Combination ADT and radiation therapy shows favorable outcomes in men with localized prostate cancer

Daniel E. Spratt, MD

An analysis conducted by Case Western Reserve University and University Hospitals in Cleveland, Ohio showed that the combination of androgen deprivation therapy (ADT) and definitive radiotherapy improves metastasis-free survival among men with localized prostate cancer.¹

“Our research team set out to conduct a first-of-its-kind, comprehensive analysis by collecting individual patient data from each and every randomized trial conducted around the world, and performed a meta-analysis of the impact of various treatment intensification strategies using hormone therapy with radiation therapy for localized prostate cancer,” said senior author Daniel E. Spratt, MD, in a recent news release.² “Our goal is to better personalize therapy for prostate cancer patients, by providing the most precise and accurate estimates of the benefit of hormone therapy.”

To gather data, the investigators of this study performed a systematic literature search, in which eligible trials evaluated the use or prolongation of ADT in men with localized prostate cancer who had received radiotherapy. All trials were published in English between January 1, 1962, and December 30, 2020. The search included MEDLINE, Embase, trial registries (Cochrane Central Register of Controlled Trials and ClinicalTrials.gov), the Web of Science, Scopus, and renowned urology and oncology conference proceedings.

Data were accessed using the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP). Trials were excluded if they did not collect data on distant metastasis or survival, used only non-steroidal anti-androgen therapy (not ADT), took place in a single center, or used lifelong ADT.

The primary outcome of this meta-analysis was metastasis-free survival. HRs for ADT use (radiotherapy alone vs radiotherapy plus ADT), neoadjuvant ADT extension, and adjuvant ADT prolongation were produced using Cox models.

After analyzing 12 trials that reflected individual data of 10,853 patients, investigators found that ADT plus radiotherapy (HR 0.83 [95% CI 0.l77-0.89], P < .0001) and adjuvant ADT prolongation (0.84 [0.78-0.91], P < .0001) both significantly improved metastasis-free survival at a follow up of 11.4 years (IQR 9.0-15.0). However, neoadjuvant ADT extension did not have the same effect (0.95 [0.83-1.09], P = .50).

In addition, results showed that there were no significant variations in treatment effects among patients receiving different radiotherapy doses, patients of different ages, or patients of different National Comprehensive Cancer Network risk groups.

“We now have estimates that show the benefit of adding and prolonging adjuvant hormone therapy for clinically relevant subsets of patients,” said Spratt. “Our team showed that treating a group of approximately 10 to 15 men with hormone therapy or extended adjuvant hormone therapy, for at least 18 months, prevented one man from developing metastatic disease 10 years after treatment. This is dependent on patient and tumor specific factors but gives us a more precise estimate to work with when it comes to recommending treatment options.”

“This work from the MARCAP consortium will bring confidence in recommending various treatment intensification strategies, and allow providers to have more accurate, shared-decision making conversations with patients about the benefits of using hormone therapy with radiotherapy for prostate cancer treatment.”

References

1. Kishan AU, Sun Y, Hartman H, et al. Androgen deprivation therapy use and duration with definitive radiotherapy for localized prostate cancer: An individual patient data meta-analysis. Lancet Oncol. Published online January 17, 2022. doi:10.1016/ S1470-2045(21)00705-1

2. Researchers show increased survival rate in prostate cancer patients with addition of hormone therapy treatments. News release. University Hospitals Cleveland Medical Center. January 18, 2022. Accessed January 18, 2022. https://www.eurekalert.org/news-releases/940306