October 31, 2014

   A Publication of the James Buchanan Brady
   Urological Institute Johns Hopkins Medical Institutions

Volume V, Winter 2000
Seeds Vs. Surgery: How Good is Interstitial Brachytherapy?

Part of the problem, is that "prostate cancer is a multi-focal disease. At the time of radical prostatectomy, the average number of individual cancers within the prostate is seven -- seven separate cancers in one prostate. This indicates that in order to cure prostate cancer, you can't risk leaving any cells behind. You have to eliminate the entire prostate."


Interstitial radiation seeds are like little grenades, inserted directly into a prostate tumor. In theory, each radioactive seed blasts a targeted area of tissue, ultimately destroying the prostate. In practice, however, it hasn't been that simple: In the 1960s and 1970s, doctors used a "freehand" technique, placing the seeds during open surgery. The coverage was unevensome of the target tissue was obliterated, but other tissue was left unscathed -- and the procedure's ability to control cancer ranked a distant third behind radical prostatectomy and external-beam radiation. At 10 years after seed implantation, overall about 90 percent of men had a detectable PSA level. However, even in the most favorable subset of patients, men with the smallest tumors, the PSA level remained low in only 60 percent of patients. The procedure wasn't well-suited for men with large or high-grade tumors; also, because most implantation regimens focused only on the tissue within the prostate and ignored the seminal vesicles and tissue outside it, the seeds were unable to reach cancer that had spread locally. Finally, the seeds did cause side effects, particularly urinary incontinence, in men who needed a TURP (transurethral resection of the prostate) to relieve prostate obstruction following treatment.

The ideal patient for radioactive seeds was (and still is) a man who is also an ideal candidate for radical prostatectomy and external-beam radiation therapy. Because both of these treatments can cure prostate cancer in men with localized disease, doctors faced a question: Is interstitial brachytherapy as good, or better, than either of those treatments? The answer 20 years ago was a definite no. Today, the answer is somewhat more difficult, because the treatment has improved: Instead of the old "free-hand" technique, doctors now use a sophisticated, high-tech approach, guided by ultrasound and CT scans, working from a custom-designed grid, or template, for each patient.

Is it better? Some doctors seem to think so. The most widely quoted data on interstitial brachytherapy come from The Pacific Northwest Cancer Foundation, a small hospital in Seattle. In 1997, doctors at this hospital reported that at seven years after the procedure, 79 percent of their patients (who had small, low-grade tumors and a small prostate) had a PSA of less than 0.5. However, these men had very small tumors.

How can doctors and patients evaluate these results? Are they really remarkable? How well do they really remarkable? How well do they hold up in comparison with the "gold standard" treatment for prostate cancer, radical prostatectomy? Urologist-in-chief Patrick C. Walsh, M.D., wondered how these men would have fared if they had undergone surgery instead.

To answer this question, a recent Johns Hopkins study examined the outcome in 76 comparable patients (matched for Gleason score and clinical stage to the patients in the Seattle study) who underwent radical prostatectomy. At seven years, 98 percent of the men who underwent radical prostatectomy had a PSA of less than 0.2 More recently, the Seattle group reported that at 10 years after the procedure, the number of men with a PSA of less than 0.5 had dropped from 79 percent to 60 percent--the same results as those from the old, "free-hand" approach, which is now nearly universally considered to have been unsuccessful.

Why arern't the results better? Part of the problem, says Walsh, is that "prostate cancer is a multi-focal disease. At the time of radical prostatectomy, the average number of individual cancers within the prostate is seven -- seven separate cancers in one prostate. This indicates that in order to cure prostate cancer, you can't risk leaving any cells behind. You have to eliminate the entire prostate." Another problem with the Seattle group's reckoning is its standard of "cure." At Hopkins, men are considered cured only if they have an undetectable PSA -- below 0.1. "The brachytherapy results should be held to the same standard as those for radical prostatectomy, If PSA levels are higher than 0.2, it is clear that prostate tissue remains, which may contain cancer cells, or which may someday turn into cancer., You have to use a precise endpoint, and you have to follow patients over a long period of time, preferably 10 years or longer, to know whether or not you've cured the cancer."

Also troubling is the higher rate of side effects associated with the radioactive seeds. Investigators from the Pacific Northwest Cancer Foundation reported that following interstitial brachytherapy, 5.1 percent of patients were incontinent, and in 1.7 percent, the incontinence was so severe that the men required a urinary diversion-- attachment of a bag, worn under the clothes, to collect urine. Three other patients also required the urinary diversion procedure because of severe strictures or urinary retention.

What about radioactive seeds combine with external-beam therapy? This approach may prove more successful. Today, however, the jury is still out; this combined approach is still too new for long-term results. Recently, doctors at the Georgia Center for Prostate Cancer Research, using "ProstRcision" (brachytherapy plus external-beam radiotherapy), reported that their 10-year disease-free survival rates were comparable to the 10-year results after radical prostatectomy at Johns Hopkins.

Between 1984 and 1993, most men in this series were treated with open retropubic implantation of radioactive seeds, and all of these men underwent removal of the lymph nodes. But the Center only reported its results on the patients who had carncer-free lymph nodes; the Hopkins study does not exclude men who turned out to have cancer in the lymph nodes (about 7 percent of the men in this study).

At 10 years, the Georgia Center reported that about 65 percent of patients had PSA less than 0.5, and about 57 percent had a PSA of less than 0.2. Excluding men with positive lymph nodes, the Hopkins results indicate that 77 percent of patients who underwent radical prostatectomy during the same time period had PSA levels less than 0.2 -- a difference of 20 percent.

The Hopkins scientists involved in the study say these results--and the different levels of PSA used as endpoints -- "emphasize the need for caution" in interpreting the ability of radioactive seeds to control prostate cancer.

FURTHER READING
Thomas J. Polascik, Charles R. Pound,
Theodore L. DeWeese, and Patrick C. Walsh,
"Comparison of Radical Prostatectomy and Iodine
125 Interstitial Radiotherapy for the Treatment
of Clinical Localized Prostate Cancer- A 7-year
biochemical (PSA) Progression Analysis."
Urology, Vol. 51: 884-890, 1998.
 

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