PCRI Insights November 2003 vol. 6, no. 4
By Peter Grimm, D.O., Charles Heaney, Ph.D., John Sylvester, M.D., and John Blasko, M.D.
Seattle Prostate Institute
Approximately 220,000 men will be diagnosed with prostate cancer in 2003. Early diagnosis, primarily due to more widespread PSA screening, has resulted in more patients being diagnosed with early stage disease.1,2 For disease that is likely confined to the prostate and the immediate surrounding area, surgery, external beam radiation (EBRT) and seed implantation are the primary treatment options. In recent years, seed implantation has become more popular as a treatment option. It has been estimated that up to 50% of patients with early stage prostate cancer are now receiving ultrasound-guided seed implantation.13 This rise in popularity is most likely due to (1) the fact that five- and ten-year disease control rates of brachytherapy equal those of the top surgical and radiation series, (2) the toxicity and side-effects are perceived to be lower, and (3) the brachytherapy involves just a single outpatient treatment.7-11,14
Ultrasound-guided transperineal interstitial permanent prostate brachytherapy with I-125 or Pd 103 radioactive seeds is a form of radiation therapy in which radioactive sources, or “seeds”, are permanently inserted into the prostate. The principal advantage of this technique is that the seeds can deliver a substantially higher radiation dose to the prostate and surrounding tissue compared with external beam irradiation. Because of the low energy of I-125 (Iodine 125) and Pd 103 (Palladium 103) isotopes, the dose falls off quickly with distance and, therefore, the seeds deliver low doses to the adjacent rectum and bladder.
Seed implantation for prostate cancer was originally suggested by Alexander Graham Bell as far back as 1903. In 1911, Louis Pasteur suggested that the insertion of radium into the prostate may eradicate this malignancy.15 Various techniques were subsequently employed with limited success. In the 1960s, Drs. Scardino and Carlton reintroduced permanent prostate brachytherapy using 198-Au (gold-198) interstitial implantation combined with external beam radiation therapy.17 At about the same time, Dr. Whitmore and colleagues at Memorial Sloan Kettering Cancer Center (MSKCC) also began to insert I-125 seeds through an open incision as a sole treatment.18 Unfortunately, these early techniques did not allow for clear visualization of the seeds as they were being inserted into the prostate and, as a result, there was often poor dose coverage of the gland.
Despite the limitations of these techniques, some important information was obtained from the early seed implant approaches. Local cancer control was better in patients who received high quality implants and who had low grade and early stage cancer.20,21,26 The group from MSKCC reported a 60% local control rate in those patients who received prescription doses of > 140 Gy (Gray) versus 20 % if the dose was less than 140Gy. The 15-year survival was 70% in patients with stage B1 prostate cancer treated with I-125 seed brachytherapy.27 These results suggested strongly that seed placement and proper patient selection were important determinants of cancer control. The subsequent development of the transperineal, ultrasound guided approach provided a means to more accurately place seeds and thereby improve dose coverage.
Technical Development of the Transperineal Approach
In the 1980s, several investigators were exploring new brachytherapy approaches to the treatment of prostate cancer.28 Martinez treated patients with EBRT combined with temporary seeds inserted using a transperineal approach.29 Drs. Syed and Puthawala pioneered a temporary seed technique of placing the needles while visualizing them through an open laparotomy.30 In 1983, Dr. Holm introduced the use of transrectal ultrasound to visualize the permanent placement of I-125 seeds via needles inserted through the perineum directly into the prostate.31 The ultrasound-guided transperineal approach resulted in relatively even distribution of seeds throughout the prostate; this marked a major advance in prostate brachytherapy in that it minimized the need for external beam radiation and allowed more precise planning of the implant prior to the procedure. These advances also significantly increased the accuracy of seed placement and insured that the prostate would receive the proper number, strength, and positioning of radioactive sources. Derivatives of this technique are in wide use today. (See Figure 1.)
The first transrectal ultrasound-guided, template-guided I-125 implant procedure was performed at the Seattle Prostate Institute in late 1985 and is now being used in over 600 centers around the world. The original Seattle approach has been modified and improved several times since the original implants. Today, the implant is planned prior to the procedure either on the day of or several weeks prior to the implant. Typically, the implant is completed in a 45-90 minute outpatient procedure under spinal anesthesia or light general anesthesia.32
As brachytherapy has become more popular, many technical improvements have been added to improve the consistency and quality of the procedure.31, 33-35 Both Pd-103 and I-125 seeds are now available in continuous strand form, increasing the likelihood that the seeds will remain in place after implantation. Compared with loose, or free seeds, these connected seeds have been demonstrated to substantially lower the incidence of seed migration to the lung.36 While slight differences in technique are expected to grow as more and more physicians perform this procedure and as more technical advances are made, the basic approach is quite similar and it remains to be determined whether any single technique will prove superior in controlling the cancer. Fundamentally, most of the active institutions currently use transrectal ultrasound guidance via a closed template-guided transperineal technique and a modified uniform seed dispersal pattern. Quality evaluation is based on postop, CT-based dosimetry. Virtually all are in agreement that the keys to successful outcomes are appropriate patient selection and a high quality implant.43-47
As shown in Figure 2, the entire implantation process consists of several discrete steps:
• Patient selection
• Treatment planning
• Seed implantation
• Post-Operative evaluation.
The three key considerations involved in the selection of patients for ultrasound-guided implantation are the stage of cancer, technical suitability, and toxicity issues. Each of these is carefully evaluated prior to treatment.
Stage and Extent of Cancer
Staging is a means to determine the extent of the cancer prior to treatment. Patients with a high likelihood of disease in the prostate and immediate surrounding area can be treated with seeds alone. Patients deemed to have a higher likelihood of diseases beyond the implant volume are treated initially with external beam radiation to a region around the prostate after which they receive an implant “boost.” Patients with distant, metastatic disease are treated with hormonal therapy or other systemic agents.
In early stages, there is a very low risk of disease in the seminal vesicles or lymph nodes, and only a modest risk of disease that extends through the outer wall, or capsule, of the prostate. Fortunately, the disease that goes through the capsule is almost always within several millimeters of the prostate and is easily covered by the implant volume.51,52 The risk of disease outside the prostate can be estimated by looking at the Partin tables 48,49 which correlate (1) the risk of extra-capsular penetration (ECP), (2) seminal vesicle involvement (SV), and (3) lymph node involvement (LN) with the Gleason score, clinical stage, and pretreatment PSA.50 Note again, however, that capsule penetration does not mean that disease is beyond the surgical or implant margin. Typically, surgical and radiation margins are 4mm – 15mm beyond the prostate. Disease that is beyond the margin can be roughly estimated from the Partin tables by the formula LN + SV + ECP (X) (X is 25% if the Gleason score is 6 and 50% if it is 7). This calculation is based on a study that showed that, for early stage patients with evidence of ECP only, 25% would fail radical prostatectomy if the Gleason score was 6 or below and approximately 50% would fail if it was 7 or higher.134
Evidence that patients with early stage (low risk) disease have a high likelihood of disease confined to the implant margin comes not only from pathologic studies, but also from clinical studies showing excellent PSA control with seed implantation alone using either 103-Pd or I-125.43,54,55,56-61 Some centers combine EBRT with implantation on all patients, even those with low risk disease, but to date, the long-term clinical results of combined treatment have not been shown to be superior to those of implantation as the sole treatment.62,63 For the majority of patients, implant alone is satisfactory. There are, however, several factors, such as the number of positive cores, that are considered in determining whether a patient requires EBRT in addition to implantation.
For intermediate risk patients, the choice of treatment is between implant alone or EBRT and seeds. A common definition of intermediate-risk is the presence of one of several unfavorable risk factors:
• PSA > 10 ng/ml,
• Gleason > 7, or
• > or = cT2c disease by DRE.
This intermediate group is a broad group with a significant range of risk of disease outside the prostate. Some of the more favorable intermediate-risk patients (e.g. those with stage T1c, Gleason < 7, a PSA between 10-15ng/ml, and a low percentage of positive biopsies) have a relatively low risk of disease beyond the margin and are often treated with implant alone. We believe that other intermediate risk patients with worse prognostic factors are probably served best by EBRT plus implantation, but further studies are necessary.
High-risk patients are considered as those with two or three of the above mentioned unfavorable risk factors.55 Patients in the high-risk group are typically treated with combined therapy which may also include hormonal therapy. Table 1 shows the current treatment guidelines recommended by the Seattle Prostate Institute, which are consistent with those advocated by the American Brachytherapy Society.
Prostate Size: In order for an implant to be done well, the physicians must be able to place the seeds accurately. We have found that if the size of the prostate is much greater than 60cc, the implant can become technically challenging since the greater number of needles required causes more swelling during the procedure. In addition, as the size of the prostate increases, there is a higher probability that a portion of the gland will be positioned behind the pubic bone, obstructing the placement of needles.
Prior Prostate Surgery: A prior TURP (Trans-Urethral Resection of the Prostate) can sometimes prevent a quality implant. TURPs can leave a large hole in the central portion of the gland (a “TURP defect”) allowing little room for seed placement. In addition, the early experience noted higher rates of incontinence when TURP patients were treated with implantation.44,71,72,73,74 Recent procedural advances that involve placing seeds further from the TURP defect have decreased this risk of incontinence. The current consensus, therefore, is that patients with small TURP defects are eligible for implantation as long as they clearly understand that their risk of incontinence may be higher than non-TURP patients.
Catheterization: The need for a temporary catheter after implantation increases as the AUA score increases. The AUA score is a measure of the blockage present before implantation. Patients with AUA scores above 15 are at higher risk of needing a temporary catheter after seed implantation, and a few of these may require treatment either before the implant or at a later date to relieve obstructive problems. For example, some patients with more severe obstructive symptoms can become candidates for implantation if their urinary symptoms respond well to alpha-blockers. Others can benefit from surgical intervention, either a TURP or, preferably, a TUIP (transurethral incision of the prostate) which is a less complicated and traumatic procedure that minimizes the risks associated with a TURP.
Also of note is that patients undergoing hormonal therapy to shrink the prostate may not experience any improvement in their obstructive symptoms. Moreover, some studies have suggested that pre-treatment with androgen ablation can slightly increase the risk of requiring a temporary catheter.135,136
All implants are planned carefully prior to the procedure either at the time of the procedure or several weeks prior to the implant. The prescription dose is determined by the isotope (Pd-103 or I-125) and whether it is to be used for implant alone (145Gy for I-125, 125 Gy for Pd 103) or in combination with EBRT (110 Gy for I-125 and 100 Gy Pd 103). This dose is the radiation dose delivered to an area (target volume) determined by the brachytherapist. In addition, the brachytherapist also defines ranges of acceptable doses to the critical nearby structures, including the urethra, rectum, and bladder. Careful planning is important to avoid areas of high dosage.
The first step in planning an implant is a volume study, which consists of a series of cross-sectional ultrasound images of the prostate. The volume study may be performed weeks prior to the procedure or in the operating room on the day of the procedure. The ultrasound images are then transferred to a computer planning system, and a skilled team consisting of the treating physician, physicists, and dosimetrists generates a plan. The plan is actually a map of the prostate and it describes precisely where each needle needs to be placed and the number of seeds per needle. The brachytherapy team follows this map carefully in the operating room, but has the leeway to add seeds if necessary.
The seeds are generally designed to be approximately 1 cm apart. The size, shape, and critical structures will modify this overall pattern slightly within the gland, creating what brachytherapists call a “modified uniform spacing” pattern to satisfy the dose requirements and to minimize high dose areas. The vast majority of centers in the USA currently use a modified uniform seed spacing approach.
I-125 and Pd 103 are the primary isotopes used in permanent seed implantation. I-125 was introduced into clinical treatment of prostate cancer in 1965, and 103-Pd was introduced in 1986. The photon energy of 28 Kev for I-125 and 21 Kev for Pd-103 are nearly identical. The primary difference between the two isotopes is the rate at which they decay. I-125 has a half-life (the time it takes to decrease by one half) of 60 days versus 17 days for Pd 103. The effect is that Pd gives up its energy more quickly. There is no evidence yet that quicker is better for prostate cancer so selection of the isotope is at the discretion of the brachytherapist. The American Brachytherapy Society does not recommend one isotope over the other.43
The doses prescribed today are the result of initial calculations and the subsequent experience from treating thousands of men. The doses delivered by implantation are significantly higher than those achievable by 3Dconformal/IMRT, external beam radiation therapy, or HDR brachytherapy. Typical doses for implants are 125-145 Gy. For EBRT, the doses are 70-80 Gy. In order for EBRT to deliver a dose equivalent to that of an implant, 120 Gy would have to be given, a dose far beyond the tolerable range for EBRT.81,92 (EBRT is typically not given in doses over 80G.)
The implant procedure itself is a 45-90 minute outpatient procedure that can be performed under spinal or general anesthesia. Most centers prophylactically treat with I.V. antibiotics at the time of the implant procedure. Physicians can use either preloaded needles or a MICK™ apparatus to deposit the seeds. With preloaded needles, the seeds are placed into the needles either individually (free seeds) or as part of a connected strand of seeds. The Mick applicator, shown in Figure 3, uses a cartridge system, and seeds are inserted into the gland individually. Many centers have published on these different techniques.35,40,56,66,99
During the procedure, great care is taken with needle and seed placement. The radiation oncologist’s job is to insure the precise placement of the seeds and, if necessary, to recommend additional seeds. The urologist’s job is to place the needles and to perform necessary urologic evaluations and procedures. For example, following successful placement and confirmation of seed position, a cystoscopy is often performed at the end of the procedure to remove any blood clots or seeds from the bladder. Typical post-operative orders include an ice pack to the perineum for 20 minutes and discharge to home with an alpha-blocker (e.g., Flomax™), an antibiotic, a non-steroidal anti-inflammatory drug, and an appointment for a CT scan used for post-operative dosimetry purposes.
The implanted seeds do not represent a significant radiation hazard to others. The energy of I-125 and 103-Pd is so low that there is minimal risk of radiation exposure to friends and relatives of the patient. In one study, the average dose a spouse received during the year following the implant was determined to be 10 mRem. This is approximately equal to living in Denver for 3-4 months or taking one round trip airplane flight from New York to Tokyo.100
The assessment of implant quality can take place, to a certain degree, during the procedure through the use of ultrasound, and possibly fluoroscopy, to visualize the needles and seeds as they are being placed. Definitive evaluation, however, takes place post-operatively using CT scans that identify the position of each seed and allow the brachytherapy team to calculate the dose delivered by the seeds to the gland. CT dosimetry shows the radioactive seeds in cross-sectional images as they lie within the prostate (Figure 4). With the aid of treatment planning software, the dose is calculated and compared to the pre-plan dosimetry (Figure 5). CT dosimetry has allowed brachytherapists to substantially improve the technique.46,108,109 As swelling of the prostate can sometimes make it difficult to accurately define the gland and to perform the required calculations, the CT study is usually performed about four weeks post-op. Most of the prostate swelling will have resolved by this time.105 However, at centers where some patients must travel long distances for treatment, practical considerations often dictate that post-op dosimetry be done on day 0 or day 1 post-op.
The goal of any implant is to achieve the prescribed dose throughout the prostate. Several studies have documented better biochemical control in the patients treated with I-125 monotherapy that achieved a dose greater than 130-140 Gy as compared with patients whose dose fell below this range.46,47 Research at the Seattle Prostate Institute has shown that monotherapy patients, treated between 1986-1987 (the first implants that were performed in the U.S.), achieved significantly worse biochemical control than did patients treated at the Institute by the same physicians between 1988-1990.60 The only factor identified as explaining the difference was the quality of the implant. These studies supported the hypothesis that higher quality implants result in better cancer control. Post-op CT dosimetry provides important, immediate feedback on each implant. If there is an area or areas with significant underdosing, the deficiency can be addressed in a timely manner with supplemental EBRT, HDR, or a second, corrective implant. Currently, the American Brachytherapy Society recommends the use of CT-based, post-op dosimetry on all patients and also recommends that such findings be included in published reports from clinical research on implantation.43
Toxicity of Modern Implantation
Major acute operative symptoms and complications are extremely rare. Surgical events such as (1) bleeding that requires transfusions, (2) admission to intensive care for any postoperative acute events, or (3) death have not typically been noted in the literature.30,111 And, it should be noted that at the Seattle Prostate Institute, where physicians have performed more than 7,000 implant procedures, no deaths or serious intra-operative or post-operative morbidity has been observed.
Moderate post-operative side-effects, however, are common, and they primarily consist of urinary irritative and obstructive symptoms such as increased urinary frequency, urgency, discomfort during urination, and weakening of the urinary stream.38,44,55,112 The symptoms are at their worst between two and six weeks post-op, but they may be bothersome for up to six months or longer. The need for a temporary catheter occurs in approximately 10% of patients.38,41,42,66,71,112,113 In one study at the Seattle Prostate Institute, the average duration of catheterization was 13 days, and 2% of the patients required a Foley, supra-pubic, or intermittent self-catheterization for more than six months. No patient has required a permanent catheter.114 In the small percentage of patients who require a catheter for more than a few weeks, self-catheterization is taught or a supra-pubic catheter is placed until the swelling and retention resolves.
Increased bowel movement frequency and urgency is uncommon and when it occurs, the symptoms respond to diet and medications such as Imodium™. Blood in the urine is to be expected for a few days (and occasionally a few weeks) after implant. Perhaps half of sexually active patients will experience some level of discomfort with orgasm, a problem that generally resolves itself gradually. Although the prostatic fluid of the ejaculate will decrease dramatically following an implant, sperm can still be present. Occasionally, blood in the ejaculate will be seen but it is not harmful or dangerous. Whether the sperm is significantly damaged by the radiation exposure is unknown; however, to be safe, birth control measures are recommended for those couples who are still fertile. Ejaculation of a seed is rarely reported. The Seattle Prostate Institute team knows of only less than five patients who have noted this event over the past 15 years.116
Quality of Life (QOL)
With evidence that the various treatments for prostate cancer are likely to be equally successful in terms of long-term cancer control, emphasis is now being placed on the quality of life after treatment. Quality of life can be difficult to measure, as men can perceive problems after treatment very differently. Previous attempts to define quality of life have been marred by the fact that patient reports of problems have differed substantially from physician reports. Therefore, studies are now incorporating the use of validated questionnaires that can help decrease, but not totally eliminate bias.
Several recent QOL studies have compared implantation, EBRT, and radical prostatectomy. In one study, the analysis showed a decrease in QOL with radical prostatectomy and implantation at one month post-op, but the overall QOL for both treatments returned to near the pre-op baseline by the one year mark.117 In another, the patients treated with radical prostatectomy reported significantly worse QOL problems in terms of urinary function and sexual function and bother (Figures 6 and 7). The patients treated with EBRT reported significantly worse QOL in regard to bowel function (Figure 8) and fear of cancer recurrence.118 More studies in this important area will help compare not only the quality of life for each of the treatments, but also will allow comparison of QOL for each of the several brachytherapy techniques currently in use, as discussed in the following paragraphs.
Rectal bleeding after implants occurs in approximately 2-5% of patients who receive an implant only, and occurs in approximately 6-10% of those treated with both EBRT and implantation. It is usually minor and not apparent until 1-2 years after the implant. Rectal bleeding rarely occurs after three years.38,42,57,67,68,71 One study demonstrated that careful planning of the dose to the rectum substantially reduced the risk of rectal bleeding.119 A severe rectal ulcer or fistula is rare in patients not undergoing electrocautery.19,111 Biopsies or electrocautery to stop bleeding are to be avoided in all patients with rectal bleeding after implant because they can increase the risk of a non-healing ulcer or fistula.
Most reports in the literature note that long-term urinary morbidity and/or incontinence is rare following implantation. In patients (1) without severe obstructive urinary symptoms, (2) with significant benign prostatic hypertrophy, and (3) without a prior TURP, the risk of chronic urinary irritation or incontinence following implantation is less than 3%.19,111
Sexual functioning and impotency are more challenging to evaluate due to differences in patient perceptions, the definition of potency, age differences, baseline functioning, comorbid diseases, and, in addition, the sexual functioning and interest of the patient’s partner. A Seattle Prostate Institute team has reported the results of a patient self-reported questionnaire. Of those seed monotherapy patients who noted full normal erection ability prior to implantation, 80% maintained the ability to obtain an erection “adequate for intercourse”, as compared to 69% of patients who were treated with EBRT plus implantation.65,97,121 In other studies, 75% of implant patients maintained erection function at one year post-implant. At three years, 81% reported the ability to maintain an erection ability.57,68 Of interest is the fact that several studies may have identified the cause of impotence in some men. The dose to the bulb of the penis may correlate to erectile dysfunction. In a small series of retrospectively reviewed patients, Dr. Merrick noted that 19 of 23 patients lost erectile function when the dose to the bulb of the penis was greater than 40% of the minimal peripheral dose, whereas 19 of 23 maintained erectile function if the dose at the bulb of the penis was less than 40% of the minimal peripheral dose.110 These findings are likely to change the planning of dose to this area in the future.
There remains considerable debate as to how best to define PSA control following surgery, EBRT, or implantation, particularly in the urological literature.122 This is because PSA levels fall at different rates after each of these treatments. PSA falls rapidly after surgery but more slowly after implantation or EBRT. For example, following an implant with Pd-103, the PSA level, on average, will fall by 50% in approximately 90 days. After surgery, conversely, the 50% reduction takes only 3.8 days.120,123 To allow meaningful comparisons of cancer control rates between surgery and implantation, the American Society for Therapeutic Radiation and Oncology (ASTRO) adopted a definition of PSA failure as being three consecutive increases in PSA level following an implant. Treatment success, therefore, is described as being “PSA Progression-Free.” PSA Progression-Free data is used today for most of the comparison studies. In addition, most experts agree that ten years is necessary before meaningful comparisons can be made between the treatments. By that time, almost all of the failures will have occurred. Using a fixed PSA value to define failure (such as 0.5 ng/ml as used in some studies) is inappropriate, since some implant patients may take as long as eight years to reach this level. The different definitions of cancer control will continue to spark debate between the radiation oncology and urology communities.
As stated earlier, ten years is considered the benchmark for evaluating the results of therapy. Because many centers have not reached this mark, five-year results are reported. Five-year results for radical prostatectomy and high dose 3D conformal EBRT are shown in Table 2 for low, intermediate, and high-risk patients.
Table 3 displays the five-year results for patients treated with implantation alone or implant plus EBRT. The five-year PSA Progression-Free rate is 88-95% for the low-risk patients, 58%-96% for intermediate risk patients, and 54-79% for high-risk patients.14,61,63,120,129 A Seattle Prostate Institute study found no significant difference in five-year results between patients treated with implant alone versus implant plus EBRT for either low or intermediate risk groups.130 While implant alone appears to be appropriate for the majority of low-risk patients, more research needs to be done with respect to what patients in the intermediate risk group can truly benefit from the addition of EBRT.
Long-term results have been reported from the Seattle group. For Pd 103, seed monotherapy, patients, 83.5% were PSA Progression-Free at nine years.137 With I-125, a ten-year PSA Progression Free rate of 87% was reported. The local control rate was 97%, and the metastatic disease-free survival rate was 97%. While 50% of the patients had died of other causes by the end of ten years, none of these patients died of prostate cancer.138 The ten-year results of 634 consecutively treated patients treated at the Seattle Prostate Institute with I-125/Pd-103 (both with and without EBRT) between the years 1987-1993 were reported at the 2001 annual ASTRO meeting. PSA Progression Free rates for low, intermediate, and high-risk groups were 87%, 74%, and 45%, respectively, at 10 years (Table 4). The long-term Seattle Prostate Institute results are very similar to those achieved with radical prostatectomy as reported by Han, Walsh, and colleagues from the Johns Hopkins series (Figure 9). Both patient groups had comparable stage and PSA characteristics (Figure 10).
Modern transrectal ultrasound-guided, interstitial permanent brachytherapy is a 45-minute, single outpatient treatment for the majority of men with early-stage prostate cancer. It has documented five- and ten-year biochemical, overall, and disease-specific relapse-free survival rates that equal the best that radical prostatectomy has thus far achieved. These favorable findings have established permanent prostate brachytherapy as a primary treatment option for early stage prostate cancer.
Quality assurance is an important part of seed implantation. Many centers are participating in quality assurance programs (e.g., ProQura.com). The learning curve that practitioners typically experience before they can perform high quality implants on a consistent basis can be formidable. Fortunately, careful intraoperative evaluation and post-implant CT dosimetry can identify any under-dosed areas, or cold spots, that may exist, allowing corrective treatment to take place in a timely manner. In this regard, developments in the field of implant dosimetry that should bring significant progress in the future are underway.
At present, it is possible to carry out pretreatment dosimetry planning either weeks before the procedure or in the OR just before the implant. Efforts are also underway to develop “real-time dosimetry” that will permit determining the accuracy of seed placement and the resulting dose to the prostate during the procedure itself. To date, however, the developmental work on instantaneous dosimetry evaluation has not yielded reliable methodologies. Finally, clinicians are continually looking to identify specific procedural techniques and seed distribution patterns that will reduce both the short- and long-term side-effects of implantation while maintaining the excellent long-term cancer control rates that have been observed to date.
About the Authors
Peter Grimm, D.O., currently the Seattle Prostate Institute’s (SPI) Director of Research, was instrumental in the establishment of SPI and the shaping of its clinical, educational, and research activities. Since his involvement in establishing the first transperineal prostate implantation program in the United States, Dr. Grimm has devoted considerable effort to bringing about improvements in technical aspects of the implant procedure. He was the principal developer of the I-125 Rapid Strand designed to eliminate movement of seeds inside the prostate and he has recently been granted a patent for an advanced design of the needles used in implant procedures. Dr. Grimm received his medical education at the Chicago College of Osteopathic Medicine and his graduate training in radiation oncologist at UCLA. He currently chairs the Prostate Brachytherapy Quality Assurance Group of the American Brachytherapy Society.
John Blasko, M.D., the Seattle Prostate Institute’s Medical Director and Clinical Professor of Radiation Oncology at the University of Washington, is recognized internationally for the quality of the clinical research he has conducted on the SPI implant series, by far the world’s largest. He was a member of the medical team that performed the first transperineal prostate implant in the U.S. in 1985. Since that time, he has developed data collection and analysis protocols that have permitted meaningful research on the long-term effectiveness of this procedure. Dr. Blasko received his medical education at the University of Maryland and his graduate training in radiation oncology at the University of Washington. Dr. Blasko is a past president and current board member of the American Brachytherapy Society.
John Sylvester, M.D., is SPI’s President and Director of Education and Training, overseeing SPI’s clinical education program that includes intensive training workshops offered on a monthly basis and larger annual scientific meetings covering a wide range of topics related the diagnosis and treatment of prostate cancer. In addition to directing the Institute’s educational program, Dr Sylvester’s innovative work has included a the development of a technique that allows more accurate ultrasound visualization of the urethra and less distortion of the prostate during implantation. Dr Sylvester received both his medical education and radiation oncology training at UCLA. In addition to his work at SPI, Dr. Sylvester established and directs the prostate implantation program of Stevens Hospital north of Seattle. He is a director of the Puget Sound Tumor Institute and the president of SPI
Charles Heaney, Ph.D. is the Clinical Projects Director at SPI where his is responsible for overseeing SPI’s research activities, managing the institute’s website, providing technical assistance to area physicians affiliated with SPI’s research and training programs, and other special projects. He joined Drs. Blasko and Grimm in the mid-1980s when the implant program was first established and developed the clinical training courses and scientific conferences for which the Seattle team is internationally recognized. Dr. Heaney received his undergraduate and graduate business and health administration training at New York University and Yale University respectively and his doctorate in Health Policy and Administration at the London School of Economics.
1. Mettlin C, Jones GW, Murphy GP: Trends in prostate cancer care in the United States, 1974-1990: observations from the patient care evaluation studies of the American College of Surgeons Commission on Cancer. Ca: a Cancer Journal for Clinicians 1993; 43:83-91
2. Garfinkel L, Mushinski M: Cancer incidence, mortality and survival: trends in four leading sites. Stat Bull Metrop Insur Co 1994; 75:19-27
3. Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE: A decision analysis of alternative treatment strategies for clinically localized prostate cancer. Prostate Patient Outcomes Research Team [see comments]. Jama 1993; 269:2650-8
4. Talcott JA, Rieker P, Propert K, al e: Complications of treatment for early prostate cancer: A prospective, multi-insitutional outcomes study. Proc. Am. Soc. Clin. Oncol. 1994 (abstr); 13:A711
5. Litwin MS: Health-related quality of life after treatment for localized prostate cancer. Cancer (Supp.) 1995; 75:2000-2003
6. Johansson JE, Adami HO, Andersson SO, Bergstrom R, Holmberg L, Krusemo UB: High 10-year survival rate in patients with early, untreated prostatic cancer [see comments]. Jama 1992; 267:2191-6
7. Blasko JC, Wallner K, Grimm PD, Ragde H: Prostate specific antigen based disease control following ultrasound guided 125iodine implantation for stage T1/T2 prostatic carcinoma. J Urol 1995; 154:1096-1099
8. Zietman AL, Coen JJ, Shipley WU, Willett CG, Efird JT: Radical radiation therapy in the management of prostatic adenocarcinoma: the initial prostate specific antigen value as a predictor of treatment outcome. J Urol 1994; 151:640-5
9. Trapasso JG, deKernion JB, Smith RB, Dorey F: The incidence and significance of detectable levels of serum prostate specific antigen after radical prostatectomy. J Urol 1994; 152:1821-1825
10. Zagars GK, Pollack A, Kavadi VS, von Eschenbach AC: Prostate-specific antigen and radiation therapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 1995; 32:293-306
11. Zagars GK: Prostate-specific antigen as a prognostic factor for prostate cancer treated by external beam radiotherapy. Int J Radiat Oncol Biol Phys 1992; 23:47-53
12. Talcott JA, Rieker P, Clark JA, Propert KJ, Weeks JC, Beard CJ, Wishnow KI, Kaplan I, Loughlin KR, Richie JP, Kantoff PW: Patient-reported symptoms after primary therapy for early prostate cancer: results of a prospective cohort study. J Clin Oncol 1998; 16:275-83
13. Prostate Canvcer Brachytherapy: Clinical and Financial Imperatives for Permanent Implantation, in Oncology Roundtable Annual Meeting. Washington, D.C., The Advisory Board Co., 2000, p 15
14. Sylsvester JE, Blasko J, Grimm P: Brachytherapy as Monotherapy, in Prostate Cancer: Principles and Practice. Edited by Kantoff P, Carroll PC, D’Amico AV. Philadelphia, Lippincot Williams & Wilkins, 2001, pp 336-357
15. Porter AT, Blasko JC, Grimm PD, Reddy SM, Ragde H: Brachytherapy for prostate cancer [see comments]. CA Cancer J Clin 1995; 45:165-78
16. Denning CL: Carcinoma of the prostate seminal vesicles treated with radium. Surg Gynecol Obstet 1922; 34:99-118
17. Scardino P, Carlton C: Combined interstitial and external irradiation for prostatic cancer, in Principles and Management of Urologic Cancer. Edited by Javadpour N. Baltimore, Williams & Wilkins, 1983, pp 392-408
18. Whitmore WF, Jr., Hilaris B, Grabstald H: Retropubic implantation to iodine 125 in the treatment of prostatic cancer. J Urol 1972; 108:918-20
19. Blasko JC, Grimm PD, Ragde H: Brachytherapy and organ preservation in the management of carcinoma of the prostate. Semin. Radiat. Oncol. 1993; 3:240-249
20. DeLaney TF, Shipley WU, O’Leary MP, Biggs PJ, Prout GR, Jr.: Preoperative irradiation, lymphadenectomy, and 125iodine implantation for patients with localized carcinoma of the prostate. Int J Radiat Oncol Biol Phys 1986; 12:1779-85
21. Fuks Z, Leibel SA, Wallner KE, Begg CB, Fair WR, Anderson LL, Hilaris BS, Whitmore WF: The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. Int J Radiat Oncol Biol Phys 1991; 21:537-47
22. Giles GM, Brady LW: I-125odine implantation after lymphadenectomy in early carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys 1986; 12:2117-2125
23. Kuban DA, el-Mahdi AM, Schellhammer PF: I-125 interstitial implantation for prostate cancer. What have we learned 10 years later? Cancer 1989; 63:2415-20
24. Schellhammer PF, Whitmore WF, Kuban DA, El-Mahdi AM, Ladaga LE: Morbidity and mortality of local failure after definitive therapy for prostate cancer. J. Urol. 1989; 141:567-571
25. Morton JD, Harrison LB, Peschel RE: Prostatic cancer therapy: comparison of external-beam radiation and I- 125 seed implantation treatment of stages B and C neoplasms. Radiology 1986; 159:249-52
26. Kovacs G, Galalae R, Loch T, Bertermann H, Kohr P, Schneider R, Kimming B: Prostate preservation by combined external beam and HDR brachytherapy in nodal negative prostate cancer. Strahlenther Onkol 1999; 175 Suppl 2:87-8
27. Hilaris B, Fuks Z, Nori D, al. e: Interstitial irradiation in prostatic cancer: Report of 10-year results, in Interventional Radiation Therapy Techniques/Brachytherapy. Edited by Rolf. Berlin, Springer-Verlag, 1991, p 235
28. Sylvester J, Blasko JC, Grimm P, Ragde H: Interstitial implantation techniques in prostate cancer. J Surg Oncol 1997; 66:65-75
29. Martinez A, Edmundson GK, Cox RS, Gunderson LL, Howes AE: Combination of external beam irradiation and multiple-site perineal applicator (MUPIT) for treatment of locally advanced or recurrent prostatic, anorectal, and gynecologic malignancies. Int J Radiat Oncol Biol Phys 1985; 11:391-8
30. Puthawala A, Syed A, Tansey L: Temporary iridium implant in the management of carcinoma of the prostate. Endocurie Hyper Oncol 1985; 1:25-33
31. Holm HH, Juul N, Pedersen JF, Hansen H, Stroyer I: Transperineal I-125odine seed implantation in prostatic cancer guided by transrectal ultrasonography. J Urol 1983; 130:283-6
32. Blasko JC, Radge H, Schumacher D: Transperineal Percutaneous Iodine-125 Implantation For Prostatic Carcinoma Using Transrectal Ultrasound and Template Guidance. Endocurietherapy Hyperthermia Oncol 1987; 3:131-139
33. Wallner K, Chiu-Tsao ST, Roy J, Arterbery VE, Whitmore W, Jain S, Minsky B, Russo P, Fuks Z: An improved method for computerized tomographyplanned transperineal 125iodine prostate implants. J Urol 1991; 146:90-5
34. Beyer DC, Priestley JB, Jr.: Biochemical disease-free survival following 125I prostate implantation. Int J Radiat Oncol Biol Phys 1997; 37:559-563
35. Grimm PD, Blasko JC, Ragde H: Ultrasound-guided transperineal implantation of Iodine-125 and Palladium-103 for the treatment of early-stage prostate cancer: technical concepts in planning, operative technique, and evaluation, in New Techniques in Prostate Surgery, vol 2. Edited by Schellhammer PF. Philadelphia, W.B. Saunders Co., 1994, pp 113-126
36. Tapen EM, Blasko JC, Grimm PD, Ragde H, Luse R, Clifford S, Sylvester J, Griffin TW: Reduction of radioactive seed embolization to the lung following prostate brachytherapy. Int J Radiat Oncol Biol Phys 1998; 42:1063-7
37. Willins J, Wallner K: CT-based dosimetry for transperineal I-125 prostate brachytherapy. Int J Radiat Oncol Biol Phys 1997; 39:347-53
38. Arterbery VE, Wallner K, Roy J, Fuks Z: Short-term morbidity from CTplanned transperineal I-125 prostate implants. Int J Radiat Oncol Biol Phys 1993; 25:661-7
39. Priestly JB, Jr., Beyer DC: Guided brachytherapy for treatment of confined prostate cancer. Urology 1992; 40:27-32
40. Stock RG, Stone NN, Wesson MF, DeWyngaert JK: A modified technique allowing interactive ultrasound-guided three- dimensional transperineal prostate implantation. Int J Radiat Oncol Biol Phys 1995; 32:219-25
41. D’Amico AV, Coleman CN: Role of interstitial radiotherapy in the management of clinically organ- confined prostate cancer: the jury is still out [see comments]. J Clin Oncol 1996; 14:304-15
42. Dattoli MJ, Wasserman SG, Koval JM, Sorace RA, Cash J, Wallner KE: Conformal brachytherapy boost to external beam irradiation for localized high risk prostate cancer. Int J Radiat Oncol Biol Phys 1995; 32, (Suppl):251. Abstract 1056
43. Nag S, Beyer D, Friedland J, Grimm P, Nath R: American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 1999; 44:789-99
44. Blasko JC, Ragde H, Luse RW, Sylvester JE, Cavanagh W, Grimm PD: Should brachytherapy be considered a therapeutic option in localized prostate cancer? Urol Clin North Am 1996; 23:633-649
45. Wallner K, Blasko J, Dattoli M: Prostate Brachytherapy Made Complicated. Seattle, Smart Medicine Press, 1997
46. Stock RG, Stone NN, Tabert A, Iannuzzi C, DeWyngaert JK: A dose-response study for I-125 prostate implants. Int J Radiat Oncol Biol Phys 1998; 41:101-8
47. Potters L, Cao Y, Calugaru E, Torre T, Fearn P, Wang XH: A comprehensive review of CT-based dosimetry parameters and biochemical control in patients treated with permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2001; 50:605-14.
48. Partin AW, Yoo J, Carter HB, Pearson JD, Chan DW, Epstein JI, Walsh PC: The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer [see comments]. J Urol 1993; 150:110-4
49. Partin AW, Kattan MW, Subong EN, Walsh PC, Wojno KJ, Oesterling JE, Scardino PT, Pearson JD: Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update [see comments] [published erratum appears in JAMA 1997 Jul 9;278(2):118]. Jama 1997; 277:1445-51
50. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD: Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium. Urology 2001; 58:843-8.
51. Davis BJ, Pisansky TM, Wilson TM, Rothenberg HJ, Pacelli A, Hillman DW, Sargent DJ, Bostwick DG: The radial distance of extraprostatic extension of prostate carcinoma: implications for prostate brachytherapy. Cancer 1999; 85:2630-7
52. Sohayda C, Kupelian PA, Ciezki J, Levin HJ, Klein EA: Extent of extracapsular extension: implications for planning for conformal radiotherapy and brachytherapy. Int J Radiat Oncol Phys 1998; 42, (Suppl):132. Abstract 16
53. Epstein JI, Carmichael MJ, Pizov G, Walsh PC: Influence of capsular penetration on progression following radical prostatectomy: a study of 196 cases with long-term followup. J Urol 1993; 150:135-41
54. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A: Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280:969-974
55. Blasko JC, Grimm PD, Ragde H: External beam irradiation with palladium- 103 implantation for prostate carcinoma. Int J Radiat Oncol Biol Phys 1994; 30 (Suppl):219
56.Wallner K: I-125 brachytherapy for early stage prostate cancer: new techniques may achieve better results. Oncology 1991; 5:115-126
57.Wallner K, Roy J, Harrison L: Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Clin Oncol 1996; 14:449-453
58. Schellhammer PF, Ladaga LE, El-Mahdi A: Histological characteristics of prostatic biopsies after 125iodine implantation. J Urol 1980; 123:700-5
59. Prestidge BR, Hoak DC, Grimm PD, Ragde H, Cavanagh W, Blasko JC: Posttreatment biopsy results following interstitial brachytherapy in early-stage prostate cancer. Int J Radiat Oncol Biol Phys 1997; 37:31-9
60. Grimm P, Blasko J, Sylsvester JE, Meier RM, Cavanagh W: 10-year biochemical (prostate-specific antigen) control of prostate cancer with I-125 brachytherapy. int J Radiat Oncol Biol Phys 2001; 51:31-40
61. Merrick GS, Butler WM, Galbreath RW, Lief JH: Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer. Int J Radiat Oncol Biol Phys 2001; 51:41-8.
62. Roy JN, Ling CC, Wallner KE, Anderson LL: Determining source strength and source distribution for a transperineal prostate implant. Endocurie/Hyperthermia Oncology 1996; 12:35-41
63. Lederman GS, Cavanagh W, Albert PS, Israeli R, Lessing J, Savino M, Volpicella F: Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy. Int J Radiat Oncol Biol Phys 2001; 49:1297-3003.
64. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Fondurulia J, Chen MH, Tomaszewski JE, Renshaw AA, Wein A, Richie JP: Clinical utility of the percentage of positive prostate biopsies in defining biochemical outcome after radical prostatectomy for patients with clinically localized prostate cancer [see comments]. J Clin Oncol 2000; 18:1164-72
65. Grimm P: Clinical results of prostate brachytherapy, in Radiological Society of North America Annual Meeting. Chicago, IL, 1998
66. Beyer DC, Priestley JB: Biochemical disease-free survival following I-125 prostate implantation. Int J Radiat Oncol Biol Phys 1995; 32, (Suppl):254. Abstract 1062
67.Wallner K, Roy J, Zelefsky M, Fuks Z, Harrison L: Short-term freedom from disease progression after I-125 prostate implantation. Int J Radiat Oncol Biol Phys 1994; 30:405-9
68. Kaye KW, Olson DJ, Payne JT: Detailed preliminary analysis of 125iodine implantation for localized prostate cancer using percutaneous approach. J Urol 1995; 153:1020-1025
69. Kupelian P, Katcher J, Levin H, Zippe C, Klein E: Correlation of clinical and pathologic factors with rising prostate- specific antigen profiles after radical prostatectomy alone for clinically localized prostate cancer. Urology 1996; 48:249-260
70. Sylvester J: Modern permanent prostate brachytherapy, in American Society of Therapeutic Radiology and Oncology 43rd Annual Meeting. San Francisco, 2001
71. Blasko JC, Ragde H, Grimm PD: Transperineal ultrasound-guided implantation of the prostate: morbidity and complications. Scand J Urol Nephrol Suppl 1991; 137:113-118
72. Talcott JA, Clark JA, Stark PC, Mitchell SP: Long-term treatment related complications of brachytherapy for early prostate cancer: a survey of patients previously treated. J Urol 2001; 166:494-9.
73. Wallner K, Lee H, Wasserman S, Dattoli M: Low risk of urinary incontinence following prostate brachytherapy in patients with a prior transurethral prostate resection. Int J Radiat Oncol Biol Phys 1997; 37:565-9
74. Stone NN, Ratnow ER, Stock RG: Prior transurethral resection does not increase morbidity following real-time ultrasound-guided prostate seed implantation. Techniques in Urology 2000; 6:123-7
75. Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES, Reuter VE, Fair WR, Ling CC, Fuks Z: Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998; 41:491-500
76. Kupelian PA, Mohan DS, Lyons J, Klein EA, Reddy CA: Higher than standard radiation doses (> or =72 Gy) with or without androgen deprivation in the treatment of localized prostate cancer. Int J Radiat Oncol Biol Phys 2000; 46:567-74.
77. Hanks GE, Hanlon AL, Schultheiss TE, Pinover WH, Movsas B, Epstein BE, Hunt MA: Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions. Int J Radiat Oncol Biol Phys 1998; 41:501-10.
78. Kupelian PA, Reddy CA, Klein CA: Factors associated with biochemical relaps after either low-dose external beam radiation, high-dose external beam radiation, or radical prostatectomy for localized prostate cancer: 8 year results. Int. J. Radiat..Oncol. Biol. Phys. 1999; 45 (Suppl.):219, Abstract 140
79. Pollack A, Zagars GK: External beam radiotherapy dose response of prostate cancer. Int J Radiat Oncol Biol Phys 1997; 39:1011-8
80. Prestidge BR, Bice WS, Prete JJ, al. e: A dose-volume analysis of permanent transperineal prostate brachytherapy. Int J Radiat Oncol Biol Phys 1997; 39 (Suppl):289
81. Ling CC: Permanent implants using Au-198, Pd-103 and I-125: radiobiological considerations based on the linear quadratic model. Int J Radiat Oncol Biol Phys 1992; 23:81-7
82. Nag S, Pak V, Blasko J, al. e: Prostate brachytherapy, in Principles and practices of brachytherapy. Edited by Nag S. Armonk, Futura Publishing, 1997, pp 421-440
83. Hastak SM, Gammelgaard J, Holm HH: Transrectal ultrasonic volume determination of the prostate–a preoperative and postoperative study. J Urol 1982; 127:1115-8
84. Paulson DF: Impact of radical prostatectomy in the management of clinically localized disease. J Urol 1994; 152:1826-30
85. Prestidge BR, Prete JJ, Buchholz TA, Friedland JL, Stock RG, Grimm PD, Bice WS: A survey of current clinical practice of permanent prostate brachytherapy in the United States. Int J Radiat Oncol Biol Phys 1998; 40:461-5
86. Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, Reuter VE, Venkatraman ES, Leibel SA: High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 2001; 166:876-81.
87. Hanks GE, Hanlon AL, Pinover WH, Horwitz EM, Price RA, Schultheiss T: Dose selection for prostate cancer patients based on dose comparison and dose response studies. Int J Radiat Oncol Biol Phys 2000; 46:823-832
88. Pollack A, Smith LG, von Eschenbach AC: External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era. Int J Radiat Oncol Biol Phys 2000; 48:507-12.
89. Nag S, Orton C, Young D, Erickson B: The American brachytherapy society survey of brachytherapy practice for carcinoma of the cervix in the United States. Gynecol Oncol 1999; 73:111-8
90. Nag S, Scaperoth DD, Badalament R, Hall SA, Burgers J: Transperineal palladium 103 prostate brachytherapy: analysis of morbidity and seed migration. Urology 1995; 45:87-92
91. Grimm PD, Blasko JC, Ragde H, Sylvester J, Clarke D: Does brachytherapy have a role in the treatment of prostate cancer? Hematol Oncol Clin North Am 1996; 10:653-673
92. Ling CC, Li WX, Anderson LL: The relative biological effectiveness of I-125 and Pd-103. Int J Radiat Oncol Biol Phys 1995; 32:373-378
93. Haustermans KM, Hofland I, Van Poppel H, Oyen R, Van de Voorde W, Begg AC, Fowler JF: Cell kinetic measurements in prostate cancer. Int J Radiat Oncol Biol Phys 1997; 37:1067-70
94. Chu C, Potters L, Ashley R, Waldbaum R, Leibel S: Isotope selection for patients undergoing prostate brachytherapy. Int J Radiat Oncol Phys 1998; 42 (Suppl):134. Abstract 19
95.Wallner K: Personal communication, 2001
96. Merrick G: Personal Communication, 2001
97. First Advanced Prostate Brachytherapy Workshop, Seattle Prostate Institute, Seattle, Washington, May 15-16, 1998
98. Sylvester JE, Grimm PD, Blasko JC: Urethral visualization during transrectal ultrasound guided interstitial implantation for early stage prostate cancer, in Annual Meeting of the Radiologican Society of North America. Chicago, IL, 1998
99.Wallner K, Roy J, Zelefsky M, Fuks Z, Harrison L: Fluoroscopic visualization of the prostatic urethra to guide transperineal prostate implantation. Int. J. Radiat. Oncol. Biol. Phys 1994; 29:863-867
100. Prostate brachytherapy seeds to not expose family members to high levels of radiation. Oncology News International 2001; 10
101. Gomella LG, Lotfi MA, Reagan GN: Laboratory parameters following contact laser ablation of the prostate for benign prostatic hypertrophy. Tech Urol 1995; 1:168-71
102. Hricak H, Jeffrey RB, Dooms GC, Tanagho EA: Evaluation of prostate size: a comparison of ultrasound and magnetic resonance imaging. Urol Radiol 1987; 9:1-8
103. Corn BW, Hanks GE, Schultheiss TE, Hunt MA, Lee WR, Coia LR: Conformal treatment of prostate cancer with improved targeting: superior prostate-specific antigen response compared to standard treatment [see comments]. Int J Radiat Oncol Biol Phys 1995; 32:325-30
104. Waterman FM, Yue N, Reisinger S, Dicker A, Corn BW: Effect of edema on the post-implant dosimetry of an I-125 prostate implant: a case study. Int J Radiat Oncol Biol Phys 1997; 38:335-9
105. Prestidge BR, Bice WS, Kiefer EJ, Prete JJ: Timing of computed tomographybased postimplant assessment following permanent transperineal prostate brachytherapy [see comments]. Int J Radiat Oncol Biol Phys 1998; 40:1111-5
106. Kaye KW, Olson DJ, Lightner DJ, Payne JT: Improved technique for prostate seed implantation: combined ultrasond and fluoroscopic guidance. J. Endourology 1992; 6:61-66
107. Ragde H, Blasko J, Schumacher D, Grimm P: Use of transrectal ultrasound in transperineal I-125 seeding for prostate cancer: methodology. J Endourol 1989; 3:209-218
108. Roy JN, Wallner KE, Chiu-Tsao ST, Anderson LL, Ling CC: CT-based optimized planning for transperineal prostate implant with customized template. Int J Radiat Oncol Biol Phys 1991; 21:483-9
109. Stock RG, Stone NN, DeWyngaert JK, Lavagnini P, Unger PD: Prostate specific antigen findings and biopsy results following interactive ultrasound guided transperineal brachytherapy for early stage prostate carcinoma. Cancer 1996; 77:2386-92
110. Merrick GS, Wallner K, Butler WM, Galbreath RW, Lief JH, Benson ML: A comparison of radiation dose to the bulb of the penis in men with and without prostate brachytherapy-induced erectile dysfunction. Int J Radiat Oncol Biol Phys 2001; 50:597-604.
111. Blasko JC, Grimm PD, Ragde H: 6 and 7 year results of permanent seed implantation, in Transperineal Brachytherapy: Into the Mainstream. Seattle, WA, Pacific NW Cancer Foundation, 1995
112. Grier D: Complications of Permanent Seed Implantation. J Brachytherapy Int 2001; 17:205-210
113. Sylsvester JE, Grimm P, Blasko J, Meier RM, Heaney CT, Cavanagh W: Transperineal permanent brachytherapy for local recurrence following external beam radiation for early-stage prostate cancer. J Brachytherapy Intl 2001; 17:181-188
114. Sylvester J: Modern Permanent Prostate Brachytherapy, in American Society of Therapeutic Radiology and Oncology. San Francisco, 2001
115. Meier R, in Second Advanced Prostate Brachytherapy Workshop. Seattle, WA, Seattle Prostate Institute, 1999
116. Stock RG, Stone NN, DeWyngaert JK: PSA Findings and Biopsy Results Following Interactive Ultrasound Guided Transperineal Brachytherapy for Early Stage Prostate Cancer, in Proceedings of the American Radium Society 78th Annual Meeting. Paris, France, 1995, p 58
117. Lee WR, Hall MC, McQuellon RP, Case LD, McCullough DL: 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; 51:614-23.
118. Davis JW, Kuban DA, Lynch DF, Schellhammer PF: Quality of life after treatment for localized prostate cancer: differences based on treatment modality. J Urol 2001; 166:947-52.
119. Snyder K, Stock R, Hong S, Lo Y, Stone N: Defining the risk of developing grade 2 proctitis following 125I prostate brachytherapy using a rectal dosevolume histogram analysis. Int j Radiat Oncol Biol Phys 2001; 50:335-341
120. Blasko JC, Grimm PD, Sylvester JE, Badiozamani KR, Hoak D, Cavanagh W: Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 2000; 46:839-850
121. Ragde H, Blasko J, Grimm P: Complications of permanent seed implantation, in Transperineal Brachytherapy: into the mainstream. Seattle, WA, Pacific NW Cancer Foundation, 1995
122. Amling C, Bergstralh E, Blute M, Slezak J, Zincke H: Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol 2001; 165:1146-1151
123. Oesterling JE, Chan DW, Epstein JI, Kimball AW, Jr., Bruzek DJ, Rock RC, Brendler CB, Walsh PC: Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy. J Urol 1988; 139:766-772
124. Cavanagh W: Seattle Prostate Institute, 2002
125. Kupelian PA, Katcher J, Levin HS, Klein EA: Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy. Int J Radiat Oncol Biol Phys 1997; 37:1043-52
126. Han M, Pound CR, Potter SR, Partin AW, Epstein JI, Walsh PC: Isolated local recurrence is rare after radical prostatectomy in men with Gleason 7 prostate cancer and positive surgical margins: therapeutic implications. J Urol 2001; 165:864-6.
127. Steinberg D, Sauvageot J, Piantadosi S, Epstein J: Correlation of prostate needle biopsy and radical prostatectomy gleason grade in academic and community settings. Amer J Surg Pathol 1997; 21:566-576
128. Epstein J: Gleason score 2-4 adenocarcinoma of the prostate on needle biopsy. Amer J Surg Pathol 2000; 24:477-78
129. Stone NN, Stock RG: Prostate brachytherapy: Treatment strategies. J Urol 1999; 162:421-6
130. Blasko JC, Grimm PD, Sylsvester JE, Cavanagh W: The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma. Radiotherapy & Oncology 2000; 57:273-8
131. Polascik TJ, Pound CR, DeWeese TL, Walsh PC: Comparison of radical prostatectomy and iodine 125 interstitial radiotherapy for the treatment of clinically localized prostate cancer: a 7-year biochemical (PSA) progression analysis [see comments]. Urology 1998; 51:884-9; discussion 889-90
132. Iczkowski KA, Bostwick DG: The pathologist as optimist: cancer grade deflation in prostatic needle biopsies [editorial]. Am J Surg Pathol 1998; 22:1169-70
133. Allsbrook WC, Jr., Mangold KA, Johnson MH, Lane RB, Lane CG, Amin MB, Bostwick DG, Humphrey PA, Jones EC, Reuter VE, Sakr W, Sesterhenn IA, Troncoso P, Wheeler TM, Epstein JI: Interobserver reproducibility of Gleason grading of prostatic carcinoma: urologic pathologists. Hum Pathol 2001; 32:74-80.
134. Epstein JI, Pizov G, Walsh PC: Correlation of pathologic findings with progression after radical retropubic prostatectomy. Cancer 71:3582-93, 1993
135. Terk M, Stock R, Stone, N. Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate. J Urol. 160:1379-1382. 1998
136.Crook J. McLean M. Catton C. et al. Factors influencing risk of acute urinary retention after TRUS-guided permanent prostate seed implantation. Int J Radiation Oncology Biol Phys. 52:453-460. 2002
137. Blasko JC, Grimm PD, Sylvester JE, et al: Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 46:839-850, 2000
138. Grimm P, Blasko J, Sylsvester JE, et al: 10-year biochemical (prostatespecific antigen) control of prostate cancer with 125-I brachytherapy. Int J Radiat Oncol Biol Phys 51:31-40, 2001