Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial.
BACKGROUND
Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common.


OBJECTIVE
To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome.


METHODS
Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years.


METHODS
Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams.


METHODS
Increasing PSA level (ie, biochemical failure) 5 years after treatment.


RESULTS
The proportions of men free from biochemical failure at 5 years were 78.8% [corrected] (95% confidence interval, 73.1%-84.6%) [corrected] for conventional-dose and 91.3% [corrected] (95% confidence interval, 87.2%-95.4%) [corrected] for high-dose therapy (P<.001), a 59% [corrected] reduction in the risk of failure. The advantage to high-dose therapy was statistically significant [corrected] in both the low-risk subgroup [corrected] (risk reduction, 84% [P<.001]) [corrected] There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater.


CONCLUSIONS
Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.
Zietman
Anthony L
AL
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. azietman@partners.org
DeSilvio
Michelle L
ML
Slater
Jerry D
JD
Rossi
Carl J
CJ
Miller
Daniel W
DW
Adams
Judith A
JA
Shipley
William U
WU
D000230:Adenocarcinoma / Q000097:blood / Q000532:radiotherapy*; D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal
D017430:Prostate-Specific Antigen