Original article
Incidence and effect of variant histology on oncological outcomes in patients with bladder cancer treated with radical cystectomy

https://doi.org/10.1016/j.urolonc.2016.12.006Get rights and content

Highlights

  • Almost one-third of patients with BCa were found with a histological variant at RC.

  • Squamous and micropapillary are the most common variants at RC.

  • Small cell variant only is associated with worse survival outcomes.

Abstract

Introduction

We sought to describe incidence of histological variants after radical cystectomy (RC) due to bladder cancer (BCa). Moreover, we investigated survival outcomes accounting for this parameter.

Methods

We retrospectively evaluated data from 1,067 patients with BCa treated with RC between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the effect of different histopathological variant on recurrence, cancer-specific mortality (CSM), and overall mortality (OM) after accounting for all available confounders.

Results

Of 1,067 patients, 729 (68.3%) harbored pure urothelial BCa while 338 (31.7%) were found to have a variant. Considering uncommon variants, 21 (2.0%) were sarcomatoid, 10 (0.9%) lymphoepitelial, 19 (1.8%) small cell, 109 (10.2%) squamous, 89 (8.3%) micropapillary, 23 (2.2%) glandular, 34 (3.2%) mixed variants, and 33 (3.1%) were found with other types of variants. With a median follow-up of 6.2 years, 343 recurrence, 365 CSM, and 451 OM were recorded, respectively. At multivariable Cox regression analyses, the presence of small cell variant was associated with higher recurrence (hazard ratio [HR] = 3.47, P<0.001), CSM (HR = 3.30, P<0.04), and OM (HR = 2.97, P<0.003) as compared with pure urothelial cancer. Conversely, no survival differences were recorded considering other histological variants (all P> 0.1).

Conclusion

Our study confirms that histological variant is not an infrequent event at RC specimen. However, in our single-center series, only patients found with small cell variant were associated with a negative effect on survival after RC.

Introduction

Bladder cancer (BCa) may present with several different morphological features that deviate from the urothelial common aspect [1], [2], [3]. It has been estimated that approximately 80% of BCa is represented by pure urothelial carcinoma (UCb), whereas the remaining is the result of urothelial and nonurothelial variants [4], [5]. In this perspective, WHO 2016 [6] has recently highlighted the importance of the morphology characteristics in BCa as a determinant of survival and driver of clinical and therapeutic managements. Morphological characteristics are directly related to molecular alterations, and in this perspective, the most frequently altered pathways are PI3K/AKT/mammalian [7], the FGFR3/RAF/RAS pathway [8], the TP53/RB1 pathway [9], immune response checkpoint modulators [10], and chromatin-regulating and remodeling genes [11]. However, in the absence of a validated tissue-based genetic test, assessing morphological features from hematoxylin and eosin-stained pathologic sections can provide information on their biologic characteristics.

However at the time, there is a paucity of data evaluating morphological tumor characteristics after radical cystectomy (RC). With this in mind, our hypothesis is to confirm that defining histological variants can affect survival outcomes after RC, and moreover could drive therapy and follow-up schemes after surgery. Therefore, we evaluated incidence and survival outcomes of a large single-center experience of patients treated with RC due to BCa.

Section snippets

Materials and methods

A total of 1,067 patients treated with RC and pelvic lymph node dissection between 1990 and 2013 at a single tertiary referral center were included in the study. The procedures were approved by the institutional review board (Vescica, 2010), and an informed consent was obtained by all patients. Patients were evaluated preoperatively with pelvic/abdominal computed tomography scan or magnetic resonance imaging, bone scan, and chest x-ray. RC with pelvic lymph node dissection was performed using

Statistical analyses

Descriptive statistics of categorical variables were focused on frequencies and proportions. Means, medians, and interquartile ranges (IQR) were reported for continuously coded variables. The Mann-Whitney test and chi-square test were used to compare the statistical significance of differences in medians and proportions, respectively. Univariable and multivariable Cox regression analyses tested the effect of different histopathological variant on recurrence, cancer-specific mortality (CSM), and

Baseline characteristics

In total, 1,067 patients were included in the study. Of these, 68.3% (n = 729) were found with urothelial BCa, whereas the remaining 31.7% (n = 338) were found with a variant. Of the 31.7% patients, 2.0% (n = 21) were found with sarcomatoid variant, 0.9% (n = 10) with lymphoepitelial, 1.8% (n = 19) with small cell, 10.2% (n = 109) with squamous, 8.3% (n = 89) with micropapillary, 2.2% (n = 23) with glandular, 3.2% (n = 34) with mixed variants, and 3.1% (n = 33) with other variants. Descriptive

Discussion

The diagnosis of a variant histology in bladder specimen either at transurethral resection (TUR) of the bladder or RC is a common event [4], [5]. However, the prevalence of this finding has increased consistently during the years. This trend has been explained considering the increased awareness on the histological variants after the 2004 and 2016 WHO guidelines [6]. Moreover, the effect of a central pathology review has shown better results than community practice in the diagnosis of these

Conclusion

Our single-center study confirmed the nonrare incidence of histological variants at RC specimen. Although differences exist in the possibility to harbor adverse pathologic characteristics at RC specimen, only small cell variant seems associated with decreased survival expectancies when all the confounders are adjusted at the multivariable analyses. Further studies assessing the role of a multimodal approach are required to understand the best strategy for these patients.

Acknowledgment

Marco Moschini is supported by the EUSP Scholarship—European Association of Urology.

References (25)

  • S.H. Culp et al.

    Refining patient selection for neoadjuvant chemotherapy before radical cystectomy

    J Urol

    (2014)
  • T. Seisen et al.

    Impact of histological variants on the outcomes of nonmuscle invasive bladder cancer after transurethral resection

    Curr Opin Urol

    (2014)
  • Cited by (0)

    View full text