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- Gårdmark, Truls, et al.
(författare)
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Analysis of clinical characteristics, management and survival of patients with Ta T1 bladder tumours in Sweden between 1997 and 2001
- 2006
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:4, s. 276-282
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To analyse the management and outcome of patients with Ta T1 urinary bladder cancer in a population-based national database. Material and methods. Between 1997 and 2001, 94% of all newly diagnosed cases of urinary bladder cancer were registered in the Swedish National Bladder Cancer Register. Data were analysed regarding gender, healthcare region, stage and grade for patients with Ta T1 tumours. The choice of initial treatment in different regions was reviewed. Survival was analysed by calculating relative survival. Results. Out of 9859 registered patients, there were 4442 Ta tumours and 2139 T1 tumours. The median age at diagnosis was 72 and 73 years for patients with Ta and T1 tumours, respectively. Seventy-six percent of the patients were men. The choice of treatment varied between different healthcare regions. A significant trend towards an increased use of intravesical therapy was seen over time. Significantly fewer older than younger patients received such therapy. There was also a tendency towards more intensive therapy in men. The bladder cancer relative 5-year survival rate was 93% for Ta and 75% for T1 tumours. Survival was similar for men and women. Conclusions. Our analysis revealed a regional variation in the treatment of bladder cancer. A large group of patients, even those at high risk, were still undertreated. However, the recent publication of guidelines may have contributed to an increased use of intravesical treatment. Urologists tended to treat TaG3 and T1G3 tumours more aggressively than T1G2 tumours. Therapeutic aggressiveness decreased as the age of the patients increased. The survival rate of patients with bladder cancer in Sweden seems to remain at the levels previously reported for the 1980s.
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- Gårdmark, Truls, et al.
(författare)
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Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
- 2005
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 95:7, s. 982-986
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires > or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.
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- Gårdmark, Truls, et al.
(författare)
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Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer
- 2007
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Ingår i: BJU International. - 1464-4096 .- 1464-410X. ; 99:4, s. 817-820
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. Patients and methods: Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1–G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. Results: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes. Conclusion: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival.
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- Gårdmark, Truls, 1965-
(författare)
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Urinary Bladder Carcinoma – Studies of Outcome of Current Management and Experimental Therapy
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis concerns the epidemiology, current and possible future treatment of urothelial cancer of the urinary bladder. The Swedish National Quality Registry for Bladder Cancer 1997-2001 was used to explore epidemiology, current therapies and outcome. More common in men, the incidence for Ta and T1 tumours peaks in the age range 70-79 years. There were differences in treatment activity between the reporting regions. An increasing activity was seen. Older patients received less intravesical treatment, which was also a tendency for women. The five year relative survival for all stages (Ta-T4) was 70%; 93% for Ta and 75% for T1. For Ta or T1 survival did not differ significantly between regions. Because the registry has only been running since 1997 a long term follow-up (ten years) of 250 patients comparing Bacillus Calmette-Guerin and Mitomycin-C, was performed. No differences regarding complementary treatment, progression or survival (overall or disease specific) were shown. Looking for new drugs, gemcitabine was tried for intravesical instillations. Patients were randomised to one of three dose schedules. The effect on a marker tumour lesion was evaluated after nine weeks. The overall complete response rate was 31% (9/29). Side effects were more common in women but generally mild; the most common was nausea. One patient stopped instillations (nausea and fever). No patients were excluded due to pathological changes in laboratory parameters. For metastasised disease, over-expression of the growth factor receptor HER2 on urothelial cancer cells was explored in primary tumours and metastases, aiming at radionuclide target therapy. With a new antigen retrieval procedure and evaluation protocol 80% of primary tumours overexpressed the receptor and 72% remained so in the metastases. In conclusion current therapies were increasingly used by clinicians. Superiority for BCG could not be proven. Prerequisites for new therapies have been explored and the way has been paved for future studies.
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- Hemdan, Tammer, et al.
(författare)
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Stathmin-1 is a promising prognostic factor and potential therapeutic target in urinary bladder cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aim: The oncoprotein 18/stathmin 1 (STMN1), involved in cell cycle progression and cell migration, has been reported to be expressed in several types of cancer, and is associated with clinical outcome in e.g. breast and liver cancer. The aims in this study were to investigate the clinical significance of STMN1 and to examine if STMN1 might be a possible therapeutic target in urinary bladder cancer.Experimental design: Immunohistochemical analyses of STMN1 protein expression were performed in a wide-range tissue microarray (115 Ta-, 115 T1-, 112 T2-4-tumors) and in a metastatic primary tumor/matched metastasis-material (90 patients). In the T24 cell line, the effect of STMN1 on cell proliferation was evaluated by inhibiting the cellular expression of STMN using STMN1-siRNA.Results: Patients with T1- or muscle-invasive disease exhibiting high expression of the STMN1 protein had a poorer overall survival (OS) and disease specific survival (DSS). In a multivariate analysis adjusting for stage, age and gender the results were for T2-T4 patients: OS (HR=1.77 95% CI 1.02-3.07; p=0.04) and DSS (HR=2.04 95% CI 1.13-3.68; p=0.02); for T1-4 patients: DSS (HR=1.83 95% CI 1.09-3.08; p=0.02). In the metastatic bladder cancer material, the majority of the patients with one metastasis (69%) and with several matched metastases (70%) were STMN1-positive in both the primary tumor and the matched metastases. Moreover, the ability of the urinary bladder cancer cell line to grow was significantly reduced after 72 hours (p<0.0001) when transfecting the cells with a siRNA targeting STMN1.Conclusion: Our results suggest that STMN1 protein-expression has a potential both as a prognostic marker and a novel treatment target in urinary bladder cancer.
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