The incidence of BC in our area of the North-East of Spain was very high in men, as reported in previous studies [9,10]. When considering the crude annual rate, such figure was similar to the one in Spain for the same period, but became higher when adjusting to the European or the World Standard Populations) [4,5,7]. When comparing with all European countries, in 2018 the incidence of BC in men, adjusted to the European Standard Population, ranked second after Greece [5,7], and third after Greece and Lebanon when adjusted to the World population . Alternatively, the incidence in women was much lower, ranking the lowest of all European countries whether considering the crude or the adjusted rate (European Standard Population), and one of the lowest when considering the incidence adjusted to the World Standard Population [4,5,7].
According to the previously published incidence of BC in our area under study during the period 1992-1994 both the crude and the age-adjusted annual incidence have risen in both sexes, although the increase in men is notably higher [9,10]. In our area of North-Eastern Spain, the high incidence of BC in men could be related to a high prevalence in this area of well-known risk factors for BC, such as smoking, residence in industrialized areas and occupational exposures to certain carcinogenic products [10,14]. In 2015, 27.7% of the population of our area under study declared to be a smoker, a percentage above the average for Catalonia, which was 25.7% . Although in our area data on the proportion of smokers by gender were not available in 2018, in Catalonia such prevalence was higher in men (30.9%) than in women (20.5%), a percentage that increased up to 40.3% in the group of men from 35 to 44 years .
In relation to the occupational exposure, historically the high incidence of BC in this area was related to the existence of an important textile industry since the mid-19th century. The decline of textile industry began in the 1970s, becoming marginal at the end of the eighties. The 1992-1994 studies, where a high incidence was observed, only found some moderate occupational risk in relation to previous and prolonged exposures in the textile industry [10,14], as a significant percentage of the population had previously worked in this sector without the current security conditions. Our study shows that, more than three decades after the receding of the textile industry, the incidence of BC in men has not decreased, in fact it is higher than before. Currently most workers in the studied area belong to the service sector (58.6%), followed by the industrial sector (32.4%), construction (8.7%) and agriculture (0.2%) . It is probable that factors, such as the textile industry, which favoured the high incidence of BC in the past, have been replaced by others related to pollution or dietary habits.
The mean age of BC diagnosis was similar to the one reported in other series [8,9,18], without differences between both genders. As in the previous study , the incidence of this cancer in our healthcare area is ten times higher in men than in women, while in the World Population it is only four times higher. The discrepancy in incidence between genders in different countries has been attributed to differences in the prevalence of tobacco use. Thus, countries like Lebanon, where smoking is culturally prevalent among women, have the highest incidence of BC [1-3]. Other factors that may reduce women's predisposition to BC would be those related to hormonal and genetic factors and lower occupational exposure to carcinogenic products in agriculture, textile, chemical or construction industries [19-21]. Finally, certain dietary habits such as the consumption of coffee and alcohol, low consumption of fruits and vegetables, and diets rich in red meat and animal proteins, are factors possibly implicated in the higher incidence in men than in women [21-24].
The histological characteristics of the tumours are similar to other series [8,18], with predominance of grade 1 and 2 low-grade tumours (51.2%), and those limited to the Ta (60.7%) and T1 mucosa (22.4%), muscle invasive tumours being rare (12.2%) and metastatic spread exceptional (2.3%). Unlike the previous study in our area, we have not found that grade 3 tumours were more frequent in those over 65 years, nor that Ta tumours were significantly more frequent in patients under 65 years of age [9,10]. Neither did we observe a relationship between the degree of infiltration and gender, so that the percentage of invasive tumours was not significantly higher in women in the present study [9,18].
The possibility that residents in our healthcare area were diagnosed and treated for BC in centres other than the referral hospitals might have led to a certain underestimation of the incidence of BC. However, according to the 2017 health survey of the National Institute of Statistics (INE), in Spain, 83.4% of the population uses the public health system exclusively, 15.4% attends both public and private centres, and only 0.9% is an exclusive user of the private health system . Another limitation, shared with other epidemiological studies on BC, is related to the difficulty of comparing different series. First, the national and international BC registries are not homogeneous because there are differences in definition and inclusion criteria [26-27]. Despite the use of systematic classifications of tumours such as the TNM classification, some specific characteristics of bladder cancer lead to great heterogeneity when labelling the tumour. Some registries include non-invasive tumours (Tis and Ta) while others only include invasive ones (T1 or higher). Furthermore, the nomenclature is prone to confusion, since the term "invasive" does not have a clear definition; it may be applied either to describe tumours that invade the lamina propia (T1) or to refer, depending on clinicians, to those that invade the bladder muscle layer (T2 or higher). In parallel, given that Ta tumours may account for up to 50% of BC, their inclusion or exclusion has an important effect when assessing incidence, survival or mortality . In addition, bladder carcinoma in situ has clinical, diagnostic, and therapeutic implications that do not correspond to the ones of carcinoma in situ of other organs; in many cancer registries, often with no participation of urologists, those cancers are not included. Secondly, it is difficult to make comparisons between adjusted rates, and it has already been suggested that incidences adjusted to the European Standard Population of 2013 are not comparable with those adjusted to the previous European population of 1976 that many registries have used. Finally, another epidemiologically relevant factor is the high rate of relapses of superficial BC delayed in time, which can be mistakenly considered as new onset cases.