Randomized Trial Comparing Conventional-Dose With High-Dose Conformal Radiation Therapy in Early-Stage Adenocarcinoma of the Prostate: Long-Term Results From Proton Radiation Oncology Group/American College of Radiology 95-09

Abstract

PURPOSE To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes. PATIENTS AND METHODS Men with T1b-T2b prostate cancer and prostate-specific antigen </= 15 ng/mL were randomly assigned to a total dose of either 70.2 Gray equivalents (GyE; conventional) or 79.2 GyE (high). No patient received androgen suppression therapy with radiation. Local failure (LF), biochemical failure (BF), and overall survival (OS) were outcomes. Results A total of 393 men were randomly assigned, and median follow-up was 8.9 years. Men receiving high-dose radiation therapy were significantly less likely to have LF, with a hazard ratio of 0.57. The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4% for conventional-dose and 16.7% for high-dose radiation therapy (P < .0001). This difference held when only those with low-risk disease (n = 227; 58% of total) were examined: 28.2% for conventional and 7.1% for high dose (P < .0001). There was a strong trend in the same direction for the intermediate-risk patients (n = 144; 37% of total; 42.1% v 30.4%, P = .06). Eleven percent of patients subsequently required androgen deprivation for recurrence after conventional dose compared with 6% after high dose (P = .047). There remains no difference in OS rates between the treatment arms (78.4% v 83.4%; P = .41). Two percent of patients in both arms experienced late grade >/= 3 genitourinary toxicity, and 1% of patients in the high-dose arm experienced late grade >/= 3 GI toxicity. CONCLUSION This randomized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation. This was achieved without an increase in grade >/= 3 late urinary or rectal morbidity.

Localized prostate cancer treated with external beam radiation therapy: Long-term outcomes at a European comprehensive cancer centre

“…Since that time, multiple randomized-controlled trials (RCTs) 1,2 have been carried out, confirming the benefits of increased doses. In 2010, Zietman et al 3 reported long-term results of a RCT which demonstrated superior long-term cancer control for high-dose radiation without any increase in G3 or higher late urinary or rectal toxicity.…”

“…As a result, long-term outcomes have been improved and toxicity decreased. 3 Dose escalation can be achieved with precise radiotherapy techniques such as 3D-CRT or intensity-modulated radiotherapy (IMRT), or by adding a boost delivered with high-dose rate brachytherapy (HDRB) or IMRT. [4][5][6][7] Overall survival in high risk patients can be further improved by combining EBRT with androgen deprivation therapy (ADT).…”

Radiotherapy for Prostate Cancer: is it ‘what you do’ or ‘the way that you do it’? A UK Perspective on Technique and Quality Assurance

“…Several randomised trials of dose escalation for prostate cancer were opened in the 1990's, following pilot studies which suggested that this approach was safe, and these trials have now all reported outcome data [2,[10][11][12][13]. Though dose-escalation is now routine practice, it was not state of the art in external beam radiotherapy for prostate cancer at the time when the UK ProtecT study was designed in the late 1990's.…”

Developments in External Beam Radiotherapy for Prostate Cancer

“…Despite higher doses, local failure still occurs in up to 20% of cases. 3 Several studies have demonstrated that local recurrence predominantly originates at the primary tumor site. 15 This led to the hypothesis that local control could be increased by simultaneously delivering a boost dose to the primary tumor within the prostate.…”