CHICAGO — The use of androgen deprivation therapy (ADT) in conjunction with radiotherapy, as well as its prolonged use in the adjuvant setting, improved metastasis-free survival (MFS) and overall survival (OS) in patients with localized prostate cancer, a meta-analysis found.
Adding ADT to radiotherapy significantly improved 12-year rates of MFS, the primary endpoint (HR 0.83, 95% CI 0.77-0.89), increasing from 43% without ADT to 51% with it. OS at 12 years improved from 48% to 55%, respectively (HR 0.86, 95% CI 0.80-0.92), reported Amar U. Kishan, MD, of the University of California Los Angeles.
In addition, the study also found that prolonged use of adjuvant ADT improved both 12-year MFS and OS:
- MFS: HR 0.84, 95% CI 0.78-0.91
- OS: HR 0.85, 95% CI 0.78-0.94
However, Kishan noted, prolonged neoadjuvant ADT was not associated with a significant benefit in any endpoint.
“The use of ADT and the prolongation of adjuvant ADT with radiotherapy provides clinically meaningful benefit and should remain the standard of care, with level 1 evidence,” he said during a presentation at the American Society for Radiation Oncology annual meeting. “Neoadjuvant ADT … should not be routinely recommended — we can say that with a fair amount of confidence.”
Daniel Hamstra, MD, PhD, of Baylor College of Medicine in Houston, told MedPage Today that the study reaffirms what radiation oncologists knew about hormonal therapy and radiation therapy in men with high-risk prostate cancer.
“This is a very nice study that pools data from multiple important studies, with long follow-up,” noted Hamstra, who was not involved in the research. “And it reassures us as far as what the standard recommendations for treatment should be.”
The individual patient data used in this meta-analysis of randomized trials came from the MARCAP consortium, which was formed from international trial groups.
The analysis included 10,853 patients from 12 radiotherapy trials, for whom the researchers analyzed outcomes related to three aspects of ADT: the addition of ADT to radiation therapy (median follow-up 12 years), and the prolongation of adjuvant ADT (median 10.9 years follow-up), and neoadjuvant ADT (median 10.3 years follow-up).
Of these 12 trials, six evaluated ADT use (in more than 5,000 patients), mostly the addition of 3 to 6 months of ADT to radiation therapy. Three trials evaluated neoadjuvant ADT prolongation (in about 4,200 patients), and compared 3 to 4 months of ADT versus prolonged ADT in the neoadjuvant setting for 6 to 9 months. Four trials evaluated prolonged adjuvant ADT (in about 3,600 patients), mostly comparing 4 to 6 months of ADT versus prolonged ADT in the adjuvant setting for 18 to 36 months.
Patients were followed for a median of 11.4 years. Almost half had high-risk disease, while 43.3% had intermediate-risk disease, and 10.1% had low-risk disease.
The primary endpoint was MFS, while secondary endpoints included biochemical recurrence, OS, and distant metastases.
“We also wanted to quantify the benefits of these interventions, so we calculated the numbers needed to treat to avoid distant metastases at 10 years,” Kishan said. “In terms of numbers needed to treat, to avoid one distant metastasis event at 10 years, we would have to treat 18 patients with intermediate-risk disease and 8.4 patients with high-risk disease.”
“There was no significant interaction in the benefit of ADT use by radiotherapy dose or NCCN [National Comprehensive Cancer Network] risk group,” he added.
“The study did not sufficiently identify which patients do not benefit or do benefit from short- or long-term ADT,” Kishan noted. “And that’s important because it tells us we need better biomarkers to really personalize treatment.”
Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.
Kishan disclosed relationships with Janssen, Varian Medical Systems, and ViewRay.