21 Urinary Bladder Cancer

Urinary Bladder Cancer

10

THE GEC ESTRO HANDBOOK OF BRACHYTHERAPY | Part II: Clinical Practice Version 1 - 21/04/2015

Depending on the dose prescribed, treatment times vary from 2.5 to 5 days. The output of urine and from the wound drain is monitored daily. The Foley catheter can be removed when the bladder incisions are completely healed. For the ssuprapubic ap- proach this is after 1-2 weeks. If laparoscopic or robot-assisted surgery has been performed, the Foley catheter is removed di- rectly at the end of brachytherapy. Removal of the brachytherapy catheters and intravesical spacers can easily be done without sedation or anaesthesia. Only very exceptionally is it necessary to resort to cystoscopy to remove the tubes.

patients who had undergone cystectomy but retrospectively were also candidates for brachytherapy on clinical staging. The 5-year disease specific survival (71% and 60%) and 5-year overall survival (57% and 52%) were similar with no statistically signif- icant difference’. Aluwini published the results of the single-centre study with the longest follow-up (33). Only patients with clinical T2 and T3 tu- mours were analysed with a mean follow-up of 106 months. The 10-year local relapse-free survival was 73%. Overall survival at 5 and 10 years was 65% and 46%, respectively. Fifty percent of the relapses were non-muscle invasive. All the studies show that for selected cases of patients with T2, limited T3 solitary and maximum of 5 cm tumours, oncolog- ical outcome with brachytherapy is not inferior to radical cys- tectomy. A direct comparison with concomitant external beam radiotherapy and chemotherapy is hampered by lack of studies. In the recent randomized study of chemoradiation, a 2-year re- currence-free rate of 67% and 5-year overall survival of 48% was found (4). The main advantage of brachytherapy over external beam radiotherapy is that the irradiated volume of bladder and bowel is probably smaller. James et al found a 38% rate of grade 3-4 toxicity with chemoradiation, which is higher than in other chemoradiation series (34). Brachytherapy side effects will be discussed in the next paragraph. Follow-up data with the emerging laparoscopic technique is lim- ited. At a median follow-up period of 1 year, a 2-year local con- trol of 77% was found (35). Table 22.1 summarises the results of recent publications. Acute adverse effects that can be expected in 5-10% after brachytherapy are urinary tract infection, wound dehiscence, postoperative ileus, hydronephrosis due to obstruction at the distal ureter, bladder bleeding, and pulmonary embolism (14, 23, 37). In about 10% of patients, urgency requiring more than 6 months anticholinergic use, can occur. With the introduction of the laparoscopic technique, hospitalisation time was reduced from average 16 days to 7 days (25). Severe late effects that have been reported are: vesico-cutaneous or vesico-vaginal fistula, stricture of the urethra and ureters, ne- crosis, and persisting urine leakage, (23, 33). The reported rate of grade 3 and 4 bladder toxicity is 5.8% and for grade 3 and 4 in- testinal toxicity 1% (33). External beam dose was found to be as- sociated with late toxicity in the Dutch cohort series (22). In The Netherlands two external beam schedules were commonly used: low dose external beam therapy of 10.5 Gy or a higher external beam dose of 40 Gy. The higher the dose the more late effects, such as fistula formation, ulceration and necrosis, were seen. Aluwini in their series with a mean follow-up time of 106 months found a cystectomy-free survival rate of 93% at 5 years and 85% at 10 years. In this analysis both cystectomy due to bladder re- lapse and severe toxicity and functional loss of bladder function were considered together. Others also reported a bladder preser- vation rate of more than 89% (14, 37, 38). Ulceration at the implantation site is regularly seen. Aluwini found these ulcerations in about 25% of cases (33). Usually these ulcerations are asymptomatic, occurring due to the high mucosal dose of brachytherapy. These ulcerations should be dis- 13. ADVERSE SIDE EFFECTS

12. RESULTS

12.1 Local Control and Survival Van der Werf-Messing from Rotterdam was the first to report extensively on clinical outcome (18-21). The local control after interstitial radium was 91% for T1 lesions, 84% for T2a (current classification), and 72% for T2b (current classification). These historical results were confirmed in a recent analysis of Blank et al. (14). The 5-year local relapse-free rate for pT1-pT3 tumours was 76%. Overall survival in this series was 73% at 5 years and 49% at 10 years. The rather low overall survival at 10 years reflects the advanced age at which patients were treated (median age 65 years). The ten-year local and distant relapse-free survival was 66%. The main goal in performing brachytherapy apart from good local control, is to preserve the bladder. In their experience, more than 90% of surviving patients maintained bladder function. The largest reported series on brachytherapy for bladder cancer is that of Koning et al (22). In this Dutch cohort study, 1040 pa- tients were retrospectively analysed. Both LDR and PDR were used for treatment delivery. The local recurrence-free proba- bility, metastasis-free probability, disease-free probability, and overall survival at 5 years were 75%, 74%, 61%, and 62%, re- spectively. In this analysis 41% of the bladder relapses occurred in non-muscle invasive tumours. The majority of these patients could be salvaged with tumour resection and possibly bladder instillations. Only 6% of all patients underwent salvage cystecto- my because of invasive tumour recurrence. There is no randomized study comparing bladder-preserving therapy for muscle-invasive bladder cancer with brachytherapy with cystectomy. These two modalities were compared with each other in a systematic review with metaregression analysis for studies published in the period 1981-2012 (31). Overall surviv- al was found to be very similar for the two modalities (10-year 40%-45%). Nieuwenhuijzen et al. retrospectively compared patients treated with brachytherapy with patients treated with cystectomy (32). The two groups were not completely comparable. There were more T2 tumours in the brachytherapy group and on the other hand more multifocal tumours in the cystectomy group. Infor- mation on tumour size was lacking for the majority of cystec- tomy patients. Nevertheless the 5-year disease specific survival (73% and 72%) and 5-year overall survival (62% and 67%) rates were similar. A similar comparative study was performed in the East-Nether- lands region (23). Brachytherapy patients were compared with