Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial

Abstract

BackgroundThe optimal protocol for 125I-transperineal prostatic brachytherapy (TPPB) in intermediate-risk prostate cancer (PCa) patients remains controversial. Data on the efficacy of combining androgen-deprivation therapy (ADT) with 125I-TPPB in this group remain limited and consequently the guidelines of the American Brachytherapy Society (ABS) provide no firm recommendations.Methods/DesignSeed and Hormone for Intermediate-risk Prostate Cancer (SHIP) 0804 is a phase III, multicenter, randomized, controlled study that will investigate the impact of adjuvant ADT following neoadjuvant ADT and 125I-TPPB. Prior to the end of March, 2011, a total of 420 patients with intermediate-risk, localized PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from 20 institutions, all of which have broad experience of 125I-TPPB. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will initially undergo 3-month ADT prior to 125I-TPPB. Those randomly assigned to adjuvant therapy will subsequently undergo 9 months of adjuvant ADT. All participants will be assessed at baseline and at the following intervals: every 3 months for the first 24 months following 125I-TPPB, every 6 months during the 24- to 60-month post-125I-TPPB interval, annually between 60 and 84 months post-125I-TPPB, and on the 10th anniversary of treatment.The primary endpoint is biochemical progression-free survival (BPFS). Secondary endpoints are overall survival (OS), clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, acceptability (assessed using the international prostate symptom score [IPSS]), quality of life (QOL) evaluation, and adverse events. In the correlative study (SHIP36B), we also evaluate biopsy results at 36 months following treatment to examine the relationship between the results and the eventual recurrence after completion of radiotherapy.DiscussionThese two multicenter trials (SHIP0804 & SHIP36B) are expected to provide crucial data regarding the efficacy, acceptability and safety of adjuvant ADT. SHIP36B will also provide important information about the prognostic implications of PSA levels in intermediate-risk PCa patients treated with 125I-TPPB.Trial registrationNCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709

Clinical Significance of Neoadjuvant Combined Androgen Blockade for More Than Six Months in Patients with Localized Prostate Cancer Treated with Prostate Brachytherapy

“…The results on univariate and multivariate analyses for intermediate-risk disease identify neoadjuvant CAB as one of the significant favorable factors (table 3), suggesting the potential benefit of neoadjuvant CAB for 6≤ months in intermediate-risk prostate cancer. A prospective, randomized, clinical trial in patients with intermediate-risk prostate cancer comparing NHT plus BT to NHT plus BT plus adjuvant hormone therapy is ongoing to clarify any additional effect of adjuvant hormone therapy [20]. In patients with high-risk localized prostate cancer, a prospective, multicenter, randomized controlled trial for tri-modality therapy with I-125 BT, EBRT and short- or long-term hormone therapy is also ongoing [21].…”

Permanent prostate brachytherapy and short-term androgen deprivation for intermediate-risk prostate cancer in Japanese men: Outcome and toxicity

“…As we introduced in the previous study (6), seed and hormone for intermediate-risk prostate cancer, which is a Phase 3 multicenter trial, is under investigation in Japan. In this trial, 420 patients with intermediate risk were randomized into two groups in which patients either do or do not receive 9 months' adjuvant therapy after PB (24). There are no reports of a prospective study in Japan evaluating the efficacy of ADT with PB for an IRG.…”

A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer

“…However, this review identified ten ongoing studies which might be able to fill gaps in the current evidence base, thereby demonstrating that RCTs are actively being conducted in this area but it should be noted that this list might not be complete [27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The ProtecT trial will help in this regard and should inform which of radiotherapy, radical prostatectomy and active surveillance should be used in daily clinical practice [40].…”