The Urothelium is defined as the transition epithelium that is contact with urine and covers the urinary system from the renal calices to the urethra.
The bladder is the most frequent site of neoplasms that originate from the transitional epithelium.
Transitional epithelium tumors may also be present in the following districts:
- In kidney calices
- In the ureters
The bladder is a hollow organ located in the pelvis and its functions is collecting urine that is produced in the kidneys and transported via the ureters (two equal and symmetrical organs that run from the renal pelvis to the bladder trigone). Bladder cancer is, in most cases (90%), a “urothelial cell” tumor (urothelium = epithelium that lines the excretory cavities – calices, renal pelvis, ureter and urinary bladder). In rare cases bladder cancer is represented by an adenocarcinoma or a squamous cell carcinoma.
Since it is in most cases a urothelial disease, the tumor can also be localized in the upper urinary tract. Bladder cancer, originating from the mucosa, usually creates vegetation within the bladder lumen (and / or less frequently, a red and flat lesion, hardly visible with non-invasive diagnostics). Some tumors appear as “superficial” lesions, limited to the mucosa and / or lamina propria; others may present deep infiltration, extending to the bladder muscle (detrusor muscle). Finally, the aggressiveness of bladder cancer cells is distinguished in “high or low degree of aggression”.
Epidemiology, Causes and Survival of Bladder Cancer
Bladder cancer, whose incidence is constantly increasing in industrialized countries, represents about 70% of the forms of cancer affecting the urinary tract and about 3% of all cancers. It is more common between 60 and 70 years of age, and is three times more frequent in men than in women. The five-year survival in Italy exceeds 70%, although much depends on the stage at diagnosis. The main causes of the development of a bladder tumor are:
– Smoke. Smoking is the most important risk factor, it is responsible for around 60% of cases. The incidence of bladder cancer is directly related to the duration of smoking, the number of cigarettes smoked, the early age of onset and the fact that they were exposed to secondhand smoke during childhood.
– Diet. Diet also plays an important role: fries and fats consumed in large quantities are in fact associated with an increased risk of getting bladder cancer. The incidence of bladder cancer is lower in people who consume large quantities of fruit and vegetables
– Professional exposure. The second most important risk factor for this neoplasm is represented by exposure to chemicals, especially benzene derivatives and aromatic amines.
– Pelvic radiotherapy. There has been an increase in the incidence of secondary bladder cancer in men or women undergoing pelvic radiation therapy for gynecological malignancies and prostate malignancies.
– Urinary schistosomiasis. Parasitic infection that is endemic in Africa, Asia, South America which is associated with the development of squamous bladder cancer.
– Chemotherapy. The use of cyclophosphamide, an antineoplastic agent used in lymphoproliferative diseases, is related to the development (with a latency of 6-13 years) of bladder cancer.
Symptoms, Diagnosis and Staging of Bladder Cancer
The main symptom of urothelial cancer is painless macrohematuria (red urine) which is present in 85% of patients. Some patients may present irritative urinary symptoms (urination urgency, burning associated with urination, the need to push more frequently during the day). Pain in the pelvic area may be present in more advanced disease. The tests that are carried out in case of clinical suspicion of bladder cancer are:
Cytological examination on three urine samples: especially useful in the follow-up of high-grade neoplasms.
Ultrasound of the urinary tract: useful to identify tumors with a diameter greater than 5 mm and for the diagnosis of hydronephrosis of the upper excretory system.
URO-CT and / or URO-MRI: used for the diagnosis of any of disease affecting the upper excretory system, and in the definition of local infiltration, borne by the urinary bladder. They are also used in staging (research of any lymph node and / or organ metastases) before radical cystectomy surgery.
Outpatient cystoscopy: fundamental examination for the diagnosis of bladder cancer. Easily performed in the clinic (particularly if the flexible, absolutely painless instrument is available), it allows for a rapid and definitive diagnosis of tumors of the urinary bladder and urethra.
Bladder Cancer Treatment
The therapeutic approach varies on the basis of tumor stage that is always distinguished in non-muscle invasive tumor and muscle invasive tumor.
To obtain this distinction, endoscopic trans urethral resection of the bladder tumor (TURBT) is always indispensable. It is an intervention that requires an average hospitalization of 2 days and allows to obtain an extremely precise diagnosis.
Superficial (non-muscle-infiltrating) bladder cancer treatment in centers of excellence: different treatments to prevent recurrence
In light of the histological report, in cases of superficial disease, it may be necessary to carry out cycles of intravesical chemotherapy followed by a close follow-up that allows an early diagnosis of any recurrence (possible in a percentage ranging from 31 to 78% of cases depending on the histopathological characteristics of the disease). Professor Montorsi has been a reference for years for the diagnosis and treatment of bladder cancer and has always been passionately dedicated to the study of the most innovative therapies in this field.
- Intravesical instillations with attenuated tuberculosis bacillus (BCG): Patients with “T1” cancer are usually referred for treatment with a biological drug called BCG (attenuated tuberculosis bacillus). The pattern of bladder instillations varies based on the drug used. Instillations are usually well tolerated and rarely cause systemic effects, which can affect the possibility of continuing treatment. The most frequently occurring disorders are linked to irritative symptomatology (increased urination frequency, urinary urgency and mild urination burning) that resolves at the end of the treatment.
- Intravesical instillations with Mitomycin C: A valid alternative to BCG in patients who do not tolerate this treatment is represented by endovesical instillations with chemotherapy: Mitomycin C. Intensive treatment has recently been introduced in clinical practice which, unlike the classic schemes treatment that involves a weekly instillation with Mitomycin C for 6 weeks, consists of a regimen of instillations 3 times a week concentrated in just 2 weeks. With this new protocol, while maintaining an optimal safety profile, without significant differences in terms of side effects, an improvement in the efficacy of the treatment was obtained, with an important increase in complete responses, defined as the disappearance of the intravesical neoplasm
- Endovesical treatment of bladder cancer with Synergo ®: The Synergo ® system allows to increase the effectiveness of conventional endovesical chemotherapy with Mitomycin by overheating the bladder, thus allowing better penetration of the drug into the bladder tissue ill.
Treatment of muscle invasive bladder cancer: radical cystectomy
In the case of muscle-invasive disease, radical cystectomy is currently the only curative therapeutic option. Depending on the pathological characteristics and the clinical presentation of the disease, there are essentially 3 surgical approaches:
- Radical cystectomy with orthotopic urinary derivations (neobladder)
- Radical cystectomy with heterotopic urinary derivations (eg ureteroileocutaneostomia or ileal conduit)
- Radical cystectomy with ureterocutaneostomy
Robotic surgery has gained an increasingly important role in this context, as it allows to obtain oncological and functional outcomes comparable to open surgery, yet guaranteeing significantly shorter hospital stays and recovery times. The robotic technique allows to operate with a visual magnification up to about 20 times and with a 3-dimensional vision. This allows the surgeon to achieve a better understanding of the depth of field, which is not possible for example with the classic laparoscopic technique. The intraoperative robotic vision allows to recognize even the smallest anatomical details and to carry out the intervention with an accuracy significantly higher than what can be obtained with classical open surgery or with classic laparoscopic surgery. It also allows a reduction in post-operative hospital stay and a significantly lower blood loss compared to open surgery. In selected cases it is also possible to carry out treatments with pre-operative chemotherapy and immunotherapy, aimed at reducing the volume of the disease allowing a better result of the surgical intervention.