Seed Brachytherapy

SYNOPSIS

Ultrasound-guided permanent seed prostate brachytherapy is an effective outpatient surgical procedure for prostate cancer, in which therapeutic radiation is placed directly within the prostate gland, through the ultrasound-guided delivery of encapsulated radioactive seeds. This is a very convenient and well-tolerated treatment option in appropriately selected prostate cancer patients, with cure rates that appear to rival those of any other treatment modality.

Genesis Healthcare was the first practice in San Diego to perform permanent prostate seed brachytherapy, and has since performed more cases than any other practice in the San Diego region, accumulating one of the largest prostate brachytherapy experiences in the State of California.

The physicians at Genesis Healthcare continue to apply and develop the brachytherapy technique in a substantial number of prostate cancer patients, including some leading edge applications. For example, Genesis Healthcare physicians performed the first Palladium strand prostate brachytherapy procedure in the United States in August 2001, and continue to investigate the advantages of this new source delivery system. Implantation under local anesthesia and conscious sedation was instituted at Genesis Healthcare in 2002 and has now become our standard method. This has allowed us to move the procedure from the hospital setting to the office setting. CT-ultrasound interactive brachytherapy, a real-time dosimetry method in which the implant is analyzed by CT scan and appropriately modified before the patient is discharged, was developed at Genesis Heatlhcare in 2002 (8). This is now our preferred brachytherapy method.

BRIEF OVERVIEW OF THE PROSTATE BRACHYTHERAPY PROCESS

The prostate brachytherapy treatment process begins with an ultrasound “prostate volume study,” which is then exported into the brachytherapy planning computer. Next, after the prostate target volume has been carefully designed on the computer, a customized seed plan is created and printed on a “seed map” to guide the physician for the subsequent procedure. Several days or weeks later, the brachytherapy procedure is accomplished in accordance with the “seed map” instructions, and the patient is discharged home the same day. Following the procedure, the patient returns for a CT scan of the prostate as well as X-rays to determine seed position. This allows accurate calculation of the radiation dose delivered by the seeds to the prostate target volume. After the implant has been completed, the radiation oncologist and nursing staff follow the patient’s progress closely until the side effects of treatment wear off over the months that follow the procedure.

CONSULTATION/PATIENT SELECTION

The prostate brachytherapy process begins with a consultation, during which the radiation oncologist will review all of a patient’s relevant medical records, interview and examine him, and render an initial opinion as to whether prostate brachytherapy or one of the other forms of prostate radiotherapy is a good treatment option. Every patient has a choice of radiotherapy treatment options, and each of these options is addressed during the consultation process.

There may be aspects of an individual patient’s case that cause the radiation oncologist to specifically recommend either brachytherapy or a different radiotherapy option as the “best” or “preferred” prostate cancer treatment for that case. In other cases a patient be equally well treated by any of several radiation therapy methods and in these cases, our radiation oncologist simply tries to give the patient a full overview of the potential benefit and risk of every radiotherapy treatment option, leaving the final decision as to which option to the patient himself. Some patients may be sure of their choice immediately, while others may find the decision making process very difficult. Patients are encouraged to take their time, research all treatment options, talk to other physicians and family members, so they may make their best treatment selection.

Patients who are good permanent source prostate brachytherapy candidates have clinically localized disease, meaning that their cancer is contained within or very near the prostate. Patients with the highest probability of satisfying this condition are those with a tumor stage (T-stage) of T1 or T2a-b (FIGURE 1), prostate-specific antigen (PSA) level less than or equal to 10ng/ml, and Gleason Score less than or equal to 6 (FIGURE 2). We normally refer to these patients as “favorable” prognosis patients.

Patients with a higher PSA or Gleason score may still be reasonable permanent seed prostate brachytherapy candidates, but will not have a cure rate as high, because they have a higher chance of cancer cells that have spread beyond the prostate, beyond the radiation volume produced by the brachytherapy seeds. This same trend to decreased cure rate in these patients with a higher PSA level or Gleason score is seen with all methods of treatment.

Depending on their exact situation, these patients may be referred to an “intermediate” prognosis or “unfavorable” prognosis patients. We have successfully implanted a number of these patients, using extra-prostatic stranded source placement (FIGURE 3) (FIGURE 4), in areas judged to be at increased risk of extra-prostatic cancer cell extension. The appropriateness of this treatment method is determined on a case-by-case basis by the radiation oncologist and patient.

Patients with locally advanced cancers (Large T2b, T3) or other “unfavorable” prostate cancers may be better treated with IMRT (FIGURE 5) or HDR brachytherapy plus 3D conformal external beam radiation therapy (FIGURE 6). Please refer to those sections for further information. No matter what type of radiation or surgical treatment is administered for prostate cancer, the probability of success will be the highest in “favorable” patients, intermediate in “intermediate” patients and lowest in “unfavorable” patients.

In addition to the cancer factors discussed above, an equally important permanent seed brachytherapy patient selection criterion is their lower urinary tract function. Permanent seed prostate brachytherapy produces prostate swelling and inflammation. In some patients this will translate to a higher chance of total urinary obstruction, which means inability to void, which may be brief or may be long lasting and miserable, though with eventual resolution in a majority of cases.

In our experience, the response to the AUA form (FIGURE 7) has most accurately predicted which patients are at higher risk of long-term urinary obstruction following their prostate brachytherapy procedure. If a patient has a high AUA score or other evidence of urinary obstruction, he may be advised to take other than brachytherapy, though again, these decisions are carefully made on a case-by-case basis. Sometimes medical or surgical corrective measures may be done to improve this situation prior to the implant, causing the patient to be able to better tolerate the procedure.

Other risk factors for urinary obstruction or complications following prostate brachytherapy may include prior pelvic radiation, hormonal therapy, large prostate volume, or a history of prior prostate surgery. If a patient has any of these factors it may or may not still be appropriate to perform brachytherapy, subject to case-by-case evaluation.

A large prostate volume in the absence of other risk factors has not been a serious risk factor for long-term problems after the procedure in our patients, though these patients have tended to have more trouble with urinary obstruction during the first several weeks after the procedure, due to the swelling of their (already large) prostate. This appears to be related to needle trauma, because larger prostates require a larger number of needle punctures, to deliver a larger number of seeds. This reaction normally settles after several weeks, after which our large prostate patients appear no different from the rest of the brachytherapy population in their side effect profile.

In summary, the ideal prostate brachytherapy candidate has a reasonable expectation of cancer confined to the prostatic region, and also has adequate lower urinary tract function to accommodate the side effects of the brachytherapy procedure.

ULTRASOUND-GUIDED PROSTATE VOLUME STUDY

The first technical step to performing the brachytherapy procedure is called the volume study. This is an ultrasound study done with the patient in the implant position. A series of prostate ultrasound pictures are made at 5mm intervals from top to bottom, encompassing the entire prostate volume, and each one of these captured in the brachytherapy-planning computer. The radiation oncologist then draws a contoured target volume around each ultrasound picture on the computer, with potential target coordinates appearing as a computer-generated dotted “grid” pattern over the ultrasound pictures, referenced by letters on the X-axis and numbers on the Y-axis (FIGURE 8).

After the contouring process has been completed, the computer then reconstructs the contours into a 3-dimensional prostate planning target volume, incorporating the targeting grid within that volume. The radiation oncologist and supporting physics staff then interact with the computer, to create a customized radioactive seed pattern that creates a customized radiation dose volume, which wraps tightly around the prostate target volume (FIGURE 9). The final plan is displayed 3-dimensionally for final review before it is approved (FIGURE 10). This information is then transferred to a “seed map” that is carried into the operating room to direct the radiation oncologist when the brachytherapy procedure is then done.

Immediately after the volume study session, the RMG nursing staff gives the patient his preparation instructions, and schedules the brachytherapy procedure, the pre-brachytherapy admitting examination, and the post-brachytherapy CT scan. In fact, one of our nurses typically spends up to an hour with the patient at this stage, to help them understand and navigate all of the logistics of the brachytherapy procedure. The nursing staff develops a relationship with the patient at this point that continues until well after the procedure, until the brachytherapy treatment-related side effects have settled. Prostate brachytherapy is a team effort, attended by a dedicated group of physicians, nursing and physics personnel.

ADMITTING EXAMINATION AND LABS

The prostate brachytherapy procedure may be performed in the office or in a hospital, depending upon a patient’s specific situation. The office setting has become our preferred brachytherapy venue unless there is a specific reason why this is not possible. If the brachytherapy procedure is performed in the office, the brachytherapy related prescriptions and nursing instructions are given to the patient at the time of his ultrasound volume study. Routine preoperative blood tests and an EKG are also ordered. If you have other medical problems, a preoperative clearance by your regular doctor may also be required.

The procedure could also be done at one of several hospital facilities within the San Diego region if necessary. Different hospitals have different admitting requirements. Typically, they require an additional office visit for a preoperative physical exam plus or minus admitting blood tests, usually about a week before the procedure. During this “admitting examination” appointment, the brachytherapy related prescription medications are given to the patient. Additionally, there is a pre-anesthesia evaluation by the anesthesiologist, and they handle the scheduling and conduct of this aspect with the patient directly.

Whether the procedure is done in the office or the hospital, the prescriptions are to be filled before the brachytherapy procedure. The exact medical regimen may change from time to time, but as of June 2003, has typically included the following:

Cipro – (Antibiotic) 500mg # 10 – one pill twice per day, starting the day before the procedure, and finishing 5 days later – To prevent infection – If the patient is allergic to this medicine, another antibiotic may be substituted.

Decadron – (Steroid anti-inflammatory) 4 mg (3 pills) Take all 3 at bedtime the night before the procedure – To reduce prostate swelling

Flomax – (Alpha-blocker – medicine that relaxes the bladder and allows a better urinary stream) 0.4 mg # 60 with 10 refills – This is the only long-lasting medicine. The prostate swelling and inflammation process usually takes 3-12 months to fully resolve, and our patients usually find this type of medication to be helpful to allow better urine flow during this time.

Medrol Dose-Pak (Steroid anti-inflammatory) – 21 pills in a card – Punch these out and take as directed as soon as you have been discharged from the hospital – To reduce prostate swelling after the procedure

Vicodin (Pain-killer) # 20 with one refill – For post-procedure pain – Most patients do not have very much pain after the procedure but there are occasional exceptions and usually Vicodin works well for them – Do not drive while taking this medication.

Sometimes substitutions or alterations may be made, particularly in the case of Flomax, where insurance plans often substitute other alpha-blocker medicines on their drug formulary.

THE BRACHYTHERAPY PROCEDURE IN DETAIL

The sterilized needles containing the seeds are delivered to the operating room prior to the beginning of the procedure. If the procedure is done in a hospital, appropriate medical evaluation and clearance by the attending anesthesiologist occurs, the patient is then anesthetized and the procedure begins. If the procedure is done in our office, the nurse will start an IV and administer sedating medication under the supervision of the radiation oncologist, who will perform local anesthesia of the perineum and prostate using injected Xylocaine. This has become our standard anesthesia method, though general anesthesia in a hospital setting still occurs from time to time for a variety of reasons. The radiation oncologist and supporting staff perform the procedure, using ultrasound and CT guidance. At this time, due to logistical issues, CT-guidance is only used for office-based cases.

The seeds are contained within thin sharp hollow needles (FIGURE 12), which are inserted one at a time through the perineum (the patch of skin behind the scrotum), and advanced to prescribed position coordinates within the prostate, using real-time ultrasound-guided visualization of the needle as it advances through the prostate. A central stylette within the needle, spacing material between the seeds, and a plug at the end of the needle secure the seed “train” in proper position within the needle, until the moment of seed discharge.

During the procedure, the prostate and needles are normally easy to see with a trained eye, using ultrasound equipment that shows a “white” needle tip, guided through the “black” prostate tissue, to within 1-2 mm of a computer-prescribed prostate target coordinate. These target coordinates appear as a computer-generated dotted “grid” pattern on a television screen, referenced by letters on the X-axis and numbers on the Y-axis, with the ultrasound prostate image displayed relative to the grid pattern (FIGURE 13a). The depth of the needle insertion relative to the “X-Y” grid reference plane controls the Z-axis, resulting in full three-dimensional control of the final needle placement (FIGURE 13b).

After the needle tip has been guided to its final “X-Y-Z” computer-planned grid coordinate, its central stylette is then manually “frozen” in that position, and the hollow needle slowly withdrawn over the seed-stylette complex, leaving a row of seeds deposited along the resulting needle tract in its prescribed position, after which the needle and stylette are removed (FIGURE 13c). This guided-needle seed delivery procedure is repeated one needle at a time, carrying row after row of computer-designed seed patterns to their prescribed target locations, until a total of 30 or more guided needle punctures have been accomplished, and the entire targeted volume three-dimensionally implanted with the radioactive seeds.

The entire operating room procedure typically takes about 45-90 minutes, and the final effect is the creation of a seed pattern that results in a very high dose three-dimensional radiation volume within and immediately around the prostate, which is individually designed and customized for each patient (FIGURE 13d). The seeds remain permanently, but their internally contained radiation is spent over several months, leaving behind inert tiny titanium capsules within the prostate (FIGURE 14). The amount of radiation delivered to this volume over the entire lifetime of the radiation sources is normally lethal to all of the cancer cells contained within, but is simultaneously carefully designed to limit the radiation dose to the urethra, bladder and rectum, all of which also lie in close proximity to the prostate target volume.

At the end of the procedure a Foley catheter is placed through the penis and into the bladder (FIGURE 15). The Foley catheter is a small rubber tube that allows the bladder to drain properly, at a time when the prostate may be swollen, causing temporary obstruction of the urethra. The catheter tube comes out through the penis and is connected to a urine collection bag that is temporarily strapped to the lower leg and easily drained when it fills (commonly called a “leg bag”). The patient is discharged from the hospital after the effects of the anesthesia have worn off, typically one to two hours after the procedure has been completed. The Foley catheter is removed the following day, right after the CT-guided post-brachytherapy dosimetry study.

PROSTATE BRACHYTHERAPY USING LOCAL ANESTHESIA AND CONSCIOUS SEDATION

Local anesthesia and conscious sedation has been in routine use at RMG since 2002 and offers several advantages, leading to its adoption as our standard brachytherapy anesthesia method. First of all, it has allowed us to move the procedure from the hospital setting to the office setting, which is typically a more comfortable environment for the patient, with a faster recovery and discharge. Second, patient acceptance of this anesthesia method has been excellent, and was the subject of a report accepted at the American Brachytherapy Society annual meeting in New York City, May 2003 (9).

• Prostate Brachytherapy – Patient Satifaction Survey
• Brachytherapy Procedure – Pain Survey
• Pain of Brachytherapy Procedure: Prostate Biopsy Comparison
• Anesthesia Survey

Finally, moving the procedure to the office setting allowed by this anesthesia technique has allowed us to develop the CT-ultrasound interactive brachytherapy treatment method, which we consider a more advanced brachytherapy technique. The logistics of coordinating an operating suite, ultrasound machine, CT scanner, planning computer and all personnel required to operate these devices is formidable and only possible in the office setting at this time.

CT-GUIDED POST-BRACHYTHERAPY DOSIMETRY STUDY

After the implant procedure a pelvic X-ray, chest X-ray and post-operative CT scan is done (FIGURE 16). The X-rays allow the most accurate seed count and the CT scan displays the location of each of those seeds within the prostate target region, and relative to the nearby bladder, rectum and urethra (urethra is only visible on CT if a Foley catheter is in the urethra). After the prostate CT, one of our nurses removes the Foley catheter, and the patient is released back home just as soon as he demonstrates an ability to void spontaneously.

The physics staff then counts and localizes all seeds, after which the computer calculates the surrounding radiation dose. The radiation oncologist then contours the prostate, urethra, rectum and bladder on every relevant CT slice, after which the computer reconstructs each of these organs, relative to the seed pattern. Finally, the resulting radiation dose is displayed in three dimensions, superimposed over the CT contoured prostate and nearby organs (FIGURE 17).

A new imaging modality that may more accurately assess our post-procedural implant dosimetry in some patients is MRI-based prostate implant dosimetry. The MRI usually gives a clearer definition of the prostate and seminal vesicle anatomy, though the CT is still needed to identify the seeds and calculate the radiation dose lines. In these cases, the CT and MRI prostate images are fused into the same space on our advanced brachytherapy planning computer, allowing the full use of the strongest aspects of both imaging modalities (FIGURE 18).

A quantitative analysis of the radiation dose received by the prostate and normal tissues is then accomplished, allowing an objective assessment of implant quality. This quantitative tool is known as a dose volume histogram (DVH) (FIGURE 19). The DVH plots the exact radiation dose level received by the prostate target volume and adjacent tissues in graphic form, and is the major quantitative method used to assess the implant adequacy.

The nuances of DVH interpretation are beyond the scope of this format but in general terms, we strive for a prostate V100* value over 90%, prostate D90* value over 90% and a urethral D10* value under 125%. It takes more than a simple DVH number analysis to judge an implant, as temporary prostate swelling and other factors complicate the analysis, but the DVH analysis does provide an implant quality assurance starting point.

*prostate V100: percent of CT or MRI-defined prostate volume receiving >= 100% of prescribed radiation dose

*prostate D90: minimum dose received by 90% of CT-defined prostate volume

*urethral D10: mimimum dose received by hottest 10% of CT-defined urethra volume

Problem implants

No matter what the level of brachytherapy expertise or experience, or where in the world it is done, these may happen from time to time. If a DVH analysis suggested that a significant area of radiation under-dosage was present in a given patient, the next step would be to assess its location on the CT prostate images.

In our brachytherapy experience, any areas of radiation dose below the prescription level have usually been small in magnitude and volume, and typically located centrally near the urethra, or anteriorly, near the anterior bladder neck or prostate apex. These locations typically do not harbor cancer cells, and are not further treated. Furthermore, our CT analysis is done on post-operative day one, which is commonly a time of significant prostate swelling, temporarily distorting the seed pattern and artificially degrading the apparent quality of the implant. We have had rare cases where the implant dosimetry was initially of concern, but subsequently looked much better after simply waiting for the prostate swelling to calm, and then repeating the CT-based DVH analysis.

If a “cold spot” were judged to be occurring in a clinically significant location and did not resolve after repeat CT dosimetry analysis, additional radiation treatment might be contemplated to correct this, particularly if the patient had an intermediate or unfavorable cancer characteristic. Unplanned additional radiation treatment has been an extremely rare event in our brachytherapy practice, and requires considerable dosimetry analysis and patient evaluation before proceeding. Less than 1% of our brachytherapy patients have had “unplanned” follow-up radiation treatment, though there is an ability to do it should the need arise, especially with the added radiation dose control afforded by the new IMRT technology, where a custom-engineered IMRT prostate “hot spot” could be superimposed right over a brachytherapy “cold spot,” effectively filling in the brachytherapy dosimetry deficit. With the CT-ultrasound interactive method, the risk of significant brachytherapy cold spots appears to shrink to zero.

Potters, et al have published Brachytherapy dosimetry quality guidelines that correlate with a good therapeutic outcome (6). Briefly, the dosimetry parameter known as the D90* has correlated with a superior 4-year PSA-defined disease-free survival, when it exceeded 90% of the prescribed brachytherapy dose. In our experience, this dosimetry requirement has been met in greater than 99% of implanted patients, and our median day one D90 value has been about 112% of the prescribed brachytherapy dose.

*prostate D90: minimum dose received by 90% of CT-defined prostate volume

CT-ULTRASOUND INTERACTIVE PROSTATE BRACHYTHERAPY

A new treatment method that allows real-time dosimetry analysis and correction

CT-ultrasound interactive prostate brachytherapy (CT-US brachytherapy) is a new method of prostate brachytherapy guidance that was pioneered in 2002 by Dr. Fuller at Radiation Medical Group (8). This method represents a form of real-time dosimetry guidance, meaning that the target volume dose coverage is analyzed and improved based on feedback from the CT, ultrasound and planning computer, before the procedure is concluded.

The CT-US brachytherapy real-time procedure method effectively addresses one of the most serious potential shortcomings of prostate brachytherapy – under dosage within and adjacent to the cancer-bearing target region. Because this method allows for more accurate dose sculpting, it allows for more consistent radiation coverage of cancer-bearing regions, while also better sparing adjacent critical normal tissues such as the urethra, from excessive radiation dose.

Description of the method:

The procedure is done in our office, where staff, computing devices, the CT-scanner, the ultrasound (US) machine and the operating suite are all located and coordinated. It begins with a standard pre-planned US-guided brachytherapy procedure, done under local anesthesia and conscious sedation in our operating suite. After that, immediate US and CT studies follow for interval prostate and urethral contouring, CT-based seed identification, co-registration of the CT and US image sets in 3 dimensions, and analysis of radiation dose coverage. The result of the co-registration process is shown in (FIGURE 1) and (FIGURE 2). The patient is then returned to our operating suite while the analysis proceeds.

After critical analysis of target volume radiation dose coverage strengths and deficiencies, additional “simulated” seeds are added on the computer if necessary, until target volume coverage is optimized and “cold spots” eliminated. During this process, normal tissue structures are also analyzed and care taken to design the supplemental seed pattern so as not to excessively irradiate those structures.

A ” mini-plan” is then designed to guide the simulated supplemental seeds to their targets, using the computer-fused ultrasound grid system as the seed guidance mechanism. The supplemental seeds are then inserted per “mini-plan” instructions, and the procedure concluded. A final CT-scan is then done for final dosimetry analysis and the patient discharged. A summary of the process is illustrated in (FIGURE 3).

In total, this process currently adds approximately one hour to a standard brachytherapy procedure, involving two CT-scans (interval and final), one ultrasound-scan (interval), five additional computer steps (immediate US contour, immediate CT contour, image co-registration, interval computerized analysis of dose coverage, computer design of supplemental seed pattern). The result is a more precise, conformal final seed implant radiation coverage result.

Results:

As of May 19th, 2003, 26 patients have been implanted at Radiation Medical Group by the CT-US interactive method. More consistent coverage of the prostate target volume region is demonstrated by the coverage statistics. The median V100 (percent of prostate volume receiving 100% of the prescribed dose) in this cohort measures 98.24% and more importantly, the minimum V100 result has measured 96.10%, indicating that this method has effectively terminated “cold spots” in every patient implanted to date – an unprecedented result in the practice of permanent source brachytherapy.
Reducing complications is just as important as curing the cancer. In this regard, we have been able to more carefully control the median and highest urethral dose by this method, potentially decreasing the risk of long-term urinary tract complications. As we move forward with the method, our effort will be to continue to maximize the coverage score, while attempting to further minimize the urethral dose. An example of urethral-sparing from the high dose radiation volume is illustrated in (FIGURE 4).

POST-OPERATIVE SIDE EFFECTS MANAGEMENT

The side effects after prostate brachytherapy typically come in two phases. The first phase occurs right after the procedure, as a result of prostate swelling and bleeding from prostate needle trauma, resulting from the needles that were used to introduce the seeds into the prostate. There is usually an intermittent passage of blood in the urine and ejaculate during this time, because invariably, the needles also traumatize the bladder, seminal vesicles and urethra to some degree. Too, an impressively black and blue area usually forms behind and around the scrotum that resolves over the following 2-3 weeks. There may also be post-procedural pain in the pelvis and penis, but this is usually mild to moderate and easily controlled with prescription pain medicines. Rectal-anal irritation may also occur but usually this is a minor and transient condition, resulting from the pre-brachytherapy bowel preparation and the presence of the ultrasound probe in the rectum to guide the procedure. It typically resolves in about a week. Rare patients with preexisting hemorrhoids have had more severe, though still temporary, rectal-anal symptoms after the brachytherapy procedure.

In about 10% of our patient population we see full-blown urinary obstruction after the procedure, where a patient is unable to urinate at all, requiring the placement of a urinary catheter for some period of time. This condition usually persists for only a few days but rarely, for long periods of time.

The first-phase side effects normally resolve within a week or two and the 5 medications discussed in Section 5 – “Admitting examination and labs” are normally sufficient to control the phase one side effects until they subside.

The second phase of side effects results from the radiation emitted from the seeds, and builds weeks to months after the brachytherapy procedure, typically lasting for 3-9 months after that. Again, urinary side effects are the predominant condition. One of the medicines routinely prescribed before the procedure, Flomax, is continued for many months after the procedure, until the urinary tract finally stabilizes.

Sometimes, depending on the circumstance, additional medicines may be prescribed. A brief synopsis follows:

Other medicines that we may recommend or prescribe for brachytherapy patients:

High-dose Prednisone (Steroid anti-inflammatory) – We often use this medicine within the first few months after the brachytherapy procedure, in patients who have worsening urinary obstruction problems. The higher the dose and the longer the duration of this medication, the more problematic become the side effects. On the other hand, it is a powerful swelling reducer and often creates a very good urinary flow improvement in our patients, when other medicines do not. We balance these factors to the best of our ability for our patients. In general, Prednisone is a short-term rather than a long-term solution to prostate swelling after the procedure.

Non-steroidal anti-inflammatory medicines: Examples include Advil, Motrin, Aleve, Celebrex, Naprosyn, Vioxx, Relafen and others – These medicines tend to help with prostate swelling and discomfort and unlike Prednisone or other steroid medications, with proper medical supervision, may be used indefinitely if needed.

Ditropan, Detrol: Occasionally used for bladder spasms or urgency

Viagra: For erectile dysfunction

Anusol HC, Metamucil: For lower bowel-anal problems that occur in rare brachytherapy patients

Antibiotics: If indicated for infection

Our nurses and doctors work together to help the patient gain control over his symptoms, until the brachytherapy side effects resolve. In patients with more challenging or severe urinary side effects, we may also ask for help in their management from the referring urologist. The typical brachytherapy reaction takes 3-9 months to resolve, sometimes extending as long as 12 months or more. With proper medication and attention though, the side effects are typically manageable, the patient’s normal lifestyle is usually maintained, and the long-term outcome is good.

LONG-TERM FOLLOW-UP AND EFFECTIVENESS OF BRACHYTHERAPY

The first follow-up appointment involves a brief office evaluation about 1 week after the prostate brachytherapy procedure to help the patient with his side effects. In our experience, this has been a very good time to review and sometimes adjust the patient’s medical regimen.

The cancer-specific follow-up begins at 3 months, and is then repeated every 6 months thereafter. If his urologist also follows the patient, we will often reduce our own follow-up visit frequency to every 12 months, having the patient alternate visits between the urologist and ourselves. After 5 years, we typically reduce the frequency of the follow-up visits to once per year. The follow-up frequency may be altered in specific cases for various reasons.

Before every visit, a PSA level will be checked, typically about 1 week prior to the appointment, so the radiation oncologist will have that result for discussion with the patient at the time of the appointment.

PSA Response to Brachytherapy

The PSA response to prostate brachytherapy may be more complicated to interpret than after other forms of prostate cancer treatment. The usual PSA response includes a steep drop in the PSA level during the first 3 – 6 months, followed by a more gradual reduction, which may evolve slowly over a number of years. Eventually, most brachytherapy patients see their PSA nadir in the 0.0 – 0.2 ng/ml range, though this may take 5 years or more to fully develop. Too, some patients will never see their PSA drop to a level this low, and yet still be apparently cured of their disease. Rarely, unfortunately, patients will develop a persistently rising PSA after the treatment. If a patient develops a persistently rising PSA after the brachytherapy procedure, this may be diagnosed as “Biochemical failure of their disease.” If this happens, the following tests, care and recommendations will vary, depending upon the exact patient situation.

The PSA “Bounce”

A fairly common PSA event after prostate brachytherapy is a temporary rise or “bounce” in the PSA level, which then spontaneously returns to a lower level after additional passage of time. The classic “PSA bounce” timing is about 1-2 years after the procedure and may be seen in up to 30% of all brachytherapy patients. Eventually, most of these “bounce” patients become long-term disease-free survivors. If there is a bounce or increasing PSA pattern occurring, more frequent PSA checks may be ordered until the final resolution is observed. Rare cases of double and even triple “bounces” have been reported.

The Prostate Cancer “Cure” Rate

Based upon contemporary literature review, it is reasonable to expect the following long-term (5-10 year) PSA-based disease-free survival probabilities in our brachytherapy patients. ^(1)(2)(3)

Favorable – 90%

Intermediate – 75-80%

Unfavorable – 30-65%

Most patients with a non-rising PSA at 10 years are likely cured of their disease, though there are no extremely long-term PSA-based data with brachytherapy, or for that matter, with any treatment option. Rare very late relapses will occur and cure is never guaranteed, but the relative lack of PSA-based treatment failures in brachytherapy patients between 5 and 10 years suggests that most of them will be cured.

POTENTIAL COMPLICATIONS OF PROSTATE BRACHYTHERAPY

The prostate brachytherapy procedure is usually well tolerated with temporary urinary tract side effects that resolve. Unfortunately, this is not always the case. Rarely, severe urologic or rectal complications have occurred following the brachytherapy procedure. A more detailed list of potential complications follows. When one reviews this list, he needs to keep in mind that similar magnitude complications may be seen following any potentially curative therapy for prostate cancer.

Mild Complications:

• Some patients may have a permanent change in quality and/or frequency of urination, usually responsive to Flomax or similar medication, and not severe enough to affect the patient’s lifestyle.
• Dysuria (pain with urination) – Rarely this will be a significant and long lasting condition after prostate brachytherapy, though with eventual resolution in the vast majority of patients who have it. Very rarely it will take several years to fully resolve.
• Blood in the urine – This may occasionally be seen long after the brachytherapy procedure. If it occurs greater than 6 months after the brachytherapy procedure, it should be fully evaluated by a urologist to exclude other causes such as a bladder tumor. If the bleeding is secondary to the brachytherapy procedure, it has normally not caused any serious health problems and eventually resolved.
• Rectal bleeding – This is seen in a minority of patients after brachytherapy, due to injury of small blood vessels in the rectum by radiation from the seeds. If seen, this condition usually responds to conservative treatment or resolves spontaneously. Rarely it will persist or require more intensive management, such as argon-plasma laser photocoagulation of bleeding points along the anterior rectal wall, over the prostate. We advise that no treatment of rectal bleeding occur without discussing it with one of our radiation oncologists first. If managed incorrectly, rectal bleeding may progress to a rectal ulcer or fistula – a more severe complication (see below).
• Seed migration to the lung – Some patients have had one or more seeds travel through the blood stream to the lung(s). There are have been no described adverse health consequences when this has occurred.
• Erectile dysfunction – The incidence of this complication depends on the age and health of the patient prior to treatment. Younger patients with good pre-existing erectile function tend to have a better chance of potency preservation, while older patients, diabetic patients, smokers or those with pre-existing erectile dysfunction have a higher chance of losing their potency function after the treatment. Some patients experience a temporary disturbance in their potency function after brachytherapy, which recovers over time. Patients that develop significant erectile dysfunction after brachytherapy often respond well to sildenafil (Viagra).

Severe or Potentially Severe:

1. Incontinence of urination – Some patients have had temporary urgency incontinence after the brachytherapy procedure (meaning if they get the call they must void immediately or they will wet themselves). This condition normally improves to complete resolution over time. Rare patients will have permanent incontinence – most likely to occur if a trans-urethral resection of prostate (known as a “TURP”) occurs after the brachytherapy procedure. In our experience, patients who have had a TURP procedure prior to the brachytherapy procedure have normally done well from a urologic viewpoint, as long as a peripheral loaded brachytherapy technique was done. The incidence of permanent severe incontinence after prostate brachytherapy is approximately 1%. If a patient develops severe permanent incontinence, he may be a candidate for urologic surgery such as an artificial sphincter placement, to attempt to improve the condition. This surgical procedure is often successful
2. Urethral stricture – This means scarring and narrowing of the urethral tube after the brachytherapy procedure. This may or may not become a severe complication, but if it occurs it may increase the chance of severe voiding problems or incontinence. Some patients will become permanently obstructed to urinary flow if this complication develops, mandating surgical correction. Surgery on a prostate after it has received brachytherapy may increase the risk of surgical complications, potentially culminating in permanent urinary incontinence. Urethral strictures are not a common occurrence after brachytherapy.
3. Rectal Ulcer – This means a chronic, potentially painful bleeding area in the anterior rectal wall over the prostate, which may cause a major disruption in the patient’s quality of life. This is a serious complication of brachytherapy whose incidence is on the order of 1%. Surgical measures or hyperbaric oxygen treatments may be required to treat it.
4. Bladder injury – Rarely a patient will develop severe urinary bleeding or scarring as a result of radiation injury to the bladder. Surgical measures or hyperbaric oxygen treatments may be required to treat it. This is rare.

Catastrophic:

1. Urethral to rectal fistula – This means a hole formed between the rectum and the urethra and requires major surgery, potentially including urinary and rectal diversion, with ileostomy and/or colostomy.
2. Colostomy (diverts the stool) – May be the end result of a fistula or rectal ulcer
3. Ileostomy (diverts the urine) – May be the result of a fistula or a very severe urinary tract injury. Fortunately, the incidence of a major surgical complication is very rare, on the order of 1/500 patients in our experience.
4. Seed migration to the heart – There has been one case described in the literature (not ours) where a patient had two seeds embolize to the heart, lodging in or near the heart’s natural pacemaker, identified as the potential cause of cardiac death in that patient. The incidence of this complication appears to be on the order of 1/100,000 patients

QUALITY OF LIFE AFTER BRACHYTHERAPY

Any cancer treatment negatively impacts a patient’s quality of life for a period of time. Different treatments do have different “personalities” and recovery periods though. In general, prostate brachytherapy and radical prostatectomy both tend to create more intensive urinary tract side effects and have a longer recovery period, while external beam radiotherapy tends to create both urinary tract and lower bowel side effects, but often less in magnitude and with a faster recovery period. A comparison of all three methods of treatment, using the FACT-P validated quality of life instrument measurement, is illustrated in (FIGURE 20) ⁽⁷⁾. There is no perfect quality of life instrument but this one does give a reasonable idea as to the typical magnitude and duration of negative quality of life effects following various treatments for prostate cancer.

PROSTATE BRACHYTHERAPY QUESTIONS AND ANSWERS:

My doctor said that prostate brachytherapy had been tried in the past and failed. Why is it a better option now?

The prostate brachytherapy procedure was developed before accurate image-based guidance and computer guidance were available to drive it. This meant that the seeds were inserted “blindly” into the prostate through a surgical incision. Predictably, the usual seed distribution that resulted from this technique was inadequate to result in complete coverage of the prostate by the proper radiation dose volume. Because of this deficiency, early attempts at prostate brachytherapy were indeed plagued by a high failure rate. To this day, some of our more senior urologists remember this experience, causing some of them to remain skeptical about this procedure, though most of them have become supportive of the modern brachytherapy technique

The first “breakthrough” technology that lead to the resurgence of the brachytherapy procedure was the development of transrectal ultrasound based imaging guidance in the 1980s, allowing the visualization of the needles and seeds within the prostate, such that the seeds could be reliably advanced to a “target” location within the prostate, with an accuracy of 1-2 mm. The second major development was the emergence of dedicated, powerful computers and software programs to allow the precision sculpting of a radiation dose volume within and around the prostate. These computing programs and imaging guidance continue to advance at a rapid rate.

Will I be able to work after a brachytherapy procedure?

Usually, the answer to this question will be yes, though there will be some issues you need to be aware of. The typical patient is able to return to work within a few days after the procedure, and some have even resumed their work duties the very next day. The main issue created by the brachytherapy procedure is one of urinary urgency and frequency, which may be long lasting for some patients. Even so, as long as there are adequate and rapidly accessible rest room facilities, one may usually work through these symptoms. Too, your doctor and nursing team will try very hard to optimize your medicines to minimize the symptoms after the procedure. Rarely, urinary symptoms following the brachytherapy procedure have been severe enough to warrant work disability, but this has not been the usual case. In general, we have found brachytherapy to be one of the more “work friendly” treatment options, because the recovery is usually faster than that after prostatectomy, and the number of office visits is fewer than with external beam radiotherapy.

My doctor said I am not as good candidate for surgery because I am severely overweight. Am I a brachytherapy candidate?

Yes, if you are otherwise a good brachytherapy candidate, obesity does not interfere with the procedure. Our larger patients have had no more difficulty tolerating this procedure than any of our other patients. Brachytherapy may even be the preferred method for treating large or obese patients, because the larger the patient, the more difficult and less accurate becomes external beam radiotherapy targeting, and the more dangerous may become the radical prostatectomy operation. With brachytherapy, we have the confidence that the intended radiation is being delivered to the prostate target, because we deposit the radioactive sources directly into the prostate volume while we watch it on a television screen, regardless of the size of the patient.

Is brachytherapy better than surgery or external beam radiation therapy?

There is no single treatment demonstrated superior to other treatments. They all appear to work well in properly selected patients. Which treatment, if any, is better than the others, remains a matter of speculation. There may be factors about an individual’s case that cause his doctor to recommend one method over the others. In other cases, the patient may be well treated by more than one of these methods, in which case he will need to make his own decision after discussing the options with his doctors, researching, weighing the potential benefit versus side effects and risks of each procedure. The 80% to 87% ten-year PSA-defined disease-free survival rates in intermediate and favorable-risk prostate cancer patients respectively with brachytherapy are encouraging, and compete well with other treatment approaches ⁽¹⁾⁽²⁾.

Do you ever combine external radiation with brachytherapy?

In the past, like many practitioners, we tended to routinely combine external beam radiotherapy with permanent seed brachytherapy for patients with locally advanced tumors (>=T2b), those with a PSA level >= 10ng/dl and/or those with a pathology Gleason score of >=7. The rationale was that these patients had a higher risk of disease beyond the prostate that would be potentially better treated by the addition of external beam radiotherapy, due to its ability to cover a larger volume. Though many practitioners still do this, in the year 2000 we essentially abandoned this combination for several reasons.

First of all, in spite of the theory espoused above, no convincing literature exists that added external beam radiation improves the cure rate, if the brachytherapy quality is high. There only reference that suggested that external beam radiotherapy improved the outcome when added to brachytherapy (4), studied a cohort of very early brachytherapy patients, treated in the late 1980s, when the technique was far less advanced than today’s technique. This studied patient cohort likely had a frequent occurrence of brachytherapy “cold” spots within the prostate and as a result, it is likely that any apparent benefit caused by the addition of external beam radiotherapy to these patients resulted because the external beam radiotherapy filled in these cold spots with additional radiation. Studies of more contemporary brachytherapy patients specifically found a lack of benefit to external beam radiotherapy added to brachytherapy ⁽³⁾⁽⁵⁾.

Concern number two regarding combined brachytherapy and external beam radiotherapy is the potential increased toxicity and complication rate. The combination of external beam radiation and prostate brachytherapy treats a larger volume of rectum and bladder to high dose than does brachytherapy or external beam radiation alone. This causes more short-term rectal and bladder-related side effects and also increases the short-term bother, fatigue, length and cost of therapy. There may also be a higher risk of delayed rectal bleeding and occasionally, more serious complications with combined therapy.

Third, careful pathology review of resected prostate cancers reveals that for low to intermediate-risk patients, even when their disease spreads beyond the prostate, it is usually still contained within a 5 mm radius of the prostate. This area is normally well within the cancer-lethal radiation zone produced by a properly performed seed implant.

REFERENCES

1. Blasko, JC, et al; Palladium-103 brachytherapy for prostate carcinoma; Int J Radiat Oncol Biol Phys; 2000 Mar 1; 46(4):839-850
2. Grimm, PD, et al; 10-year biochemical (prostate-specific-antigen) control of prostate cancer with I-125 brachytherapy; Int J Radiat Oncol Biol Phys; 2001 Sept 1;51(1):273-278
3. Potters L, et al; The role of external beam irradiation in patients undergoing prostate brachytherapy; Urol Oncology, 2000 Apr 1; 5(3):112-117
4. Ragde, H, et al; Modern prostate brachytherapy. Prostate-specific antigen results in 219 patients with up to 12 years of observed follow-up; Cancer; 2000 Jul 1;89(1):135-141
5. Blasko, JC, et al; The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma; Radiother Oncol, 2000 Dec; 57(3):273-278
6. Potters, L, et al; A comprehensive review of CT-based dosimetry parameters and biochemical control in patients treated with permanent prostate brachytherapy; Int J Radiat Oncol Biol Phys; 2002 Jul 1;50(3):605-614
7. Lee, WR, et al; A prospective quality of life study in men with clinically localized prostate carcinoma treated with radical prostatectomy, external beam radiotherapy or interstitial brachytherapy; Int J Radiat Oncol Biol Phys; 2001 Nov 1; 51(3): 614-623
8. Fuller, D.B., et al, Office-based CT-ultrasound interactive transperineal prostate brachytherapy: a real-time dosimetry analysis and quality improvement method – report of 14 cases. Brachytherapy, vol. 2(1), May 2003, p-63
9. Fuller, D.B., et al, Prostate brachytherapy using conscious sedation and local anesthesia: patient satisfaction survey, morbidity assessment and implant quality assessment. Brachytherapy, vol. 2(1), May 2003, p 63-64