Clinicopathological Analysis of Patients with Nonmuscle-Invasive Bladder Cancer Who Underwent Radical Cystectomy

Naotaka Nishiyama, Hiroshi Kitamura, Masatoshi Mutoh, Masahiro Yanase, Hiroyuki Iwaki, Tadashi Hasegawa, Taiji Tsukamoto

Departments of Surgical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Departments of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Divisions of Pathology, Sunagawa City Medical Center, Sunagawa, Japan.
Divisions of Urology, Sunagawa City Medical Center, Sunagawa, Japan.

DOI: 10.4236/ss.2012.37068                

Abstract

Objectives: Surgical specimens obtained at the time of the last transurethral resection of bladder tumor (TURBT) for patients with nonmuscle-invasive bladder cancer (NMIBC) who underwent radical cystectomy were retrospectively evaluated in order to investigate the relationship between pathological variation and upstaging of NMIBC. Methods and Materials: Twenty patients (19 men, 1 woman; aged 69.4 ± 12.1 (mean ± SD) years) diagnosed with NMIBC underwent radical cystectomy during follow-up. Results: Five of the 20 patients (25%) had pathological upstaging in the radical cystectomy specimens. There was a statistical association between pathological upstaging and cancer death (p = 0.002). There were three patterns of pathological variation in the upstaged specimens: 1) in patients with BCG-resistant NMIBC, urothelial carcinoma invaded through the lamina propria; 2) urothelial carcinoma showed diffuse invasion beyond the deep lamina propria, and the cancer cells had infiltrated as single cells and formed nodules; 3) TURBT specimens showed a micropapillary variant. Conclusions: Since these pathological variations correlated with pathological upstaging, they may provide an indication for cystectomy in NMIBC patients.

Keywords

Clinicopathological Examination; Nonmuscle-Invasive Bladder Cancer; Radical Cystectomy, Pathological Upstaging

1. Introduction

Approximately 70% - 75% of bladder tumors are nonmuscle-invasive bladder cancer (NMIBC) confined to the mucosal and submucosal layers (stage Ta, Tis, T1) of the bladder at the time of initial evaluation. The 5-year cause-specific survival rate for NMIBC is high and it is curable by transurethral intervention, although the intravesical recurrence rate is higher than 50% [1-5]. However, high-risk NMIBC—having a high histological grade and lamina propria invasion—has a poor clinical outcome. High-risk NMIBC is associated with progression, metastasis, and cancer death, with between 30% - 50% of patients having progressive disease. The 5-year causespecific survival after radical cystectomy is 40% - 80% [6-10]. To decrease the recurrence rate and improve causespecific survival, early cystectomy is recommended for high-risk NMIBC [9,10]. However, radical cystectomy, despite advances in urinary diversion techniques, has its disadvantages: it impairs quality of life, some patients are overtreated with this aggressive therapy, and the morbidity and mortality are 20% and 1% - 4%, respectively [8].

It is thus important to restrict the criteria for radical cystectomy to high-risk NMIBC. Several studies have shown that the heterogeneous biological behavior of stage T1 NMIBC is related to depth of invasion beyond the lamina propria [11-18]. Although there is a correlation between depth of invasion within the lamina propria and prognosis, these classifications have not gained formal acceptance. In this study, surgical specimens from transurethral resection of bladder tumor (TURBT) and cystectomy for NMIBC patients were evaluated in order to investigate the relationship between pathological variations and upstaging of NMIBC.

2. Patients and Methods

2.1. Patients and Tissue Samples (Tables 1 and 2)

Between January 1998 and November 2008, 138 patients

Table 1. Patients characteristics.

were diagnosed with NMIBC (stage Ta, T1 or Tis) at the Sunagawa City Medical Center, Sunagawa, Japan. All these patients underwent TURBT as initial treatment. Usually, we confirmed the condition of the muscularis propria as far as was possible at the time of TURBT. Twenty of those patients whose TURBT specimens did not reveal muscle invasion of the bladder (19 men, 1 woman; aged 69.4 ± 12.1 (mean ± SD) years) underwent radical cystectomy during follow-up. Patients who had had upper urinary tract disease were excluded. Eleven of these 20 patients underwent radical cystectomy after the initial TURBT. The remaining patients had this radical surgery after recurrence and intravesical treatment showed no muscle invasion. Because the TURBT specimens showed that these patients were at high risk for progression, we performed radical cystectomy without a second TURBT. They underwent radical cystectomy because transurethral resection could not control NMIBC due to tumor multiplicity or multiple intravesical recurrences after intravesical instillation of bacillus Calmette-Guerin (BCG), anti-cancer drugs, or both.

All TURBT and cystectomy specimens were reviewed

Table 2. Clinicopathological characteristics and outcomes of patients who underwent radical cystectomy for NMIBC.

by two pathologists independently. The pathological variations of urothelial carcinoma (UC) invading the lamina propria was analyzed in the TURBT specimens. Those patients whose TURBT specimens revealed invasion through the muscularis propria were excluded. Among all specimens at the time of the last TURBT, 7 and 13 were graded as Grade1-2 (G1-2) and Grade3 (G3) UC, respectively, on the basis of the 1973 WHO classification system, and 6, 1, and 13 were classed as Tis, Ta, and T1, respectively according to the TNM system. Pathological upstaging was defined as UC with muscularis propria invasion or lymph node metastasis in the cystectomy specimens.

2.2. Statistics

Correlations between the prognosis and pathological upstaging of NMIBC were analyzed using the unpaired t test. Differences at p < 0.05 were considered significant.

3. Results

Twenty patients underwent radical cystectomy for NMIBC based on the pathological diagnosis in TURBT specimens. The mean follow-up interval from the first diagnosis was 57.8 ± 29 months (mean ± SD). The reasons for radical cystectomy were intravesical recurrence after BCG therapy in 8 patients, multiple and large tumors that were difficult to control by TURBT in 6 patients, and a high risk of progression as classified by the EAU guidelines in 6 patients (http://www.uroweb.org/gls/pdf/05_Ta T1_Bladder_Cancer.pdf). Five of the 20 patients (25%) had pathological upstaging to MIBC in which UC invaded through the muscularis propria at the time of cystectomy; the remaining patients had no pathological upstaging. Three of the 5 upstaged patients died due to UC, whereas none of 15 patients without upstaging died of UC (Table 2). There was a significant association between pathological upstaging and cancer death (p = 0.002).

Figure 1 shows pathological specimens from last TURBTs and cystectomies. Three pathological patterns were identified in the specimens from patients with upstaging: macroscopically flat UC invasion after BCG therapy, nodular and single-cell infiltration, and a micropapillary variant. In the first pattern, the cystectomy specimens revealed that macroscopically flat UC had invaded beyond the perivesical tissue but could not be recognized as exophytic tumor lesions. However, microscopically at

Conflicts of Interest

The authors declare no conflicts of interest.

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