Bladder cancer treatment - early stage

Bladder cancer is the most common urinary tract cancer. In Western societies, median age at diagnosis is around 70, and it is more common in men than women. Smoking is the most important risk factor, followed by aromatic amines, occupational carcinogen exposure (metal, paint, leather and textiles) and HPV infection.

Bladder cancer symptoms

The most common bladder cancer symptom is painless blood in the urine (hematuria). Other symptoms include painful urination, pain above the pubic area, fatigue and weight loss.

The bladder is broadly examined in three layers

1. the inner lining (urothelium),
2. the thick middle muscle layer (detrusor muscle), and
3. the outer lining (adventitia)

Bladder cancer stage, and consequently treatment, depends on whether the tumor starting in the inner lining has spread into the middle muscle layer or outward. Accordingly, we evaluate bladder cancers in 3 stages:

1. Bladder cancer not reaching the muscle layer (non-muscle-invasive)
2. Bladder cancer spreading into the muscle layer (muscle-invasive), and
3. Metastatic bladder cancer (spread to other organs)

Around %80 of bladder cancers have not reached the muscle layer at diagnosis. The main treatment at this stage is TUR-M (transurethral resection - bladder), entering the urinary tract with a camera-tipped cystoscope and scraping the tumor-bearing inner lining. Reaching the muscle layer during scraping is extremely important. The pathology report after TUR-M must establish whether the tumor is superficial or extends deeply (invasion). Nevertheless, disease recurs in %50-80 of TUR patients and progresses to more invasive disease in %20-25.

Early-stage bladder cancer treatment

Frequent local recurrence despite early-stage disease has made a recurrence-risk classification necessary:

• Low-risk bladder cancer: patients without muscle involvement at diagnosis, no recurrence during the first 1 year after TUR, tumors smaller than 3 cm, and 3 or fewer low-grade tumors. Low-risk bladder cancer treatmentis TUR alone or TUR with a single dose of intravesical chemotherapy (usually mitomycin).
• High-risk bladder cancer: patients with numerous recurrences, more than 3 lesions or any intravesical tumor larger than 3 cm, inability to remove tumors completely because of extensive bladder involvement, and poorly differentiated cancer cells microscopically. High-risk non-muscle-invasive bladder cancer treatment, is intravesical drug administration after TUR (BCG or mitomycin).

Known as the tuberculosis vaccine, BCG’has a mechanism in bladder cancer that is not fully known, but it is thought to activate immune cells against bladder cancer cells. Recurrence is less frequent in patients receiving BCG than in those not receiving it.

Used today as a cancer drug, mitomycin-Cwas originally discovered as an antibiotic. Its ability to kill cancer cells was later discovered, and it showed effectiveness in bladder and liver cancer treatment. Mitomycin-C acts on DNA, which carries the cell's genetic code; it is a DNA-alkylating agent causing DNA breaks and preventing DNA replication necessary for cell division.

How should patients be followed after early-stage bladder cancer treatment?

After these treatments according to risk group, bladder cancer patients enter surveillance . This usually involves cystoscopy every 3-6 months and/or urine cytology to screen for cancer cells. If disease recurs, intravesical treatments are repeated. Disease resistant after 1-2 intravesical treatment cycles can be treated by complete surgical bladder removal (cystectomy) as treatment.

Hyperthermia for high-risk bladder cancer without muscle involvement

In bladder cancer, hyperthermia-heat treatmentwas evaluated as a method to reduce recurrence in high-risk disease, involving 160 patients in a 10-year study. All patients received intravesical chemotherapy together with simultaneous microwave local hyperthermia as treatment. The primary aim was to assess the time without disease recurrence (recurrence-free survival).

At the end of the study;

• For all patients, 1-year and 2-year recurrence-free survival rates were %60 and %47. Among the 160 patients, only %4 had recurrence involving the muscle layer.
• Before hyperthermia, patients with 2 or fewer TUR procedures had significantly longer recurrence-free survival than those with more than 2. This indicated that early hyperthermia may improve success.

In conclusion, for high-risk non-muscle-invasive bladder cancer when standard treatments fail, hyperthermia combined with intravesical chemotherapy offers an effective treatment option. Earlier use may be considered particularly in patients with high recurrence likelihood.

Summary

Bladder cancer, the most common urinary tract malignancy, is a disease of older age. It is closely associated with smoking, and painless bloody urine is its prominent symptom. Around %80 are early-stage at diagnosis (the tumor has not yet involved the muscle layer). Treatment involves deeply scraping the bladder tumor with the surgical method TUR-M, followed by intravesical chemotherapy and/or the tuberculosis vaccine BCG to eliminate remaining cancer cells and reduce future recurrence. Frequent recurrence is the main problem. Particularly in high-risk patients, intravesical chemotherapy delivered with special heat-generating hyperthermia devices and/or sequential BCG vaccination may therefore be preferred. An important warning is that patients diagnosed and treated for early-stage bladder cancer must not overlook recurrence risk and should follow their physicians' surveillance schedules.