Interview of the Month

February, 1998

In an effort to help you make an informed decision as to the appropriate treatment for your particular situation, this month we speak with Dr. Haakon Ragde from the Northwest Hospital in Seattle who has been a pioneer in the procedure.

Dr. Ragde, please give us some background on the use of radiation in the treatment of prostate cancer through to your current application of prostate brachytherapy.

HR: I'd like to share one of my favorite quotes on this subject. In 1903, Alexander Graham Bell wrote: "....there is no reason why a tiny fragment of radium sealed in a fine glass tube should not be inserted into the very heart of the cancer thus acting directly upon the diseased material. Would it not be worthwhile making experiments along this line?"

Prostate brachytherapy is the oldest radiation therapy technique for the treatment of prostate cancer. Early approaches around the turn of the century included radium inserted free hand into the prostate through needles and left in place for a specified time.

In 1983, Hans Henrik Holm, M.D. at the University of Copenhagen, Denmark was the first physician to perform the "closed" or "non-surgical" implant method using a rectal ultrasound probe to visualize the prostate. In 1984, I observed the procedure in Denmark and returned to Northwest Hospital in Seattle to develop patient selection guidelines and methods to use here in the States. Over the last 12 years I have performed over 2,000 ultrasonically guided radioisotope implants for the treatment of prostate cancer and have published research data that shows efficacy results after 7 and 8 years equal to the best surgical prostatectomy results, with less cost (as most have been done as outpatients) and fewer complications.

VS: While you have noted that you performed the first ultrasound-guided seed implantation back in 1985, the procedure is actually much older than that. Please identify for us the major differences.

HR: In the early 1970's at Memorial Sloan-Kettering Cancer Center in New York City Drs. Whitmore and Hilaris were the first physicians to perform prostate seed implants. They used open surgery to implant the seeds freehand into the exposed prostate gland. This generally resulted in an inaccurate and uneven implant. The consequence was a high rate of local failure, i.e. the cancer persisted in the gland. Advances in external beam therapy and radical prostatectomy techniques of that time period eventually led to a waning interest in brachytherapy as a treatment for prostate cancer.

During the 1980's several technological advances became available that would remedy the shortcomings of the open implant technique. Dr. Hiroki Watanabe, Chairman of Urology at Japan's Kyoto Prefecture University of Medicine, introduced an incremental method of measuring the prostate volume using transrectal ultrasound. Then, as mentioned previously, Dr. Hans Henrik Holm of the University of Copenhagen, introduced the landmark technique of implanting the prostate with radioisotopes transperineally under transrectal ultrasound and template guidance. Understanding the prostate cancer's presentation and disease progression improved, and this led to more appropriate patient selection for curative therapy. At the same time post-treatment PSA (prostate specific antigen) levels and prostate biopsies led to improved evaluation of treatment results. New radioisotopes became available. In addition, sophisticated radiation treatment planning computers became available for quickly determining seed numbers, activity and selection of seed locations for optimal results.

These improvements have led to increasing use of seed implantation as a minimally invasive technique to treat localized prostate cancer. For example, in 1994 only 8% of urologists in the United States performed the seed implant procedure; while in 1997, 16% used the technique. That number is expected to double again in 1998.

VS: We have heard of ultrasound-guided as well as CT-guided procedures. Whatís the difference and is there a measurable effectiveness for each?

 HR: Most urologists today use the ultrasound technique. Although the CT guided procedure continues to be used in isolated centers, visualization of the prostate is far more accurate with transrectal ultrasound.

VS: Assume that Iím a patient diagnosed with Pca and Iím considering seed implants. Take me through the procedures that you utilize in confirming diagnosis and through the actual treatment process.

 HR: At Northwest Hospital we review the clinical records - the pre-treatment PSA, Gleason scores; perform a careful physical exam and transrectal ultrasound. We review the biopsy slides,as well as a proprietary technique of evaluating new blood vessel formation around the tumor, to get a reasonable assurance that the cancer is confined to the prostate. Additional studies are ordered as necessary and all appropriate treatment options are discussed with the patient. Though Partin tables are often used in determining likelihood of capsular containment with radical prostatectomy surgery, we have not found them to be as reliable in radiation procedures.

If seed implantation is chosen as the appropriate treatment therapy, the next step is the prostate volume study which is done by transrectal ultrasound in the physician's office. The volume study results in a geometric map, the parameters of which form the basis for the individual treatment plan. The treatment plan is developed using a computer to construct a three dimensional model of the prostate pinpointing the placement of each seed so that the cancerous prostate is effectively radiated and the adjacent healthy tissue spared from radiation injury.

The procedure itself is done as a "non-surgical" or "closed" technique in an outpatient hospital setting by a urologist and assisted by a radiation oncologist. Spinal anesthesia is administered and the needles containing the seeds are inserted through the perineum under ultrasound visualization using the individual treatment plan. Once the needle is in the correct position, it is slowly withdrawn ejecting the seeds into the computer designated positions in the prostate. When the implant is completed proper placement of the seeds is verified by taking a CT scan of the prostate. The implant procedure takes about an hour and the patient returns home the same day. Short term side effects may consist of urinary frequency and possibly some burning on voiding. This is not unusual after the implant and is caused by the radiation to the prostate. These side effects may last from a few days to several weeks.

VS: There has been a lot of discussion on the merits of Iodine versus Palladium implants. Please comment on the pros and cons of each.

HR: Both types of radioisotopes are contained in tiny titanium casings which the body tolerates on a long term basis. Both isotopes give off low energy radiation, most of which is released over a short time period - Palladium: 3 months; Iodine: 6 months - the main difference is in the half-life and rate of radiation delivery. Although there is no clinical evidence that one is more effective than the other, investigators often use Iodine-125 for the lower Gleason grade cancers and Palladium-103 for the higher grades.

VS: One of the potential, and not always discussed, side-effects of radiation therapy is delayed incontinence and/or impotence. Does seed implant therapy improve the odds against these events occurring?

HR: Long term side effects such as incontinence and impotence occur less frequently after the radioactive seed implant procedure than after surgical removal of the prostate or traditional external beam radiation treatment. There is generally no incontinence following seed implantation if the patient has not had a previous transurethral prostate resection (TURP). A small percentage of patients having had that operation prior to seed implantation may suffer mild incontinence which should dissipate with the half-life of the radiation. Impotence rates after seed implants often correlate with the age of the patient. If fully potent prior to the implant, impotence is rare below the age of 60, less than 20% for ages between 60 and 70 years, and 35 to 50% above 70 years. It must be noted that all of these rates are lower than the incidence after surgical procedures.

VS: Again, a recent innovation is the use of hormonal therapy in conjunction with radiation to achieve a more effective ìcureî of the disease. How do you utilize hormonal or chemical therapies pre, post or in conjunction with seed implantation?

HR: One common use of hormones prior to seed implantation is to reduce the size of an overly enlarged prostate. There is also some evidence from studies using external beam therapy that pre-treatment with hormones may sensitize the prostate to radiation, resulting in a more favorable outcome.

VS: Please comment on the efficacy of "boost" therapy and whether it can enhance the effectiveness of brachytherapy.

HR: We use "combination therapy" - the use of external beam radiation with seed implants - depending upon the patient's presentation based on Gleason scores and disease staging.

VS: We are seeing a building concern over the use of aggressive screening techniques to identify potential Pca patients. The question arises as to whether its the screening or the aggressive treatment that may result after diagnosis that is at issue. Do you believe that everyone who is diagnosed with Pca is a candidate for radiation therapy?

HR: There are essentially four major treatment options for prostate cancer and, depending on the stage of the cancer, there are factors to help determine which option may be most appropriate. The patient needs to receive information and education on each option in order to make an informed decision. The patient selection criteria for implantation is similar to selecting patients for radical surgery: there must be strong evidence that the cancer is confined to the prostate.

VS: Itís noted in your press release that you were part of the team that discovered the PSA (Prostate Specific Antigen) test. How would you counsel our readers in its best uses?

HR: PSA is today the best marker available to us in medicine, both for diagnosis and follow-up after treatment. However, PSA is not an ideal marker. An ideal marker(s) should detect the cancers, identify the malignant potential and its stage on the progression pathway. Researchers at Northwest Hospital's Pacific Northwest Cancer Foundation are currently working on such a test. The American Cancer Society and the American Urological Association recommend that both the PSA test and the digital rectal exam (DRE) be offered annually beginning at age 50, and to younger men who are at high risk. Information should be provided to patients regarding potential risks and benefits of screening.

VS: We have heard of instances of "bad" implant procedures. How does a patient insure that the hospital or doctor is best qualified to do the procedure?

HR: There are a wide range of skills being seen today and, unfortunately, there are not yet standardized credential procedures in place. The key point to ascertain is how comfortable the physician is with ultrasound technique and how well can he/she visualize the prostate. Additional points for consideration are - Is the doctor capable of executing a total plan from pre to post treatment. How capable is the entire team: urologist, radiation oncologist, ultrasound technician, radiation physicist. Has the physician trained under a proctor for a certain number of procedures to insure proficiency in the technique.

VS: From where do you see new developments in Pca treatment modalities emanating?

HR: Significant research in prostate cancer is progressing in several institutions. This will give doctors a better understanding of the malignant process which in turn will lead to better methods of prevention and treatment. Researchers at Northwest Hospital's Pacific Northwest Cancer Foundation have several projects underway. One of the most exciting is a Phase II clinical trial with patients having a treatment (immunotherapy) that is based on eliciting and enhancing the body's own immune system to mount an effective anti-immune attack against prostate cancer in much the same manner as the body fights bacterial and viral infections.

In addition, our researchers are concentrating on discovering better diagnostic methods, less invasive curative treatment procedures and improved ways of following patients after treatment. One of the projects that researchers are working on is the development of a new prostate marker - Prostate Specific Membrane Antigen - that promises to have prognostic as well as diagnostic potential. They are also working on a standardization of the PSA blood test and studies involving cell mappings of prostate cancer cells.

Publisher's Note: we will have detailed coverage of these projects in upcoming pages. 

VS: How can our readers obtain more information about Northwest Hospital or the Pacific Northwest Cancer Foundation?

 HR: Our toll-free patient information line is staffed by nurses with health information and physician referrals and can be reached at:

1. 888. NWHSeed

Our Web sites are:

http://www.prostatecancer.org

http://www.nwhospital.org

Or you can contact our Media and PR coordinator, Ms. Suzi Beerman, at:

phone: 206.633.4636

VS: Thank you very much, Dr. Ragde, for this informative session.

If you know of a story that should be told here, let us know via E-mail at:
vhsimons@prostate-online.org