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Abstract
External beam radiation therapy (EBRT) combined with brachytherapy (BT) is an attractive treatment option for select patients with clinically localized prostate cancer. Either low- or high-dose rate BT may be combined with EBRT (‘LDR-BT boost,’ ‘HDR-BT boost,’ respectively). HDR-BT boost has potential theoretical benefits over LDR-BT boost or external beam radiation therapy monotherapy in terms of radiobiology, radiophysics and patient convenience. Based on prospective studies in this review, freedom from biochemical failure (FFBF) rates at 5 years for low-, intermediate- and high-risk patients have generally been 85–100%, 68–97%, 63–85%, respectively; late Radiotherapy and Oncology Group Grades 3 and 4 genitourinary and gastrointestinal toxicities are seen in <8% of patients. HDR-BT boost is now a relatively well-established treatment modality for certain intermediate-risk and high-risk prostate cancer patients, though limitations exist in drawing conclusions from the currently published studies.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
• From a radiobiological perspective, high-dose rate brachytherapy (HDR-BT) boost is advantageous because the shortened course of HDR-BT boost (vs external beam radiation therapy [EBRT] alone) minimizes cancer cell repopulation; and given the lower α/β ratio for prostate cancer than late-responding tissues, there is potential for therapeutic gain and minimized toxicity to surrounding tissues with larger fraction sizes.
• From a radiophysics perspective, HDR-BT is advantageous because a remote afterloading system (RALS) automatically deploys and retracts a single small radioactive source along the implant needle at specific positions. The RALS and inverse dose optimization planning allows HDR-BT to maximize the dose delivered to the prostate and minimize the dose delivered to the bladder and rectum.
• From the patient’s perspective, with HDR-BT boost, the total time of conventionally fractionated EBRT is minimized typically to about 20 fractions over 4 weeks.
• HDR-BT boost schedules vary among institutions. Generally, EBRT is delivered to a total dose of 36–54 Gy, 1.8–2.0 Gy per fraction, for about 20 fractions that span over ∼4 weeks. HDR-BT is typically delivered to a total dose of 12–30 Gy, 5–15 Gy per fraction, for 1–4 fractions.
• FFBF rates at 5 years for low-, intermediate- and high-risk patients have generally been 85–100%, 68–97%, 63–85%, respectively. Five year rates of prostate cancer-specific mortality (PCSM), overall survival (OS), local recurrent (LR) and distant metastasis (DM) have been 99–100%, 85–100%, 0–8% and 0–12%, respectively.
• HDR-BT boost dose-escalation studies show that outcomes are improved with BEDs > ∼200–220 Gy (combined from HDR-BT and EBRT). Other factors predicting outcome include Gleason score (GS) and prostate-specific antigen (PSA) nadir.
• The most significant late toxicity of HDR-BT boost is urethral stricture, which occurs in up to 8% of patients.
• Certain limitations exist in drawing conclusions from the currently published studies, including limited number of patients; definitions of risk groups; definitions of biochemical failure; and unrefined reports of toxicity.
• Comparative effectiveness (CER) research will help to define the proper role of HDR-BT for specific prostate cancer patients its combination with other treatment modalities.