CLINICAL INVESTIGATION Prostate COMBINATION EXTERNAL BEAM RADIATION AND BRACHYTHERAPY BOOST WITH ANDROGEN SUPPRESSION FOR TREATMENT OF INTERMEDIATE-RISK PROSTATE CANCER: AN INITIAL REPORT OF CALGB 99809 MARK D. HURWITZ, M.D.,* SUSAN HALABI,PH.D., y SAN-SAN OU, M.S., z LAMAR S. MCGINNIS, M.D., x MICHAEL R. KEUTTEL, M.D., k STEVEN J. DIBIASE, M.D., { AND ERIC J. SMALL, M.D.** * Dana-Farber/Brigham & Women’s Cancer Center, Boston, MA; y Harvard Medical School, Boston, MA; z CALGB Statistical Center, Duke University Medical Center, Durham, NC; x Southeast Cancer Control Consortium, Winston Salem, NC; k Roswell Park Cancer Institute, Buffalo, NY; { University of Maryland Medical Center, Baltimore, MD; and ** University of California at San Francisco Comprehensive Cancer Center, San Francisco, CA Purpose: Transperineal prostate brachytherapy (TPPB) can be used with external beam radiation therapy (EBRT) to provide a high-dose conformal boost to the prostate. The results of a multicenter Phase II trial assessing safety of combination of EBRT and TPPB boost with androgen suppression (AST) in treatment of intermediate-risk pros- tate cancer are present here. Materials and Methods: Patients had intermediate-risk prostate cancer. Six months of AST was administered. EBRT to the prostate and seminal vesicles was administered to 45Gy followed by TPPB using either 125 I or 103 Pd to deliver an additional 100Gy or 90Gy. Toxicity was graded using the National Cancer Institute CTC version 2 and the Radiation Therapy Oncology Group late radiation morbidity scoring systems. Results: Sixty-three patients were enrolled. Median follow-up was 38 months. Side effects of AST including sexual dysfunction and vasomotor symptoms were commonly observed. Apart from erectile dysfunction, short-term Grade 2 and 3 toxicity was noted in 21% and 7%, primarily genitourinary related. Long-term Grade 2 and 3 tox- icities were noted in 13% and 3%. Two patients had Grade 3 dysuria that resolved with longer follow-up. The most common Grade 2 long-term toxicity was urinary frequency (5%). No biochemical or clinical evidence of progres- sion was noted for the entire cohort. Conclusions: In a cooperative group setting, combination EBRT and TPPB boost with 6 months of AST was gen- erally well tolerated with expected genitourinary and gastrointestinal toxicities. Further follow-up will be required to fully assess long-term toxicity and cancer control. Ó 2008 Elsevier Inc. Radiation, Brachytherapy, Prostate, Clinical trial, Brachytherapy boost. INTRODUCTION Since the 1990s, brachytherapy has become a commonly used treatment strategy for patients with prostate cancer. The introduction of stereotactic transrectal ultrasound guid- ance in the late 1980s led to the widespread use of transper- ineal prostate brachytherapy (TPPB) for treatment of clinically localized prostate cancer. In patients at greater risk for extracapsular extension of disease, a brachytherapy boost can be combined with external beam radiation therapy (EBRT) to ensure an adequate margin of coverage of sur- rounding tissues in case of minimal spread of disease. With mounting evidence that dose escalation leads to decreased rates of treatment failure (1–3), the ability to provide a very conformal high-dose boost to the prostate with brachytherapy has led to increased utilization of this treatment strategy. Dose escalation to enhance the prospect of tumor eradica- tion must, however, be tempered by concern for treatment morbidity. Increased external beam doses have been linked with increased bladder and rectal morbidity (4, 5). The asso- ciation of brachytherapy boost with morbidity remains to be fully defined. Some single institution reports suggest no in- creased toxicity (6–9), whereas others have found an increase in morbidity (10–12). The Radiation Therapy Oncology Group (RTOG) recently reported the results of a Phase II trial of EBRT with TPPB boost with the finding of acceptable rates of toxicity with this approach (13, 14). The use of andro- gen suppression, which itself is associated with morbidity Reprint requests to: Mark D. Hurwitz, M.D., Brigham and Women’s Hospital, Department of Radiation Oncology, 75 Francis Street, ASBI, L2, Boston, MA 02115. Tel: (508) 235-5700; Fax: (508) 235-5432; E-mail: mhurwitz@lroc.harvard.edu Supported by NCI Grant CA33601. Conflict of interest: none. Acknowledgments—The authors wish to acknowledge the contribu- tions of Steven Milito and Anthony D’Amico in the development of this study. Received Oct 11, 2007, and in revised form Dec 13, 2007. Accepted for publication Jan 13, 2008. 814 Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 3, pp. 814–819, 2008 Copyright Ó 2008 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/08/$–see front matter doi:10.1016/j.ijrobp.2008.01.010