TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY

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1 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 1 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY BRENDAN CAREY, MD

2 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 2 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY DR. BRENDAN CAREY, CONSULTANT RADIOLOGIST, ST JAMES INSTITUTE OF ONCOLOGY, LEEDS, UK Modern prostate brachytherapy has been established over the past three decades as an effective treatment for localized prostate cancer with high patient tolerability and acceptable morbidity outcome data. With transrectal ultrasound (TRUS)-guided brachytherapy, radiation is delivered directly into the gland. This allows for intra-prostatic doses of radiation that are unachievable by external beam radiation therapy (EBRT) techniques alone with the potential convenience of a single-day outpatient procedure. Prostate brachytherapy can be delivered in two different ways: permanent seed implants using iodine or palladium seeds (Low Dose Rate, or LDR) or using temporary removable implants with iridium wires (High Dose Rate, or HDR). Biplane transrectal ultrasound is essential for accurate imaging guidance to place the radioactive sources into the prostate using a template-guided transperineal technique. TRUS technology and radiation planning software continue to evolve, and selection criteria for prostate brachytherapy in terms of patient selection, treatment planning, treatment technique, post-implant evaluation, and biochemical and quality-of-life outcomes have been established and published. INTRODUCTION Prostate cancer interventions have been greatly facilitated by developments in ultrasound transducer design and technology. Radiotherapy for prostate cancer can be delivered in different ways: conventionally, using external beam techniques, or by implanting the radioactive sources directly into the prostate (brachytherapy). The role of various ablation techniques including brachytherapy as an alternative to radical prostatectomy or EBRT techniques for the definitive treatment of prostate cancer have gained in popularity. The modern era of prostate brachytherapy began in the 1980 s with the development of the closed transperineal implant technique using transrectal ultrasound guidance. Transrectal ultrasound guidance facilitates a closed percutaneous transperineal approach to the prostate for placement of radioactive sources. The development of biplane transrectal ultrasound transducer technology, like BK Medical s endocavity biplane transducer, 8848, has improved the safety and accuracy of the technique and the outcome data over recent years has confirmed that it is an effective treatment with high patient tolerance and acceptable morbidity. There is growing comprehensive evidence on the excellent clinical outcome after prostate brachytherapy. Advances in diagnostic imaging and TRUS-guided biopsy techniques have the potential for more accurate localization of cancers within the prostate, and there is growing interest in the concept of focal therapies driven by downward stage migration, improved biopsy and imaging techniques, and the prevalence of unifocal dominant cancers. Focal prostate brachytherapy is being explored as a future treatment option for clinically localized prostate cancer.

3 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 3 Prostate brachytherapy is a valid alternative to radical prostatectomy and external beam radiotherapy for localized prostate cancer. The exact choice of brachytherapy technique will vary depending on the stage of the prostate cancer and disease-specific parameters such as the Serum PSA at presentation and the Gleason Score from the prostate biopsy. LDR Brachytherapy is performed with permanent implantation of radioactive seeds into the prostate, usually iodine-125 with a half life of 60 days, although palladium-103 sources with a half life of 17 days can also be used. HDR Brachytherapy uses temporary placement of iridium wires into the prostate, and these are then removed after the treatment is completed. Whatever technique is used, the transrectal ultrasound procedure is similar: the prostate is scanned to obtain an accurate volume and shape, and this information is used by the radiation planning software such as the Varian system to generate a 3-dimensional dose plan for each patient. Prostate brachytherapy is a valid alternative to radical prostatectomy and external beam radiotherapy for localized prostate cancer. The ultrasound data collected from this pre-treatment volumetric assessment is the basis for calculating the required number and location of sources for that particular patient and consists of both prostate volume acquisition and accurate 3D volume-rendered dosimetry. The radioactive sources are then inserted, transperineally, into the gland using a template-guided technique under real-time biplane ultrasound guidance, for which the BK Medical biplane transducer 8848 together with the Flex Focus system are ideally suited. Brachytherapy techniques have evolved since the original Seattle 2-step technique for LDR brachytherapy. More sophisticated TRUS and treatment planning software have been introduced and seem to have a significant impact on the accuracy of source placement and on ultrasound-based dosimetry. Whatever technique is used, the TRUS set-up is similar and general principles apply. TRANSRECTAL ULTRASOUND SETUP The procedure is performed in the operating room with the patient in the dorsal lithotomy position. General anaesthesia is generally used although, occasionally, spinal anaesthesia may be utilized. An inflatable (water)standoff probe cover can be used with the biplane transducer 8848 to facilitate elevation and optimum access for source positioning within the prostate gland during implantation. The TRUS transducer is positioned in a stepping device that allows the prostate to be scanned systematically in both axial and sagittal planes. 1 TRUS setup for Brachytherapy with 5mm grid overlay. 2 Biplanar imaging to monitor source placement in prostate.

4 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 4 The bladder may be catheterized, and radiographic contrast can be introduced into the bladder to facilitate fluoroscopy of the bladder base. Aerated ultrasound gel or a urethral catheter can also be used to delineate the urethra and aid urethral recognition during implantation. An implant grid, mounted onto the stepping unit, is placed against the perineum to guide needle and source placement within the prostate. This implant grid is calibrated to an on-screen superimposition of the grid matrix over the ultrasound image (Fig. 1). Advanced software in the BK Medical ultrasound system permits very accurate volume and surface outline calculations of the prostate and seminal vesicles. The software also includes a matrix offset and a user-defined option which can be programmed to compensate for any non-standard matrix. The transducer can be used for seed implantation with a choice of specially designed brachytherapy matrix templates. Using the ultrasound data, the requisite number and distribution of radioactive sources is calculated for the patient. The Brachytherapy Pro Package with the ultrasound system contains all the essential setups and measurements for precise volumetric assessment of the prostate gland, simultaneous biplane imaging and tissue harmonic imaging. 3-dimensional imaging also facilitates assessment of the gland during implantation. Biplane ultrasound with the endocavity transducer 8848 allows each needle to be monitored as it is inserted transperineally into the prostate. The sources are then loaded into the prostate, through these needles, under direct, real-time ultrasound guidance (Fig. 2). Great care must be taken to avoid inadvertent trauma to the bladder, urethra and rectum during insertion. Biplane ultrasound with the transducer 8848 greatly facilitates identification of needle and source deposition in the prostate and enhances the development of these newer implantation modifications. LDR BRACHYTHERAPY LDR brachytherapy is most frequently used in low-risk patients. The original Seattle 2-step technique has stood the test of time in terms of outcomes, but in recent years intraoperative-planned techniques have emerged in an effort to overcome some of the acknowledged limitations of the pre-planned technique. The specific aims are to design the optimal treatment plan using intraoperative 3D anatomical information, to implement the treatment plan with precision, and to analyze the dosimetric outcome while the procedure is still in progress. 3 3D imaging to monitor needle and source placement during implant. 4 Post-implant image showing HDR source location in prostate.

5 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 5 This offers the opportunity to improve the quality of implants by appropriate modification in the seed implants and replanning during the procedure itself (Fig. 3). Inverse-radiation planning optimization techniques for optimal seed placement, 3D ultrasound technology with real-time needle guidance are some examples of technological improvements already used in LDR brachytherapy. Based on the volume of the prostate, generally between 70 and 150 radioactive seeds are preloaded into needles and inserted into the prostate. The seeds are deployed into the gland and the needles are then removed. The seeds remain in the prostate permanently, with radioactive decay times of 60 days for iodine-125 and for 17 days for palladium-103. During this time, the patient must observe basic but minimal radiation precautions. Travel and contact with adults are not restricted; however, small children and pregnant women should not be in direct prolonged contact with the patient during this period. Sexual intercourse can usually be resumed after about one month. Most patients will experience some urinary symptoms after prostate brachytherapy, and acute urinary retention generally occurs in about 15% of patients following LDR brachytherapy. Nocturia and daytime frequency are very common, and overall urinary morbidity does correlate with higher pre-treatment International Prostate Symptom Score (IPSS) urinary scores. The relationship between urethral dose and urinary toxicity is unclear, although most patients benefit from routine use of alpha blockers (smooth muscle relaxants) during the initial weeks after implantation. Prolonged urinary catheterization is unusual, and surgery to improve urinary flow should be avoided, if at all possible, as it has a high risk of causing incontinence afterwards. Rectal complications are uncommon and usually consist of self-limited proctitis. Long-term bowel dysfunction after brachytherapy is very unusual. Preservation of sexual function after brachytherapy, as with other prostate cancer treatments, is difficult to assess. There seems to be no clear evidence so far for factors influencing erectile dysfunction after brachytherapy. HDR BRACHYTHERAPY In patients with intermediate and high-risk prostate cancers, there is increasing dosimetric and clinical evidence for the efficacy of HDR prostate brachytherapy. This can be delivered as a radiation boost combined with external beam radiotherapy or as monotherapy. Combined HDR brachytherapy and EBRT is used for patients with locally more advanced disease those with higher PSA levels or higher pathology (Gleason 8-10) grade. HDR brachytherapy permits delivery of a large radiation dose to the prostate in a small number of treatment doses (fractions). The setup implant technique itself is identical to that for LDR: under TRUS guidance and using a template transperineal technique, up to 20 blind-ended needles are inserted into the prostate (Fig. 4). Source dwell positions and times are determined using specialist planning software, and the radiation treatment is delivered using a single iridium source via an afterloading unit. Following treatment, the needles and source are removed, and once haemostasis is achieved, the urinary catheter is also removed. Acutely, HDR brachytherapy commonly leads to an increase in urinary symptoms. However, this is generally short lived, and catheterisation is rarely needed. Acute and late rectal toxicity rates are low following HDR brachytherapy. CONCLUSION Prostate brachytherapy has become a widely accepted and valid method for the treatment of localized prostate cancer. Implant techniques continue to evolve and future options will include focal brachytherapy. Biplane transrectal ultrasound guidance, enabled by the BK Medical 8848 transducer and ultrasound system with its specially designed Brachytherapy Pro Package software and fully integrated 3D capabilities, greatly assists the safety and accuracy of the procedure.

6 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 6 FLEX FOCUS FOR ULTRASOUND GUIDANCE Our BK products are the market leaders for ultrasound-guided brachytherapy. We lead the field because we have dedicated development resources specifically to ultrasound-guided brachytherapy and have built up strong ties with the leading providers of brachytherapy seeds to the advantage of our customers who can purchase a complete brachytherapy package for the prostate. The 8848 transducer delivers confidence in precise prostate brachytherapy. Simultaneous biplane imaging (sagittal and transverse view), provides better orientation during needle placement and greater confidence in source placement in the prostate gland. Endocavity Biplane (8848)during implant. Flex Focus Endocavity Biplane (8848) scanning planes

7 TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BRACHYTHERAPY 7 This ebook is distributed by BK Ultrasound. Please visit us at: bkultrasound.com/applications/urology REFERENCES 1. Holm H, Juul N, Pederson J, et al. Transperineal I 125 seed implantation in prostatic cancer guided by transrectal ultrasoundography. J Urology 1983; 130: Morton G, Loblaw A, Cheung P, et al. Is single fraction 15Gy the preferred high dose-rate brachytherapy boost dose for prostate cancer? Radiother Oncol. 2011;100: Morton GC, Loblaw DA, Chung H, et al. Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer. Int J Radiat Oncol Biol 4. Pellizzon AC, Nadalin W, Salvajoli JV, et al. Results of high dose rate afterloading brachytherapy boost to conventional external beam radiation therapy for initial and locally advanced prostate cancer. Radiother Oncol 2003;66: Henry A, Al-Qaisieh B, Gould K, et al. Outcomes following iodine-125 monotherapy for localized prostate cancer: the results of Leeds 10-year single-center brachytherapy experience. Int J Radiat Oncol Biol Phys 2010;76: Hinnen K, Battermann J, van Roermund J, et al. Long-term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2010;76: Prada P, Juan G, Gonzalez-Suarez H, et al. Prostate-specific antigen relapse-free survival and side-effects in 734 patients with up to 10 years of follow-up with localized prostate cancer treated by permanent iodine implants. BJU Int 2010;106: Sylvester J, Grimm P, Wong J, et al. Fifteen-year biochemical relapse-free survival, cause-specific survival, and overall survival following I(125) prostate brachytherapy in clinically localized prostate cancer: Seattle experience. Int J Radiat Oncol Biol Phys 2011;81: Demanes D, Martinez A, Ghilezan M, et al. High-dose-rate monotherapy: safe and effective brachytherapy for patients with localized prostate cancer. Int J Radiat Oncol Biol Phys 2011;81: Ash D, Al-Qaisieh B, Gould K, et al. Long term outcomes following iodine-125 monotherapy for localized prostate cancer: the Cookridge 10 year results. Clin Oncol (R Coll Radiol) 2007; S Kovacs G, Potter R, Loch T, et al. EC/ESTRO-EAU recommendations on temporary brachytherapy using stepping sources for localised prostate cancer. Radiother Oncol 2005; 74(2): Polo A, Salembier C, Venselaar J, et al. Review of intraoperative imaging and planning techniques in permanent seed prostate brachytherapy. Radiother Oncol 2010; 94(1): Lubbe W, Cohen R, Sharma N, et al. Biochemical and clinical experience with real-time intraoperatively planned permanent prostate brachytherapy. Brachytherapy 2012; 11(3):

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