Background

In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.

Method

The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.

Design

The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.

Discussion

This is the first report on a selenium randomized trial in bladder cancer patients.

Trial registration

ClinicalTrials.gov identifier: NCT00729287

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Prostate cancer cells have an exquisite tropism for bone, which clinically translates into the highest rate of bone metastases amongst male cancers. Although in the latest years there has been an active development of new “bone targeted” therapies, modern diagnostic techniques for bone metastases still relies mostly on 99mTc bone scanning (BS) and plain X-ray. BS dramatically lacks specificity and sensitivity. Recent publications using modern imaging technologies have clearly pinpointed that BS grossly underestimates the true prevalence of bone metastasis. In addition BS does not allow tumour measurement and is, therefore, not appropriate to monitor response to therapy. This might be extremely important in patients harbouring high-risk localized disease that are eventually candidate for local therapy. Here we reviewed what are the emerging imaging strategies that are likely to supplant BS and to what extent they can be used in the clinic already.

As the adult population is increasing, prostate cancer (PCa) will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA) and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic.

The objective of this review is to provide information on cardiovascular risk following androgen-deprivation therapy (ADT) in prostate cancer patients and to suggest potential prevention and management strategies. Androgen deprivation therapy can cause peripheral insulin resistance, increase fat mass and low-density lipoprotein cholesterol, and induce type 2 diabetes. While recent studies have reported an association in patients with prostate cancer between ADT and increased risk of cardiovascular events, other studies have not detected the association. However, at this time, it is plausible that ADT could increase cardiovascular risk because of the adverse effect of ADT on risk factors for cardiovascular disease. It is advisable that prostate cancer patients in whom ADT is initiated be referred to their physician, who will carefully monitor them for potential metabolic effects. Therefore, physicians should be informed about these potential side effects. This especially applies to men aged >65 years and those with pre-existing cardiovascular comorbidities. Adopting a healthy lifestyle including a balanced diet and regular physical activity is recommended. Patients with cardiovascular disease should receive appropriate preventive therapies, including lipid-lowering, antihypertensive, glucose-lowering, and antiplatelet therapy. ADT should preferably not be unnecessarily administered to prostate cancer patients with pre-existing cardiovascular disease, certainly not to those in whom the risk of prostate cancer-specific mortality is low. The physician should carefully weigh the potential benefits of ADT against the possible risks in individual patients with prostate cancer.

Purpose

Positive surgical margin (PSM) status following radical prostatectomy (RP) is a well-established prognostic factor. The aim of the present study is to evaluate whether number of PSMs or bilaterality of PSMs might have prognostic significance for biochemical recurrence (BCR) in the population with a PSM status following RP.

Methods

We evaluated 1,395 RP pathology reports from our center between 1980 and 2006. All patients who underwent (neo)-adjuvant therapy were excluded, leaving a cohort of 1,009 patients, with 249 (24.7%) subjects having a PSM at RP of whom 29.4% had multiple PSMs (≥ 2 sites), while 13.6% had bilateral PSMs. Median follow-up was 40 months (range 0–258 months). We used BCR-free survival as the primary study outcome. BCR was defined as any rise in PSA above or equal to 0.2 ng/ml.

Results

Of patients with a PSM status, 41% (95% CI: 33–49%) developed BCR within 5 years, compared to 12% (95% CI: 9–15%) in the population without a PSM. Multivariable analysis identified PSA at diagnosis and RP Gleason score as independent predictive factors for BCR. Increasing number and/or bilaterality of PSM did not lead to significant higher rates of BCR.

Conclusion

In patients with a PSM, the number of positive sites or bilaterality of PSM status does not add prognostic information for risk of BCR. Survival curve slopes were different for patients with bilateral PSM, showing a significant tendency to progress to BCR earlier during follow-up than patients with unilateral PSM.

Introduction

While adjuvant immunotherapy with Bacille Calmette Guérin (BCG) is effective in non-muscle-invasive bladder cancer (BC), adverse events (AEs) are considerable. Monocyte-derived activated killer cells (MAK) are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM®) to BCG in patients after transurethral resection (TURB) of BC.

Materials and methods

This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM). Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint) and prophylactic effects (secondary endpoint) were assessed.

Results

Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE), respectively (p < 0.001). Recurrence occurred significantly less frequent with BCG than with BEXIDEM (12% vs. 38%; p < 0.001).

Discussion

This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted.

Trial registration

The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.