Is it better to use radiation as a salvage therapy than as an adjuvant therapy after radical prostatectomy?
The question of whether to administer radiation immediately after radical prostatectomy or to wait for a detectable prostate-specific antigen level is mostly an issue in patients with positive surgical margins.
The presence of positive margins is an important risk factor for biochemical relapse of prostate cancer. In a recent study, patients with extracapsular extension were significantly less likely to be free from biochemical relapse if they had positive margins than if they had negative margins (J. Urol. 1995;154:1818-24).
The role of surgical margins in determining progression-free probability is also shown by the Memorial Sloan-Kettering Cancer Center nomogram. According to the nomogram, a postradical prostatectomy patient with a pretreatment PSA of 10 ng/mL, established prostate capsule invasion, and a pathology Gleason score of 7 has a 7-year progression-free probability of 65%; this declines to 25% if positive surgical margins are added to the calculation.
Salvage, or "rescue," radiation therapy works only if you give it. A recent study clearly showed that salvage therapy was given to only a small percentage of patients with biochemical failure. According to this study, data on 303 radical prostatectomy patients in the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) national longitudinal registry who had biochemical failure defined by a PSA of 0.2 ng/mL or higher on two occasions showed that of 102 men who received a second treatment, only 43% had radiation therapy and 57% had androgen deprivation. (J. Urol. 2004;171:215-9).
Salvage radiation is effective when it is given relatively early after biochemical failure. The probability of being free from relapse afterward depends on the PSA level at the time the radiation is given.
In a series of about 1,100 patients with more than 12 months of follow-up, the probability of biochemical failure was 45% for a group of 307 patients who were relatively common candidates for salvage radiation therapy, with PSA values ranging from 0.2 to 0.99 ng/mL, negative seminal vesicle invasion, and a Gleason score of 2-7.
Biochemical failure was much more common for patients with more advanced disease.
In a retrospective study of 501 patients who received salvage radiation therapy when their disease recurred following radical prostatectomy, 50% of patients experienced disease progression after salvage therapy. But overall, the patients had a 4-year progression-free probability of 45% (JAMA 2004;291:1325-32).
PSA level is a great marker for early disease recurrence. If patients are referred early after biochemical failure, the results of radiation therapy are pretty good. Only the highest-risk patients who can be identified postoperatively probably should receive adjuvant radiation therapy.
Howard M. Sandler, M.D., is a professor of radiation oncology and urology at the University of Michigan, Ann Arbor.
The fact that 50% or more of pathologic high-risk patients experience biochemical failure within 5-10 years after radical prostatectomy provides the rationale for using adjuvant radiation therapy. About half of these high-risk patients develop distant metastases within 7 years, although this may vary with different factors such as PSA doubling time.
Adjuvant radiation therapy is defined as treatment for patients with an undetectable PSA after radical prostatectomy. External beam radiation is typically given within 6 months but may be extended up to 1 year, depending on the level of urinary continence. Salvage radiation therapy patients are typically considered to be those who have a persistently detectable postoperative PSA or a delayed rise in PSA levels from formerly undetectable levels.
Freedom from biochemical failure is about twice as high with adjuvant radiation as with radical prostatectomy alone. Adjuvant radiation was reported to be more effective in improving the probability of biochemical failure than radical prostatectomy alone in virtually all series comparing the two strategies. In one randomized trial, patients who received adjuvant radiation had 20% greater freedom from biochemical failure than did those who received radical prostatectomy alone, although there was no benefit of adjuvant radiation on overall survival.
In studies comparing adjuvant and salvage strategies, adjuvant therapy consistently has a higher probability of freedom from biochemical failure than does salvage radiation therapy, although these retrospective comparisons are flawed because we do not know what selection biases may have occurred. One of the problems is that often freedom from biochemical failure is calculated from the time that radiation is given, which may bias the results in favor of adjuvant radiation unless the calculation is performed from the time of radical prostatectomy.
The morbidity associated with adjuvant radiation therapy is relatively low. The typical dose of adjuvant radiation (60-64 Gy) is lower than that given to patients treated for salvage (64-68 Gy).
Patients with T1-2 disease who have positive surgical margins, or those with seminal vesicle involvement, will stand to benefit from adjuvant radiation therapy.
One study reported that in patients with positive surgical margins who were treated with adjuvant radiation therapy after radical prostatectomy, only 6% of those with positive surgical margins and without seminal vesicle involvement had biochemical failure after 5 years, compared with 35% of those who had seminal vesicle involvement (Int. J. Radiat. Oncol. Biol. Phys. 2003;56:755-63).
There is no clear sign that we are curing anyone with salvage radiation therapy. In a multicenter study of more than 1,100 patients, about 80% of patients who received salvage therapy had biochemical failure after 10 years, even if a less strict definition of biochemical failure was used (PSA 0.4 ng/mL or higher after nadir).
Alan Pollack, M.D., is chairman of radiation oncology at the Fox Chase Cancer Center, Philadelphia.
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|Title Annotation:||PRO & CON|
|Author:||Sandler, Howard M.; Pollack, Alan|
|Publication:||Internal Medicine News|
|Date:||May 1, 2005|
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