High-dose Radiation Reduces Risk Of Prostate Cancer Recurrence

The majority of cases of prostate cancer now diagnosed in the UnitedStates are detected while the disease is still clinically localized,according to background information in the article. External beamradiation is one of the options used to treat more than 26,000 U.S. menannually. Failure after treatment with conventional radiation therapyis common, with a resultant increase in prostate-specific antigen (PSA)levels, secondary treatment, and, ultimately, clinical recurrence.Increasing the delivered radiation dose may increase the probability oflocal tumor control but carries a risk of greater adverse effectsunless the volume of normal tissue treated along with the tumor can bereduced.

In the 1990s a number of computed tomography-based techniquesbecame available to deliver radiation more accurately and thus allowthe delivery of higher doses. These techniques are together known as"3-dimensional conformal therapy" and include the use of conformalphoton beams, intensity-modulated photon beams, and proton beams.

Anthony L. Zietman, M.D., of Massachusetts General Hospitaland Harvard Medical School, Boston, and colleagues conducted a study todetermine whether tumor control could be improved in patients withprostate cancer, including those with low-risk disease, by the use ofhigher radiation doses. The study included 393 patients with stage T1bthrough T2b prostate cancer and prostate-specific antigen (PSA) levelsless than 15 ng/mL, randomized between January 1996 and December 1999.The median (middle) value for PSA levels was 6.3 ng/mL, and the medianfollow-up time was 5.5 years. Patients received either external beamradiation to a total dose of either 70.2 Gy (radiation dose unit;conventional dose) or 79.2 Gy (high dose). This was delivered using acombination of conformal photon and proton beams.

The researchers found that the proportions of men free frombiochemical failure (increasing PSA level) at 5 years were 61.4 percentfor conventional-dose and 80.4 percent for high-dose therapy, a 49percent reduction in the risk of failure. The advantage to high-dosetherapy was observed in both the low-risk and the higher-risk subgroups(risk reduction, 51 percent and 44 percent, respectively). There hasbeen no significant difference in overall survival rates between thetreatment groups. Only 1 percent of patients receivingconventional-dose and 2 percent receiving high-dose radiationexperienced acute urinary or rectal problems of Radiation TherapyOncology Group (RTOG) grade 3 or greater. So far, only 2 percent and 1percent, respectively, have experienced late problems having RTOG grade3 or greater.

"This randomized trial shows that when men with clinicallylocalized prostate cancer are treated with high-dose rather thanconventional-dose external radiation therapy, they are more likely tobe free from an increasing PSA level 5 years later and less likely tohave locally persistent disease," the authors conclude.

(JAMA. 2005; 294:1233 - 1239. Available pre-embargo to the media at www.jamamedia.org.)

Editor's Note: This trial was supported by a grant from the National Cancer Institute.

Editorial: Radiation Dose Escalation as Treatment for Clinically Localized Prostate Cancer - Is More Really Better?

In an accompanying editorial, Theodore L. DeWeese, M.D., andDanny Y. Song, M.D., of Johns Hopkins University School of Medicine,Baltimore, comment on the study and on radiation dose level forprostate cancer.

"Based on the study by Zietman et al, it is possible to nowstate with more certainty that higher radiation doses can be safelydelivered to men with clinically localized prostate cancer and thatthis increased dose is associated with improved biochemical control ofdisease. However, whether this increase in PSA control will necessarilytranslate into improvement in clinically meaningful end points such aslonger survival is not yet known. As such, this study has not answeredthe important question of whether patients should accept the modest butreal incremental risk of higher radiation doses for the uncertainultimate benefit derived."

"Several other questions also remain unanswered: (1) Wouldhigher radiation doses beyond 79 Gy provide even greater benefit? (2)What is the optimal radiation method of dose escalation? and (3) Giventhat the addition of androgen suppression to radiotherapy has recentlybeen shown to improve survival in some patients, is dose escalationeven the best way to improve radiotherapeutic outcomes in this disease?Nevertheless, these randomized trial data support the use of higherradiation doses in men with lower-risk prostate cancer, and thesefindings will serve as an important foundation for future work," theywrite.

(JAMA. 2005; 294:1274 - 1276. Available pre-embargo to the media at www.jamamedia.org.)