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Open Access Study protocol

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

Hiroyuki Konaka1*, Shin Egawa2, Shiro Saito3, Atsunori Yorozu4, Hiroyuki Takahashi5, Keiko Miyakoda6, Masanori Fukushima6, Takushi Dokiya7, Hidetoshi Yamanaka8, Nelson N Stone9 and Mikio Namiki1

Author Affiliations

1 Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

2 Department of Urology, Jikei University School of Medicine, Tokyo, Japan

3 Department of Urology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

4 Department of Radiology, National Hospital Organization Tokyo Medical Center, Tokyo, Japan

5 Department of Pathology, Jikei University School of Medicine, Tokyo, Japan

6 Translational Research Informatics Center, Foundation for Biomedical Research and Innovation, Kobe, Japan

7 Department of Radiation Oncology, Saitama Medical College, Irima, Japan

8 Institutes of Preventive Medicine, Kurosawa Hospital, Takasaki, Japan

9 Department of Urology and Radiation Oncology, Mount Sinai School of Medicine, New York, NY, USA

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BMC Cancer 2012, 12:110  doi:10.1186/1471-2407-12-110

Published: 22 March 2012

Abstract

Background

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.

Methods/Design

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.

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.

Discussion

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.

Trial registration

UMIN000003992

Keywords:
Prostate cancer; Trimodality; Radiation therapy; Brachytherapy; External beam radiation therapy; Hormone therapy; Randomized controlled trial; Biochemical progression-free survival