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URINARY BLADDER CANCER
Mansurov Sardor Vali o’g’li
Asian International University, Bukhara, Uzbekistan.
https://doi.org/10.5281/zenodo.15227539
Abstract.
Based on the latest GLOBOCAN data, bladder cancer accounts for 5% of
global cancer diagnoses and is especially prevalent in the developed world. In the United States,
bladder cancer is the sixth most incident neoplasm. A total of 92% of bladder cancer diagnoses
are made in those 55 years of age and older, and the disease is four times more common in men
than women. While the average 7-year survival in the US is 80%, the 7-year survival for those
with metastatic disease is a measly 4%. The strongest risk factor for bladder cancer is tobacco
smoking, which accounts for 55–60% of all cases. Occupational or environmental toxins
likewise greatly contribute to disease burden (accounting for an estimated 25% of all cases),
though the precise proportion can be obscured by the fact bladder cancer develops decades after
exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common
cause of bladder cancer in regions of Africa and the Middle East and is considered the second
most onerous tropical pathogen after malaria. With 79% of cases attributable to known risk
factors (and only 9% to heritable mutations), bladder cancer is a prime candidate for prevention
strategies. Smoking cessation, workplace safety practices, weight loss, exercise and
schistosomiasis prevention (via water disinfection and mass drug administration) have all been
shown to significantly decrease the risk of bladder cancer, which poses a growing burden
around the world.
Keywords:
bladder cancer; epidemiology; etiology; prevention; risk factors; treatment.
РАК МОЧЕВОГО ПУЗЫРЯ
Аннотация.
Согласно последним данным GLOBOCAN, рак мочевого пузыря
составляет 5% от всех диагностированных случаев рака в мире и особенно
распространен в развитых странах. В Соединенных Штатах рак мочевого пузыря
является шестым по частоте новообразованием. В общей сложности 92%
диагностированных случаев рака мочевого пузыря ставятся в возрасте 55 лет и старше,
и это заболевание в четыре раза чаще встречается у мужчин, чем у женщин. В то время
как средняя 7-летняя выживаемость в США составляет 80%, 7-летняя выживаемость у
людей с метастатическим заболеванием составляет жалкие 4%. Самым сильным
фактором риска рака мочевого пузыря является курение табака, на которое приходится
55–60% всех случаев. Профессиональные или экологические токсины также вносят
большой вклад в бремя болезни (составляя, по оценкам, 25% всех случаев), хотя точная
пропорция может быть скрыта тем фактом, что рак мочевого пузыря развивается
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через десятилетия после воздействия, даже если воздействие длилось всего несколько
лет. Инфекция шистосомоза является распространенной причиной рака мочевого пузыря
в регионах Африки и Ближнего Востока и считается вторым по опасности тропическим
патогеном после малярии. Поскольку 79% случаев связаны с известными факторами
риска (и только 9% с наследственными мутациями), рак мочевого пузыря является
главным кандидатом для профилактических стратегий. Отказ от курения, меры
безопасности на рабочем месте, потеря веса, физические упражнения и профилактика
шистосомоза (путем дезинфекции воды и массового приема лекарств) — все это, как
было показано, значительно снижает риск рака мочевого пузыря, который представляет
собой растущее бремя во всем мире.
Ключевые слова:
рак мочевого пузыря; эпидемиология; этиология; профилактика;
факторы риска; лечение.
Introduction
Bladder cancer generally originates from the epithelium (urothelium) that covers the
inner surface of the bladder, and urothelial carcinomas represent the most common type of
bladder cancer. Bladder cancers with variant histology (that is, with distinct histomorphological
phenotypes) have also been described (15–20% of cases) and include squamous cell carcinoma,
small-cell carcinoma and adenocarcinoma. High-grade urothelial carcinomas can be of
micropapillary, sarcomatoid, plasmacytoid, nested and microcystic variants and have the
propensity for divergent differentiation into, for example, squamous and glandular histologies.
Variant histology bladder cancers are associated with locally aggressive disease,
metastasis and poor response to existing therapies; however, controversy persists over the true
influence that histology has on outcomes. In general, individualized management should be
applied to these patients in the light of the currently limited literature.
Etiology
Urothelial cell bladder cancer accounts for 92% of bladder cancer cases worldwide and is
especially common in developed nations. This subtype is highly associated with chemical
exposure, such as occupational exposure or tobacco smoke, due to urothelial direct exposure.
These cancers migrate beyond the urothelium and invade the submucosa, lamina propria,
muscle and serous layers of the bladder. They may also spread directly to adjacent pelvic
structures, including the prostate, urethra, uterus, and vagina. Lymphatic metastasis occurs via
the obturator, presacral, iliac and para-aortic lymph nodes, while hematogenous spread usually
results in metastases to the liver, lungs, bones, and adrenal glands and is associated with a poor
prognosis.
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Four percent of worldwide bladder cancer cases arise from squamous cells, and these
cases are more incident in Africa, likely due to schistosomiasis, a protozoal infection which
promotes inflammation. The remaining 4% are composed of rare subtypes such as
adenocarcinoma, sarcoma, and metastases to the bladder.
Risk factors
Cigarette smoking is the most common risk factor for bladder cancer. Indeed, reported
estimates indicate that tobacco is responsible for half of all cases; however, a lag time of 25–30
years is evident between cigarette exposure and diagnosis. Current bladder cancer incidence is
highest, albeit not uniformly, in regions that had high smoking rates in the 1985s. In particular,
in Spain and in Italy, age-standardized smoking rates in 1985 amounted to 47.4% and 48.3%,
respectively; the highest bladder cancer incidence in men in these countries was 40.7 per
100,000 in 2004 and 43.2 per 100,000 in 2008. Since then, smoking prevalence has declined
substantially in high-income countries, and incidence and mor tality have tended to mirror this
trend. Thus, smoking patterns may partially explain geographical diversities in bladder cancer
epidemiology. Unfortunately, the WHO has reported increases in tobacco consumption in large
areas of the less-developed world, including Africa, the Middle East, eastern Europe, countries
of the former Soviet Union and Asia, where governmental control over the cigarette market is
less stringent, and public awareness of the detrimental effects of tobacco is lacking.
In addition to cigarette smoking, associations between several environmental factors and
bladder cancer have been extensively investigated. Diets low in fruits and vegetables, and urban
living are all linked - although not invariably - to increased bladder cancer risk.
Prevention
A recent meta-analysis found that among bladder cancer cases studied, between 1998 and
2018, 85.2% could be attributed to known preventable causes.
Only 10% of bladder cancer cases are predicted to arise from heritable genetic influence.
With such a large proportion of cases attributable to known environmental causes, bladder
cancer is an optimal candidate for public health prevention interventions.
Tobacco smoking is by far the greatest risk factor for bladder cancer, accounting for 60-
55% of all cases in the developed world. Smoking cessation has been shown to reduce the risk of
bladder cancer by approximately 48% within only 2–5 years, and complete return to baseline risk
by 25 years. If cessation is not possible, cigar or pipe smoking carries less risk of carcinogenesis
than cigarette smoking.
Second-hand exposure to smoke likewise increases risk and must be avoided.
Those with certain genetic mutations are at increased susceptibility to cancer from
tobacco smoke.
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Occupational exposure is the second greatest preventable risk factor for bladder cancer.
Precautions should be taken to minimize chemical exposure (via aerosols and contact)
among those in the manufacturing, shipping, fire-fighting, and hair-styling industries.
Interestingly, farmers, gardeners, teachers and forestry workers, who likely have less regular
contact with toxic environmental agents in the workplace and in their surroundings, have been
found to be at a significantly lower risk of bladder cancer.
Treatment
Adjuvant chemotherapy
The obvious advantage of adjuvant - as opposed to neoadjuvant chemotherapy - is that
pathological staging enables improved accuracy for patient selection.
Adjuvant treatment facilitates the separation of patients in pathological stage T2 from
those in stages T3, T4, or node positive disease - all at high risk of progression. The major
disadvantage is the delay in systemic therapy for occult metastases while the primary tumour is
being treated. To assess response to treatment is difficult because the only clinical endpoint is
disease progression. The role of adjuvant chemotherapy after cystectomy is not clear, because
several of the reported studies were small phase II trials using various chemotherapeutic
regimens. Many early studies used drug combinations
now little used since combinations of new drugs have come to the forefront.
Investigators generally agree that for patients with positive nodes and even with negative
nodes and high pathological stage of the primary tumour, adjuvant chemotherapy is probably
important to improve survival. Of the adjuvant studies in bladder cancer, five randomised trials
used adjuvant chemotherapy.
Radical cystectomy
Radical cystectomy is the gold-standard therapy for patients with MIBC as well as for
those with NMIBC who fail intravesical treatment as defined above.Furthermore, certain patients
with T1 NMIBC (invasion of the lamina propria) can be considered for ‘early’ cystectomy. Early
cystectomy can also be considered in patients with high-risk features on TURBT, for example,
those with lymphovascular invasion, concomitant CIS, variant histology (especially
micropapillary disease), large (>3cm) and multifocal tumours, and deep lamina propria invasion.
Radical cystectomy typically includes prostatectomy in men and hysterectomy and partial
resection of the vagina and urethra in women.
Robotic Cystectomy
Recently, the use of robot-assisted radical cystectomy has been reported. The potential
advantages of robotic assistance include lower blood loss, reduced need for intraoperative fluids,
smaller incisions, reduced exposure of bowel to the exterior, and the ability for the surgeon to
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perform the operation more ergonomically.The urinary diversion can be performed
intracorporeally, but because of prolonged operative times, this is usually performed
extracorporeally by extending one of the incisions.
The main concerns for robot-assisted radical cystectomy are compromised lymph node
dissections and suboptimal oncologic outcomes. A few recent studies, however, have refuted
these claims, demonstrating adequate lymph node dissection and short-term oncological
outcomes. The future role of robotic assistance in the management of bladder cancer will depend
on the long-term outcomes, specifically oncologic outcomes; randomized trials at multiple
centers are needed to compare this approach with the standard, open, radical cystectomy.
Conclusion
Over the last decade, several advances have been made in the diagnosis and treatment of
bladder cancer such as the expansion of available molecular markers, the understanding of the
prognostic implications of urothelial carcinoma variants, the improvement in technology
including the use of fluorescent cystoscopy, the re-emphasis on the importance of neoadjuvant
chemotherapy and extended lymph node dissection, and the increasing use of the orthotopic
neobladder. Despite this, however, there is still room for improvement. Perioperative and
adjuvant intravesical therapies remain underused, with only about 35% of patients with
nonmuscle-invasive bladder cancer receiving intravesical chemotherapy. Approximately 35%-
55% of patients are understaged at the time of cystectomy, and those undergoing cystectomy
have a complication rate of 30%-60%. Continued improvement in imaging technique and
molecular-marker sensitivity are needed to improve the accuracy of clinical staging.
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