Elsevier

European Urology Focus

Volume 8, Issue 5, September 2022, Pages 1270-1277
European Urology Focus

Urothelial Cancer
Survival Outcomes After Immediate Radical Cystectomy Versus Conservative Management with Bacillus Calmette-Guérin Among T1 High-grade Micropapillary Bladder Cancer Patients: Results from a Multicentre Collaboration

https://doi.org/10.1016/j.euf.2021.07.015Get rights and content

Abstract

Background

Literature lacks clear evidence regarding the optimal treatment for non–muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies.

Objective

To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC.

Design, setting, and participants

We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19–64).

Intervention

Patients underwent immediate RC versus conservative management with bacillus Calmette-Guérin.

Outcomes measurements and statistical analysis

Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis.

Results and limitations

Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study.

Conclusions

Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis.

Patient summary

Bacillus Calmette-Guérin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.

Introduction

Approximately 75% of all bladder cancers (BCa) occur as non–muscle-invasive bladder cancer (NMIBC) confined to mucosa and lamina propria [1], which could effectively be treated with transurethral resection of the bladder (TURB) and intravesical bacillus Calmette-Guérin (BCG) immunotherapy in high-risk disease [1]. Management of NMIBC is aimed at preventing recurrence and progression to a muscle-invasive disease requiring radical cystectomy (RC), and several meta-analyses have shown the effectiveness of BCG administered to T1 pure urothelial carcinoma (UC) in reducing both disease recurrence and progression to T2 or higher [2], [3].

However, in approximately 30% of patients [4], BCa may exhibit histological features that differ from those of usual pure UC and correlate with worse prognosis [5], requiring individualised therapy. Among these variant histologies, micropapillary bladder cancer (MPBC) is a highly aggressive carcinoma characterised by the tendency to develop invasive and metastatic diseases [6], [7]. At present, the most effective therapy is still debated [8], [9], especially in an early NMIBC stage, and different approaches are performed. Some authors advocate a conservative management for MPBC confined to lamina propria in an attempt to preserve the bladder without compromising survival outcomes [10], [11], while others, considering its aggressive behaviour, suggest immediate RC even in T1 disease [7], [12], [13]. Currently, due to its rarity and the presence of only small sample size and single-centre studies, literature lacks clear evidence regarding the optimal therapeutic strategy to be performed.

Following these considerations, we retrospectively analysed a large multicentre dataset of 119 patients to assess survival outcomes after immediate RC versus conservative management for T1 high-grade (HG) non–muscle-invasive MPBC.

Section snippets

Study population

After the approval from each centre’s review board, data of 119 patients with an initial TURB diagnosis of T1 HG MPBC between 2005 and 2019 at 15 European and Asian tertiary referral centres were analysed retrospectively. No neoadjuvant chemotherapy was performed in our T1 cohort [1]. The therapeutic strategy was at the surgeon’s discretion, patient’s preference, and characteristics, such as comorbidities, performance status, and life expectancy. Immediate RC consisted of RC with pelvic lymph

Study population

Descriptive characteristics of the cohort are summarised in Table 1. The majority of patients were men (74.8%), with a median age of 70 yr (IQR 62–76). Pure MPBC, concomitant LVI, and CIS were observed in 41.2%, 25.2%, and 22.7% of patients, respectively. A comprehensive flow chart of different strategies is depicted in Figure 1. Immediate RC and conservative management were performed in 32 (27%) and 87 (73%) patients, respectively. Within a median follow-up time of 35 mo (IQR: 19–64), 21

Discussion

MPBC, first described in 1994 by Amin et al [22], is a rare variant histology of BCa, the prototype of which is represented by the papillary serous carcinoma of the ovary. It exhibits aggressive behaviour, resulting in an increased incidence of lymph node invasion and distant metastasis compared with pure UC [7], [18]. At present, studies with only small sample size and single-centre experience were published, and little is known about the most effective therapy for T1 MPBC. Indeed, even in the

Conclusions

Conservative management with BCG immunotherapy could achieve satisfactory results compared with immediate RC among T1 non–muscle-invasive MPBC patients. However, the risk of disease recurrence and progression among individuals with pure MPBC or LVI suggests preferring conservative management only among T1 MPBC patients with neither pure MPBC nor LVI at initial diagnosis. At present, in the absence of trials evaluating the optimal therapeutic strategy for this rare disease, our study represents

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    †

    These authors shared first authorship.

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