The two forms of brachytherapy performed today for the treatment of prostate cancer are low dose rate (permanent seed) and High Dose Rate (HDR) brachytherapy. Our physicians did hundreds of permanent seed implants before switching to HDR in 1991 for reasons explained in this page. To date, our center has done over 2,900 HDR brachytherapy implants for prostate cancer.

Back to Top2. Prostate HDR Brachytherapy

HDR Brachytherapy can be used in combination with external beam or as the only treatment method (monotherapy). HDR Brachytherapy is also used as a salvage treatment for men whose cancers have recurred after radical prostatectomy, external beam or permanent seed implantation.

Back to TopHDR Brachytherapy is recommended for patients:

• as an alternative to radical prostatectomy, external beam or permanent seeds
• any stage localized disease, Stages T1-T3b
• who have extra-capsular extension, seminal vesicle or perineural involvement
• any PSA value with no evidence of metastatic disease
• any Gleason score
• Prior transurethral resection of the prostate (TURP) with recurrent local disease after radical prostatectomy, external beam or permanent seed implants (salvage)

Back to TopHDR Brachytherapy Procedures

• The physician determines what course of treatment the patient should follow after reviewing the patient's history and recent test results. This is discussed during the consultation. The usual time between consultation and the first implant is 3 to 4 weeks. The day before the implant, the patient comes to the clinic for a pre-op exam and blood test.


• In the OR, the patient is given spinal anesthesia, which numbs the patient from the waist down. The patient's legs are placed in stirrups and the pelvis is positioned by the physician for access to the perineum (the space between the scrotum and anus).


• CET physicians use a non-fixed template technique for placing the treatment catheters, called '"flexiguides'" around and through the prostate. The rubber template has pre-drilled holes arranged in two concentric circles, rather than the square grid arrangement of the fixed template technique. Our physicians feel the circular distribution conforms better to the natural shape of the prostate. The template is held in one hand, while the flexiguides are inserted with the other. Holding the template, rather than having it clamped to the table as in the fixed template technique, allows the physicians to tip and angle the template, resulting in more control over where they can place the flexiguides. Our physicians can flare the flexiguides to encompass any size prostate, perineural or extracapsular disease or seminal vesicle involvement that may be present. This ability to flare the flexiguides enables our physicians to treat larger prostates without having to increase the number of flexiguides, which is 17. The pubic bone can sometimes interfere with the placement of rigid steel needles used in permanent seed implants, but using the non-fixed technique and plastic flexiguides, the pubic bone poses much less of a problem. This means that the patient doesn't have to take pre-implant hormones in order to shrink the gland, a common practice if permanent seeds are used.


• Once the flexiguides are in position, the template is sutured to the perineum to stabilize the implant. A radio-opaque catheter is placed in the bladder for urine drainage and urethral visualization. A rectal catheter is inserted to allow liquid contrast to be inserted into the rectum for radiographic visualization. After a brief stay in the recovery room, the patient is brought to our clinic for radiographic imaging (films and/or CT). Once the images of the implant are obtained, the patient waits for the customized treatment plan to be generated.


• After the physician has approved the treatment plan, the patient is moved into the treatment booth, where the protruding ends of the catheters are connected to transfer tubes, which are in turn connected to the afterloader. Although the patient is alone in the treatment booth, he is constantly monitored via closed circuit TV and intercom. The patient will hear the afterloader click and whir as the source is directed into each of the flexiguides. The Iridium-192 source delivers the radiation dose in about 10 minutes. After the treatment, the source withdraws into the afterloader. The patient is no longer radioactive.
  
  

		Fig 1: This patient is receiving his treatment. The afterloader is in the lower right corner.

• The patient goes to his hospital room for the overnight stay. He is allowed to roll from side to side, but not sit upright as that would place pressure on the protruding ends of the flexiguides. The next morning, the second treatment is given This second treatment requires much less time because the simulation and treatment planning procedures do not need to be done again. However, a pre-treatment fluoroscopy is done to make certain that the implant hasn't moved during the night. After the second treatment (or third treatment if the patient is having HDR monotherapy), the template and treatment flexiguides are removed. During the removal process, there is some slight bleeding, which is stopped by the nurse or therapist by applying firm pressure to the perineal area with gauze pads. The patient goes back to his hospital room where the nurses make sure that the patient can urinate before going home.
  
• The second implant is done a week later, following the same procedure as described above.
  
  

Back to TopSide Effects

The possible post-HDR acute side effects, usually lasting two to four weeks, are urinary frequency, dysuria, and urinary retention. There may also be some slight rectal irritation. The perineal area will be tender for a few days so activities like bicycle riding that put pressure on this area should be avoided. Medications are prescribed to help alleviate these temporary side effects.

Back to Top3D CT Based Dosimetry

One of the great advantages of HDR over permanent seeds is the ability to evaluate the implant in 3-D and know what the doses are going to be before any treatment is given. The ability to control the time the source spends in each dwell position allows for much greater target conformality and normal tissue sparing.

	Fig 2: These four images are used to evaluate the implant using the 3D CT based software. The upper left image shows the implant in 3D. The physician can rotate the implant to assess the radiation coverage by the prescription dose "cloud" from any angle, and the proximity of the implant to other structures, such as the rectum and bladder. Clockwise, three CT images show the radiation dose levels at the top, middle and bottom of the gland.
	Fig 3: This close-up 3-D image of the 100% isodose cloud, showing near complete coverage of not only the prostate plus 5mm margin, but also the proximal seminal vesicles, shown semi-transparently. Notice how the dose cloud is shaped posteriorly to spare the anterior rectal wall.
	Fig 4: This view evaluates the implant from the top. The red areas are the small portions of the target volume that are spared the full prescription dose: the bladder neck and the lower bulbous urethra to prevent urinary incontinence and urethral stricture respectively.

Back to TopDose Volume Histograms

Another way of evaluating the implant is to plot a dose volume histogram (DVH). A DVH tells the physician how much of the target volume is covered by the 100% prescription dose, and how much of the prescription dose the rectum and urethra receive. At CET, we routinely see 95% or higher, coverage to the target volume, which includes the proximal seminal vesicles and a 5mm margin around the prostate to include any extracapsular extension. The actual prostate receives 10% to 25% higher than the prescription dose. This results in a D90 (the dose 90% of the prostate volume receives) of 105 to 113% compared to most permanent seed implants which are considered 'optimal' if the D90 is 90%.

	Fig 5: This DVH shows that 97.4 % of the target volume is being encompassed by the prescription dose. 35% of the urethra received doses slightly higher than the prescription dose, with the maximum dose being around 110% of the prescription dose. The maximum anterior rectal wall dose our physicians allow is 75% of the prescription dose, versus up to 100% with seeds or external beam.

Back to TopRadiograph Based Dosimetry

There are some instances where CT cannot be used to do the dose calculations. Hip prostheses cause artifacts in the CT images making the prostate and catheters hard to identify. Patients with severe claustrophobia have a problem being scanned. This technique, while not resulting in 3-D images, is a highly accurate technique that has been used for years before CT imaging became available.

	Fig 6: This is an "AP" (front view) radiograph of a CET prostate implant. The blue markings are the rectal outline and dose calculation points for the bladder, urethra and rectum. "Dummy" markers are inserted in the catheters. Contrast is introduced into the bladder (cystogram). Contrast is also used to inflate the foley balloons in the bladder and rectal catheters. The bladder catheter is made of a radio-opaque material to see the urethra clearly. Notice how the catheters can be made to flare in order to encompass any extracapsular extension.
	Fig 7: This is a lateral (side view) of the CET prostate implant. The physicians try to lift the prostate away from the rectum to help achieve low rectal doses. Notice how the tips of the catheters are against the bladder. This ensures that any tumor in the base of the gland is adequately treated, yet by adjusting the time the source spends in the tip "dwell" positions, the bladder doses are controlled.

Back to TopTypical CET HDR Dose Distributions

anterior rectum, separated by a thin layer of tissue, called fascia. The non-fixed template technique allows the physician to slightly lift the prostate away from the rectum, reducing rectal dose. The HDR system allows for dose adjustments and the treatment is delivered in minutes while the rectum is empty. These advantages over permanent seeding are the reasons why the leading centers that perform HDR implants are all reporting very low, if any, rectal complications. A major point to consider is that these doses are what the prostate actually receives. Permanent seeds can shift from their original ideal positions resulting in the actual dose distribution not being like the approved pre-plan. With the HDR system, the prostate is held in position by the catheters and the catheters are held in position by the template. If the patient moves, the implant moves with him. HDR is the most accurate method of radiation dose delivery available.

Back to TopTumor Specific Boosting

	Fig 9: Specific Radiation Boosting: CET was the first center to realize and use the ability of the HDR system to send the source to specific positions in the catheters allowing us to give an additional "boost" dose to the cancer nodules. The image on the left shows the 3-D boosted area in blue at it extends out past and into the (red semi-transparent) prostate. The transverse view CT image with the isodose levels is on the right.

Composite Dose Distribution

	Fig 10: Composite Dose Distribution
	This is the resulting isodose pattern of the initial whole gland plan combined with the boost, which we call the composite plan. The numbers are the isodose values in cGy (HDR). The highest dose areas are in the peripheral zone of the prostate, where most prostate tumors arise. Notice the larger boosted area that is covered by the 900 cGy (HDR) isodose line. The prescription dose, 600 cGy (HDR), is the inner red line going around the prostate. Note that the 600 cGy prescription is occurring 5mm out from the prostate capsule. If necessary, we can create an

even larger margin simply by increasing the dwell times, while maintaining the lower doses to the nearby structures and urethra. This ensures that any extracapsular extension (ECE) or perineural disease is adequately treated. The radiation from permanent seeds cannot reach much more than 2 to 3 mm outside the prostate capsule. Knowing this, some seed physicians try to treat ECE by placing permanent seeds in the loose, connective tissue around the prostate. If seeds shift within and migrate out of the firmer tissue of the prostate, it is questionable as to where seeds intentionally placed outside the prostate end up and the coverage and accuracy of the dose supposedly delivered to treat ECE.

Back to TopExample of HDR Conformity and Accuracy: Sparing a TURP defect

A common procedure done to relieve pressure of an enlarged prostate on the urethra is called a transurethral resection of the prostate (TURP). An incision is made in the urethra and part of the urethra and prostate tissue is removed. Some men experience some incontinence after this procedure. In order to avoid exacerbating this situation, we spare the TURP defect as much as possible by limiting the radiation dose to less than 105% of the prescription dose. We have found that this dose is tolerated by the urethra while still delivering the necessary tumoricidal dose to the prostate.
The HDR system allows for much greater conformality than permanent seeds. With seeds, one hopes that they don't move near or into the defect and the dose to the defect is not known after the one month post-implant dosimetry is done. With HDR, we can accurately shape the radiation dose to avoid the defect while knowing what the doses will be before any treatment is given.

	Fig 11: HDR Conformity and Accuracy Sparing a TURP defect: This image shows how we can accurately shape the radiation dose (white line) to go around the contrast-filled TURP defect. This precision is not possible with EBRT or permanent seeds.

Back to Top3. Permanent Seed or LDR Brachytherapy

Permanent seed implants are a form of interstitial, Low Dose Rate (LDR) brachytherapy. Iodine-125 and Palladium-103 are the two radio-isotopes used in seed implants. In general, brachytherapists choose isotope for treatment based on the aggressiveness of the tumor. Iodine-125 has a slower dose rate and is used on slower growing tumors, where as, Palladium-103 has a higher dose rate and is used on faster growing tumors. This selection method has not been verified in any formal studies as an effective method. Implant isotope seed is tiny, 1mm x 5 mm in size. They are permanently inserted into the prostate and left there to radioactively decay.
Permanent seed implants alone (monotherapy) are used to treat prostate cancer which has a high probability of being confined to the prostate.

Back to TopThe criteria for permanent seed monotherapy are:

• Stage T1-T2a
• Prostate volume < 60 cc at time of implant
• PSA<10
• Gleason score < 6
• No significant obstructive symptoms
• No perineural or extracapsular extension
• < 3 of 6 sextant biopsies positive

Back to TopProcedure for Permanent Seed Brachytherapy

Prior to the permanent seed implant, a trans-rectal ultrasound examination is done to determine the shape and size of the prostate. The prostate is "mapped" on a square grid template and a pre-plan calculation is done to determine which holes in the template the needles need to be inserted and how many seeds to deposit through each needle in order to adequately irradiate the prostate.

In the operating room, the patient is placed under general or spinal anesthesia. The ultrasound probe, rather than being able to be maneuvered free-hand as in the non-fixed technique, is attached to the "stepper" assembly that also holds the square grid template against the perineum. The physician pushes stainless steel needles through the pre-determined holes in the template, into the perineum and then the prostate, guided by the images seen on the ultrasound. After each needle is in the proper position, the seeds are inserted, according to the pre-plan dosimetry. The physician can modify the seed placement from the pre-plan based on skill and experience. For example, the physician may decide to place additional seeds in areas of the gland that look to be potential "cold" spots. Once a seed is deposited, nothing that can be done to change its position. Physician experience is paramount in doing a successful seed implant.

The number of seeds used depends on the size of the prostate. Most prostate implants require 60 to 120 seeds. With the insertion of the seeds, the patient is now radioactive. Radiation safety precautions are followed to minimize the radiation exposure to hospital staff and family members. It is recommended that pregnant women, and children should avoid close contact with the patient for about two months, until the sources have decayed to a lower level of radioactivity.

Some seeds may migrate out of the implant. They have appeared in the urine, in the ejaculate, and in the lungs of some patients. It is not necessary to retrieve the seeds that are passed in the urine. Before engaging in sex, men should use a condom to catch any seeds that may be in the ejaculate. Any seed loss should be reported to the radiation oncologist. To date, there is no evidence of any ill-effects caused by seed migration to the lungs.

After one month, a CT scan and special x-ray films are done in order to do the final "post plan" calculation to determine what radiation doses the prostate and surrounding organs actually received due to the shifting and migration of the seeds.  A chest x-ray is  done to see if any seeds migrated into the lungs.

Back to Top4. Comparing HDR and Permanent Seed

The following table was compiled by the HDR Prostate Working Group and presented to radiation oncologists at the American Society of Therapeutic Radiology and Oncology (ASTRO) meeting in Phoenix, October 1998. Comparison of High Dose Rate Temporary Implants and Permanent Seed Implants

Table 1: Comapre HDR and Permanent Seed

Treatment attributes	High Dose Rate	Permanent Seed
Conformal treatment	++++	+++
Target accuracy	++++	+++
Ability to treat extracapsular extension	++++	+
Ability to treat seminal vesicles	++++	++
Ease of control of radiation	++++	++
Lack of cold/hot spots	++++	++
Control of critical organ dose	++++	++
Modify dose distribution	++++	+
Need for external beam	Yes, at present*	Sometimes
Monotherapy	***	+++
Experience of Physician	Crucial	Crucial
Pre-planning dosimetry	not needed	Extensive (TRUS)
Post implant dosimetry	not needed	Extensive (CT)
Stages treated	All, T1-T3	T1-T2
Gland volume>60 ccat time of implant	less difficulty	more difficulty
Pubic Arch interferenceat time of implant	less of a problem	can't be done
Prior TURP	less of a problem	can't always be done
Final Dose Verification	pre-treatment	post treatment
Symptom duration	weeks	months
Implant cost	comparable	comparable

Our physicians disagreed with the authors of the above chart who said  that EBRT is necessary with HDR.   Our physicians reasoned that if permanent seeds can be used as a monotherapy treatment for low risk disease (T1 - T2a), then so can HDR. In 1996, we began our Monotherapy Program. A select group of patients are eligible for HDR monotherapy if they meet the following criteria:

1. Clinical stage T1a - T2a (possible T2b)
2. Gleason score 7(must be 3 + 4, not 4 +3 ) or less
3. PSA 10 or less
4. 50% or less of the biopsy cores positive

Patients who have had a TURP are NOT excluded.   The treatment consists of 2 implants, one week apart. Each implant is given three fractions for a total of six fractions. We have submitted abstracts for presentation at the American Brachytherapy Society and ASTRO annual meetings in 2004. See Prostate Publications Section for more information.

Back to Top5. Consideration for Choosing HDR

• There are no seeds to migrate into the bladder, rectum, urethra, seminal vesicles or lungs
• Radiation exposure to others is eliminated
• Dose accuracy and control is much higher than with seeds
• The doses to other structures are known before any treatment is given
• Pubic arch interference is much less of a concern, so pre-treatment hormones, and their side effects, are avoided
• Post implant morbidity (side effects) is less and of shorter duration than with seeds
• Post implant costs are  less with HDR due to the lessened use of medications and very rarely needed catheterization.