A clinico-pathological study of non-urothelial bladder cancers in a cohort of patients from a tertiary care urology unit in Sri Lanka

Bladder cancer is the ninth most commonest cancer worldwide. The spectrum of bladder cancer is quite diverse and the majority (90-95%) of cancers are urothelial in origin [1]. Non-urothelial bladder cancers are known to occur in around 5% of all bladder cancers [1]. Due to the rarity of non-urothelial bladder cancers, understanding of the clinico-pathological characteristics and effective management strategies are poor, particularly in the South Asian region [2]. Therefore, this study aimed to describe the clinico-pathological characteristics of non-urothelial bladder cancers.


Introduction
Bladder cancer is the ninth most commonest cancer worldwide.The spectrum of bladder cancer is quite diverse and the majority (90-95%) of cancers are urothelial in origin [1].Non-urothelial bladder cancers are known to occur in around 5% of all bladder cancers [1].Due to the rarity of non-urothelial bladder cancers, understanding of the clinico-pathological characteristics and effective management strategies are poor, particularly in the South Asian region [2].Therefore, this study aimed to describe the clinico-pathological characteristics of non-urothelial bladder cancers.

Methods
All patients with newly diagnosed bladder cancer referred to a urology unit of the National Hospital of Sri Lanka from January 2007 to December 2016 were recorded in a database and were analysed retrospectively.Staging and categorisation of tumours were done according to the World Health Organization (WHO) classification guidelines [3].During the study period 312 patients presented with primary bladder tumours.Histology was available in 310 (99.4%) patients of which 25 (8.0%) were non-urothelial malignancies.All data were recorded prospectively at the operating theatre, before discharge and during clinic visits to ensure accuracy.Urothelial bladder cancers containing non-urothelial elements or mixed tumours were considered as variants of urothelial bladder cancers and were not analysed as non-urothelial bladder cancers.Ethical approval was obtained from the Ethics review committee of the National Hospital of Sri Lanka.

Discussion
Non-urothelial bladder cancers are rare bladder tumours consisting of 5% of all bladder tumours [1].Due to its rarity, there is no consensus regarding treatment.Studies have reported a wide variety of non-urothelial bladder cancer tumour types.The different histological types are briefly described below.

Squamous cell carcinoma of the bladder
Squamous cell carcinoma accounts for 2.7% of bladder cancers in the developed world [4].It is the second most common primary bladder cancer next to urothelial cancers.In a study by Kassouf et al 27 patients of nonbilharzial squamous cell carcinoma were described [5].Of the participants, 13 had cT2, 9 had cT3, 5 had cT4 lesions.Thus, this series showed that this group had aggressive tumours with poor outcome.In a study by Dahm et al squamous cell carcinoma was the commonest type of non-urothelial bladder cancer with an incidence of 3 to 5 %, followed by adenocarcinoma (0.5-2 %) [1].In the present study, majority of squamous cell carcinomas were large (n=8; 80%,), solid tumours (n=8; 80%,), muscle invasive (n=8; 80%,) and high grade (n=7; 70%,), which are well known characteristics of aggressive tumours.

Adenocarcinoma of the bladder
Primary adenocarcinoma of the bladder is seen in 1.4% of bladder cancers undergoing radical cystectomy in the developed world [4].The prevalence is reported to be considerably higher in the developing world, accounting for up to 11% [6].In a series by Ravi et al from India, out of 21 non-urothelial tumours, 9 (42.8 %) were adenocarcinoma with a mean age of 49.33 years [2].Male to female ratio was 2: 1.Two (22.2%) were urachal tumours and 4 (44.44%) were moderately differentiated while 5 (55.55%) were poorly differentiated [2].In a study by Grignon, out of 72 patients with adenocarcinoma 24 patients had urachal and 48 patients had non urachal

Research letter
adenocarcinoma [7].The study concluded that variations in the histological type did not show a significant difference in the outcome.In the present study, all were non-urachal in origin and around 78% (n=7) were muscle invasive and high grade tumours.

Sarcomatoid carcinoma
This is a rare biphasic variant of urothelial carcinoma with a reported incidence of 0.2% to 4.3%.It is known to be associated with poor outcome [8].There are only a few studies regarding the treatment for this type.In the present study, of the 4 patients with, three had solid tumours and one patient had muscle invasive disease.
In this series, we found that the non-urothelial bladder cancers in general were more aggressive with higher rates of muscle invasion and solid tumours compared to the urothelial bladder cancers.Furthermore, a female preponderance was seen among non-urothelial bladder cancer.There were several limitations to this study.Even though we collected data from patients over a 10 year period, due to the rarity of the disease we had only small number of patients.Furthermore, it was a retrospective analysis of a single tertiary care referral centre.

Conclusion
In our study, characteristics of non-urothelial bladder cancers were different and more aggressive compared to urothelial bladder cancers.The current evidence of nonurothelial bladder cancers in the South Asian region is restricted to a few case series and studies including a small sample size.A collective effort by multiple institutions to form a national or regional registry is necessary to advance our understanding, which will enable us to evaluate and optimise management strategies in future.