. Statistical significance was set at P < 0.05. tumor such as cT4 and ypT4 (vs. ypT2; HR = 3.33, P = 0.009) were
significantly associated with a high risk of disease recurrence,
3. Results whereas no independent prognostic factor was found in the
multivariate analysis. Similar results were seen in the univariate
3.1. Patient characteristics and pathological response to NAC
analysis of CSS (ypT4 vs. ypT2; HR = 3.74, P = 0.02), and OS
Clinicopathological characteristics of the 95 patients consisting (ypT4 vs. ypT2; HR = 2.55, P = 0.03). Multivariate analysis was
41 with bladder cancer and 54 with UTUC are depicted in Table 1. not performed in CSS and OS because the univariate analysis did
Of note, the number of NAC cycles was 2 or less in 78% of patients not show multiple prognostic factors.

Table 1. Characteristic of patients with yielding pathological T2≤ and/or N+ urothelial carcinoma after neoadjuvant chemotherapy
Variables Overall Bladder cancer cohort UTUC cohort
N (%) 95 (100%) 41 (100%) 54 (100%)
Age (years-old), mean±standard deviation 69.3±9.5 69.7±8.8 69.0±10.1
Sex
Male 73 (77%) 31 (76%) 42 (78%)
Female 22 (23%) 10 (24%) 12 (22%)
ECOG-PS
0 77 (81%) 37 (90%) 40 (74%)
1 12 (13%) 4 (10%) 8 (15%)
2 2 (2.1%) 0 2 (3.7%)
Unknown 4 (4.2%) 0 4 (7.4%)
Tumor multifocality
Single 65 (68%) 31 (76%) 34 (63%)
Multiple 25 (26%) 10 (24%) 15 (28%)
Unknown 5 (5.3%) 0 5 (9.3%)
(Contd...)

DOI: http://dx.doi.org/10.18053/jctres.09.202306.23-00106