High-dose external radiation therapy is associated with reduced risk for recurrence compared with conventional-dose radiotherapy for men with localized prostate cancer, according to an article in the September 14 issue of the Journal of the American Medical Association.

The majority of cases of prostate cancer now diagnosed in the United States are detected while the disease is still clinically localized, according to background information in the article. Failure after treatment with conventional radiation therapy is common, with a resultant increase in prostate-specific antigen levels, secondary treatment, and, ultimately, clinical recurrence. Increasing the delivered radiation dose may increase the probability of local tumor control but carries a risk of greater adverse effects unless the volume of normal tissue treated along with the tumor can be reduced.

In the 1990s a number of computed tomography-based techniques became available to deliver radiation more accurately and thus allow delivery of higher doses. These techniques are together known as three-dimensional conformal therapy and include the use of conformal photon beams, intensity-modulated photon beams, and proton beams.

Anthony L. Zietman, MD, and his American colleagues conducted a study to determine whether tumor control could be improved in patients with prostate cancer, including those with low-risk disease, by the use of higher radiation doses. The study included 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen levels less than 15 ng/mL, randomized between January 1996 and December 1999.

Median prostate-specific antigen level was 6.3 ng/mL, and median follow-up time was 5.5 years. Patients received either external beam radiation to a total dose of either 70.2 Gy or 79.2 Gy delivered with a combination of conformal photon and proton beams.

The researchers found that the proportions of men free from biochemical failure at 5 years were 61.4 percent for conventional-dose and 80.4 percent for high-dose therapy, a 49 percent reduction in the risk of failure.

The advantage to high-dose therapy was observed in both the low-risk and the higher-risk subgroups (risk reduction, 51 percent and 44 percent, respectively). There has been no significant difference in overall survival rates between the treatment groups. Only 1 percent of patients receiving conventional-dose and 2 percent receiving high-dose radiation experienced acute urinary or rectal problems of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2 percent and 1 percent, respectively, have experienced late problems that were RTOG grade 3 or greater.

In an accompanying editorial, Theodore L. DeWeese, MD, and Danny Y. Song, MD, of Johns Hopkins University School of Medicine, Baltimore, commented on the study and on radiation dose level for prostate cancer: "Based on the study by Zietman et al, it is possible to now state with more certainty that higher radiation doses can be safely delivered to men with clinically localized prostate cancer and that this increased dose is associated with improved biochemical control of disease. However, whether this increase in prostate-specific antigen control will necessarily translate into improvement in clinically meaningful end points such as longer survival is not yet known. As such, this study has not answered the important question of whether patients should accept the modest but real incremental risk of higher radiation doses for the uncertain ultimate benefit derived."

The editorial went on to say, "Several other questions also remain unanswered: (1) Would higher radiation doses beyond 79 Gy provide even greater benefit? (2) What is the optimal radiation method of dose escalation? and (3) Given that the addition of androgen suppression to radiotherapy has recently been shown to improve survival in some patients, is dose escalation even the best way to improve radiotherapeutic outcomes in this disease? Nevertheless, these randomized trial data support the use of higher radiation doses in men with lower-risk prostate cancer, and these findings will serve as an important foundation for future work."