A combination of androgen deprivation therapy (ADT) and external beam radiation therapy (EBRT) is better at delaying disease progression and extending survival of patients with locally advanced prostate cancer than ADT alone, a Phase 3 trial shows.
Previous studies have shown that EBRT, the most common type of radiation therapy, together with ADT, a hormone therapy that aims to slow disease progression by reducing levels of male hormones, led to significant improvements in patients’ survival compared to EBRT alone.
More recently, the Phase 3 clinical trials NCT00002633 and ISRCTN01534787, plus a third trial, have shown that a combination therapy of ADT and EBRT led to better clinical outcomes compared to ADT alone in patients with locally advanced prostate cancer — that which has spread outside the prostate, but not yet to other tissues and organs.
In this multi-center, randomized, open-label, Phase 3 clinical trial (NCT01122121), researchers aimed to confirm these findings and report the long-term effects of the combination therapy of ADT and EBRT compared to ADT alone.
The study, called TAP 32, enrolled 263 patients with locally advanced prostate cancer who were randomly assigned to receive either ADT alone or a combination of ADT and EBRT.
ADT was similar in both groups, with patients receiving 11.25 mg of leuprorelin for three years. Patients placed in the combination therapy group also received radiation therapy in the whole pelvis at a dose of 46 Gy (a measure of radiation) and 20-28 Gy specifically in the prostate.
The trial’s primary endpoint was to assess the time patients lived without the disease worsening, a measure called progression-free survival.
Secondary endpoints included overall survival, disease-specific survival, locoregional progression-free survival (the time patients lived without lesions in pelvic lymph nodes), metastasis-free survival (the time patients lived without cancer spreading) and treatment tolerability.
Patients were followed for a median of 7.3 years. Results showed that a significantly higher percentage of patients treated with the combination lived past the eight-year mark without disease worsening, compared to those on ADT alone (48% versus 7%).
Overall survival at eight years was also higher for those in the combination (65%) compared to ADT alone (57%). The risk of death from prostate cancer was significantly lower in patients from the combination therapy group compared to those on ADT only.
Although no significant differences in the time to metastasis or death were found between the two groups, patients receiving the combination therapy lived longer without developing lesions in pelvic lymph nodes.
Safety analysis showed that after six months of treatment, a higher percentage of patients treated with ADT plus EBRT experienced side effects (26% versus 2%). However, these values tended to decrease gradually throughout follow-up.
“The present results show a trend in favor of combined arm in order to delay metastatic progression, reinforcing the idea that local control could impact disease’s distant spread even for patients presenting strong micro-metastatic risk,” the investigators stated.
“The long-term results of this study corroborate that standard dose-level prostate EBRT combined with prolonged hormone therapy significantly improves oncological outcomes for locally advanced prostate cancer,” they said.