Eur J Cancer 2020 Dec 03
Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial.
Abstract
Background
The role of androgen deprivation therapy (ADT) in combination with radiotherapy (RT) in intermediate-risk prostate cancer (IRPC) remains controversial, particularly in patients receiving dose-escalated RT (DERT). We compared outcomes between patients with IRPC treated with ADT and two different doses of RT vs. RT alone.
Methods
From December 2000 to September 2010, 600 patients with IRPC were randomised to a three-arm trial consisting of 6 months of ADT plus RT 70 Gy (ADT + RT70) vs. ADT plus a DERT of 76 Gy (ADT + DERT76) vs. DERT of 76 Gy alone (DERT76). Primary end-point was biochemical failure (BF), and secondary end-points were overall survival (OS) and toxicity. RT toxicity was assessed by Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer criteria.
Findings
With a median follow-up of 11.3 years (interquartile range: 10.9-11.7), patients receiving DERT76 alone, compared with patients receiving ADT + RT70 and ADT + DERT76, had higher rates of BF (32%, 18% and 14%, respectively, p < 0.001), higher rates of prostate cancer progression (12%, 4.5% and 3.3%, respectively, p = 0.001) and more deaths due to prostate cancer (6.5%, 3.0% and 1.5%, respectively, p = 0.03) with no significant difference seen between ADT + RT70 and ADT + DERT76. There was no significant difference in OS between the 3 arms. A higher dose of RT (76 Gy) increased late gastrointestinal (GI) toxicity grade ≥ II compared with lower dose (70 Gy) (16% vs 5.3%, p < 0.001) with no statistical difference for late genitourinary toxicity.
Interpretation
In IRPC, the addition of 6 months of ADT to RT70 or DERT76 significantly improves BF and appears to decrease the risk of death from prostate cancer compared with DERT76 alone with no difference in OS. In the setting of IRPC, ADT plus RT 70 Gy yields effective disease control with a better GI toxicity profile. Clinicaltrials.gov#NCT00223145.
Related Questions
What radiation treatments would you offer an older man with unfavorable intermediate-risk prostate cancer, with comorbid conditions, if you don't feel he is a good candidate for full-course radiation therapy with ADT?
What is the point of treatment at all if an elderly patient has significant comorbid conditions? I would first consider the likelihood that they would even live 5 to 10 years and fully discuss the side effects of all treatments. There is nothing wrong with watching these patients and not making deci...
What is the optimal duration of ADT for unfavorable intermediate risk or high risk localized prostate cancer treated with SBRT instead of conventionally fractionated or hypofractionated RT?
There is no available data from randomized trials to support any modification in the choice of ADT (GnRH agonist vs antagonist) or use of abiraterone acetate, or on the duration of ADT (4-6 mo vs 2-3 years) based on the form of radiation, and thus I follow the NCCN guidelines that provide recommenda...