BLADDER CANCER: causes, symptoms and therapy of bladder cancer

Bladder cancer

What is bladder cancer and epidemiology

Bladder neoplasm is an overgrowth of cells in the bladder wall. The meaning of the terms tumor, neoplasm or cancer are equivalent, so in the article they will all be used to refer to the same bladder pathology. Bladder cancer typically originates from the urothelium, or transitional epithelium, which is the type of tissue that characterizes all the urinary tract starting from the renal pelvis to the urethra.

From an epidemiological point of view, bladder cancer and in particular urothelial carcinoma (94% of the total bladder tumors), represents about 4% of all malignant tumors, with a 3 times higher incidence in males than in females: in Italy, the incidence is 30 men and 10 women per 100,000 people per year, for a total of about 18,000 cases and 7,000 deaths.

Classification

Bladder tumors account for 99% of cases malicious, within which urothelial carcinoma (94% of the total; also called transitional carcinoma), squamous or squamous cell carcinoma (less than 4%; more frequent in North Africa, especially Egypt), adenocarcinoma (less than '1%) and finally small cell bladder cancer (extremely rare).

The remaining 1% of cases is instead benign, among which bladder polyps can be found, bladder papillomas such as benign bladder papilloma or inverted urothelial papilloma (more frequent in children), or nephrogenic adenoma (which in 30% of cases is localized in the ureters).

Within the most frequent type of tumor, namely urothelial carcinoma, there is a further classification: this neoplasm can be morphologically papillary (90% of cases; pedunculated or sessile) or non-papillary (solid exophytic, often ulcerated or warty, or flat , which develops towards the outside of the bladder); single or multi-focal (more frequent); superficial (80% of cases; it does not infiltrate the muscular layer but have a marked tendency to progress and relapse) or infiltrating (20%, in which the muscular layer has already been overcome and in 5% of cases it already has metastases).

Risk factors

The main risk factors for bladder cancer are the following:

  • Cigarette smoke: up to 50% of bladder carcinoma cases are attributable to cigarette smoking. In addition to the action of multiple harmful substances, an important role is played by 2-naphthylamine, a compound that is absorbed through the lungs and subsequently modified by the liver through a conjugation with glucuronic acid to be excreted in the urine. In the conjugated form, this compound has no carcinogenic action, but this bond is broken down in the urine and 2-naphthylamine leads to tumor transformation of the bladder wall cells.
  • Working activity within textile industry factories: approximately 25% of bladder cancer cases, especially in the past, were due to contact with fabrics and dyes used in textile factories. Also in this case the role of 2-naphthylamine has been observed, contained in some substances used in the coloring and treatment processes of leather and rubber.
  • Coffee and alcohol
  • Infections: the specific form of squamous cell carcinoma is linked to the presence of the parasite Schistosoma Haematobium, endemic to Egypt, Tanzania and Malawi.
  • Radiation (used in prostate or rectal cancer) and drugs (cyclophosphamide).
  • A long history of infections or kidney trauma it has been linked to the onset of nephrogenic carcinoma. In this particular tumor, 70% of cases is in the bladder, while the remainder is in the ureters.
  • Some bladder malformations are associated with bladder adenocarcinoma. Among these, the most important are the persistence of uraco (an embryonic residue) and bladder exstrophy.

As there are currently no effective screening tests, it is extremely important to put in place preventive measures to reduce risk factors.

Bladder cancer: Favored by risky behaviors such as cigarette smoking, often manifested by blood in the urine (hematuria).

Evolution and prognosis

In the absence of diagnosis and therefore of therapy, the tumor develops in size going to protrude inside the bladder lumen but also infiltrating the wall, eroding the muscular layer and affecting all areas of the bladder (such as the bladder trigone, the urethral sphincter internal, the outlet of the ureters), giving lymph node metastases (pelvic, hypogastric, obturator and internal iliac lymph nodes) and to the bones, lungs and liver.

The life expectancy of patients with bladder cancer essentially depends on the early diagnosis, the evolution of cancer cells and the implementation of therapies. In general, the prognosis is very good in the early stages (88-98% at 5 years), and decreases in the intermediate forms (46-63% at 5 years) and in advanced ones with metastases (15% at 5 years).

Symptoms and clinical manifestations

From the point of view of symptomatology, about 80% of cases is present hematuria, or the presence of blood in the urine. In almost all cases, this hematuria is macroscopic or visible to the naked eye, the so-called macrohematuria: The urine will then appear more red, flesh-washed or Coca Cola colored. Typically, this hematuria is recurrent (it is not always present, it can come and go) and is often accompanied by clots of blood; furthermore, it is typically present at the end of urination and is therefore defined terminal hematuria. In about 30% of people with bladder cancer, symptoms of irritability of the bladder due to bladder inflammation that is established, such as pollakiuria (increased frequency of urination), stranguria (difficulty urinating), urinary urgency is tenesmus (feeling of need to urinate despite being unable to urinate).

Late, especially if the tumor is infiltrating the bladder trigone, this can obstruct the outflow of the ureters and cause hydronephrosis and ache colic; may be present bladder pain and symptoms due to bone, liver or lung metastases.

Diagnosis

The diagnostic procedure for bladder cancer provides that there is a diagnosis of suspicion (but not certain) already at the time of the medical history: a subject who reports macroscopic hematuria must be considered suffering from bladder cancer until proven otherwise, and therefore the first diagnostic investigations are aimed in this sense. It is therefore important to detect the presence of any risk factors, characterize and confirm the presence of hematuria (if it is absent it is necessary to do a urinalysis and search for microhematuria) and symptoms related to inflamed bladder.

Subsequently, a rectal examination or a 'vaginal exploration if you suspect the presence of a large tumor, which could then be detected on palpation.

The most important tests in diagnostics are the cytological examination of urine (CTM, malignant tumor cells), the lower abdominal ultrasound (which, however, fails to detect the presence of flat tumors), cystoscopy (insertion of an optical tube through the urethra to the bladder) and uroTC.

The cytological examination of urine, the urinary cytology, it is performed on 3 urine collection samples for 24h (then 3 days of urine): through microscopic analysis, flow cytometry, DNA analysis using the FISH method and search for BTA (bladder tumor antigen) this test provides a solid basis, when positive, for the diagnosis of bladder cancer; however it cannot give a diagnosis of certainty.

Through the investigation of cystoscopy the site, the size, the number of lesions and the appearance of the tumor can be verified with certainty, as well as providing fundamental information for any surgical intervention.

Finally, with an investigation by uroTC and magnetic resonance imaging can stage the tumor, detecting the presence of any metastases to lymph nodes or other tissues.

Therapy

Are there adequate treatments for bladder cancer? There are two different situations on the basis of the level of tumor development: when superficial, a surgical approach is possible through the TURB procedure (trans - urethral resection of the bladder), thanks to which it is possible to remove the tumor mass entering the bladder through the urethra, therefore in the absence of external scars and related surgical risks.

After the procedure, an intravesical chemoprophylaxis treatment follows: drugs capable of stimulating the immune system to react vigorously against a possible tumor recurrence are instilled into the bladder via catheter. These adjuvant drugs are: mitomycin, BCG (Calmette-Guérin bacillus), doxorubicin, gemcitabine and epirubicin.

As regards infiltrating tumors (ie those that go beyond the muscular wall of the bladder), first of all the degree of malignancy of the tumor must be confirmed through the removal of the visible mass in the bladder, through an endoscopic intervention. If elevated malignancy is confirmed, the bladder must be removed completely (cystectomy, or cysto-prostate-vesiculectomy in men) to remove the entire mass and prevent recurrence.

Clearly, since the subject at this point is deprived of an important organ, an intervention is necessary to create a urinary derivation through which the urine can be expelled. This can be done in three different ways:

  1. Uretero-cutaneous-ostomy: the ureters (ducts through which urine is normally carried from the kidney to the bladder) are sutured to the skin and two urine collection bags are placed; or, the ureters are joined into a single cutaneous outlet.
  2. Uretero-ileo-cutaneous-ostomy: the ureters are sutured to an intestinal loop, which is in turn sutured to the skin. In this way, the intestinal loop plays a role as a reservoir, preventing the reflux of urine into the ureters.
  3. Creation of a neobladder: an intestinal loop is used, which in this case is connected to the ureters on one side and to the urethra on the other. In this way it is possible to avoid the creation of stoma on the abdomen.

In the last two cases in particular, the patient's quality of life is marked by the fact that there is no urge to urinate, that one has to press on the abdomen to do so, that it is necessary to take mucolytics for life (the intestinal loops continue, as usual , to produce mucus) and by the fact that, since the intestinal loops maintain the absorption capacity, it is necessary to make frequent checks to verify that there are no serious alterations in the acid-base balance in the blood.

Additional therapies are radiotherapy (which can give good results in patients who cannot undergo surgery) and chemotherapy (reserved for advanced patients with metastases).

 

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