Combination External Beam Radiation and Brachytherapy Boost With Androgen Suppression for Treatment of Intermediate-Risk Prostate Cancer: Long-Term Results of CALGB 99809

Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Cancer (Impact Factor: 4.89). 12/2011; 117(24):5579-88. DOI: 10.1002/cncr.26203
Source: PubMed


Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long-term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate-risk prostate cancer are presented.
Intermediate-risk patients per Memorial Sloan-Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I125 (100 Gy) or Pd103 (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease-free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate-specific antigen rises>1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan-Meier method was used to estimate DFS and overall survival.
Sixty-one of 63 enrolled patients were eligible. Median follow-up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six-year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six-year overall survival was 96.1%.
In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate-risk prostate cancer.

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    • "With regard to toxicity, HDR-BT boost was hypothesized to have a dose distribution that would better conform to the target and spare healthy organs, thus minimizing toxicity. Compared to historical data, HDR-BT boost RTOG late toxicity appears similar to LDR-BT monotherapy [11] [12] [13] [14] [15] [16] or LDR-BT boost [17] [18], and decreased compared to EBRT [4] [5] [6] [7] [8] (Fig. 4). In direct comparisons (Table 4), toxicity reports are inconsistent; whether this is due to the EBRT portion of the therapy or dose is unclear. "
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    ABSTRACT: Studies of dose-escalated external beam radiation therapy (EBRT) and low dose rate brachytherapy (LDR-BT) have shown excellent rates of tumor control and cancer specific survival. Moreover, LDR-BT combined with EBRT (i.e. "LDR-BT boost") is hypothesized to improve local control. While phase II trials with LDR-BT boost have produced mature data of outcomes and toxicities, high dose rate (HDR)-BT has been growing in popularity as an alternative boost therapy. Boost from HDR-BT has theoretical advantages over LDR-BT, including improved cancer cell death and better dose distribution from customization of catheter dwell times, locations, and inverse dose optimization. Freedom from biochemical failure rates at five years for low-, intermediate-, high-risk, and locally advanced patients have generally been 85-100%, 80-98%, 59-96%, and 34-85%, respectively. Late Radiation Therapy Oncology Group grade 3-4 toxicities have also been encouraging with <6% of patients experiencing any toxicity. Limitations of current HDR-BT boost studies include reports of only single-institution experiences, and unrefined reports of toxicity or patient quality of life. Comparative effectiveness research will help guide clinicians in selecting the most appropriate treatment option for individual patients based on risk-stratification, expected outcomes, toxicities, quality of life, and cost.
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