Brachytherapy (Radioactive Seed Implantation Therapy) in Prostate Cancer Technique

Dosimetric planning of the implant should be performed in all patients before or during seed insertion. Debate persists as to whether intraoperative planning or preplanning is preferred (see Periprocedural Care). A modified peripheral loading plan is preferred when the sources are placed.

The dose is quantified in terms of the unit of absorbed energy per weight of tissue. For example, the basic unit of radiation, the gray (Gy), is 1 J/kg of tissue.

In brachytherapy, the sharp radiation dose falloff allows a high degree of rectal sparing and permits delivery of a higher total dose to the prostate gland itself. Similar advantages can be obtained with conformal intensity-modulated radiation therapy (IMRT), but whereas brachytherapy has a much lower initial dose rate than IMRT, its aggregate radiation delivery is higher. The average dose rates are 10 Gy/wk for IMRT, 40 Gy/wk for Pd-103 brachytherapy implants, and 13 Gy/wk for I-125 brachytherapy.

A perineal template and either transrectal ultrasonography (TRUS) or computed tomography (CT) are used to guide placement of the needles into the prostate. Once the final needle position is established, the seeds are delivered.

The emergence and widespread use of multi-parametric MRI provides unparalleled assessment of the prostate and periprostatic anatomy, making it a very beneficial imaging modality to facilitate prostate BT treatment planning, imaging and implantation, and follow-up. ^[26]

Benefits of a new brachytherapy technique: 4D brachytherapy

Although the theory and principles of brachytherapy have been around for decades, there are still ways to improve efficiency and precision while decreasing the number of complications. In February 2012, an article was published on 4D brachytherapy, a novel real-time prostate brachytherapy technique using stranded and loose seeds, that explains an innovative approach to the brachytherapy technique.

4D brachytherapy is a one-stage prostate brachytherapy technique that uses stranded and loose seeds. The advantage of placing loose seeds in the center of the prostate gland and stranded seeds in the periphery of the prostate gland is decreased migration of seeds to other organs. This can potentially decrease bladder and rectal complications. In addition, the loose seeds placed centrally can increase the dosage of radiation to the prostate apex and thus improve its dosimetry (median D⁹⁰ 143 and 153Gy [P< .005] and median V¹⁰⁰ 88% and 93% [P< .005] for the Seattle technique and 4D brachytherapy implant technique, respectively). ^[27]

Efficiency in the operating room is another area of brachytherapy that needs improvement. 4D brachytherapy is a one-stage technique that can be performed in less than 45 minutes, compared with other one-stage techniques, which can take 2-3 hours. In previous one-stage techniques, the radiation oncologist and the dosimetry technician performed the TRUS and seed mapping while the patient is under anesthesia the same day of seed placement in the operating room. The 4D brachytherapy technique uses an initial outpatient TRUS to measure the height, width, length, and 2 parasagittal lengths of the prostate. These measurements are factored into a nomogram created from more than 1000 brachytherapy procedures in order to map out the seed implants beforehand. The stranded and loose seeds are then preloaded prior to the procedure, ultimately reducing operative and anesthesia time, in addition to less time for patients being in the dorsal lithotomy position. ^[27]

Prospectively collected data show significantly improved dosimetry compared with other brachytherapy techniques. The improved dosimetry reduces short-term urinary morbidity, which was assessed using the international prostate symptom score. ^[27] Improved urinary morbidity can be attributed to the placement of loose seeds in the apex of the prostate, allowing for more control of radiation delivery to the region. This minimizes the dose to surrounding structures at risk for unnecessary radiation, such as the membranous urethra and penile bulb. Decreased urethral stricture and erectile dysfunction have been seen with improved dosimetry. ^{[28, 29]}

Stepwise approach to 4D brachytherapy is as follows:

1. Outpatient TRUS: Height, width, length, and 2 parasagittal lengths of prostate measured

2. Seed order: Measurements of height, width, length, 2 parasagittal lengths plugged into Web-based nomogram, which can calculate proper seed order

3. Seed placement: Implant preloaded stranded seeds peripherally, followed by implanting loose seeds centrally

4. Dosimetric assessment: Each seed order comes with an extra 15 loose seeds in case of under-dosed region of prostate

Postimplant CT scanning is recommended within 24 hours of the procedure.

While the basic approach for brachytherapy has not really changed, multiple innovations, like the multi-source rotating shield brachytherapy that performs precise simultaneous angular and linear measurements and positioning, have been suggested for delivering less radiation to adjacent healthy tissues like the rectum or urethra. Other centers have tested using endorectal probe sensors for better imaging of seed implants. ^[30]      

TRUS guidance

A biplanar TRUS probe with a frequency of 5, 6, or 7.5 MHz is preferable. Attach the probe to the stepping unit, which moves the probe in a cephalad or caudal direction at 0.5-cm intervals. To differentiate the bladder from the prostate, use a urinary catheter to visualize the urethra, or instill diatrizoate into the bladder. Secure the scrotum out of the perineal field with tape or towel clips.

Match the probe image to the planning image. Adjust the needle-guide template against the perineum, leaving 1-3 cm of space between the skin and the template. When intraoperative planning is being used, recreation of the images is not necessary. The benefits of intraoperative planning are that optimal settings are determined in real time and that variations are minimized (which means that there is no need to reproduce an earlier plan). A drawback is that the operating time is longer; however, the patient needs to come in only once.

Insert the needles through holes in the template, and then through skin (see the image below). Watch for deflection, and reposition needles as necessary. Avoid anterior pubic bones. Burnished-tip needles are easier to see when the sonogram becomes distorted by previously placed needles. Avoid piercing the urethra, and ensure that no needle is closer than 0.5 cm to the rectal wall.

Adjust the needle depth on the basis of the preplan zero plane. Use a longitudinal ultrasonographic view. To mark the location of the bladder neck, perform fluoroscopy using a Foley balloon catheter, or instill diatrizoate.

For source placement, afterloading or Mick applicator (Mick Radio-Nuclear Instruments, Mount Vernon, NY) techniques can be used. Remove the needle slowly to avoid source migration in the afterloading technique. Observe seed positioning under fluoroscopy.

CT guidance

Obtain a planning CT scan several days before the procedure, with a urinary catheter in place. The catheter and the diatrizoate serve to mark the bladder-prostate border. The prostate is scanned at 5-mm intervals with images that are 5 mm thick.

At the start of the procedure, place a urethral catheter that has wire through it and lead markers at 1-cm intervals. Mount the template stand against the perineum. Most brachytherapists do not use a rectal marker.

Initially, insert 2 needles simultaneously just posterior to the urethra on either side of the midline. Next, insert all anterior needles to limit prostate mobility. Anterior sources are placed first. Then, place posterior needles again, using the 1-cm markers on the urethral catheter for guidance.

For source placement with the Mick applicator, pull the needle back from the zero plane in 5-mm steps. Use preloaded needles. Rigid Absorbable Permanent Implant Device (RAPID; Amersham Health, Princeton, NJ) Strand seeds (ie, I-125 seeds adsorbed onto a silver rod) are an option. Watch the placement of each source, using repeat CT scanning. Obtain a final CT scan of the prostate, and perform postimplant dosimetry.

Suboptimal Implantation:

Suboptimal permanent seed brachytherapy implantation and a D₉₀ of < 130 Gy can be predictive factors for biochemical failure. In these cases, other factors are taken into consideration before recommending further treatments. One study with a follow-up time of 8 years of suboptimal implanted seeds reported that patients with a PSA-D < 0.15 would be less likely to have biochemical failure. These results will have to be ultimately verified in large cohorts. ^[31]

 

Allow the patient to recover from anesthesia. Patients are discharged home the same day. Continue antibiotic prophylaxis, using oral antibiotics, for several days postoperatively. Initiate a voiding trial. If the patient cannot void, a catheter is reinserted, and another trial is performed in 5-7 days.

A final CT scan of the prostate and postimplant dosimetry are performed (only in TRUS-guided cases) 1-30 days after the procedure. If a “cold spot” is observed, reimplantation can be performed.

Many brachytherapists perform cystoscopy to look for sources in the bladder or the urethra. Additional plain radiographs should be obtained to verify the seed count (see the image below).

Until the ideal postoperative interval for CT scanning has been determined, each institution should perform dosimetric evaluation of prostate implants at a consistent postoperative interval. This interval should be reported. Isodose displays should be obtained at 50%, 80%, 90%, 100%, 150%, and 200% of the prescription dose and displayed on multiple cross-sectional images of the prostate.

Dose-volume histography of the prostate should be performed, and all centers should report the D90 (ie, the dose to 90% of the prostate gland). Additionally, the following should be reported and ultimately correlated with clinical outcome in the research environment:

• D80 (the dose to 80% of the prostate gland)

• D100 (the dose to 100% of the prostate gland)

• Fractional V80, V90, V100, V150, and V200 (ie, the percentage of prostate volume receiving 80%, 90%, 100%, 150%, and 200% of the prescribed dose, respectively)

• Rectal and urethral doses

Urbanic et al reported that a review of 4 series confirms that freedom from recurrence depends on adequate dosimetry. ^[32]

Perineal, urinary, and rectal symptoms may complicate brachytherapy, as may sexual dysfunction.

Perineal symptoms

The perineum is tender and bruised and may have slight bleeding at needle puncture sites. Treatment predominantly consists of application of ice and administration of mild analgesics.

Urinary symptoms

Hematuria is expected for the first 1-2 weeks, and all patients experience dysuria. Irritative symptoms (eg, dysuria, frequency, and urgency) last from days to months. Studies have shown that 34-45% of patients have symptoms that persist for up to 1 year.

The incidence of incontinence is 10-35% in the first few months. Few patients have any leakage at 1 year. 

Interesting data suggest that the incidence of lower urinary tract symptoms decline with increasing institutional experience with brachytherapy. In this study, more than 75% of the patients reported complete resolution of urinary symptoms by 24 months after brachytherapry. ^[33]

In most cases, perioperative edema resolves within the first 48 hours; virtually all resolve within the first week. A small subset of patients continues to have difficulty voiding beyond that period. These patients are taught the technique of clean intermittent catheterization.

If voiding does not return within 3 months, urodynamics testing may be considered to confirm that the cause is truly obstruction rather than bladder dysfunction. If obstructive symptoms are present, patients are started on alpha-blockers and maintained on this therapy for 9 months. In patients with true obstruction, transurethral resection of the prostate (TURP) may be performed.

Rectal symptoms

As many as one third of patients who have undergone brachytherapy report urge, diarrhea, and painful bowel movements. These symptoms improve over the first year. Nonsteroidal anti-inflammatory drugs and mesalamine suppositories may help.

At 1 year, only 2% have persistent symptoms. Some studies report that as many as 20% of patients have bright-red blood per rectum. Symptoms have been reported to persist as long as 49 months after the procedure.

Prostatorectal fistulas occur in 1-7% of all patients in published series. Data from the primary authors’ institution suggest that after brachytherapy, these fistulas result from biopsy of the anterior rectal wall by gastroenterologists. The wall probably appears irritated and ulcerated after brachytherapy, thus prompting the biopsy. Patients should be counseled to undergo colonoscopy before or 1 year after brachytherapy.

Sexual dysfunction

Generally, 33% of patients experience a decrease in sexual function and activity. Decreased seminal volume is observed. Studies report widely varying impotence rates, ranging from 2.5% to 25%. In some studies, 40% of the patients experienced some degree of erectile dysfunction after radiation therapy. Many studies comparing brachytherapy to EBRT or radical prostatectomy suggest better erectile functional outcomes with brachytherapy when taking into consideration the impact of age. ^[34]