CHICAGO--When physicians squared off on the issue of brachytherapy (interstitial radioactive seed placement) for prostate cancer at the Prostate Cancer Shootout II conference, the lines could not have been drawn more clearly.
Brachytherapy proponent John C. Blasko, MD, professor of radiation oncology, University of Washington School of Medicine, Seattle, said that "brachytherapy may be the simplest, least expensive, and best tolerated treatment available for early stage prostate cancer." For locally advanced disease, he said, "the addition of brachytherapy provides high intraprostate radiation doses, which results in improved local control but less extraprostate tissue toxicity relative to external beam radiotherapy."
However, Jeffrey D. Forman, MD, professor of radiation oncology, Wayne State University, Detroit, said that brachytherapy is still unproved. Data on the procedure are based on short-term surrogate measures of effectiveness, such as positive biopsy rates and PSA levels, he said, so no clear survival advantage has been shown.
In addition, Dr. Forman said, the optimal candidates for brachytherapy have not been defined, the adequacy of seed implantation is highly variable, and correction of improperly placed radioactive seeds is difficult if not impossible.
In Dr. Blasko's experience, brachy-therapy has been equivalent to radical prostatectomy and external beam irradiation in the treatment of localized prostate cancer. He studied 320 consecutive men with clinically staged T1b or T2a-b disease, Gleason score of 2 to 7, initial median PSA level of 7.9 ng/mL, and average age of 70 years.
At seven years post-treatment, 97% of the men exhibited local control of the disease, 95% were free of distant metas-tases, 92% were free of prostate cancer, and 99% had not died from cancer.
Dr. Blasko's studies also have shown brachytherapy in combination with external beam irradiation to be superior to conventional external beam irradiation alone for men with locally advanced prostate cancer.
He studied 232 consecutive men with clinically staged prostate cancer ranging from stage T1b to T3. More than one third of patients (36%) had Gleason scores higher than 6. The mean PSA level was 15.6 ng/mL. At 96 months, 91% of the men had local control of their prostate cancer, 83% had no distant metastases, 74% were disease free, and 96% had not died of cancer.
However, Dr. Forman believes that Dr. Blasko's comparisons are "potentially misleading." The men in Dr. Blasko's studies had median PSA levels of 10 ng/mL, he said, while those in Southwestern Oncology Group trials of external beam irradiation had median PSA levels in excess of 40 ng/mL.
In addition, Dr. Forman said, "the patients with a large volume of extracapsular disease who do well with combination brachytherapy and external beam irradiation also would do well with high-dose external beam irradiation by itself, which may be cheaper."
Technical Difficulties
While there are technical problems with all forms of treatment for prostate cancer, they are well known and, for the most part, manageable. With brachy-therapy, however, Dr. Forman pointed out, "we are not even sure how to define an inadequate implant. Is it when the total amount of radiation is too small for the volume of the gland? Should we get post-treatment volume histograms to assess the adequacy of the implants? Should there be some minimum dose at the periphery of the gland for the implant to be judged adequate?"
Moreover, he said, there is wide disparity in performance of brachytherapy. Even in the best of hands, between 15% and 20% of interstitial seed implantations are not ideal, and in the community at large, many radiation oncologists are "on the upswing of the learning curve," Dr. Forman said.
Although it is possible to re-enter the prostate gland and place more radioactive seeds in areas that were missed the first time around, few radiation oncolo-gists have the ability to do so, he said.
And, he asked, what can be done if seeds deliver too much radiation to an area that is not affected by prostate cancer? Dr. Forman described one patient who received a dose of 25,000 rads along the anterior rectal wall when radiation oncologists overloaded seed placement on the right side of the gland where palpable nodules had been detected. Such situations cannot be corrected "because we can't take the seeds back," he said.
Nevertheless, brachytherapy was the overwhelming choice among members of the conference audience for a hypothetical 62-year-old man with a history of hypertension, diabetes, and myocardial infarction diagnosed with stage T2a, Gleason 3 plus 3 adenocarcinoma of the prostate, with a PSA of 6 ng/mL and cancer present in one of six cores on the initial biopsy. Brachytherapy was the choice of 56% of the audience while 25% chose radical prostatectomy, 17% external beam irradiation, and 1% each watchful waiting and cryosurgery.
