Staffan Jahnson

Results of second-look resection after primary resection of T1 tumour of the urinary bladder.

Objectives. To provide a descriptive review of the establishment of the National Prostate Cancer Register (NPCR) in Sweden, to present clinical characteristics at diagnosis and to calculate the relative survival of different risk groups after 5 years. Material and methods. Since 1998, data on all newly diagnosed prostate cancers, including TNM classification, grade of malignancy, prostate-specific antigen (PSA) level and treatment, have been prospectively collected. For the 35 223 patients diagnosed between 1998 and 2002, relative survival in different risk groups has been calculated. Results. Between 1998 and 2002, 96% of all prostate cancer cases diagnosed in Sweden were registered in the NPCR. The number of new cases increased from 6137 in 1998 to 7385 in 2002. The age-standardized rate rose in those aged <70 years, while it was stable, or possibly declining from 1999, in the older age groups. The proportion of T1c tumours increased from 14% to 28% of all recorded cases. The age-adjusted incidence of advanced tumours (M1 or PSA >100 ng/ml) decreased by 17%. The proportion of patients receiving curative treatment doubled. Patients with N1 or M1 disease or poorly differentiated tumours (G3 or Gleason score 8–10) had a markedly reduced relative 5-year survival rate. Conclusions. It is possible to establish a nationwide prostate cancer register including basic data for assessment of the disease in the whole of Sweden. The introduction of PSA screening has increased the detection of early prostate cancer in younger men and, to a lesser extent, decreased the incidence of advanced disease. The effect of these changes on mortality is obscure but the NPCR in Sweden will serve as an important tool in such evaluation.

Bacillus Calmette-Guérin Is Superior to a Combination of Epirubicin and Interferon-α2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study ☆

BACKGROUND Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. OBJECTIVE To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours. DESIGN, SETTING, AND PARTICIPANTS This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. MEASUREMENTS The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. RESULTS AND LIMITATIONS A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. CONCLUSIONS For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

Epidermal growth factor receptor expression: predictive value for the outcome after cystectomy for bladder cancer?

To determine whether epidermal growth factor receptor (EGFR) immunostaining of tumour cells is associated with cancer‐specific death after cystectomy for locally advanced bladder cancer.

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

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.

PREDICTIVE VALUE OF p53 AND pRb IMMUNOSTAINING IN LOCALLY ADVANCED BLADDER CANCER TREATED WITH CYSTECTOMY

PURPOSE We elucidate the association between altered immunostaining for retinoblastoma gene protein (pRb) and p53 nuclear proteins, and cancer specific death in patients treated with cystectomy for locally advanced bladder cancer. MATERIALS AND METHODS The hospital records of 173 patients treated with cystectomy for advanced urothelial bladder cancer between 1967 and 1992 were retrospectively reviewed. Representative biopsies obtained before treatment were sectioned and stained using the standard immunohistochemical technique with antibody DO-7 (p53) and antibody PMG3-245 (pRb). A tumor was considered to have an altered p53 expression if 20% or more of tumor cells exhibited nuclear staining. Similarly, if no tumor cell had nuclear immunostaining the tumor was considered to have an altered pRb expression. RESULTS An altered expression was observed for p53 in 98 tumors (57%) and for pRb in 60 (35%). In a proportional hazards analysis no association was found between an altered expression of pRb or p53 and cancer specific death. This finding was also true in another analysis when the results of immunostaining for pRb and p53 were combined. CONCLUSIONS An altered expression for pRb and/or p53 was not correlated to cancer specific death. Thus, these parameters could not be used as predictors of treatment outcome after cystectomy for locally advanced bladder cancer.

Tumor Mapping of Regional Immunostaining for p21, p53, and mdm2 in Locally Advanced Bladder Carcinoma

The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.

5-Year Outcome of a Randomized Prospective Study Comparing bacillus Calmette-Guérin with Epirubicin and Interferon-α2b in Patients with T1 Bladder Cancer

PURPOSE In a multicenter, prospectively randomized study we evaluated the 5-year outcomes of bacillus Calmette-Guérin alone compared to a combination of epirubicin and interferon-α2b in the treatment of patients with T1 bladder cancer. MATERIALS AND METHODS Transurethral resection was followed by a second resection and bladder mapping. Stratification was for grade and carcinoma in situ. Followup entailed regular cystoscopy and cytology during the first 5 years. The end points assessed in this analysis were recurrence-free survival, time to treatment failure and progression, cancer specific survival and prognostic factors. RESULTS The study recruited 250 eligible patients. The 5-year recurrence-free survival rate was 38% in the combination arm and 59% in the bacillus Calmette-Guérin arm (p = 0.001). The corresponding rates for the other end points were not significantly different, as free of progression 78% and 77%, treatment failure 75% and 75%, and cancer specific survival 90% and 92%, respectively. The type of treatment, tumor size and tumor status at second resection were independent variables associated with recurrence. Concomitant carcinoma in situ was not predictive of failure of bacillus Calmette-Guérin therapy. An independent factor for treatment failure was remaining T1 stage at second resection. CONCLUSIONS Bacillus Calmette-Guérin was more effective than the tested combination therapy. The currently recommended management with second resection and 3-week maintenance bacillus Calmette-Guérin entails a low risk of cancer specific death. More aggressive treatment in patients with infiltrative tumors at second resection might improve these results. In particular, concomitant carcinoma in situ was not a predictive factor for poor outcome after bacillus Calmette-Guérin therapy.

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%) (χ2=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, χ2=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.

Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours

Abstract Objective. Stage T1 urothelial carcinoma of the bladder (UCB) exhibits heterogeneous clinical behaviour, and the treatment is controversial. The aim of this study was to evaluate prognostic factors for UCB in a defined, population-based cohort comprising patients with a first time diagnosis of primary stage T1 UCB. Material and methods. The study population initially consisted of 285 patients with primary stage T1 UCB reported to the regional Bladder Cancer Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The histological specimens were re-evaluated concerning stage, substaging of T1, World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour volume and total resected volume. Hospital records provided data on tumour size and multiplicity, occurrence of possible relapse and/or progression, death from UCB and whether treatment was given. Results. After re-evaluation, the study population comprised 211 patients. The median follow-up time was 60 months. LVI was a prognostic factor for UCB progression and recurrence. Tumour size larger than 30 mm and multiplicity increased the risk of recurrence. T1 substaging, tumour volume and total resected volume were not associated with recurrence or tumour progression. Conclusions. LVI is significantly correlated with progression and recurrence in patients with primary stage T1 UCB. Therefore, the presence of LVI should be evaluated in every new case of T1 UCB.

HER2 status in primary stage T1 urothelial cell carcinoma of the urinary bladder

Abstract Objective. The HER2 receptor is involved in pathways essential for cell proliferation, and is an important predictive and prognostic factor in breast cancer. HER2 probably plays a critical role in many types of cancer, including urothelial carcinoma of the bladder (UCB). Stage T1 UCB exhibits heterogeneous clinical behaviour, and the frequency of HER2 expression in such disease has not been thoroughly examined. The aim of this study was to use an immunohistochemical technique to evaluate the frequency of HER2 expression in a defined population-based cohort of patients registered as having primary stage T1 UCB. Material and methods. The initial study population comprised 285 patients registered as having primary stage T1 UCB. The original histological specimens were re-evaluated with regard to T stage and World Health Organization grade. Hospital records provided information on tumour size, multiplicity, possible presence of histologically proven recurrence and progression. The patients were followed for at least 5 years or until death. In tumours still considered stage T1 after re-evaluation, HER2 was investigated by immunohistochemistry of paraffin-embedded material and scored according to the guidelines used in breast cancer. Results. After histopathological re-evaluation, 201 patients were still T1 UCB and could be investigated regarding HER2 expression. HER2 overexpression was observed in 25 of those patients (12.4%). HER2 status was not significantly associated with recurrence or progression. Conclusions. HER2 was overexpressed in 12.4% of the present cohort of patients with primary stage T1 UCB. There was no significant association between tumour HER2 status and prognosis.