Original articleIncidence and effect of variant histology on oncological outcomes in patients with bladder cancer treated with radical cystectomy
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.
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2022, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :However, due to the relatively low incidence of UTUC, the optimal postoperative follow-up protocol after RNU has not been well-established. The presence of histological variants (HV) is associated with biologically aggressive cancer features and lower survival rates compared to pure urothelial carcinoma (UC) [3–8]; however the significance of HV in UTUC is not well understood. In contrast, lymphovascular invasion (LVI) has been shown to be an important biomarker after RNU in systematic reviews and meta-analyses [9–11].