Management of superficial bladder cancer
Uitgegeven: 25-12-2006
 |
The incidence of bladder cancer is 18 to 30/100.000 individuals, ranking it as one of the five most common cancers. The incidence is 3-fold higher in males compared to females. Of these patients approximately 75% present with non-invasive bladder cancers stages Ta, T1, and Tis. In spite of improvements in diagnostic and therapeutic interventions the incidence of bladder cancer is either moderately rising or remaining stable in most developed countries. The problem of non-invasive bladder cancers is the recurrences (up to two-thirds of patients within 5 years) and the chance of progression to muscle-invasive disease (in selected groups up to 50-80%). Because many patients will survive long, the prevalence of bladder cancer is among the highest of all cancers and this has also implications for the involved costs, which are among the highest of all cancers. One of the most important causes for the development of bladder cancer is smoking, however, naphtalamine, phenacetine and frequent consumption of bacon among others are also risk factors. It has been shown that patients that continue smoking once they have been treated for bladder cancer have a worse prognosis compared with those patients that stop smoking. Usually the diagnosis of bladder cancer is made once the patient presents with macroscopic hematuria, although irritative bladder symptoms can also be a sign of bladder malignancy. Since the most prevalent location of urothelial cancer is the bladder, the question is if upper tract imaging should still be included in the work-up of hematuria, a synchronous upper tract malignancy is found in only 0.3 – 2.3%. If you want to perform a proper investigation of the upper urinary tract IVU or uro-CT/MRI are the investigations of choice, but it is to be expected that IVU will disappear from the diagnostic armamentarium. The use of urinary markers has been disappointing until now and none of these can be advised for the primary diagnosis of bladder cancer, due to the low sensitivity. Once a bladder cancer has been diagnosed a good, complete TUR is the cornerstone of the further treatment of the patient. The specimen should include muscle in order to come to an exact staging of the tumor, in case the bladder wash out is negative and the rest of the bladder urothelium looks normal, random biopsies are not necessary. In order to perform a complete resection, re-resection is advised in patients with high risk parameters. Photodiagnostic resection using aminolevulanic acid or one of its derivatives has been shown to reduce the recurrence rate, but this has to be confirmed by other studies. Another technique is the use of Optical Coherence Tomography, a new modality allowing non-invasive examination of the internal structure of biological tissue in vivo. Using OCT bladder lesions can be evaluated and the depth of tumor penetration can be determined. In the future this technique could possibly be a surrogate for bladder biopsies. Once the resection has been performed the pathologist should provide the urologist with the exact type, grade and stage of the tumor. The presence of Tis should be indicated and the amount of muscle should be mentioned. A bladder diagram indicating the location, size and number of tumors resected or biopsies could be very helpful in order to obtain the optimal information about the bladder cancer of the patient. Recently, a new WHO consensus classification of urothelial neoplasms of the urinary bladder has been introduced, but it is not commonly used in most places and the new classification system should be confirmed with the old classification. Following TUR the tumor can be classified as non-invasive versus muscle-invasive bladder cancer, and in case of a non-invasive bladder cancer the patient can be categorized as low, intermediate or high risk for recurrence and progression. The EORTC-GU group developed risk group tables based on individual data for 2596 stage Ta/T1 bladder cancer patients entered in 7 EORTC-GU group studies between 1979 and 1989. The most important prognostic factor for recurrence was number of tumor, prior recurrence rate and tumor size, for progression carcinoma in situ, grade and T-category were the most important factors. By entering these data in the risk table the chance for recurrence and progression can easily be determined for the individual patient. Several studies have shown that in the low risk group one immediate (<6-12 hours following TUR) chemotherapeutic instillation reduces the chance for recurrence with 50%, in the intermediate risk group there is no consensus, but usually a course of chemotherapeutic instillations is advised and has shown to reduce the recurrence. For the high risk group a course of BCG instillations is recommended, although in some countries immediate cystectomy is performed in case of T1G3 +/- Tis. A recently published meta-analysis including 24 trials with a total of 2658 patients demonstrated a 27% reduction in the odds for progression if BCG was given in a maintenance schedule compared to no BCG. In case of failure of BCG in the high risk patient, however, a cystectomy is recommended. New developments in the treatment of non-invasive bladder cancer are the use of techniques that promote penetration of the chemotherapeutic agent into the bladder wall, e.g. Synergo (combination of intravesical instillation with hyperthermia) and EMDA (electromotive drug administration). No definitive results are available at the moment. New intravesical agents that are evaluated at the moment are EOquin (a mitomycin derivative), gemcitabine and BCG cell wall skeleton, but we have to await the outcome of ongoing studies. The follow-up of non-invasive bladder cancer patients can be adapted based on the risk groups. All patients should always have a three-month cystoscopy, but in the low risk group (50% of all cases) the follow-up cystoscopy can be delayed until 9 months and yearly thereafter until 5 years, For the high risk patients (15% of all cases) a cystoscopy should be performed every three months for a period of 2 years, every 4 months in the fourth year and every 6 months thereafter until 5 years, and yearly thereafter. The intermediate group patients should have an in- between foloow-up scheme. Upper tract imaging is recommended to be done at a yearly base. The role of urinary markers in the follow-up of non-invasive bladder cancer patients is still very limited, most studies show too low sensitivity and methodological flaws. The role of new techniques e.g. Proteomic analysis of the urine using Seldi Mass Spectrometry are under investigation. |