Application of an interstitial and biodegradable balloon system for prostate-rectum separation during prostate cancer radiotherapy: a prospective multi-center study.

BACKGROUND AND PURPOSE: Rectal toxicity presents a significant limiting factor in prostate radiotherapy regimens. This study evaluated the safety and efficacy of an implantable and biodegradable balloon specifically designed to protect rectal tissue during radiotherapy by increasing the prostate-rectum interspace. PATIENTS AND METHODS: Balloons were transperineally implanted, under transrectal ultrasound guidance, into the prostate-rectum interspace in 27 patients with localized prostate cancer scheduled to undergo radiotherapy. Patients underwent two simulations for radiotherapy planning--the first simulation before implant, and the second simulation seven days post implant. The balloon position, the dimensions of the prostate, and the distance between the prostate and rectum were evaluated by CT/US examinations 1 week after the implant, weekly during the radiotherapy period, and at 3 and 6 months post implant. Dose-volume histograms of pre and post implantation were compared. Adverse events were recorded throughout the study period. RESULTS: Four of 27 patients were excluded from the evaluation. One was excluded due to a technical failure during implant, and three patients were excluded because the balloon prematurely deflated. The balloon status was evaluated for the duration of the radiotherapy period in 23 patients. With the balloon implant, the distance between the prostate and rectum increased 10-fold, from a mean 0.22 ± 0.2 cm to 2.47 ± 0.47 cm. During the radiotherapy period the balloon length changed from 4.25 ± 0.49 cm to 3.81 ± 0.84 cm and the balloon height from 1.86 ± 0.24 cm to 1.67 ± 0.22 cm. But the prostate-rectum interspace distance remained constant from beginning to end of radiotherapy: 2.47 ± 0.47 cm and 2.41 ± 0.43 cm, respectively. A significant mean reduction in calculated rectal radiation exposure was achieved. The implant procedure was well tolerated. The adverse events included mild pain at the perineal skin and in the anus. Three patients experienced acute urinary retention which resolved in a few hours following conservative treatment. No infections or thromboembolic events occurred during the implant procedure or during the radiotherapy period. CONCLUSION: The transperineal implantation of the biodegradable balloon in patients scheduled to receive radiotherapy was safe and achieved a significant and constant gap between the prostate and rectum. This separation resulted in an important reduction in the rectal radiation dose. A prospective study to evaluate the acute and late rectal toxicity is needed.

Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies.

CONTEXT: The clinical benefit of photodynamic diagnosis (PDD) with 5-aminolevulinic acid or hexaminolevulinate in addition to white-light cystoscopy (WLC) in bladder cancer has been discussed controversially. OBJECTIVE: To assess in a systematic review the effect of PDD in addition to WLC on (1) the diagnosis and (2) the therapeutic outcome of primary or recurrent non-muscle-invasive bladder cancer investigated by cystoscopy or transurethral resection. EVIDENCE ACQUISITION: An electronic database search of Medline, Embase, the Cochrane Library, and CancerLit was undertaken, plus hand searching of relevant congress abstracts and urologic journals. Trials were included if they prospectively compared WLC with PDD in bladder cancer. The review process followed the guidelines of the Cochrane Collaboration. Two reviewers evaluated independently both trial eligibility and methodological quality and data extraction. EVIDENCE SYNTHESIS: The primary end point of diagnostic accuracy was additional detection rate. The primary end points of therapeutic outcome were residual tumour at second resection and recurrence-free survival (RFS). Seventeen trials were identified. Twelve diagnostic trials used WLC and PDD with the same patients. Seven reported results for the subgroup of patients with carcinoma in situ (CIS). Five randomised trials studied therapeutic outcome. The results were combined in random effects meta-analyses if end points, designs, and populations were comparable. Twenty percent (95% confidence interval [CI], 8-35) more tumour-positive patients were detected with PDD in all patients with non-muscle-invasive tumours and 39% (CI, 23-57) more when only CIS was analysed. Heterogeneity was present among diagnostic studies even when the subgroup of patients with CIS was investigated. Residual tumour was significantly less often found after PDD (odds ratio: 0.28; 95% CI, 0.15-0.52; p<0.0001). RFS was higher at 12 and 24 mo in the PDD groups than in the WLC-only groups. The combined p value of log-rank tests of RFS was statistically significant (0.00002). CONCLUSIONS: PDD detects more bladder tumour-positive patients, especially more with CIS, than WLC. More patients have a complete resection and a longer RFS when diagnosed with PDD.

Degarelix and its therapeutic potential in the treatment of prostate cancer.

Degarelix is a gonadotropin-releasing hormone (GnRH) antagonist for the treatment of patients with prostate cancer in whom hormonal therapy is indicated. Two phase II trials and one phase III have been published as full papers in the literature. In the dose-finding phase II studies an initial dose of 240 mg degarelix sc followed by a monthly injection of 80 mg or 160 mg degarelix sc was sufficient to keep testosterone levels < or = 0.5 ng/ml. In a phase III trial it was demonstrated that degarelix was not inferior (in terms of testosterone suppression and prostate-specific antigen [PSA] decline) compared to standard hormonal therapy, ie, a GnRH agonist such as leuprolide. In fact, degarelix was associated with a faster testosterone suppression and PSA decline than leuprolide. Adverse events such as injection site reactions (40% vs <1%) and chills (4% vs 0%) were more commonly associated with degarelix. Also, degarelix is currently only available as one-month depot whereas in daily practice three-month depots (of GnRH agonists) are the preferred regimen. However, degarelix was recently approved by the US Food and Drug Administration for the treatment of advanced prostate cancer.

Degarelix for prostate cancer.

The growth of prostate cancer cells is hormone dependent in the majority of patients with the disease. Lowering testosterone either surgically or medically (usually with a gonadotropin releasing hormone (GnRH) agonist) is the standard of care in patients with metastatic prostate cancer. Degarelix is a new GnRH antagonist for the treatment of patients with prostate cancer. In contrast to GnRH agonists, the development of GnRH antagonists was hindered for a long time owing to histamine-releasing activity and lack of potency and water solubility. Recently, however, degarelix has been approved by the FDA for the treatment of advanced prostate cancer. This review summarizes the preclinical and clinical data available for degarelix and describes its potential role in the market of prostate cancer therapeutics.

Prostate cancer vaccines: current status and future potential.

Standard systemic treatment of prostate cancer today is comprised of antihormonal and cytostatic agents. Vaccine therapy of prostate cancer is principally attractive because of the presence of tumor-associated antigens such as prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), prostate-specific membrane antigen (PSMA), and others. Most prostate cancer vaccine trials have demonstrated some activation of the immune system, limited clinical success, and few adverse effects.One strategy to overcome the problem of limited clinical success of vaccine therapies in prostate cancer could be strict patient selection. The clinical course of patients with prostate cancer (even in those with PSA relapse following surgery or radiotherapy with curative intention, or those with metastatic disease) can vary significantly. In patients with organ-confined prostate cancer, the most promising immunotherapeutic approach would be an adjuvant therapy following surgery or radiotherapy. Patients with PSA relapse following surgery or radiotherapy could also benefit from immunotherapy because tumor burden is usually low. However, most patients in prostate cancer vaccine trials had metastatic hormone-refractory prostate cancer (HRPC). High tumor burden correlates with immune escape phenomena. Nevertheless, 2 years ago, it was demonstrated, for the first time, that a tumor vaccine can prolong survival compared with placebo in patients with HRPC. This was demonstrated with the vaccine sipuleucel-T (APC-8015; Provenge), a mixture of cells obtained from the patient's peripheral blood by leukapheresis followed by density centrifugation and exposition. The Biologics License Application for this vaccine was denied by the US FDA in mid 2007, however, because the trial had failed to reach the primary endpoint (prolongation of time to tumor progression). Nevertheless, clinical trials with sipuleucel-T are ongoing, and the approach still looks promising. Another interesting approach is a vaccine made from whole tumor cells: GVAX. This vaccine is presently being studied in phase III trials against, and in combination with, docetaxel. The results from these trials will become available in the near future. Besides the precise definition of the disease status of patients with prostate cancer, combinations of vaccine therapy with radiotherapy, chemotherapy, and/or hormonal therapy are approaches that look promising and deserve further investigation.

Intensity modulated high-dose-rate brachytherapy boost complementary to external beam radiation for intermediate- and high-risk localized prostate cancer patients--how we do it in Lübeck/Germany.

The Kiel University technique of intensity modulated brachytherapy boost implantations complementary to external beam radiation used in the treatment of prostate cancer patients was improved by involving real-time three-dimensional transrectal ultrasound analysis of the prostate gland both before implantation and after the implantation but before capture of the transrectal ultrasound images for real-time dynamic treatment planning. Implantation technique, treatment planning procedure, and dose delivery are described as practiced at the University Hospital Schleswig-Holstein Campus Lübeck, Germany.

Drug evaluation: Therion's rV-PSA-TRICOM + rF-PSA-TRICOM prime-boost prostate cancer vaccine.

Therion Biologics Corp is developing PROSTVAC-VF-TRICOM, a prime-boost vaccine regimen that consists of a priming injection with a recombinant attenuated vaccinia virus expressing PSA and TRICOM (the company's proprietary triad of costimulatory molecules: ICAM-1, B7.1 and lymphocyte function-associated antigen-3), and a booster injection with a fowlpox virus expressing the same combination, for the potential treatment of prostate cancer. Phase II clinical trials are underway.

Drug evaluation: Degarelix--a potential new therapy for prostate cancer.

Ferring Research Ltd and licensee Astellas Pharma Inc are developing the gonadotropin-releasing hormone antagonist degarelix as a potential subcutaneous treatment for prostate cancer.