Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p

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

<p>Abstract</p> <p>Background</p> <p>The 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.</p> <p>Methods/Design</p> <p>Seed 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.</p> <p>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.</p> <p>Discussion</p> <p>These 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.</p> <p>Trial registration</p> <p>NCT00664456, NCT00898326, JUSMH-BRI-GU05-01, JUSMH-TRIGU0709</p