Additional prospective data about proton beam radiation
Posted Feb 14 2010 12:00am
The published data available to assess the merits of proton beam radiation therapy (PBRT) in the treatment of prostate cancer is very limited. It is therefore pleasing to see the publication of the long-term results from the Proton Radiation Oncology Group/American College of Radiology study 95-09.
This prospective study enrolled 393 men with T1b-T2b prostate cancer and a PSA level ≤ 15 ng/ml, and the 5-year results of this trial were initially reported in 2005. The patients were randomly assigned to one of two forms of first-line treatment with conformal beam PBRT: either a conventional dose of 70.2 Gray equivalents (GyE) or a high dose of 79.2 GyE. No patient received any form of androgen deprivation therapy (ADT) in association with their radiation. The outcomes of the study were defined as local failure (LF), biochemical failure (BF), and overall survival (OS).
The long-term results now reported for this study by Zietman et al. are as follows:
Median patient follow-up was 8.9 years.
Men receiving high-dose PBRT were significantly less likely to have LF than men treated with conventional dose PBRT (hazard ratio = 0.57).
Overall rates of BF for all patients were 32.4 percent for conventional dose PBRT and 16.7 percent for high dose PBRT at 10 years.
Rates of BF for patients with low-risk disease (227/393 or 57.8 percent)) were 28.2 percent for conventional dose PBRT and 7.1 percent for high dose PBRT.
Rates of BF for patients with intermediate-risk disease (144/393 or 36.6 percent) were 42.1 percent for conventional dose PBRT and 30.4 percent for high dose PBRT (which shows a strong trend toward a statistically significant result, but is not actually statistically significant).
11 percent of patients subsequently required ADT for treatment of recurrent disease after conventional dose PBRT compared with 6 percent after high dose PBRT.
As yet there is no statistically significant difference in rates of OS between the treatment arms (78.4 v 83.4 percent).
2 percent of patients in each arm experienced late grade 3 or grade 4 genitourinary toxicity.
1 percent of patients in the high-dose arm experienced late grade 3 or grade 4 gastrointestinal toxicity.
As the authors correctly conclude, this randomized, controlled trial shows “superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional dose radiation” using PBRT.
Over half the patients enrolled in this trial had low-risk prostate cancer. It is not possible to tell from the abstract of this paper how many of these patients would have been candidates for active surveillance based on current NCCN guidelines (i.e., what percentage of these patients had a life expectancy of 15 years or less). However, the effectiveness of PBRT in low-risk patients has never really been in question. The question has always been whether the cost of this form of therapy can be justified by the outcomes compared to other forms of management. This trial, unfortunately, does nothing to resolve that issue.