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Dose-escalated radiation improves survival in intermediate- and high-risk prostate cancer
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Dose-escalated external-beam radiation therapy improved OS in men with intermediate- or high-risk prostate cancer, according to results of a retrospective, nonrandomized comparative effectiveness study.
However, dose escalation did not improve outcomes among men with low-risk prostate cancer.
In multiple trials, dose-escalated external-beam radiation therapy (EBRT) improved biochemical and local control, however there has been little data on its effect on survival.
Anusha Kalbasi, MD, resident in the department of radiation oncology at University of Pennsylvania Perelman School of Medicine, and colleagues sought to examine the impact dose-escalated vs. standard-dose EBRT had on OS among patients by prostate cancer stratified by risk group.
Anusha Kalbasi
Researchers identified 42,481 patients diagnosed with prostate cancer between 2004 and 2006 using the National Cancer Data Base. The cohort included men with low-risk (n = 12,229), intermediate-risk (n = 16,714) and high-risk (n = 13,538) disease.
Within each risk cohort, the researchers divided patients into two treatment groups: standard- dose (68.4 Gy to ˂ 75.5 Gy) or dose-escalated (≥ 75.6 Gy to 90 Gy) EBRT.
OS between treatment groups in each cohort — assessed using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach — served as the primary outcome measure. Secondary analyses included evaluations of dose response for survival.
Overall, dose-escalation significantly improved survival for patients with intermediate-risk (IPW-PS–adjusted HR = 0.84; 95% CI, 0.80-0.88) and high-risk (IPW-PS–adjusted HR = 0.82; 95% CI, 0.78-0.85) disease; however, this association did not persist in the low-risk group (IPW-PS–adjusted HR = 0.98; 95% CI, 0.92-1.05).
Each 2 Gy increase in dose conferred a 7.8% (95% CI, 5.4-10.2) reduction in the hazard for death for the intermediate-risk group and a 6.3% (95% CI, 3.3-9.1) reduction for the high-risk group.
“Our findings are concordant with the growing literature that most men with low-risk prostate cancer have excellent survival without radical treatment,” Kalbasi and colleagues wrote. “The association of dose-escalated EBRT with improved survival for patients with intermediate- and high-risk prostate cancer is consistent with two efficacy dose-escalation trials and extends the evidence to routine real-world clinical practice.”
The reduction in hazard of death with each 2 Gy increase suggests a possible incremental dose-response, according to the researchers. However, 76-Gy doses and above in the intermediate-risk patients and 81-Gy doses and above in high-risk patients appeared to be the only significant dose levels.
“These may represent threshold doses that need to be achieved to derive the mortality benefit observed,” they wrote. “Beyond this threshold, our data do not exclude the possibility that even higher doses of EBRT, as delivered by approaches such as combined EBRT and brachytherapy, would be associated with better outcomes.”
The researchers also identified an association between dose escalation and improved survival even in the presence of androgen deprivation therapy. In the intermediate-risk cohort, 49% of the patients received ADT and 77% of the patients in the high-risk cohort received ADT.
The study’s observational design prohibits the suggestion of a casual association, according to the researchers. Other limitations of the analysis include that the National Cancer Data Base does not track ADT duration or treatment-related toxicities; its dose records are subject to heterogeneity as dosage can vary by as much as 10% between the isocenter and the target periphery; and it collects data only from Commission on Cancer-approved facilities, limiting the patient population to large, urban facilities.
“Our results add to the body of evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity,” Kalbasi and colleagues concluded. – by Anthony SanFilippo
Disclosure: The researchers report no relevant financial disclosures.
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