Abstract
PurposeTo assess the impact of increasing dose on overall survival (OS) for prostate cancer patients.MethodsTreatment data were obtained on more than 20,000 patients in the National Oncology Data Alliance®, a proprietary database of merged tumor registries, who were treated for prostate cancer with definitive radiotherapy between 1995 and 2006. Eligible patients had complete data on total dose, T stage, use and timing of androgen deprivation therapy (ADT), and treatment start date (n = 20,028). Patients with prior malignancies were excluded.ResultsOn multivariate analysis, dose, T stage, grade, marital status, age, and neoadjuvant ADT were significant predictors of OS. Hazard ratios for OS declined monotonically with increasing dose, reaching 0.63 (95 % Confidence Interval 0.53–0.76) at ≥80 Gy. On subset analysis, neoadjuvant ADT significantly improved OS in high risk patients but was not significant in lower risk patients. The dose response was maintained across all risk groups. Medical comorbidities were balanced across all dose strata and sensitivity analysis demonstrated that other prognostic factors were unlikely to explain the observed dose response.ConclusionsThis study suggests that increasing dose significantly improves OS in prostate cancer patients treated with radiotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0419-3) contains supplementary material, which is available to authorized users.
Highlights
Dose-escalated radiotherapy provides superior freedom from clinical and biochemical failure in men treated for prostate cancer (PCa) [1,2,3,4,5] and is widely used in clinical practice [6]
androgen deprivation therapy (ADT) was administered in 40 % of patients as neoadjuvant or concurrent therapy with radiotherapy, defined as beginning within 6 months of the radiotherapy start date
A retrospective analysis cannot account for all patient factors, the dose response was durable across a number of clinical scenarios and this analysis accounted for potential disparities in medical comorbidities
Summary
Dose-escalated radiotherapy provides superior freedom from clinical and biochemical failure in men treated for prostate cancer (PCa) [1,2,3,4,5] and is widely used in clinical practice [6]. Combined androgen deprivation therapy (ADT) and radiotherapy have demonstrated an OS advantage in intermediate and high risk patients in multiple randomized clinical trials (RCTs), albeit at doses ≤70 Gy [7,8,9,10]. With a median follow-up of 7 years, Radiation Therapy Oncology Group (RTOG) 0126 showed significant improvements in the rates of biochemical failure and distant metastases with dose-escalated radiotherapy, but no OS benefit has been observed with higher doses to date [12]. The optimal radiotherapy dose must balance the risks and benefits of improved local control relative to
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