Adjuvant Radiation Treatment After Radical Prostatectomy May Improve Survival
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC and is Editor of Clinical Oncology Alert. Dr. Ershler is on the speaker’s bureau for Amgen and does research for Ortho Biotech.
Synopsis: In this large, randomized trial, the question of whether immediate postoperative radiation therapy for those prostate cancer patients treated by initial radical prostatectomy and found to have disease extending through the capsule (pT3) had added clinical benefit. Data with regard to local control and duration of biochemical (PSA) remission support the application of this approach. It will take additional time to be certain whether such intermediate positive outcomes translate to less metastatic disease and improved overall survival.
Source: Bolla M, et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet. 2005;366:572-578.
Prostate cancer is a leading cause of cancer-related mortality in the world. Radical prostatectomy is often curative for people who present with localized disease. Complete cure is less achievable for patients with cancer extending beyond the capsule. In that case, the risk of recurrence after radical prostatectomy ranges from 10-50 percent. Factors that impact on the recurrence rate include the initial prostate-specific antigen (PSA), the presence of positive surgical margins, and the Gleason score, each of which is considered an independent predictor for relapse.
The purpose of this study was to evaluate the role of adjunctive radiation therapy immediately after radical prostatectomy for patients with positive surgical margins or cancer extending beyond the capsule (pT3) with associated risk factors for progression.
Patients (n = 1005 ) between the ages of 61 and 69 years entered the study after radical prostatectomy performed between November 1992 and December 2001. All subjects had positive surgical margins and were randomly assigned to receive either radiation therapy (502) or observation (503). The primary end point was progression-free survival (PFS) and analysis was by intention to treat. The 5-year biochemical PFS rates by Kaplan-Meier estimate were 52.6% for the observation group and 74.0% for the adjunctive radiation group. The clinical PFS was also improved with a reduction in the rate of locoregional failure. Although severe toxicity was rare, there was an increase in Grade 2 or 3 late effects in the radiation therapy group.
Commentary
Non-randomized studies had previously suggested that postoperative external beam radiation eradicates residual microscopic prostate cancer cells at the surgical site1 and reduces the local relapse and PSA failure rates, but not overall survival, for those who primarily treated by radical prostatectomy.2 In the current European multicenter, randomized prospective trial, the issue was focused upon those who had disease extending beyond the capsule (pT3) but without evidence for nodal or distant metastases. The trial took nearly a decade to complete and this report is likely to be the first of several that will establish to role of adjuvant radiation in this setting. The preliminary analysis looks impressive in that local control and duration of PSA remission was clearly favorably influenced by postoperative radiation. Furthermore, added toxicity, although present, was manageable, and not severe. Of course, overall survival will be the measure of how enthusiastically the added therapy will be incorporated into standard care, but longer follow-up is needed before meaningful conclusions can be made.
As is generally the case with large-scale clinical trials, especially those that take several years, such as this, there are significant limitations that may influence outcome. Included here would be the more refined techniques currently available (for both surgery and radiation) and the variability in approaches taken in the ‘wait and see’ group with regard to salvage therapy. In the current trial, guidelines for introducing ‘salvage’ radiation were not uniform. Thus, some patients in the ‘wait and see’ group had treatment initiated with a rising PSA (from postoperative non-detectable), whereas others were treated only when clinically palpable or biopsy proven recurrences were found. This heterogeneity will complicate the analysis of overall survival. Yet, the numbers are quite large and the local control and PSA findings of significant magnitude that the long-term analysis to define survival benefit from immediate postoperative radiation is likely to be demonstrable by this trial if it indeed exists. This would be a significant advance.
References
1. Ray GR, et al. External-beam megavoltage radiation therapy in the treatment of post-radical prostatectomy residual or recurrent tumor preliminary results. J Urol. 1975;114:98-101.
2. Perez CA, et al. Postradical prostatectomy irradiation in carcinoma of the prostate. American College of Radiology. ACR Appropriateness Criteria. Radiology. 2000;215 Suppl:1419-1439.
In this large, randomized trial, the question of whether immediate postoperative radiation therapy for those prostate cancer patients treated by initial radical prostatectomy and found to have disease extending through the capsule (pT3) had added clinical benefit. Data with regard to local control and duration of biochemical (PSA) remission support the application of this approach. It will take additional time to be certain whether such intermediate positive outcomes translate to less metastatic disease and improved overall survival.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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