Salvage Radiation Therapy After Biochemical Relapse Following Radical Prostatect
Salvage Radiation Therapy After Biochemical Relapse Following Radical Prostatectomy for Prostate Cancer
Abstract & Commentary
Synopsis: Once patients who have been treated for prostate cancer with radical prostatectomy develop a biochemical relapse optimal management is not well defined. In this series of 60 patients treated with radiation therapy to the prostatic bed, 50% of the patients normalized the PSA levels and those levels remained normal throughout a median follow-up time of three years.
Source: Do T, et al. Salvage radiotherapy for biochemical and clinical failures following radical prostatectomy. Cancer J Sci Am 1998;4:324-330.
The risk of prostate cancer recurrence after radical prostatectomy is influenced by the stage of disease defined at surgery (positive pelvic lymph nodes, seminal vesicle involvement, capsular penetration, and positive margins are poor risk factors) and tumor histologic grade (Gleason grade > 7 is a poor risk factor). In patients who do not have lymph node involvement and whose resection is complete (no positive margins), between 15% and 40% of patients will experience a biochemical relapse, defined as an increase in serum levels of prostate-specific antigen (PSA), within three years of surgery, depending on the Gleason grade and the presurgery PSA level.1 Biochemical relapse is generally followed by clinical relapse. Thus, intervention on the basis of increasing levels of PSA is routinely recommended, but no studies in this setting have demonstrated a survival benefit as yet.
Do and colleagues have performed a retrospective analysis of 60 patients with node-negative prostate cancer treated initially with radical prostatectomy; 83% of the patients had tumors of Gleason grade 4-7. Patients received salvage radiation therapy to the prostate bed after developing a rising PSA level with or without palpable nodules on digital rectal examination. All patients had a negative workup for metastatic disease that included bone scan, magnetic resonance imaging, computed tomography, and pelvic lymph node sampling. The radiation therapy was delivered with a four-field approach, opposing front and back and opposing lateral fields, to a total dose of 64.8 Gy in 1.8 Gy fractions.
With a mean follow-up time of three years, 40 of 60 patients (67%) are free of PSA progression. Thirty patients have PSA levels of 0. Do et al defined biochemical failure after salvage RT as two consecutive rises in PSA level after a PSA nadir had been reached or failure to reach a PSA nadir within three months after completion of radiation therapy. For the 20 patients with biochemical failure of therapy, the median time to detection of biochemical failure was 10 months. Half of the patients with biochemical evidence of disease progression developed metastatic disease.
Several factors predicted the success of the radiation therapy at controlling the disease. Notably, the presence of a palpable abnormality on digital rectal examination did NOT influence success. However, patients whose initial preoperative PSA levels were above 20 ng/dl, whose relapse PSA level was more than 1 ng/dl, or who had perineural invasion or seminal vesicle invasion in the surgical specimen all had a significantly lower likelihood of responding to salvage radiation therapy.
The radiation therapy was associated with some toxicity. Of the 27 patients who had recovered sexual potency after surgery, six (22%) have become impotent after radiation therapy. No rectal bleeding, urinary incontinence, or bone marrow suppression was noted.
Commentary
This series of patients makes some important points and fails to make some others. On the positive side, this experience documents that radiation therapy following radical prostatectomy is relatively safe. In addition, Do et al define patients who are unlikely to respond to radiation therapy at the time of biochemical relapse; these include patients with seminal vesicle involvement, perineural involvement, PSA levels of more than 20 ng/dl at diagnosis and more than 1 ng/dl at relapse.
However, the influence of salvage radiation therapy on long-term survival cannot be readily determined from this experience. Patients such as these with no node involvement have a five-year survival rate of 92%. Johansson and colleagues have shown that a group of untreated patients with early stage prostate cancer and Gleason grade 4-7 tumors has five-year survival of 92% and 10-year survival of 85%.2 Given the short follow-up (3 years) in this study, it is difficult to discern whether the therapy has made an effect on survival.
A second concern about the study is the definition of biochemical failure. Little consensus has emerged on this point; however, if one uses conventional criteria for response, it would be expected that PSA levels would be undetectable in patients who had responded completely to the therapy. Using this more stringent definition, only half of the treated patients responded to the therapy. Peschel has pointed out that statistically significant differences can be discerned in data that show no differences if one uses alternative definitions for biochemical failure.3 The definition of biochemical failure is important because that measureable end point is frequently used as a surrogate marker for overall survival. However, the relationship between PSA levels and survival is not completely defined and it cannot be assumed that an intervention that influences PSA levels will also influence survival.4
Thus, the question of the most appropriate intervention in a patient with prostate cancer who has undergone radical prostatectomy and now presents with a rising PSA level cannot be viewed as having been answered definitively. Radiation therapy in this setting appears to be relatively safe and may benefit some of the patients (perhaps half or more). However, the positive effect of radiation therapy on survival of such patients has not yet been demonstrated and is unlikely to be shown from retrospective analysis of selected patient populations. What is needed are prospective randomized trials evaluating radiation therapy perhaps with hormonal therapy vs. hormonal therapy alone in this setting using appropriate stratification for known risk factors and overall survival as the end point.
References
1. D’Amico AV, et al. J Clin Oncol 1997;15:1465-1469.
2. Johansson JE, et al. JAMA 1992;267:2191-2196.
3. Peschel RE. Int J Radiat Oncol Biol Phys 1996; 35:749-750.
4. Peschel RE. Cancer J Sci Am 1998;4:300-301.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.