A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer.
OBJECTIVE
A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).


METHODS
Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, gamma(50), is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies.


RESULTS
Nonrandomized studies produced a statistically significantly higher gamma(50) than randomized studies for intermediate- to high-risk patients (gamma(50) = 1.63 vs. gamma(50) = 0.93, p = 0.03) and a borderline significantly higher (gamma(50) = 1.78 vs. gamma(50) = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in gamma(50) was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of gamma(50) = 0.84 with 95% confidence interval 0.54-1.15.


CONCLUSIONS
Nonrandomized studies overestimate the steepness of the dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients.
Diez
Patricia
P
Clinical Physics Department, Mount Vernon Centre for Cancer Treatment, Northwood, Middlesex, UK.
Vogelius
Ivan S
IS
Bentzen
Søren M
SM
D000465:Algorithms; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D017430:Prostate-Specific Antigen