Abstract
For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities.
Highlights
180,000 new cases of prostate cancer are estimated to be diagnosed in 2019 [1, 2]
The American Society of Clinical Oncology (ASCO)/Cancer Care Ontario (CCO) Joint Guideline Update published in 2017 explicitly states that for patients with high-risk prostate cancer receiving External beam radiation therapy (EBRT) and androgen deprivation therapy (ADT), brachytherapy boost should be offered to eligible patients [8]. This recommendation is largely based on the ASCENDE-RT trial which demonstrated a significant improvement in the rates of biochemical relapse for patients treated with a brachytherapy boost [9]
Despite the difference in androgen suppression duration, this study found that among patients with Gleason 9–10 disease, treatment with EBRT plus brachytherapy and ADT was associated with significantly better prostate cancer-specific mortality and longer time to distant metastases compared to surgery or ADT and EBRT alone [37]
Summary
180,000 new cases of prostate cancer are estimated to be diagnosed in 2019 [1, 2]. The American Society of Clinical Oncology (ASCO)/Cancer Care Ontario (CCO) Joint Guideline Update published in 2017 explicitly states that for patients with high-risk prostate cancer receiving EBRT and androgen deprivation therapy (ADT), brachytherapy boost (either LDR or HDR) should be offered to eligible patients [8] This recommendation is largely based on the ASCENDE-RT trial which demonstrated a significant improvement in the rates of biochemical relapse for patients treated with a brachytherapy boost [9]. The ASCENDERT trial was a randomized Phase III study comparing EBRT alone (78 Gy/39 fractions) to EBRT (46 Gy/23 fractions) plus an LDR brachytherapy boost (115 Gy using 125I) in patients with intermediate or high-risk prostate cancer [9] Both arms included 12 months of androgen deprivation therapy. The improved survival outcome persisted in multivariable analysis and with propensity score matching, the study cannot fully account for selection bias in the choice of treatment
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