Saturday, May 1, 2004

Incurable PCa? Consider Brachytherapy

Over the past decade, prostate brachytherapy has gained increasing popularity for the treatment of prostate cancer, especially in view of the favorable side-effect profile when compared to alternative therapies. The number of patients treated with this modality is now on par with both radical prostatectomy and full-course external beam radiotherapy (EBRT) as the primary treatment for early stage prostate cancer.
Despite entering the mainstream, patients diagnosed with intermediate and locally advanced high-risk prostate cancer are often discouraged from undergoing brachytherapy. Instead, their physicians frequently recommend radical prostatectomy, full-course external radiation with or without hormones, or hormones alone.

In contrast to these practices, prostate brachytherapy can be an effective treatment option for these patients. A recent report in Cancer (2003; 97:979-983) demonstrates patients undergoing palladium 103 (Pd-103) brachytherapy (using TheraSeed, Theragenics Corp.), along with supplemental 3-D conformal EBRT, experience long-term outcomes superior to either radical prostatectomy or full-course EBRT – with fewer side effects.

These data are important because the vast majority of patients treated in the study were considered categorically incurable using any other treatment method, especially radical prostatectomy. Still, 79% of these patients remain cancer-free after 10 years without the subsequent need for hormonal therapy or chemotherapy.

Another advantage to radioactive implants vs. conventional therapy such as surgery is that it is an outpatient procedure. The patient returns to routine activities within a day or two, in contrast to weeks or even months to fully recover from a radical prostatectomy. Meanwhile, supplemental 3-D conformal EBRT is delivered on an outpatient basis, takes only minutes per day, and is associated with minimal symptoms. This reduced side effect profile can be attributed to the fact that the combined radiation/brachytherapy regimen requires an attenuated external beam dose when compared to full-course radiation regimens. The implants remain in place permanently and become inactive in approximately two to three months.

Physicians at Memorial Sloan-Kettering Cancer Center in New York first began using brachytherapy to treat prostate cancer in the early 1970’s, but had no way to position the seeds other than making an abdominal incision and exposing the prostate gland. They used needles to insert seeds one-by-one in a blood-filled field, making satisfactory seed distribution difficult. As a result, the implant procedure was not always successful and fell into disrepute.

However, the development of transrectal ultrasound imaging in the early 1980’s made it possible for physicians to use real-time imaging to guide seed-bearing needles into the prostate. Ultrasound-guided implants enabled physicians to more easily deposit radioactive seeds throughout the gland. Success rates improved dramatically. In the aforementioned report in Cancer, there is evidence supporting the use of this procedure in intermediate- and high-risk patients.

The study included 161 patients with advanced high-risk prostate cancer treated with brachytherapy between 1991 and 1995. Each patient had at least one of the three high-risk features (see Table); 77% had at least two or more high-risk features; and 66% had all three. The median patient age was 67.

All patients’ pre-treatment risk factors, except for staging, were independently reviewed by a team of physicians at the University of Washington in Seattle. Clinical staging using DRE was not included because it was subjective rather than objective (although 60% of patients had locally advanced T3 malignancies). Forty-three percent of patients had PSAs greater than 15; 70% had PSAs greater than 10, and 30% had elevated PAPs. Sixty-five percent of patients had Gleason scores greater than 7.

Patients were treated with Pd-103 seeds with a minimum brachytherapy dose of 8,000 to 9,000 centigray and supplemental external beam radiation doses of 4,140 to 5,040 centigray. None of the patients in the study received iodine (I-125) implants; the investigators prefer Pd-103 seeds because of their non-migrating concave shape and steep radiation fall-off.

Despite the aggressive nature of the cancers in this study group, no local recurrences were documented, even in patients with biochemical failure, all who underwent restaging prostatic biopsies. Ten years later, 79% of patients had PSAs of less than 0.2 ng/mL, which is considered disease-free by the strictest of biochemical measures. In addition, 70% of patients in the study retained potency. No patient experienced rectal ulceration and only one patient – who had undergone two transurethral surgeries – experienced low-volume stress incontinence.

The failure rate is not as significant as it may seem at first glance. Only two of the 20% of patients with rising PSAs following treatment died from their disease; the remainder were considered failures because a very low PSA nadir was chosen to denote cure, and they simply did not meet this strict post-treatment PSA criteria. In fact, many have stable PSAs between 0.3 and 4.0. They are functioning well, believe they are cured, and probably are cured. Finally, with the advent of Intensity Modulated Radiation Therapy (IMRT), coupled with Pd-103 seeds, even fewer side effects are anticipated.

Dr. Dattoli is a board-certified radiation oncologist, and a noted author and speaker in this complex field of medicine. He is currently physician-in-chief at the Dattoli Cancer Center & Brachytherapy Research Institute, Sarasota, Florida.
Renal & Urology News (Volume 3 No. 5) May 2004. © Renal & Urology News

Michael Dattoli, MD