Temporary Seed Implant with High Dose Rate Brachytherapy
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PCRI Insights November 2003 vol. 6, no. 4
By Glen Gejerman M.D.,
Hackensack University Medical Center

During the past decade, prostate seed implantation has been increasingly used as monotherapy or in combination with external beam radiotherapy (EBRT).1-4 Exponential growth has been forecasted so that while only 4% of men diagnosed with prostate cancer in 1996 were treated with brachytherapy, it is estimated that approximately half of the men diagnosed in 2006 will be implanted.5 A 1999 Medicare utilization review estimated that brachytherapy may eventually supplant prostatectomy as the treatment of choice for localized prostate cancer.6

While the majority of prostate interstitial brachytherapy is performed with permanent seed implants, the use of a different implant technique known as temporary high dose-rate (HDR) brachytherapy has been increasing. During an HDR implant, small flexible needles are inserted through the perineum (the skin between the testicles and rectum) and a high dose of radiation is delivered to the prostate gland using a computer guided radioactive Iridium wire.

HDR brachytherapy provides many advantages including treatment optimization, accurate dose delivery, and radiation protection. Certain patients who are not good candidates for permanent seed implant may be better treated with HDR. Nevertheless, because the awareness of the HDR technique is not widespread, patients are often not offered this option. The intent of this article is to describe the procedure, its possible advantages over permanent seed implant, and the growing body of long-term results so that patients can include this modality when considering options for local PC therapy.

Implant Procedure

Treatment Preparation

HDR prostate brachytherapy is generally combined with external beam radiotherapy, and it is delivered prior to or several weeks following 45-50Gy pelvic radiotherapy. Before the implant procedure, patients undergo a bowel prep consisting of a full liquid diet and Golytely or Magnesium Citrate. The purpose of this bowel cleansing is twofold: (1) to prevent stool or gas in the rectum from interfering with the ultrasound images required during the implant and (2) to avoid abdominal cramping during the 24 hour hospitalization.

After the patient is brought to the operating room and anesthesia is induced, he is placed in the dorsolithotomy position (on his back with knees flexed). A transrectal ultrasound probe is introduced into the rectum and the probe is then secured into a floor mounted stepping device. A needle guide/perineal template is attached to the stepping unit and pushed up against the perineal skin (the skin between the testicles and rectum). This template is composed of two parts: 1) a needle guide which has holes every 0.5cm through which the needles are introduced into the perineum, and 2) a perineal template which contains a 3mm thick silicone insert designed to grip and prevent movement of the catheters. The transrectal ultrasound probe is advanced until a good image of the prostate gland is obtained. A catheter is placed into the lower urethra, 30cc of an aerosolized Surgilube mixture is injected, the prostate is imaged from the base (top of the gland) to the apex (bottom of the gland) in 5mm transverse sections, and the urethral location is delineated.

Metal needles are placed through the template, pushed through the perineum, and advanced to the midgland. The number of needles placed depends on the size of the gland; 18-23 needles will encompass most glands. The needles are then removed and replaced with hollow plastic needles called “ flexiguide interstitial catheters” and advanced to the base as seen on the ultrasound images. The perineal template is detached from the needle guide and the TRUS probe and the stepping unit are removed. (See Figure 1.)

Perineal template sutured to perineal skin with flexiguide catheters
Figure 1. Perineal template sutured to the perineal skin
with flexiguide catheters.
Needle template being separated form the
Figure 2. Needle template being separated from the
perineal template after placement of interstitial
catheters.

The perineal template is sutured flush to the perineum (Figure 2), and the patient is taken out of the dorsolithotomy position and placed in a frog-legged position. A flexible cystoscope (a scope used to examine the inner lining of the bladder) is inserted through the penis, and the floor of the bladder is examined to ensure that tenting of the bladder mucosa has been achieved; this indicates that the flexiguide interstitial catheters have been pushed through the entire prostate gland but not through the bladder floor. If any of the catheters have traversed the bladder lining, they are identified and withdrawn to a submucosal position. The cystoscope is then removed and a three-way urinary catheter (which allows simultaneous irrigation and drainage of the bladder) is inserted. The implant procedure takes 45–60 minutes after which the patient is wakened and transferred to the recovery room for a two-hour period.

Treatment Planning
Upon recovery, the patient is brought to the Radiation Oncology department and transferred to a custom mattress with a hole in the lower half to avoid pressure on the interstitial catheters. He is transferred to the CT table, a rectal marker is placed, 40cc of contrast is injected into the bladder, and a pelvic CT scan is obtained. During this critical part of the treatment planning, the position of each interstitial catheter is determined relative to the prostate gland, rectum and bladder. The patient’s position is checked with alignment lasers, and triangulating fiducial markers are placed on the patient. The interface between each catheter and the template is marked so that this intersecting point can be checked prior to each brachytherapy treatment. This quality assurance step is taken to ensure that the catheters have not been displaced in a downward direction from the prostate gland.

At the start of the CT, scout films are obtained to determine whether the patient had been properly positioned and to confirm that the interstitial catheters are advanced far enough (up to the bladder). Transverse images of the implant volume are collected in 5mm abutting slices. These images are reviewed, and catheters can be advanced or added if necessary. The prostate gland, urethra, and rectum are outlined and digitized into the computer planning system. This planning system calculates how long the radioactive source spends (dwell time) in specified 5mm steps (dwell position) along the length of the interstitial catheter.

To deliver the desired dose distribution to the prostate gland, the computer program must optimize the dwell times in each dwell position. The relative weight for each dwell position is adjusted to enhance the prostate coverage while maintaining the urethral dose below 110% and the rectal dose at 100% of the dose prescribed to the prostate gland. By adjusting dwell times and dwell positions, a dosimetry plan is individualized to deliver a high dose of radiation to the prostate gland while minimizing the dose to the urethra and rectum. A dose-volume histogram analysis is then performed to ensure that the urethral and rectal doses are within the specified limit.

HDR Treatments

When the treatment plan has been approved, the patient is transferred to a shielded HDR treatment room and monitored via intercom and video. Prior to each brachytherapy treatment, the catheter-template interface is checked to rule out catheter displacement from the template, and the protruding ends are connected to the HDR unit. (See Figure 3.)

Transfer tubes connecting catheters to unit
Figure 3. Transfer tubes connecting the interstitial
catheters to the HDR unit (not shown).

This computer-controlled HDR unit contains a source drive mechanism that moves the radioactive Iridium wire through the interstitial catheters sequentially in accordance with the loading pattern determined by the dosimetry plan. The Iridium source moves rapidly from the HDR safe position to the first dwell position in each catheter and remains there for the predetermined dwell time (from a fraction to several seconds). The source then moves to the next dwell position and remains for its dwell time.

Once the source has stopped at all dwell positions in the catheter, it is retracted into the HDR unit and is then sent to the first dwell position in the next catheter. This process is repeated until all the catheters have been utilized. During the 10-15 minute treatment time, the patient will hear the clicking and whirring sound of the drive mechanism as it advances and withdraws the radioactive Iridium wire through each interstitial catheter. Patients receive from two to four 15-minute HDR treatments between which there is a six-hour interval that is spent back in the hospital room between fractions. The patient is only radioactive while connected to the HDR unit – when the Iridium wire is inserted in the catheters. There is no radioactive exposure when in the hospital room or at home.

During the 24-36 hour hospitalization, patients are confined to a hospital bed and movement is discouraged in order to avoid displacing the flexiguide catheters. Patients have a urinary catheter, are fed a fiber restricted diet, and are given medication to cause constipation to obviate the need to get out of bed to use the bathroom. With the use of patient-controlled analgesia (PCA), most men report only minimal discomfort. These PCA devices allow patients to press a button for a supplemental dose of pain medication while a computer controls the amount of additional dose and the maximum number of administrations in one hour. After the final HDR treatment, the sutures holding the perineal template in place are removed and the template and catheters are removed. Bleeding is controlled by applying pressure over the perineum for several minutes, and patients are discharged from the hospital a few hours later. Possible side effects, which may include perineal tenderness, urinary discomfort, and urinary frequency, can last for 1-2 weeks.

Possible Advantages

Since HDR brachytherapy can mitigate the technical difficulties sometimes encountered during an implant procedure, it has several potential advantages over permanent seed implants. The success of a permanent seed implant is dependent upon the correct delineation of the target volume and optimal placement of needles and seeds. Several studies7 have documented variations in the volume and shape of the prostate gland when comparing (1) the preplanning volumetric study (obtained several weeks before the implant) to (2) the intraoperative ultrasound image. Occasionally, because of narrow pubic arch anatomy, needles cannot be placed anteriorly enough. Additionally, needle deflection during the implant may lead to deposition of seeds in a slightly different pattern than called for based on the preplanning dosimetry. These problems, plus the seed migration that can occur after implantation, may affect the final dose distribution.

Because treatment planning and dose optimization of HDR brachytherapy is performed after the implant, the risk that prostate movement, needle deflection, and seed migration will impair the intended dosimetry is avoided. Narrow pubic arch anatomy is less of an obstacle in HDR brachytherapy because of the HDR procedure’s ability to optimize dwell positions and dwell times in the anteriolateral catheters. This will allow adequate dosimetric coverage even if pubic arch interference prevents ideal needle placement. This ability to plan, optimize the prostate dose, and limit the radiation dose to the urethra and rectum after needle insertion but before treatment is a major advantage of HDR brachytherapy. In contrast to permanent seed implants where one calculates the dosimetry after the implant is made, HDR implants allow for dosimetric calculation and modification before treatment is delivered. This is of particular benefit for those patients who are at significant risk for developing urinary problems after seed implant.

Relative Side-Effects

The following three groups of patients who are at increased risk for uropathy after seed implant should consider HDR:

1. High IPSS Score: Patients who have baseline urinary frequency, urgency, a weak stream, and frequent nocturia are at higher risk for developing urinary problems after seed implantation. These urinary symptoms are graded using a 0-35 scoring system known as the International Prostate Symptom Score (IPSS) (also called AUA Symptom Score). Terk8 found an association between the baseline IPSS score and the risk of urinary retention after seed implantation. IPSS scores of < 10, 10-19, and > 20 correlated with retention rates of 2%, 11%, and 29% respectively. Gelblum9 reported that men with a baseline score greater than 7 had a 59.2% rate of significant urinary toxicity and a greater chance of having residual symptoms after one year. Bucci10 demonstrated that a high IPSS score was predictive for the need for and the duration of catheterization. The mean IPSS value for patients not requiring a catheter was 6 whereas the value for patients requiring a catheter was 10 (p=0.004).

2. Large Prostate Volume: An increased risk of urinary morbidity has been found for patients with prostate gland volumes greater than 35- 40cc. Gelblum9 found that patients with prostate volumes greater than 35cc had a 52.6% grade 2 urinary toxicity rate compared with 35% in patients whose glands were smaller than 35cc. Lee11 reported a 25% risk of retention for patients whose pretreatment planning ultrasound target volume measured more than 45cc. Crook12 demonstrated that the prostate volume was a significant predictor of acute urinary retention and that the risk increased for any given size when androgen suppression was used to downsize the prostate.

3. Prior TURP: Patients who have undergone a transurethral resection (TURP) prior to permanent seed implantation have a higher risk for urinary incontinence.13,14 While the risk of urethral injury is decreased when a peripheral loading technique is employed, most brachytherapists consider a prior TURP to be a relative contra-indication. HDR brachytherapy can accurately achieve highly conformal radiation dose to the prostate while limiting the dose to the TURP defect. Since the urethral dose is kept to tolerance level, the risk of subsequent incontinence is minimized.

HDR Impact on Uropathy Risk Groups

HDR optimization makes it possible to accurately cover the prostate volume while simultaneously setting tolerance constraints for the urethra and rectum. By limiting the dwell time in the catheters closest to the urethra, the urethral dose can be significantly limited. This differential dosing is particularly useful for patients at higher risk for post-implant urinary toxicity. Here at Hackensack, we have used HDR to treat over 250 patients who were not good candidates for seed implant because of high IPSS scores, large volumes, or prior TURP. This group experienced only minimal urinary toxicity (1-2 weeks of frequency and hesitancy). Over 98% of post-TURP patients remained continent, and even patients with glands larger than 50cc maintained their ability to freely urinate. Acute gastrointestinal toxicity was not encountered, and with up to four years of follow-up, no patient has developed rectal bleeding.

Other advantages of HDR brachytherapy include the lack of radiation exposure to hospital personnel and family members and the ability to implant HDR catheters in periprostatic tissues so that patients at risk for seminal vesicle or extraprostatic disease can be adequately treated. Finally, recent radiobiological calculations (of a low a/ß ratio) for prostate cancer suggests that the use of HDR brachytherapy may increase the therapeutic ratio and lead to better tumor control.

Long-Term Results

Long-term (5-6 year) results of patients treated with HDR are now becoming available, and analyses indicate that these results are similar to those achieved with permanent seed implantation. Pooled data from three large centers that treated over 600 patients with external beam radiotherapy and dose escalating HDR brachytherapy was analyzed for treatment outcomes.15 With a mean follow up of six years, PSA-free survival was 96% for patients with low-risk disease (defined as less than or equal to stage T2a, Gleason score 6, and PSA 10). Patients with high risk disease had a 69% disease-free survival (at a mean follow up of five years).

Gejerman_tempseeds_Table1

Summary

In summary, the ability to plan and analyze dose distribution after the implant and before treatment is a unique feature of HDR brachytherapy. Since the HDR implant dose coverage of the prostate can be optimized while allowing for dose constraint at the urethra and rectum, a more conformal treatment is achieved. However, as indicated in Table 1, there are fewer physicians trained in HDR techniques than in permanent seed implant, and fewer facilities have the equipment that is necessary for a successful program. Given the many potential advantages of HDR, though, patients should seek out those capable of this treatment and consider it as a therapy option. 

About the Author

Glen Gejerman, M.D. is Director of Radiation Oncology at Hackensack University Medical Center and co-director of the Prostate Cancer Institute of New Jersey. After receiving his medical degree at UMDNJ- New Jersey Medical School, Dr. Gejerman completed his residency at the Albert Einstein College of Medicine. He then served as chief resident there, and after completing his training, he joined the staff as an Assistant Professor of Radiation Oncology. Since becoming Director of Radiation at Hackensack University Medical Center, he has developed an active Prostate Cancer research program and has published several articles on external beam radiotherapy and brachytherapy.

References

1. Ragde H, Abdel-Aziz AE, Snow PB, et al. Ten year disease free survival after transperineal sonography guided Iodine-125 brachytherapy with or without 45-Gray external beam irradiation in the treatment of patients with clinically localized low to high Gleason grade prostate carcinoma. Cancer 1998; 83:989-1001.
2. Blasko JC, Grimm PD, Sylvester JE, et al. Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 2000; 46:839-850.
3. Dattoli M, Wallner K, Sorace R, et al. Palladium –103 brachytherapy and external beam irradiation for clinically localized high risk prostatic carcinoma. Int J Radiat Oncol Biol Phys 1996; 35:875-879.
4. Critz FA, Williams H, Levinson KA, et al. Simultaneous irradiation for prostate cancer: intermediate results with modern techniques. Urology 2000; 164:738-743.
5. Nag S. Brachytherapy for prostate cancer:summary of american brachythearpy society recommendations. Seminars in Urologic Oncology 2000 Vol 18, No 2 May.
6 . Hudson R. Brachytherapy treatments increasing among Medicare Population. Health policy brief of the American Urologic Association, Inc. 1999;9:1-8.
7. Gewanter RM, Wuu CS, Laguna JL, et al. Intraoperative preplanning for transperineal ultrasound-guided permanent prostate brachytherapy. IJROBP, 2000; 48:377.
8. Terk MD, Stock RG, Stone NN. Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate. J Urol 1998; 160:1379-1382.
9. Gelblum DY, Potters L, Ashley, R, et al. Urinary morbidity following ultrasound guided transperineal seed implantation. Int J Radiat Oncol Biol Phys 1999; 45:59-67.
10. Bucci J, Morris WJ, Keyes M, et al. Predictive factors of urinary retention following prostate brachytherapy. Int J Radiat Oncol Biol Phys 2002; 53:91-98.
11. Lee N, Wuu C, Brody R, et al. Factors predicting for postimplantation urinary retention after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2000; 48:1457-1460.
12. Crook J, McLean M, Catton C, et al. Factors influencing the risk of acute urinary retention after trus-guided permanent prostate seed implantation. Int J Radiat Oncol Biol Phys 2002; 52:453-460.
13. Ragde H, Blasko JC, Grimm PD, et al. Interstitial I-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma. Cancer 1997;80:442-453.
14. Wallner K, Blasko JC, Cavanagh W. Brachytherapy in the management of prostate cancer. In Radiotherapeutic management of prostate adenocarcinoma. 1999.Oxford University Press, New York.
15. Galalae R, Martinez A, Mate T, et al. Long term outcome by risk factors using conformal high dose rate (HDR) boost for prostate cancer. Int J Radiat Oncol Biol Phys 2002;54 (2 Supplement) page 36.