Female gender is associated with higher risk of disease recurrence in patients with primary T1 high-grade urothelial carcinoma of the bladder.

PURPOSE: An increasing body of evidence suggests gender differences in the presentation and prognosis of bladder cancer. We aimed to assess the impact of gender on outcomes in patients with primary T1 high-grade (HG) urothelial carcinoma of the bladder (UCB). METHODS: We retrospectively analysed the data from 916 patients with primary T1HG UCB from 7 tertiary care centres. Patients were treated with transurethral resection of the bladder with or without intravesical instillation therapy (IVT). Univariable and multivariable Cox regression analyses assessed the effect of gender on outcomes. RESULTS: Within a median follow-up of 42.8 months, 365 (39.8 %) patients experienced disease recurrence, 104 (11.4 %) progression, 59 (6.4 %) cancer-specific mortality and 190 (20.7 %) mortality of any cause. Overall, 634 (69.2 %) patients received IVT of which 234 (25.5 %) received BCG therapy. Female gender (n = 190, 20.7 %) was associated with higher risk of disease recurrence (HR:1.359;1.071-1.724, p = 0.012) in all patients and in a subgroup of patients treated with BCG therapy (HR:1.717;1.101-2.677, p = 0.017). There was no difference between genders with regard to disease progression, cancer-specific mortality and any-cause mortality. In multivariable analyses that adjusted for the effects of concomitant carcinoma in situ (CIS), tumour size, number of tumours, and IVT, gender remained an independent predictor for disease recurrence (p = 0.026) when analysed in all patients, but not in the subgroup of BCG treated patients (p = 0.093). CONCLUSIONS: In patients with T1HG UCB, female gender is associated with higher risk of disease recurrence, but not with disease progression. This gender disparity may be due to differences in care and/or biology of UCB.

Long-term follow-up after radical cystectomy with emphasis on complications and reoperations: a Swedish population-based survey.

OBJECTIVE: To evaluate outcome after radical cystectomy for primary bladder cancer in a large population-based material. MATERIAL AND METHODS: Between 1997 and 2002 all patients treated with radical cystectomy within 3 months after diagnosis of primary bladder cancer without distant metastasis were retrieved through the Swedish Bladder Cancer Registry. A follow-up questionnaire was distributed to all units where the primary registration of patients was performed. Follow-up data on recurrence date were retrieved from the patient charts and causes of death were obtained from the Swedish Cause of Death Registry until 2003. RESULTS: During the study period radical cystectomy was performed in 39 units in Sweden, of which only five units were considered high-volume hospitals performing 10 or more procedures annually. Mean blood loss was 2300 ml (median 2000 ml) and the 90-day mortality rate was 5.7%. Blood loss was higher in high-volume units than in hospitals with lower hospital volumes, but the 90-day mortality rates were similar. During a median follow-up of 3.5 years, 24% of the patients were submitted to a reoperation. Reoperation rates were significantly higher in patients who received a continent urinary diversion (29%) compared with an ileal conduit (22%, p < 0.015). CONCLUSIONS: Radical cystectomy was associated with a reoperation rate of 24% in Sweden during the study period. The reoperation rates were higher in patients receiving a continent cutaneous diversion or bladder substitution. Blood loss was higher in high-volume units; otherwise, surgical volume did not affect mortality rates, cancer-specific survival or reoperation rates.

A randomized trial comparing 2 doses of polidocanol sclerotherapy for hydrocele or spermatocele.

PURPOSE: Polidocanol sclerotherapy for hydrocele or spermatocele combines high efficiency with low morbidity, but the optimal dose is not known. We compared the efficacy and morbidity of 2 or 4 ml polidocanol sclerotherapy for hydrocele or spermatocele. MATERIALS AND METHODS: From 1993 to 2005 a double-blind randomized clinical trial was conducted using 2 or 4 ml polidocanol (30 mg/ml) for sclerotherapy of hydrocele/spermatocele in 224 evaluable patients at 3 university hospitals. Fluid was evacuated and 2 or 4 ml polidocanol was administered by a nurse, with the amount injected concealed from others present. At 3-month followup morbidity was ascertained using a questionnaire completed by the patients. Fluid recurrence was determined clinically and generally re-treated. RESULTS: After the first treatment, cure was observed in 59% and 47% in the 4 and the 2 ml group, respectively (p = 0.04). More patients in the 4 ml group had complications (31% vs 18%, p = 0.04). Complications were mostly of low or moderate intensity and seldom required medication. After 1 to 4 treatments 200 of 224 patients (89%) were cured and another 10 (5%) had small amounts of residual fluid, with no difference between the groups. Of the patients with hydroceles/spermatoceles larger than 175 ml, 58% and 34% were cured after the first treatment in the 4 and 2 ml groups, respectively (p = 0.012), with no differences in complications between the groups. CONCLUSIONS: Polidocanol sclerotherapy was effective for the treatment of hydrocele or spermatocele in our patients, with 94% satisfactory results after 1 to 4 treatments. A dose of 4 ml was superior to 2 ml, particularly for larger hydroceles/spermatoceles.

Upper urinary tract carcinoma in Lynch syndrome cases.

PURPOSE: Patients with Lynch syndrome are much more likely to have generally rare upper urinary tract urothelial carcinoma but not bladder urothelial carcinoma. While the risk has been quantified, to our knowledge there is no description of how this population of patients with Lynch syndrome and upper urinary tract cancer differs from the general population with upper urinary tract cancer. MATERIALS AND METHODS: We obtained retrospective data on a cohort of patients with Lynch syndrome from the Hereditary Cancer Center in Omaha, Nebraska and compared the data to those on a control general population from western Sweden. These data were supplemented by a new survey about exposure to known risk factors. RESULTS: Of the patients with Lynch syndrome 91% had mutations in MSH2 rather than in MSH1 and 79% showed upper tract urothelial carcinoma a mean of 15.85 years after prior Lynch syndrome-type cancer. Median age at diagnosis was 62 years vs 70 in the general population (p <0.0001). Only half of our patients had a significant smoking history and the male-to-female ratio was 0.95. Of patients with Lynch syndrome 51% had urothelial carcinoma in the ureter while it occurred in the renal pelvis in 65% of the general population (p = 0.0013). Similar numbers of high grade tumors were found in the Lynch syndrome and general populations (88% and 74%, respectively, p = 0.1108). CONCLUSIONS: Upper urinary tract tumors develop at a younger age and are more likely to be in the ureter with an almost equal gender ratio in patients with Lynch syndrome. It has high grade potential similar to that in the general population.

Late bacille Calmette-Guérin infection with a large focal urinary bladder ulceration as a complication of bladder cancer treatment.

OBJECTIVE: • To report a late bacille Calmette-Guérin (BCG) complication previously not described in the literature. PATIENTS AND METHODS: • We reviewed our database with 858 patients treated with BCG from 1986 to 2008 and identified 13 male patients (1.8% of all male patients) who had a large tuberculous-like bladder ulcer. RESULTS: • All patients had high-grade tumours and seven had tumours invading lamina propria before BCG treatment. A solitary ulceration or inflammatory lesion, 10-50 mm in diameter, was seen at routine follow-up cystoscopy 2-34 months (median 8 months) after the first instillation. Significantly more patients had been treated with BCG-RIVM than with BCG-Tice (10/320 vs. three of 454, P < 0.01). BCG was cultured from urine 3-34 months (median 14 months) after the last instillation. • So far, eight patients have been successfully treated with rifampicin and isoniazid. Nine patients are still tumour-free 15-66 months (median 44 months) after the last transurethral resection before BCG treatment. • Another three patients had one to two non-invasive recurrences. One patient had an invasive recurrence and underwent cystectomy. The present study is limited by biases associated with its retrospective design. CONCLUSIONS: • This is the first report on persisting BCG infections with large inflammatory lesions in the bladder. Treatment is effective and the oncological outcome is good. • Mycobacterial cultures of the urine should be performed in BCG-patients with unclear inflammatory lesions in the bladder since a delayed diagnosis of a persistent BCG infection could result in a permanently reduced bladder capacity. • Large studies are warranted to study differences in efficacy and side-effects between different BCG strains.

Defecation disturbances after cystectomy for urinary bladder cancer.

OBJECTIVE: • To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions. PATIENTS AND METHODS: • During their follow-up we attempted to contact all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. • During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. • Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval. RESULTS: • The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively. CONCLUSIONS: • Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). • Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.

Hygiene and urinary tract infections after cystectomy in 452 Swedish survivors of bladder cancer.

OBJECTIVES: To determine whether or not an improved hygiene can lessen the incidence of symptomatic urinary tract infections (UTIs) in patients treated by cystectomy for urinary bladder cancer. PATIENTS AND METHODS: We attempted to contact during their follow-up all men and women aged 30-80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified hygienic measures and included them in a study-specific questionnaire. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results presented as relative risks (RR) with 95% confidence interval. RESULTS: We received the questionnaire from 452 (92%) of 491 identified patients. The proportion of patients who had a symptomatic UTI in the previous year was 22% for orthotopic neobladder and cutaneous continent reservoir, and 23% for non-continent urostomy diversion. The RR for a UTI was 1.1 (0.5-2.5) for 'never washing hands' before handling with catheters or ostomy material. Patients with diabetes mellitus had a RR of 2.1 (1.4-3.2) for having a symptomatic UTI. CONCLUSIONS: We could not confirm lack of hygiene measures as a cause of UTI for men and women who had a cystectomy with urinary diversion. Patients with diabetes mellitus have a greater risk of contracting a UTI.

Urinary diversion after cystectomy for bladder cancer: a population-based study in Sweden.

OBJECTIVE: To investigate the type of urinary diversion performed after cystectomy in patients with muscle-invasive bladder cancer in Sweden, using data from a population-based national register. MATERIAL AND METHODS: Since 1997, the Swedish Bladder Cancer Register has included more than 90% of all patients with newly diagnosed bladder cancer. The different types of urinary diversion performed in 1997-2003 were analysed, comparing non-continent diversion (ileal conduit) with continent reconstruction (bladder substitution or continent cutaneous diversion). RESULTS: During the study period, 3463 patients were registered with clinical T2-T4 non-metastatic bladder cancer. Cystectomy was performed in 1141 patients with ileal conduit in 732 (64%) and continent reconstruction in 409 (36%). Ileal conduit was used more frequently in females than males (p = 0.019), in patients older than 75 years (p < 0.00001), and in those with less favourable TNM classification. Continent reconstruction was done more often at university hospitals than at county hospitals (p < 0.00001), but rarely in the northern and western healthcare regions compared with other regions (p < 0.00001). Nationwide, the proportion of registered continent reconstructions decreased, although the absolute number was relatively stable (50-60 per year). CONCLUSIONS: Continent reconstruction after cystectomy for muscle-invasive bladder cancer is performed more often in some healthcare regions and in patients at university hospitals than in county hospitals, indicating a substantial provider influence on the choice of urinary diversion. Over time, the proportion of these procedures has decreased, while the absolute number has remained low and stable; therefore, concentration in high-volume hospitals specialized in bladder cancer and continent reconstruction seems appropriate.

Is bladder tumour fulguration under local anaesthesia more painful than cystoscopy only?

Objectives: To prospectively register self-reported pain levels associated with office cystoscopy with or without bladder tumour biopsy and fulguration.Patients and methods: During a 15-month period, patients examined with cystoscopy under local anaesthesia graded their pain level using the Visual Analogue Scale (VAS). All patients were examined in the lithotomy position and lidocaine gel was used in all. A bladder instillation or a submucosal injection of lidocaine was given mainly in patients treated with extirpation of larger tumours.Results: The pain perception was graded by the patients as none (VAS = 0) or mild (VAS = 1-3) in 86% of the 1,314 cystoscopies. Fewer patients (65% out of 258) reported VAS 0-3 when cystoscopy with biopsy and fulguration of bladder tumour was performed. More than 97% of all patients stated that they would prefer treatment under local anaesthesia in the case of a future recurrence.Conclusion: The VAS-scores after diagnostic cystoscopy are in accordance with those previously reported, with the absolute majority reporting no or mild pain. Patients treated with extirpation of bladder tumours reported higher levels of pain but still within acceptable limits. This confirms the potential of treating most patients with small-sized bladder tumour recurrences under local anaesthesia.

A population-based study of patterns of care for muscle-invasive bladder cancer in Sweden.

OBJECTIVE: To analyse the management of muscle-invasive bladder cancer in a population-based national register, and specifically to investigate the role of curative therapy (i.e. cystectomy or radiotherapy) in relation to patient, tumour and hospital characteristics. MATERIAL AND METHODS: The Swedish Bladder Cancer Register covers more than 90% of all patients in the country who have been diagnosed with such disease since 1997. Results from 1997-2003 were analysed regarding curative-intent treatment given within 3-6 months of diagnosis of muscle-invasive bladder cancer. RESULTS: In total, 3463 patients with clinical T2-T4 bladder cancer were included in the analysis. Of those patients, 1426 (41%) received curative-intent treatment in the form of radiotherapy (285, 20%) or cystectomy (1141, 80%). Male gender, age < 76 years, favourable TNM category and registration at a high-volume hospital were associated with such treatment. Curative-intent treatment was given to significantly more patients registered at high-volume hospitals (1003/2227, 45%) than at low-volume hospitals (423/1235, 34%) (chi(2)=37.7, p<0.00001). Cystectomy was performed more often in those registered at high-volume than at low-volume hospitals (826/2227, 37%, and 316/1235, 26%, respectively, chi(2)=47.3, p<0.00001). CONCLUSIONS: Lower rates of curative-intent treatment were found in patients registered at low-volume than at high-volume facilities, and the same was seen when comparing females with males, and patients aged 76-80 years with younger patients. Since many of these bladder cancer patients were registered at and eventually treated at hospitals handling fewer than 10 such cases annually, it seems desirable to concentrate treatment of this disease at more specialized centres.

A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences.

PURPOSE: We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. MATERIALS AND METHODS: A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. RESULTS: Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. CONCLUSIONS: We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

Impact of age on outcomes of patients with non-muscle-invasive bladder cancer treated with immediate postoperative instillation of mitomycin C.

OBJECTIVES: To evaluate whether age affects the clinical benefit afforded by immediate postoperative intravesical instillation of mitomycin C in a contemporary cohort of patients with NMIBC. PATIENTS AND METHODS: A total of 4,258 patients with NMIBC treated with transurethral resection of the bladder with (n = 2,605, 61%) or without (n = 1,652, 39%) one immediate instillation of mitomycin C from 5 institutions (study period: 2000-2007) were included. No patients received adjuvant instillations. A multivariable Cox proportional hazards regression model adjusting for standard clinical and pathological features tested the potential interaction term between age and administration of mitomycin C with regard to disease recurrence. RESULTS: A total of 2,063 patients experienced disease recurrence with a median follow-up of 48 months for those who did not recur. In multivariable Cox regression analysis, immediate postoperative instillation of mitomycin C (HR: 0.62; 95% CI: 0.56-0.68; P<0.0001) and age (HR: 1.04; 95% CI: 1.00-1.09; P = 0.036) were associated with disease recurrence. We observed only slight decreases in recurrence-free survival with age irrespective of treatment administration of mitomycin C or not. CONCLUSION: We confirmed reduced disease recurrence rates associated with 1 immediate postoperative intravesical instillation of mitomycin C in NMIBC patients. The benefit on recurrence-free survival of a postoperative intravesical instillation was preserved across all ages and therefore age by itself should not be taken into consideration when deciding to use it.

Second-look resection for primary stage T1 bladder cancer: a population-based study.

OBJECTIVE: This study aimed to evaluate the use of second-look resection (SLR) in stage T1 bladder cancer (BC) in a population-based Swedish cohort. MATERIALS AND METHODS: All patients diagnosed with stage T1 BC in 2008-2009 were identified in the Swedish National Registry for Urinary Bladder Cancer. Registry data on TNM stage, grade, primary treatment and pathological reports from the SLR performed within 8 weeks of the primary transurethral resection were validated against patient charts. The endpoint was cancer-specific survival (CSS). RESULTS: In total, 903 patients with a mean age of 74 years (range 28-99 years) were included. SLR was performed in 501 patients (55%), who had the following stages at SLR: 172 (35%) T0, 83 (17%) Ta/Tis, 210 (43%) T1 and 26 (5%) T2-4. The use of SLR varied from 18% to 77% in the six healthcare regions. Multiple adjuvant intravesical instillations were given to 420 patients (47%). SLR was associated with intravesical instillations, age younger than 74 years, discussion at multidisciplinary tumour conference, G3 tumour and treatment at high-volume hospitals. Patients undergoing SLR had a lower risk of dying from BC (hazard ratio 0.62, 95% confidence interval 0.45-0.84, p < .0022). Five-year CSS rates were as follows, in patients with the indicated tumours at SLR (p = .001): 82% in those with T1, 90% in T0, 90% in Ta/Tis and 56% in T2-4. CONCLUSIONS: There are large geographical differences in the use of SLR in stage T1 BC in Sweden, which are presumably related to local treatment traditions. Patients treated with SLR have a high rate of residual tumour but lower age, which suggests that a selection bias affects CSS.

Patients with High Grade Bladder Cancer, and Tumor-Free 3 and 6-Month Cystoscopy after bacillus Calmette-Guérin have a Good Prognosis without Further Maintenance bacillus Calmette-Guérin.

INTRODUCTION: The benefit of 3 years of maintenance bacillus Calmette-Guérin has been questioned. The outcome is reported for bacillus Calmette-Guérin treated patients who had negative 3 and 6-month cystoscopy results and were subsequently not treated with maintenance bacillus Calmette-Guérin. METHODS: A retrospective, population based study of patients with high grade nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin was performed. Patients were included in analysis who had tumor-free cystoscopy findings 3 and 6 months after the start of treatment. No patient was treated with maintenance bacillus Calmette-Guérin after the 6-month cystoscopy. The Kaplan-Meier estimated 5-year survival rates were calculated. RESULTS: Three and 6-month cystoscopy revealed no tumor in 196 patients with a median age of 72 years. Of the patients 84% had carcinoma in situ or multiple and/or recurrent high grade tumors. Five-year recurrence-free, progression-free and disease specific survival was 69%, 95% and 98%, respectively. Median followup in 119 patients who were alive at the last contact was 79 months. Recurrence developed in 62 of 196 patients (32%), disease stage progressed to at least T2 in 13 (7%) and 7 (3%) died of bladder cancer. CONCLUSIONS: Patients without maintenance bacillus Calmette-Guérin after tumor-free 3 and 6-month cystoscopy have a low rate of progression and bladder cancer death. An alternative to 1 to 3 years of bacillus Calmette-Guérin maintenance may be no maintenance after the second tumor-free cystoscopy with re-treatment with bacillus Calmette-Guérin in case of recurrence.

Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

OBJECTIVE: The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. MATERIALS AND METHODS: All patients with newly detected bladder cancer reported to the SNRUBC during 1997-2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. RESULTS: The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997-2001) and 72.5 years in the last subperiod (2007-2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2-T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2-T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2-T4 tumours, or in the whole cohort. CONCLUSIONS: This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

Gender-related differences in urothelial carcinoma of the bladder: a population-based study from the Swedish National Registry of Urinary Bladder Cancer.

OBJECTIVE: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. MATERIAL AND METHODS: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. RESULTS: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2-T4 (p < 0.001), and women also had more G1 tumours (p < 0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette-Guérin or intravesical chemotherapy, and a larger proportion of men with stage T2-T4 underwent radical cystectomy (38% men vs 33% women, p < 0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p < 0.001), and the relative survival at 5 years was 72% for men and 69% for women (p < 0.001). CONCLUSIONS: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment.

Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?

CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer.

BACKGROUND AND PURPOSE: High dose rate brachytherapy (HDR-BT) in prostate cancer (PC) is receiving increasing interest. The steep dose gradient gives a possibility to escalate the dose to the prostate. If the alpha/beta ratio is low for PC, hypofractionation will be of advantage. A retrospective analysis of outcome in patients (pts) consecutively treated with combined HDR-BT and conformal external beam radiotherapy (ERT) was performed. MATERIAL AND METHODS: Data from 214 pts treated consecutively from 1988 to 2000 were analysed. The median age was 64 years (50-77). Median follow up was 4 years (12-165 months). Pre-irradiatory endocrine therapy was given to 150 pts (70%). The pts were divided into low-, intermediate- and high (80/87/47 pts) risk groups according to the occurrence of none, one, or more risk factors defined by T-classification, PSA and histopathology. ERT was given with 2 Gy fractions to 50 Gy. HDR-BT consisted of two 10 Gy fractions. RESULTS: Overall 5-year biochemical no evidence of disease (bNED) was 82%, and for the low-, intermediate-, and high-risk group bNED was 92, 88 and 61%, respectively. PSA-relapse was found in 17, local recurrence in 3 and distant metastases in 13 pts. Five pts died of PC. No recurrences were observed after 5 years. Severe late complications were few. Urethral stricture (13 pts) was the most frequent. No severe rectal complications were seen. CONCLUSION: Dose escalation with HDR-BT is safe and effective in radiotherapy of localised PC.