Brachytherapy for Localized Prostate Cancer
EVA MARIE SUAREZ
HARRY S. CLARKE
DAVID T. MARSHALL
The term brachytherapy describes the process of placing a radioactive source directly inside or in close proximity to the intended target. The use of brachytherapy in prostate cancer was first reported by Pasteau and Degrais in 1913 (1), and various techniques have been explored since. Retropubic implantation of radioactive sources was used initially until the introduction of the transrectal ultrasound (TRUS) probe in the early 1980s (2). Significant advancements in ultrasound technology have led to ultrasound-guided transperineal prostate brachytherapy as the currently accepted technique used for prostate brachytherapy and has experienced substantial growth over the last 20 years.
Brachytherapy offers several advantages over radical prostatectomy, including patient convenience, no surgical incision, decreased anesthesia requirement, minimal blood loss, rapid recovery, and less risk of incontinence. Brachytherapy also offers advantages over external beam radiation therapy (EBRT). Proper brachytherapy technique can lead to decreased radiation dose to surrounding structures, thereby limiting normal
tissue toxicity. Evidence continues to accumulate demonstrating the importance of dose escalation in prostate cancer. In order to deliver an acceptable dose via EBRT, patients may undergo several weeks of treatment, whereas brachytherapy can be completed during an outpatient procedure or a short hospitalization. Finally, the position of the prostate and surrounding critical organs may be difficult to reproduce daily during a protracted course of treatment, which may lead to an increased dose to normal tissues or a decreased dose to the prostate. Potential disadvantages to brachytherapy compared to external beam radiotherapy are that it may take longer to develop brachytherapy skills, is at least minimally invasive with a higher risk of urinary retention, and requires anesthesia. Compared to surgery, the risk of bowel changes and toxicity may be greater with brachytherapy.
tissue toxicity. Evidence continues to accumulate demonstrating the importance of dose escalation in prostate cancer. In order to deliver an acceptable dose via EBRT, patients may undergo several weeks of treatment, whereas brachytherapy can be completed during an outpatient procedure or a short hospitalization. Finally, the position of the prostate and surrounding critical organs may be difficult to reproduce daily during a protracted course of treatment, which may lead to an increased dose to normal tissues or a decreased dose to the prostate. Potential disadvantages to brachytherapy compared to external beam radiotherapy are that it may take longer to develop brachytherapy skills, is at least minimally invasive with a higher risk of urinary retention, and requires anesthesia. Compared to surgery, the risk of bowel changes and toxicity may be greater with brachytherapy.
Three isotopes (125I, 103Pd, and 131Cs) are now available for low-dose-rate (LDR) brachytherapy. The majority of the radiation dose is delivered over 2 to 10 months, depending on which isotope is used. The timing and severity of acute side effects have been described regarding the different sources; however, no convincing evidence is available to recommend one source over another. LDR brachytherapy involves the transperineal placement of radioactive seeds into and around the prostate. The seeds remain in place permanently but lose radioactivity over time. High-dose-rate (HDR) brachytherapy has been increasingly utilized as well. Catheters are placed within the prostate as described in the following text for LDR needles, and a dosimetric plan is developed with computerized tomography (CT) or TRUS imaging and computer planning. An iridium-192 source can then be moved in and out of each catheter remotely via a computer-controlled robotic device. The time the radioactive source spends in each catheter and at each dwell position within each catheter can be manipulated via computer control to achieve a conformal radiotherapy plan. HDR brachytherapy typically requires a short hospital stay and 2 to 10 treatments over a 1- to 5-day period.
DIAGNOSIS
The diagnosis and risk stratification of prostate cancer is via 12 to 16 core prostate biopsies following an elevated prostate-specific antigen (PSA) or abnormal digital rectal exam. Patients with high risk of seminal vesicle involvement, such as those with large nodules on exam or perineural invasion seen on prostate biopsy, should undergo TRUS-guided biopsy of the seminal vesicles. Magnetic resonance imaging (MRI) can also be used to detect otherwise occult seminal vesicle involvement or extracapsular extension. Pelvic lymphadenectomy is not commonly performed for patients with low-risk disease. Patients with high risk of lymph node involvement (patients with seminal vesicle involvement, Gleason score >7, PSA >20) may benefit from laparoscopic pelvic lymph node dissection as nodal involvement changes treatment recommendations.
INDICATIONS FOR SURGERY
When considering brachytherapy as monotherapy for prostate cancer, it is critical to carefully select patients with lowrisk disease or those with favorable intermediate risk disease. A number of tools have been developed to aid the physician when making this selection, including the Partin tables (3) and the Roach formulas (4,5). These tools can help estimate the risk of extraprostatic extension, seminal vesicle invasion, and pelvic lymph node involvement. Recommendations have been made regarding classification of patients into low-, intermediate-, and high-risk categories as illustrated in Table 34.1. Lowrisk prostate cancer can be summarized as PSA <10, Gleason score <7, and clinical stage <T2b. Other risk factors, such as presence of perineural invasion or lymphovascular space invasion, and number of cores positive on biopsy, should be considered when stratifying patients and choosing appropriate treatment modalities. Recent literature also demonstrates acceptable outcomes when treating patients with favorable intermediate risk disease with brachytherapy as monotherapy. Typically, patients who have only one intermediate risk factor are considered (6,7), but data is emerging demonstrating excellent control rates for higher risk patients with or without a short course of androgen deprivation therapy (ADT) (6,8,9).
TABLE 34.1 PATIENT SELECTION FACTORS | |||||||||||||||||||||
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Brachytherapy alone is not generally recommended as monotherapy for higher intermediate or high-risk patients. However, there is a growing body of evidence supporting the use of brachytherapy as a boost when combined with EBRT and ADT for higher risk disease (10,11,12,13,14). Brachytherapy is used in this situation as a very effective method of dose escalation. One recently reported trial from Canada, called the Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) trial, randomized patients to dose-escalated EBRT with short-course ADT versus EBRT plus LDR brachytherapy with short-course ADT (15). In preliminary reports, LDR brachytherapy was shown to improve PSA control. Nine-year Kaplan-Meier relapse-free survival estimates were 63% for dose-escalated EBRT versus 83% for EBRT plus LDR brachytherapy.
ALTERNATIVE THERAPY
Prostate brachytherapy can be an ideal treatment for men with localized, low-risk prostate cancer, but good alternatives exist and may be more appropriate in certain situations. Men with high International Prostate Symptom Scores (IPSS), large prostate volume, or history of previous transurethral resection of the prostate (TURP) may tolerate EBRT or prostatectomy better than brachytherapy while achieving a similar therapeutic outcome. High IPSS before treatment predicts significant
risk of severe lower urinary tract symptoms (LUTS) and acute urinary obstruction following brachytherapy (16). Similarly, large prostates have been shown to be at increased risk for urinary retention (17), although the absolute risk may still be low depending on the technique used (18). Patients with a history of prior TURP may be at increased risk for significant toxicity, including incontinence, if LDR brachytherapy is used (19,20), especially if the residual TURP deficit is large. This risk may be less with HDR brachytherapy (20a).
risk of severe lower urinary tract symptoms (LUTS) and acute urinary obstruction following brachytherapy (16). Similarly, large prostates have been shown to be at increased risk for urinary retention (17), although the absolute risk may still be low depending on the technique used (18). Patients with a history of prior TURP may be at increased risk for significant toxicity, including incontinence, if LDR brachytherapy is used (19,20), especially if the residual TURP deficit is large. This risk may be less with HDR brachytherapy (20a).
LOW-DOSE-RATE BRACHYTHERAPY
Selection of Isotope
Three isotopes (125I, 103Pd, and 131Cs), as noted earlier, are currently being used for LDR prostate brachytherapy. Each delivers radiation to a volume of tissue within millimeters of each source. They differ in initial activity, dose rate, and half-life, as illustrated in Table 34.2. Some investigators believe 103Pd may be more effective than 125I at eradicating more rapidly proliferating tumors due to higher initial activity (20 to 25 cGy per hour and 7 to 10 cGy per hour, respectively). This belief has been propagated by convincing mathematical models and has led to the emergence of 131Cs (32 cGy per hour) as another option. However, no conclusive clinical evidence proving this theory has yet been published, and one clinical trial has shown equivalence between 125I and 103Pd regarding PSA control at 3 years (21). The current recommended doses for the three isotopes in monotherapy and in combination with external beam therapy are shown in Table 34.3.
Treatment Planning
Prostate LDR brachytherapy has evolved significantly over the years, and two methods now predominate: preplanned implant as popularized by the Seattle Prostate Institute and intraoperative planning as developed at Mount Sinai School of Medicine (MSSM) in New York.
Preplanning Approach
With this approach pioneered in Seattle (22), the patient is placed in the dorsal lithotomy position (Fig. 34.1) and an imaging study of the prostate is performed using TRUS (Fig. 34.2) 1 to 2 weeks before the implant. This image data set is imported into the brachytherapy planning software and utilized to develop an optimized plan. The number of seeds ordered for the procedure is then determined from this preplan. The patient is taken to the operating room (OR) on the day of the procedure and is positioned as he was on the day of planning. It is critically important that the patient’s preplanning position is reproduced as accurately as possible in the OR. Seeds are then placed within the prostate with TRUS guidance (Fig. 34.3) using needles preloaded with seeds or strands of connected seeds according to the previously developed plan. Alternatively, seeds may be placed with a gun-type applicator, such as the Mick applicator (Mick Radio-Nuclear Instruments, Mount Vernon, New York), based on the planning study completed earlier. With the preplanned approach, the Mick applicator allows the practitioner to make minor adjustments to more accurately reproduce the preplanning study. A combination of preloaded needles and free seeds placed with the Mick applicator can also be used.
TABLE 34.2 CHARACTERISTICS OF THE MOST COMMONLY USED PERMANENT SOURCES | ||||||||||||||||||||
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TABLE 34.3 TYPICALLY PRESCRIBED MINIMUM PERIPHERAL DOSES FOR 125I AND 103PD | ||||||||||||||||
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Real-time Intraoperative Planning Approach
With this approach developed by Stock et al. at MSSM (23), no preplanning study is acquired; however, the prostate volume is measured via a CT, MRI, or TRUS study at some point prior to the day of the implant in order to determine how many seeds to order for the procedure. This can be the
volume determined at TRUS done for the initial biopsy. The patient is then brought to the OR and placed in the dorsal lithotomy position. TRUS is used to localize the bladder, urethra, prostate, seminal vesicles, and anterior rectal wall in three-dimensional space, and these data are recorded in the intraoperative treatment planning software (Fig. 34.4). An initial intraoperative plan is then developed based on a prostate volume-to-activity nomogram developed at MSSM. Needles are placed in the periphery of the prostate at approximately 1-cm intervals (Fig. 34.5). Once the needles are placed, images are reacquired to account for changes in size, shape, and position of the prostate that occurs with the inflammation induced
by multiple needle placement (Fig. 34.6). The plan is optimized for actual position of the needles and for any changes in shape of the prostate due to needle placement. Longitudinal views on the TRUS are used to observe placement of the seeds into the prostate according to the intraoperative plan (Fig. 34.7). Seeds are most often placed using a Mick applicator. Typically 75% of the required activity is placed in the periphery of the gland, while 25% is placed in the interior of the gland. Then needles are placed in the central portion of the gland and the Mick applicator is then used to place the remaining 25% of the required activity in the gland according to the intraoperative plan. The majority of the inner seeds are placed at the apex and base of the gland in order to “cap” the prostate. Using modern treatment planning software and TRUS, the actual seed location can be documented as the seeds are placed and the intraoperative plan can better reflect reality, allowing for dosimetric inadequacies to be detected and corrected during the procedure.
volume determined at TRUS done for the initial biopsy. The patient is then brought to the OR and placed in the dorsal lithotomy position. TRUS is used to localize the bladder, urethra, prostate, seminal vesicles, and anterior rectal wall in three-dimensional space, and these data are recorded in the intraoperative treatment planning software (Fig. 34.4). An initial intraoperative plan is then developed based on a prostate volume-to-activity nomogram developed at MSSM. Needles are placed in the periphery of the prostate at approximately 1-cm intervals (Fig. 34.5). Once the needles are placed, images are reacquired to account for changes in size, shape, and position of the prostate that occurs with the inflammation induced
by multiple needle placement (Fig. 34.6). The plan is optimized for actual position of the needles and for any changes in shape of the prostate due to needle placement. Longitudinal views on the TRUS are used to observe placement of the seeds into the prostate according to the intraoperative plan (Fig. 34.7). Seeds are most often placed using a Mick applicator. Typically 75% of the required activity is placed in the periphery of the gland, while 25% is placed in the interior of the gland. Then needles are placed in the central portion of the gland and the Mick applicator is then used to place the remaining 25% of the required activity in the gland according to the intraoperative plan. The majority of the inner seeds are placed at the apex and base of the gland in order to “cap” the prostate. Using modern treatment planning software and TRUS, the actual seed location can be documented as the seeds are placed and the intraoperative plan can better reflect reality, allowing for dosimetric inadequacies to be detected and corrected during the procedure.
 FIGURE 34.1 Patient prepared for TRUS in the dorsal lithotomy position. |
 FIGURE 34.2 TRUS probe in ratcheting cradle/stepper. |
 FIGURE 34.3 Schematic of the closed, ultrasound-guided implantation technique. |
 FIGURE 34.4 Ultrasound imaging of the prostate, urethra, seminal vesicles, and rectum in the intraoperative treatment planning system before needle placement. This data set is used to create the “preplan” in the OR.
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