3D Computed Tomography-Guided Pararectal Brachytherapy

3D CT-Guided Pararectal Brachytherapy differs from EBRT in the following respects::

  • Delivery of double or more dose of radiation to the prostate to kill the cancer
  • Diminished radiation toxicity to the urinary bladder and rectum adjacent to the prostate
  • Treatment within one day rather than eight weeks
  • Ability to repeat the treatment in the future if needed
  • Ability to treat patients over 70 years
  • Ability to treat patients with medical conditions prohibiting surgery
  • Ability to treat patients with extracapsular extension of tumor
  • Ability to treat patients with seminal vesicle invasion
  • Patient preference after explanation of alternative treatment options

3D CT-Guided Pararectal Brachytherapy differs from surgery in the following respects::

  • Organ preservation
  • Diminished complications such as impotence and incontinence
  • Treatment on an outpatient basis without major surgery or hospitalization

3D CT-Guided Pararectal Brachytherapy differs from transrectal ultrasound-guided transperineal brachytherapy in the following respects:

  • Ability to treat patients patients without rectum; the rectum has been removed because of colorectal cancer or other causes
  • Ability to treat patients with penile prosthesis
  • Ability to treat patients with seminal vesicle invasion
  • Ability to treat patients with large glands; patients whose prostate size is >= 60 cm3
  • Ability to treat patients with protusion of the prostate within the urinary bladder
  • Ability to treat patients with pubic arch interference
  • Ability to treat patients with prior TURP defects; prior TURP is usually not peformed with transperinal ultrasound-guided brachytherapy
  • Ability to treat patients with large prostate calcification; large prostate calcification is usually not peformed with transperinal ultrasound-guided brachytherapy
  • Ability to treat obese patients
  • Ability to treat patients with urinary obstruction
Comparison of treatment options against contraindications to undergo the procedure
Prostate cancer with:
Treatment Options
Sugery (Radical Prostatectomy)
Transrectal Ultrasound-Guided Transperineal Brachytherapy
3D Computed-Tomography-Guided Pararectal Brachytherapy
low risk
penile prosthesis
x
seminal vesicle invasion
x
x
large glands (60 – 180 cm3)
x
large glands (> 180 cm3)
x
x
x
prostate of the prostate within the urinary bladder
x
pubic arch interference
x
prior TURP defects
x
large prostate calcification
x
obese patients
x
urinary obstructions
x
age over 70 years
x
medical conditions prohibiting surgery
x
extracapsular extension of tumor
x
patient preference
x
metastatic cancer
x
x
x
medical conditions prohibiting spinal anesthesia
x
x
x
x-Denotes contraindication against procedure (the patient cannot undergo the procedure).


Patient Selection
3D CT-guided pararectal brachytherapy is indicated in patients with localized prostate cancer including those who have

  1. large volumes (60 – 180 cm3)
  2. post transurethral resection (TURP)
  3. seminal vesicles cancer invasion
  4. salvage brachytherapy after failed EBRT, brachytherapy, or failed radical prostatectomy
  5. surgical removal of the rectum

The contra-indications for 3D CT-guided pararectal brachytherapy are

  1. metastatic cancer
  2. prostate volume greater than 180 cm3
  3. medical conditions prohibiting spinal anesthesia

 


Pre-treatment
Pre-treatment planning is done with computed tomography (CT) imaging and pre-dosimetry with Varian BrachyVision software. 3D reconstruction of the prostate volume is calculated with computers from the CT images, and the number of seeds is calculated with 10 mm square grids superimposed over the CT images and dosimetry with Varian BrachyVision.

Because very often the prostate cancer is multicentric and multigraded and the extent of the tumor is underestimated with ultrasound-guided biopsy, we treat the entire gland spacing the radioactive seeds on average 10 mm apart. Because 35% of localized prostate cancer infiltrates microscopically the capsule and surrounding fat we extend the treatment target 5 – 10 mm outside the capsule (except the portion of the prostate near the anterior rectal wall).

We also include treatment planning of the entire seminal vesicles if involved. To deliver the prescribed dose of 144 Gy with 125 I or 120 Gy with 103 Pd seeds, we use Varian BrachyVision dosimetry software. Seeds with lesser activity are used in the center, near the urethra, and prostate gland adjacent to the anterior rectal wall. Seeds with higher activity are used in the periphery of the prostate.

Twenty-four hours prior to procedure, the patient begins bowel preparation and prophylactic antibiotic treatment as follows:

  1. Ciprofloxacin , 500 mg, b.i.d. for 10 days beginning 24 hours prior to procedure. (Note: in special cases an antibiotic is administered Via IV at the beginning of the Implant.)
  2. Flagyl, 250-500 mg, one tablet every six hours for three days beginning 24 hours prior to implant. No alcohol while taking Flagyl.
  3. Clear liquid diet 24 hours prior to implant .
  4. Phospho-soda 1,5 ounces, 20 hours prior to procedure. Pour into one-half glass of cold clear liquid, drink and follow immediately with one full glass of water.
  5. Forced fluids taken orally 20 hours prior to implant procedure.
  6. Four Dulcolax tablets 12 hours prior to implant procedure.

One Dulcolax suppository and rectal Tannic acid 2 hours prior to implant procedure.


Treatment
Identification of the patient is assured by technologist and secretary checking the name, social security number, and date of birth. Identification of patient is further assured after consultation with the radiation oncologist, anesthesiologist, and urologist.  

The procedure is performed with the use of patented and FDA-approved three dimensional stereotactic system. The patient voids and a Foley catheter is then placed in the urinary bladder with 10 cc’s of air in the balloon. Spinal or epidural anesthesia with standard monitoring is performed by an anesthesiologist. The patient is placed in the prone position on the CT table. A bolster pad is placed under his pelvis. The PGK three dimensional stereotactic system is placed over the patient. The rectum is constricted with tannic acid, and a tube is inserted into the rectum to remove possible fluid. The patient is prepped and draped in the usual sterile manner.

Five-millimeter pararectal tomographic cuts are obtained of the prostate and seminal vesicles. To compensate for changes of the prostate volume after the insertion of needles, a final CT planning for the procedure is performed and the number of needles, number of seeds per needle, and depth and corresponding guiding hole on the template are calculated and posted in a summary chart.

The entire gland is treated because prostate cancer is often multicentric and multigraded, and the extent of the disease is underestimated with ultrasound transrectal biopsy.

Afterloading needles are inserted through the template 10 mm apart in the predetermined depth in the prostate gland as determined in the treatment CT plan. Needles are arranged in an orthogonal array with 4 – 6 needles 1 cm apart to form a row in one direction, and 4 – 7 rows are formed 1 cm apart. The template has an orthogonal array of perforations, 32×40 holes 1 mm in diameter, and 2.5 mm apart in either direction. The 3D stereotactic template is adjusted as needed to avoid needle penetration through rectum or obstruction of insertion of the needles by the coccyx or sacrum. The stereotactic template (8 x 10cm 2 ) can cover a large target and has perforations that are 2.5 mm apart in either direction for fine needle correction if needed.

To eliminate seed migration and cold spots we use only seeds in strand. Pre-loaded needles are not used because their tips are plugged and we are unable to identify the bleeder. Our technique enables the identification of the bleeder and thus to change the position of the needle as required. During the extraction of the needles, the seed may migrate along the path of the needle or through the blood vessels distally in the lungs. The correct position of the needles is verified with CT prior to loading with seeds. After verification of the correct needle positions and identification and avoidance of bleeding, an attachment to the 3D stereotactic template is used for instant loading and implant of seeds in strand.

A repeat CT scan is performed of each transverse row of needles beginning at the apex of the prostate. Some of needles are adjusted in depth and spacing to compensate for prostate motion, needle deflection and verification of the correct needle position in each transverse row prior to the implant. Seeds of 125I or 103Pd averaging 10 mm apart are implanted throughout the treated target. A repeat CT scan is performed of the prostate beginning from the apex to the seminal vesicles for quality of implant determination. Immediately, post-implant images are obtained with the patient in supine position for post-implant dosimetry. The radiation dosage, or dose volume histogram (DVH), of the prostate, seminal vesicles, urethra, rectum, and urinary bladder are calculated using the Varian Variseed software. Post-implant dosimetry is performed at 1 month for more accurate results after post-procedure bleeding and swelling have subsided. The prescribed dose of radiation is 120 Gy with 103Pd or 144 Gy with 125I for the target including 5 to 10 mm of the surrounding fat.

Patients with seminal vesicle invasion (T3b) are treated with brachytherapy including the entire seminal vesicle. Our experience has previously been reported of brachytherapy of patients with seminal vesicle invasion (Reference). Extracapsular extension in localized prostate cancer has been reported in 35% of patients after radical prostatectomy. The treatment target includes 5 – 10 mm outside the capsule except the portion on the prostate adjacent to the anterior rectal wall.


Post-Treatment
In transrectal ultrasound-guided transperineal brachytherapy a CT dosimetry is performed after termination of the procedure. In contrast, a CT is performed prior to termination of 3D CT-guided brachytherapy to determine the coverage of the seeds and cold spots. CT dosimetry is performed with Varian Variseed software. In addition, a CT dosimetry is performed 1 month post-implant (after the edema in the prostate has subsided) for more accurate dosimetry.

Immediately post-implant, all seeds implanted in the prostate are accounted. Radiation exposure readings are obtained at various distances from the patient to assure acceptable limits prior to discharge. Post implant instructions are given to the patient. The patient is normally given prescriptions for alpha blockers and Pyridium. The patient leaves the facility ambulatory on the same day, usually within an hour following the implant.


Radiation Precautions
The radioactivity of the radioactive sources is absorbed by 95% with 4 cm from the source. Strict adherence to the following safety precautions and guidelines is highly recommended. If the patient does not wear a lead shorts after the procedure, in keeping with the guidelines of the Nuclear Regulatory Agency, it is recommended that 1) no child under 18 years be permitted to sit on your lap and they should be kept at least 6 feet away from you for the first 4 weeks with 103Pd and 16 weeks with 125Iseeds, and 2) pregnant women should be kept at least 6 feet away from you fro the first 8 weeks with 103Pd and 16 weeks with 125I. We also recommend the following:

  • No lifting anything over 10 lbs for at least 2 weeks.
  • Do not sit for more than 2 hours at a time.
  • Restrain from exercise programs for at least 2 weeks.
  • Stay with any dietary restrictions you already have, and stay away from greasy or fried foods.

Blood in the urine may be observed in the first 2 days after implant, but begin to clear up after 48 hours. The use of aspirin is permitted up to 3 days after the implant if you used it prior to the implant. Rectal bleeding may be observed several months after the implant as the delayed effects of radiation.


Success
A PSA blood test is a reliable marker to determine the success of treatment. You should have a PSA test every 3 months during the first year after implant, every 6 months after the first year up to the fifth year, and yearly thereafter.

As long as the PSA drops and remains below 1.0 ng/mL, you should not undergo any additional tests such as a bone scan or biopsy. If you received short-term hormone therapy, testosterone levels should be obtained every 3 months until it returns to normal. Hormone levels returns to normal usually in 3 – 15 months (more rapidly in younger patients than older patients).

A DRE is performed as needed. A CT volume reconstruction to determine the regression of the volume and distribution of seeds will also be performed after brachytherapy.


Symptoms after 3D CT-Guided Pararectal Brachytherapy
Treatment related symptoms after brachytherapy are due to irritation from the lower urinary tract (urinary bladder, prostate, and urethrea), “GU,” or from the gastrointestinal tract (mainly rectum), “GI.”

The patient is advised he may have transient treatment-related symptoms with frequency of urination and burning sensation and/or loose bowels. The symptom of urethritis may increase at the first half-life of 125I or 103Pd seeds two months or 4 weeks, respectively, and usually responds to alpha-blockers and Pyridium if needed.

Adverse conditions after brachytherapy include pain during urination (dysuria), blood in the urine (hematuria), frequent urination, urinary retention, hesitancy or difficulty to urinate, or urinary incontinence. The extent of these symptoms depends on how many were present before implant. After radiation, these symptoms are caused because the urethra and bladder may absorb up to one tenth of the total radiation dosage (10 Gy or 100 cGy). This amount is equal to the amount of radiation a person would receive from the sun while bathing on the beach for more than one hour. Each individual has different sensitivity.

Mild hematuria is common 1 – 2 days post-implant, however, because of the late effects of radiation hematuria may also develop later (as late as 6 months and up to 4 years). Radiation leads to occlusion of small blood vessels, after which new blood vessels will grow by neovascularity (telegiectasia) to provide blood and oxygen to radiated tissues. These vessels may bleed with microscopic hematuria (Grade 1), with transient gross hematuria without clots (Grade 2), or may have gross hematuria with clots requiring transfusion or catheterization. Only 1% of our patients have this for hematuria. The most serious complication is necrosis of the bladder with ulceration Grade 4, which requires open surgery, and we have no cases of this type.

The patient may develop mild rectal bleeding (Grade 1) asymptomatic after the implant because of the development of new vessels in the rectum to provide oxygen. However, if bleeding persists, the patient should have a colonoscopy to rule out other causes such as polyps, second malignant tumors, inflammatory disease, divertcoulosis, etc. The patient should remind the physician who perform colonoscopy to not biopsy the anterior rectal wall adjacent to the prostate because there is no significant tissue between the anterior rectal wall and urethra and may cause a fistula between the prostate and urethra.

Bleeding from the urethra or rectum requiring transfusion is less than 0.5% in our patients. Urinary infection may occur after the procedure, and in particular in patients with retention of the urinary bladder. No patient has incontinence following this procedure as compared to radical prostatectomy. However, some patients may have transient stress incontinence (unable to hold the urine for a long time) initially after brachytherapy.

Very few patients (1%) may have pain in the penis during ejaculation. Less than 1% of patients may require light transurethral resection (TUR) if they develop urinary retention. The TUR should not be performed in the first year after the procedure because the tissue will still be radiated. If retention occurs, the patient will be treated with a temporary catheter.

There is no incontinence after 3D CT-guided brachytherapy except a mild Grade 1 in patients who have TUR before or after brachytherapy. The incidence of incontinence is less than 1%.

Seventy-five (75%) of patients will maintain erectile function as prior to implant. There is diminished amount of ejaculate. Some patients using Flomax may have retro grade ejaculation (no semen after intercourse) and the medication will be changed to Cardura or Hytrin. The patient may see some blood in the ejaculate and this observation should not raise serious concern. There may also be some transient pain in the distal penis during ejaculation. The 25% of the patients with diminished erectile function usually respond to treatment with Viagra or other medications.


Rise in PSA
PSA may rise after brachytherapy under the following conditions:

  • PSA spike or PSA bounce (temporary rise of PSA which subsequently drops without treatment)
  • infection (prostatitis)
  • local recurrence
  • distant metastasis (systemic disease)
  • local recurrence and distant metastasis

An investigation will be made with CT scan of the abdomen and pelvis, bone scan, and computed dosimetric analysis as well as DRE.

The phenomenon of temporary rising of PSA after radiation therapy has been reported by others as PSA spike or PSA bounce. PSA spike was observed after 15 months in 30% of our patients. The reason for PSA spike being calculated after 15 months was because 63% had neoadjuvant androgen ablation 3 months prior to implant. Eighteen percent had minor PSA spike (<= 0.2 ng/ml), and 11% had major PSA spike (> 0.2 ng/ml). The PSA of these patients returned to normal without any specific treatment.

The cause PSA spike or PSA bounce is not known, however, it may be due to the release of PSA from dead cancer cells. This phenomenon should not cause any anxiety by the patients or physicians, and should not be treated unnecessarily with hormone therapy, salvage reimplant or radical surgery without biopsy-proven local recurrence and clinical evidence of local disease.

Local recurrence
The diagnosis of local recurrence should be made with DRE, negative bone scan, CT scan, and positive biopsy. The diagnosis of distal metastasis is performed with positive bone, CT, MRI, and Prostascint scan.

Patients with clinical evidence of distant metastasis (systemic disease) with bone or CT scan are usually treated with hormone therapy and/or EBRT. Additionally, the patient may have a combination of both local recurrence and distant metastasis and should be treated with hormone therapy and/or EBRT.