Everything you need to know about the latest developments in the diagnosis and treatment of bladder cancer by Dr. M. Karavitakis

The ladder cancer is one of the most common human cancers.

This page aims to provide comprehensive information about bladder cancer, from epidemiology and diagnosis to the most advanced treatment methods. 

Bladder cancer is a subject of clinical, surgical, and research interest for Dr. M. Karavitakis, whose articles are published in leading scientific journals (European Urology, Nature) and in Campbell-Walsh Urology, the reference textbook for international urology. Dr. Karavitakis is also a frequent speaker at conferences. 

Learn about the prevalenceetiology , as well as the as well as the methods of diagnosis and treatment of bladder cancer. 

bladder

General Information About Bladder Cancer

What is the Bladder?

The bladder is an organ that stores urine before it leaves the body. It is a hollow organ located in the pelvis with flexible, muscular walls.

The bladder can expand or contract as it fills with urine.

Urine is transported to the bladder through small tubes called ureters.

Urination begins when the muscles of the bladder contract, allowing urine to exit through a tube called the urethra.

What is Bladder Cancer?

Bladder cancer is a pathological condition in which the cells lining the bladder wall begin to multiply uncontrollably, leading to the formation of tumors within the bladder.

The bladder wall has many layers made up of different cell types. Most bladder cancers start in the urothelium or transitional epithelium, the inner lining of the bladder. Transitional cell carcinoma is the cancer that forms in the urothelial cells.

Bladder cancer worsens as it spreads to other layers of the bladder wall. Over time, the cancer can spread outside the bladder to nearby organs and tissues. Bladder cancer can also spread to the lymph nodes and metastasize to the bones, lungs, liver, and other parts of the body.

How Common is Bladder Cancer?

Bladder cancer is the 6th most common cancer.

In the United States, nearly 81,000 people will be diagnosed with bladder cancer in 2019.

Bladder cancer is more common in men than in women, with men being four times more likely to develop the condition.

The frequency of bladder cancer increases with age, most commonly occurring in the 75-84 age group.

Causes of Bladder Cancer

Smoking as a Major Cause

Smoking is responsible for half of all bladder cancer cases. People can increase their risk of developing bladder cancer when they are exposed to tobacco smoke or other carcinogens.

Exposure to certain carcinogens in the workplace, particularly those found in chemicals used to make plastics, paints, textiles, leather, and rubber, also increases the risk of bladder cancer.

There are also risks associated with genetics and certain types of infections.

Another known risk factor is the administration of radiation therapy to the pelvis.

Patients with other cancers, such as lymphomas and leukemia, who are treated with the drug cyclophosphamide, may have a higher risk of developing bladder cancer.

Symptoms of Bladder Cancer

The presence of blood in the urine, known as hematuria, is the most significant symptom of bladder cancer.

Generally, hematuria is painless and does not cause discomfort. However, blood in the urine does not always indicate bladder cancer, as it can also be caused by other conditions such as kidney stones or urinary tract infections. Additionally, a small amount of blood in the urine can be normal for some individuals.

Other symptoms that may be associated with bladder cancer include: 

  • Frequent and urgent urination
  • Pain during urination
  • Pain in the lower abdominal area

Diagnosis of Bladder Cancer

The diagnosis of bladder cancer usually begins with the investigation of the symptom of hematuria and involves a series of tests, which include:

  • Urine Cytology. This test evaluates the cells in the urine under a special microscope.
  • Ultrasound of the Kidneys and Bladder. This is typically the first test performed when bladder cancer is suspected.
  • CT Scan (Computed Tomography) A CT scan is often a key test for assessing hematuria.
  • Cystoscopy: A thin tube with a light and camera at the end (cystoscope) is passed through the urethra into the bladder, allowing for a visual inspection of the bladder cavity. Usually, a flexible cystoscope and local anesthesia are used.
  • Rigid Cystoscopy: A rigid cystoscope, which does not bend and is used under some form of anesthesia, may be employed. This larger cystoscope has a light at the end and can pass special surgical instruments through it. It allows for more extensive procedures, such as transurethral resection of bladder tumor (TURBT), which is described below.

Bladder cancer diagnosis is confirmed when the doctor sees the tumor during cystoscopy and performs a biopsy using TURBT.

TURBT is a crucial procedure for accurately staging and classifying the disease.

Staging of Bladder Cancer

Bladder cancer staging is done after histological examination of the biopsy sample and with the help of imaging tests such as CT scans. Staging allows for prognosis evaluation and planning of further treatment if needed. 

The histological grade and stage are two important ways to describe the aggressiveness and prognosis of the cancer. The tumor grade indicates how aggressive the cancer cells are, while the tumor stage indicates how deeply the cancer has invaded the bladder wall and if it has spread to other organs.

Tumor Grade

The grade is a parameter that evaluates the characteristics of the cancer cells and indirectly the aggressiveness of the cancer.

Low-Grade: Cancer cells are less aggressive. High-Grade: Cancer cells are very abnormal and poorly organized, indicating high aggressiveness.

Cancer Stage

The stage describes the spread of the disease within the bladder wall or beyond. The grade and stage of the cancer are assessed through the biopsy taken during the transurethral resection of the bladder tumor (TURBT). A pathologist examines the sample under a microscope to determine the grade and stage of the cancer.

Stages of Bladder Cancer:

  • Ta: Tumor on the bladder surface that does not invade any layers of the bladder.
  • Tis: Carcinoma in situ (CIS) - a flat, high-grade tumor that appears as a reddish, velvety patch on the bladder surface.
  • T1: Tumor invades the layer beneath the surface but does not reach the muscle layer.
  • T2: Tumor grows into the muscle layer of the bladder.
  • T3: Tumor extends through the muscle layer into the surrounding tissue, usually the fat around the bladder.
  • Τ4: Tumor has spread to nearby structures such as the prostate in men or the vagina in women.
 
Non-Muscle-Invasive Bladder Cancer (NMIBC) 

NMIBC is confined to the surface cells of the bladder lining and does not invade the muscle layer. These tumors are classified from Ta (lowest stage) to T1 (highest stage for NMIBC).

Recurrence and Progression: Over half of the patients with low-grade cancers will experience tumor recurrence. About 6% will progress to a higher stage. High-grade T1 cancers recur in approximately 45% of cases, with 17% potentially progressing to a higher stage.

Survival Rates: Once diagnosed, survival rates for NMIBC are quite favorable. High-grade disease survival ranges from approximately 70-85% at 10 years, with much higher rates for low-grade disease. Early diagnosis is crucial for predicting the disease course and selecting the best treatment.

Muscle-Invasive Bladder Cancer (MIBC) 

MIBC represents a more aggressive form of the disease and differs from NMIBC in that it invades the bladder's muscle wall. This stage of cancer requires more urgent and aggressive treatment. MIBC is typically classified as stage T2 or higher, up to T3 and T4, based on the depth of invasion into the muscle wall.

Survival rates can vary depending on the stage of the disease and the response to initial treatment.

The 5-year relative survival for patients with MIBC generally ranges from about 50% to 70%, depending on the disease stage and response to initial treatment. Patients with advanced MIBC (stages T3-T4) often have lower survival rates, sometimes significantly below 50%.

Response to treatments like surgery, chemotherapy, and radiation therapy significantly affects patient survival. Those who respond well to treatment have better survival prospects.

It's important to note that these survival rates are general estimates and may have exceptions. A patient's exact prognosis depends on many factors and should be discussed with their physician based on the specific case.

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Treatment of Bladder Cancer

The treatment of bladder cancer depends on the degree of tumor invasion into the bladder walls and may include:

  • Transurethral Resection of Bladder Tumor (TURBT): This procedure involves the removal of the tumor using a cystoscope passed through the urethra. After the tumor is removed, the patient undergoes regular cystoscopic monitoring.
  • Intravesical Therapy (Chemotherapy and Immunotherapy)
  • Radical Cystectomy and Urinary Diversion 
  • Radiation Therapy
  • adjuvant chemotherapy either before (neoadjuvant) or after (adjuvant) surgery

Key Factors in Treatment Selection influenced by several factors, including: 

  • Invasiveness: Whether the cancer is muscle-invasive or non-muscle-invasive (indicating deep invasion into the bladder wall).
  • Risk of Recurrence and Progression: Likelihood of the cancer returning or advancing to a more severe stage.
  • Patient Age: Age can affect treatment tolerance and overall health.
  • Comorbidities: Other existing health conditions that the patient may have.
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Endoscopic Treatment - Transurethral Resection of Bladder Tumor (TURBT)

What is Transurethral Resection of Bladder Tumor (TURBT)?
TURBT is a surgical diagnostic and therapeutic procedure that allows the surgeon to remove the bladder tumor and take a biopsy to confirm the cancer diagnosis and determine its stage and grade.

TURBT is typically performed under anesthesia (general or epidural). The surgery is done during a cystoscopy, so no abdominal incision is necessary.

A rigid cystoscope, which has a light at the tip and is large enough to allow the insertion of surgical instruments, is used. This enables the surgeon to take samples and resect the tumor.

If a tumor is clearly visible, the doctor will attempt to remove it entirely. The doctor may also take biopsies from other areas of the bladder that appear abnormal. These samples will be examined to determine the grade and stage of the cancer. A catheter may be left in the bladder for a few days.

Difference Between Cystoscopy and TURBT
Cystoscopy is often used to detect the presence of bladder cancer. If cancer is detected, TURBT is performed to remove the tumor and determine whether it has spread into the muscle layer of the bladder wall.
 
Success Rates of TURBT
Even after the tumor is removed with TURBT, up to 50% of patients may experience a recurrence of cancer within 12 months. Due to this high recurrence rate, adjuvant (supplementary) therapy is usually recommended.
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Intravesical Therapy (Chemotherapy and Immunotherapy)

Intravesical therapy involves delivering a drug (chemotherapeutic or immunotherapeutic) directly into the bladder.

The medication is instilled into the bladder using a thin catheter and remains in the bladder for one to two hours before being expelled through urination.

Intravesical chemotherapy is usually administered immediately after surgery, while intravesical immunotherapy is administered after a few weeks.

Intravesical Immunotherapy

Immunotherapy boosts the immune system's ability to fight cancer.

The drug used in intravesical immunotherapy is BCG (Bacillus Calmette-Guérin), which is also the tuberculosis vaccine.

The initial treatment lasts about six weeks, followed by maintenance doses at regular intervals. Usually performed on an outpatient basis.

BCG activates the immune system to attack bladder cancer cells and is one of the most effective treatments, especially for carcinoma in situ. Not recommended for patients with a weakened immune system or certain symptoms.

Side effects may include:

  • Frequent urination
  • Pain during urination
  • Flu-like symptoms
  • Joint pain
  • Fever or chills
Intravesical Chemotherapy

Typically administered immediately after surgery.

Because the medicines only reach the surface of the bladder, this type of treatment is only recommended for non-infiltrating bladder cancer.

Mitomycin C is usually given right after the initial TURBT to prevent cancer cells from spreading and to reduce recurrence rates.

Administered in a regimen similar to BCG, often over six weeks. Side effects may include:

  • Frequent urination
  • Painful urination
  • Flu-like symptoms
  • Skin rash
Maintenance Intravesical Therapy

Maintenance therapy involves repeated doses following the initial intravesical treatment. Usually applied to patients who received BCG and less frequently to those who had chemotherapy.

Administered for up to three years after treatment, typically every six months for three weeks at a time.

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Surgical Treatment: Radical Cystectomy

What is Radical Cystectomy?

Radical cystectomy is a surgical procedure recommended for aggressive bladder cancer that involves the removal of the bladder.

Radical Cystectomy Includes:

  • In Men: Removal of the bladder and prostate.
  • In Women: Removal of the bladder, uterus, ovaries, and the anterior wall of the vagina (unless organ preservation is applied).

In both men and women, the procedure also includes the removal of pelvic lymph nodes and the selection of a method for urine diversion.

What is Urine Diversion?

Urine diversion refers to the method chosen to allow urine to exit the patient's body after bladder removal.

Methods of Urine Diversion:

  • Ureterostomy: Ureters are attached directly to the patient's skin, with a bag to collect urine.
  • Ileal Conduit (Bricker):  Ureters are connected to a piece of intestine, which is then brought out to the skin, with a bag for urine collection.
  • Orthotopic Neobladder: Ureters are connected to a segment of intestine reshaped to form a new bladder, which is connected to the urethra, allowing urine to exit normally without an external bag.

Each method has advantages and disadvantages and specific limitations.

Selecting the method involves thorough discussion with the patient, considering factors like age, cancer location, comorbidities, and compliance level.

Other parameters such as the age of the patient, the location of the cancer, comorbidities, level of compliance, etc.

How is Radical Cystectomy Performed?

Radical cystectomy can be performed:

  • with the Open Method
  • with the Minimally Invasive Methods including laparoscopic and robotic techniques

The difference between the open method and the minimally invasive methods is the fact that in the open method the surgery is performed through a large incision in the abdomen while in the minimally invasive methods the surgery is performed through small incisions in the patient's skin.

There is no difference in cancer-related outcomes between the open and minimally invasive methods. However, the minimally invasive approaches offer the benefits such as 

  • less postoperative pain
  • reduced blood loss
  • faster hospital discharge
  • quicker recovery, and return to normal activities

Learn more about laparoscopic and radical cystectomy

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Radiotherapy for Bladder Cancer

What is Radiotherapy for Bladder Cancer?

Radiotherapy is a specialized treatment for bladder cancer that uses high-energy radiation to destroy cancer cells. In bladder cancer, radiotherapy can be used either as a primary treatment option in combination with chemotherapy or to relieve symptoms in advanced stages.

How is Radiotherapy Administered?

The dosage of radiotherapy for bladder cancer is carefully determined based on factors such as the size and location of the tumor, the patient's overall health, and the goal of the treatment.

Radiotherapy is usually given in multiple sessions over a specified period. This approach allows healthy tissue to recover between treatments while maximizing the effect on cancer cells.

Side Effects of Radiotherapy

While radiotherapy is generally well tolerated, there are potential side effects.

These are usually temporary and include fatigue, skin irritation or redness in the treated area, and changes in urination, such as frequent urination or pain during urination.

In some cases, long-term side effects may occur, such as changes in urination and bowel habits. However, modern radiotherapy techniques have significantly reduced the risk of such effects.

Indications for Radiotherapy

Radiotherapy for bladder cancer has the following indications:

  1. Definitive Therapy: Radiotherapy can be used as the primary treatment for patients who are not suitable candidates for surgery. It can target and destroy cancer cells, leading to remission or control of the disease. In this case, radiotherapy is combined with chemotherapy.
  2. Palliative Therapy: For patients with advanced bladder cancer that has spread to other areas, radiotherapy can help relieve symptoms.
 

Χημειοθεραπεια στον καρκίνο της ουροδόχου κύστης

Τι είναι η χημειοθεραπεία για τον καρκίνο της ουροδόχου κύστης;

Η χημειοθεραπεία είναι μια συστηματική θεραπεία που χρησιμοποιείται για την καταπολέμηση του καρκίνου, στοχεύοντας στην καταστροφή των γρήγορα διαιρούμενων κυττάρων, συμπεριλαμβανομένων των καρκινικών κυττάρων.

Ποια είναι η δοσολογία της χημειοθεραπείας; 

Η δοσολογία της χημειοθεραπείας για τον καρκίνο της ουροδόχου κύστης εξαρτώνται από διάφορους παράγοντες, όπως ο τύπος και το στάδιο του καρκίνου, η συνολική υγεία του ασθενούς και τα φάρμακα που χρησιμοποιούνται. Η χημειοθεραπεία συχνά δίνεται σε κύκλους, με μια περίοδο θεραπείας ακολουθούμενη από μια περίοδο ανάπαυσης για να επιτρέψει στο σώμα να ανακάμψει από τυχόν πιθανές παρενέργειες.

Ποιες είναι οι παρενέργειες της χημειοθεραπείας;

Η χημειοθεραπεία επηρεάζει τόσο τα καρκινικά όσο και τα υγιή κύτταρα, πράγμα που μπορεί να οδηγήσει σε διάφορες παρενέργειες. Συνήθεις  παρενέργειες της χημειοθεραπείας για τον καρκίνο της ουροδόχου κύστης περιλαμβάνουν:

  • Ναυτία και Εμετός: Η χημειοθεραπεία μπορεί να επηρεάσει το γαστρεντερικό σύστημα, προκαλώντας αίσθηση ναυτίας και εμετού. Συνήθως, χορηγούνται φάρμακα για τη διαχείριση αυτών των συμπτωμάτων.
  • Κόπωση: Πολλοί ασθενείς βιώνουν κόπωση ως αποτέλεσμα της επίδρασης της χημειοθεραπείας στα υγιή κύτταρα.
  • Απώλεια Μαλλιών: Η απώλεια μαλλιών είναι συνήθης παρενέργεια λόγω της επίδρασης στα γρήγορα διαιρούμενα κύτταρα των μαλλιών.
  • Αποδυνάμωση του Ανοσοποιητικού Συστήματος: Η χημειοθεραπεία μπορεί προσωρινά να αποδυναμώσει το ανοσοποιητικό σύστημα, καθιστώντας τους ασθενείς πιο ευάλωτους σε λοιμώξεις.
  • Καταστολή του μυελού των οστών: Η χημειοθεραπεία μπορεί να επηρεάσει την ικανότητα του μυελού των οστών να παράγει αιμοσφαίρια, προκαλώντας αναιμία, αυξημένο κίνδυνο αιμορραγίας και αυξημένη ευαισθησία σε λοιμώξεις.
  • Έλκη στο Στόμα: Η χημειοθεραπεία μπορεί να προκαλέσει ερεθισμό και εξελκώσεις στο στόμα και το λαιμό.
Πότε χρησιμοποιείται η χημειοθεραπεία στον καρκίνο της ουροδόχου κύστης;

Η χημειοθεραπεία για τον καρκίνο της ουροδόχου κύστης είναι ενδεδειγμένη σε διάφορες καταστάσεις, συμπεριλαμβανομένων:

  1. Προχωρημένη ή Μεταστατική Νόσος: Η χημειοθεραπεία μπορεί να χρησιμοποιηθεί ως πρωταρχική θεραπεία για προχωρημένο ή μεταστατικό καρκίνο της ουροδόχου κύστης, με στόχο τον έλεγχο της ανάπτυξης και εξάπλωσης των καρκινικών κυττάρων.
  2. Προεγχειρητική Θεραπεία: Η χημειοθεραπεία μπορεί να δίνεται πριν από τη χειρουργική επέμβαση (προεγχειρητική-νεοεπικουρική χημειοθεραπεία) για τη συρρίκνωση των όγκων και τη διευκόλυνση της χειρουργικής αφαίρεσής τους.
  3. Μετεγχειρητική Θεραπεία: Μετά τη χειρουργική επέμβαση, η χημειοθεραπεία μπορεί να χορηγηθεί για την εξάλειψη τυχόν υπολειμμάτων καρκινικών κυττάρων και τη μείωση του κινδύνου επανεμφάνισης.
  4. Συνδυασμένη Θεραπεία: Η χημειοθεραπεία μπορεί να συνδυαστεί με άλλες θεραπείες, όπως η ακτινοθεραπεία ή η ανοσοθεραπεία, για βελτίωση της αποτελεσματικότητας της θεραπείας.
  5. Ανακουφιστική θεραπεία: Στις περιπτώσεις όπου ο καρκίνος δεν μπορεί να θεραπευτεί, η χημειοθεραπεία μπορεί να χρησιμοποιηθεί για την ανακούφιση των συμπτωμάτων και τη βελτίωση της ποιότητας ζωής του ασθενούς.