ASTRO 2021: 10-Year Results of a Phase III Randomized Trial of High-Dose Radiotherapy and Risk-Adapted Androgen Deprivation Therapy in Localized Prostate Cancer

( In a session at the American Society for Radiation Oncology (ASTRO) Annual Congress focused on the care of patients with intermediate and high-risk prostate cancer, Dr. Zapatero presented 10-year results of a phase III randomized trial of high-dose radiotherapy and risk-adapted androgen deprivation therapy in localized prostate cancer.

This study, with 5-year results initially presented at the ASTRO 2014 meeting, sought to assess whether long-term androgen deprivation therapy (ADT) is superior to short-term ADT in patients with intermediate and high-risk disease receiving high-dose radiotherapy. Patients were randomized in a 1:1 fashion to receive either 4 months of neo-adjuvant and concomitant ADT followed by 3D-conformal radiotherapy with a dose of 76 grade or higher or the same approach followed by an additional 24 months of adjuvant ADT.

The primary endpoint was biochemical disease free survival, using the Phoenix definition. Secondary endpoints included overall survival, metastasis free survival, cause-specific survival, and toxicity (measured using both the RTOG and CTCAE definitions). In this report, the authors describe 10 year outcomes calculated from the date of randomization to the date of treatment failure or last follow-up. The authors used Cox proportional hazards models for overall survival and Fine and Gray competing risks analyses for assessment of cancer-specific death, metastasis-free survival, and biochemical-recurrence-free survival, using non-prostate cancer mortality as the competing event.

The authors included 354 patients, of whom 177 were randomized to each arm. The groups were well balanced in terms of baseline characteristics.

As previously reported, the 5-years outcomes demonstrated that the addition of 2 years of adjuvant ADT to 4 months of neoadjuvant and concomitant ADT along with high-dose radiotherapy improved biochemical control and overall survival, particularly in patients with high-risk disease, though at the expense of an increased risk of non-fatal cardiovascular events.

With further 10-year follow-up, Dr. Zapatero demonstrated no improvements in biochemical disease free survival (70% vs 62%, HR 1.2, p=0.40), metastasis-free survival (96% vs 84%, HR 1.1, p=0.06), or overall survival (78% vs 73%, HR 1.2, p=0.51). However, among the subset with high risk disease, there was a greater absolute magnitude of difference (biochemical disease free survival: 67% vs 54%; metastasis-free survival: 77% vs 65%; overall survival: 79% vs 67%), however, the comparisons were not statistically significant. Among patients with high risk disease, Dr. Zapatero highlighted a borderline significant overall survival effect (HR 1.74, 95% CI 0.99-3.06, p=0.054).

In terms of cause of death, prostate cancer was the third most common cause of death in this cohort, behind secondary cancers (lung, colorectal, and hematologic) and cardiovascular disease.


Rates of secondary cancer death were statistically higher among patients receiving short-term ADT.

In conclusion, Dr. Zapatero emphasized that this study was designed to assess 5-year outcomes and failed to account for losses at 10 years. As a result, the small sample size left it underpowered for subgroup analyses. Thus, while there was a potentially clinical relevant improvement in overall survival among patients with high-risk disease, this was not statically significant.

Presented by: Almudena Zapatero, MD PhD, Hospital Universitario de la Princesa, Madrid, Spain

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.



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