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Brachytherapy: state-of-the-art radiotherapy in prostate cancer Michael W.T. Chao, Peter Grimm*, John Yaxley†, Raj Jagavkar‡, Michael Ng§ and Nathan Lawrentschuk¶** Radiation Oncology Victoria, Ringwood East, Vic., Australia, *Prostate Cancer Center of Seattle, Seattle, WA, USA, † Wesley Hospital, Brisbane, Qld , ‡St Vincent’s Hospital, Darlinghurst, NSW, §Radiation Oncology Victoria, Epping, ¶ Department of Surgery and Olivia Newton John Cancer Research Institute, Austin Hospital, and **Department of Surgical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia
Introduction Contemporary treatment options for prostate cancer are considered to have similar efficacy; therefore, other differences, such as treatment-related toxicities, impact on quality of life, convenience, treatment time and cost, become important considerations in influencing treatment choice. The goal of brachytherapy is to achieve high precision, targeted radiotherapy (RT) using advanced computerized treatment planning and image-guided delivery systems to achieve a tailored ablative tumour dose to the prostate whilst sparing surrounding organs to minimize potential toxicities. Two different brachytherapy techniques can be used to treat prostate cancer: low-dose rate (LDR) brachytherapy, in which radioactive seeds are permanently implanted into prostate tissue or high-dose rate (HDR) brachytherapy, in which the radioactive source is temporarily placed into the prostate via implanted needles. When compared with external beam radiation therapy (EBRT) and radical prostatectomy (RP), both LDR and HDR brachytherapy have similar cancer control [1] and long-term survival rates, with a reduced risk of side effects [2,3]. Brachytherapy is also associated with much shorter recovery times than RP, resulting in less interference to the lives of patients [2], and offers significantly reduced overall treatment times compared with EBRT. When combined with lower infrastructure outlay, it is also cost-effective [4,5]. We would therefore contend that brachytherapy for prostate cancer is an effective, well-tolerated treatment option that offers significant quality-of-life benefits to patients and cost-saving efficiencies to healthcare providers.
Patient Selection Patients with localized prostate cancer can be divided into three risk groups according to their pretreatment factors: PSA level, biopsy Gleason score (GS) and clinical tumour staging (cT stage). Combining these prognostic factors allows patients to be separated into three basic prognostic groups or risk classifications: low, intermediate or high risk. There are a
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number of such guidelines available to define these risk group classifications such as the D’Amico [6], Memorial Sloan Kettering Cancer Centre [7], European Society of Therapeutic Radiation Oncology [8] and National Comprehensive Cancer Network (NCCN) [9] classifications. The American Brachytherapy Society recommends the NCCN guidelines [10]: low risk: GS ≤6 and PSA 20 ng/mL or cT3–4. Preoperative evaluation includes CT or MRI of the pelvis, and bone scan in selected patients in the intermediate- and highrisk groups. The use of multiparametric MRI can improve primary tumour staging in patients with intermediate- to high-risk disease, identifying men with advanced T3 disease with >95% specificity [11]. It can also assist with radiation planning, improving target volume delineation by identifying extra prostatic extension or seminal vesicle involvement [12].
Absolute and Relative Contraindications The absolute contraindications to brachytherapy include the presence of distant metastases, absence of rectum, which precludes a TRUS probe and radiation sensitivity syndromes such as ataxia telangiectasia. Although there is no absolute upper or lower age limit for brachytherapy, patients should have a good performance status and life expectancy of at least 10 years. The relative contraindications to brachytherapy include severe urinary obstruction, previous pelvic irradiation, previous TURP, large prostate volumes (>50 mL) and inflammatory bowel disease. The degree of urinary obstruction is assessed by a selfadministered IPSS questionnaire [13] and urinary flow rate studies. An IPSS 50 mL) may also pose technical challenges in patients undergoing LDR and HDR brachytherapy. A larger prostate volume will increase the likelihood of obstructing median lobes and pubic arch obstruction. For patients with prostate glands >50 mL, shortcourse androgen deprivation therapy (ADT) of 2–4 months can reduce the prostate volume by ~35–45%, making such patients suitable implant candidates [24,25]. Volume reduction in patients with prostates >70 mL may require ADT for >4 months to achieve sufficient downsizing.
Indications for Prostate Brachytherapy Currently, LDR monotherapy is considered optimal in a regimen for patients with low-risk prostate cancer who are generally suitable for active surveillance or alternatively surgery; however, LDR brachytherapy may be used in patients with intermediate-risk disease who have a favourable risk factor profile. LDR brachytherapy can also be combined with EBRT in patients in the unfavourable intermediate- or highrisk groups. HDR brachytherapy is primarily used in combination with EBRT in patients in the intermediate- and high-risk groups. HDR monotherapy can be used in patients in more favourable intermediate- and low-risk groups. Low-Risk Prostate Cancer Brachytherapy with LDR monotherapy is as effective as EBRT or RP in low-risk prostate cancer. The Prostate Cancer Results Study Group (PCRSG) undertook a comprehensive review of the literature on the efficacy of brachytherapy [1]. The PCRSG evaluated >50 000 patients with low-, intermediate- or high-risk disease treated with all available
options including EBRT, RP, protons, ADT, high-intensity focused ultrasonography or cryotherapy. The criteria for studies to be included in the review were: stratification into recognizable pretreatment risk groups; median follow-up of at least 5 years; and inclusion of at least 100 patients with lowand intermediate-risk disease and 50 patients with high-risk disease. For studies that assessed EBRT, patients had to receive at least 72 Gy to the prostate. Patients with low-risk prostate cancer treated with LDR monotherapy had excellent PSA recurrence-free survival (RFS) rates, sustained at long-term follow-up, similar to those for EBRT and RP, including robot-assisted prostatectomy. Potters et al. [26] reported long-term 12-year biochemical RFS of 89% for patients with low-risk disease treated with LDR monotherapy. The Seattle Group reinforced this result, reporting their long-term 15-year biochemical RFS of 85.9% for patients with low-risk disease treated with LDR monotherapy [3]. No additional EBRT or ADT is necessary. The latter can be used to downsize the prostate before brachytherapy. Intermediate-Risk Prostate Cancer For intermediate-risk disease, the combination of LDR or HDR brachytherapy combined with EBRT appears to be equivalent to LDR or HDR monotherapy, and superior to EBRT or RP [1]. Even contemporary EBRT techniques with intensity-modulated radiation therapy (IMRT) to 81 Gy appear to be inferior to HDR brachytherapy combined with EBRT [27]. ADT is rarely used in this group. Selection issues may play a role, however, in differences in outcomes between these treatment options. LDR monotherapy is often used in selected favourable intermediate-risk disease with low-volume disease (percent cores involved
