Radiotherapy Plus Hormone Therapy Boosts Prostate Cancer Outcomes

SAN ANTONIO — Adding metastasis-directed therapy (MDT) to intermittent hormone therapy significantly improved progression-free survival (PFS) in patients with oligometastatic prostate cancer, allowing patients relief from hormone therapy, researchers found.

More specifically, the combination therapy was associated with a 75% increase in PFS compared with hormone therapy alone as well as a significant increase in the time men spent with normal, or eugonadal, testosterone levels.

Results from the phase 2 randomized basket trial suggest that combining MDT with intermittent hormone therapy helps maintain “excellent disease control in men with oligometastatic prostate cancer” and allows for “time off from hormone therapy,” said Chad Tang, MD, associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston.

Tang presented the findings from the EXTEND trial at the American Society for Radiation Oncology (ASTRO) Annual Meeting on October 25.

Nima Aghdam, MD, a radiation oncologist at Beth Israel Deaconess Medical Center, Boston, Massachusetts, told Medscape Medical News that the study is “very important for our field, because it allows us to answer the significant question: What does radiation in the metastatic setting add to the standard of care?” He was not part of the EXTEND study team.

Aghdam, who described the trial as “well controlled and elegantly run,” explained that the study presents a real-world treatment option for patients with oligometastatic prostate cancer.

Previous studies have demonstrated that patients benefit from upfront hormone therapy and that synergy exists between radiation and hormone therapy, but there have been no randomized trials exploring the combination of these treatments in prostate cancer.

In addition, Tang noted, there have been several strategies to limit patients’ exposure to hormone therapy, such as intermittent treatment courses, but these approaches have “fallen out of favor” since the results of SWOG-9346 suggested that intermittent hormone therapy was not non-inferior to continuous treatment in metastatic prostate cancer.

In the current trial, Tang and colleagues randomly assigned 87 patients with oligometastatic prostate cancer to MDT with radiotherapy plus 6 months of hormone therapy (n = 43) or to hormone therapy alone (n = 44). A planned break from hormone therapy occurred 6 months after enrollment and restarted only when patients progressed.

Patients had a histologic diagnosis of prostate cancer with up to 5 metastases and had been on hormone therapy for at least 2 months. The most common disease stage at enrollment was M1b — meaning the cancer had spread to the bones — in about two thirds of patients.

Over a median follow-up of 22.1 months, Tang and colleagues found a significant difference in the primary endpoint of PFS between the two treatment groups.

Patients who received the combination therapy had significantly improved PFS (median not reached) vs 15.8 months with hormone therapy alone (hazard ratio [HR], 0.25; P < .001).

In an exploratory analysis, the researchers found that the significant PFS benefit achieved with the dual therapy appeared largely unaffected when stratifying patients by prostate-specific antigen (PSA) levels, disease stage, prior primary treatment, use of second-generation hormone therapy, hormone therapy duration, or number of metastatic lesions.

The team also found a significant increase in the time from eugonadal testosterone levels above 150 ng/dL to disease progression in patients receiving both therapies vs hormone therapy alone (median not reached vs 6.1 months; P = .03). In addition, three grade 3 toxicities were observed in each group.

Tang noted a “number of caveats” to the study, such as high PSA levels at diagnosis and a high cut point for resuming hormone therapy, which suggest that the study population may not represent patients with oligometastatic prostate cancer in the clinic today.

In a press conference, Howard M. Sandler, MD, said he found the study findings “pretty exciting.”

Hormone therapy can “have devastating consequences for men’s vitality” and intermittent hormone therapy “might be appropriate” to give men a “holiday from hormone therapy so they can resume their normal lives to a certain extent,” said Sandler, chair of Radiation Oncology at the Oschin Cancer Institute, Cedars-Sinai Medical Center in Los Angeles. In other words, the extended time off hormone therapy would be “clinically meaningful to patients” and improve their quality of life.

However, Sandler noted that the MDT in the study was exclusively radiation to metastatic sites, and he wondered whether other therapies could have been used, such as cryotherapy.

On Twitter, several radiation oncologists chimed in on the study findings.

Stuart Burri, MD, agreed that giving less hormone therapy means “winning for our prostate cancer patients.”


And Shankar Siva, MD, PhD, added that the time that men can “enjoy” being off androgen deprivation therapy is an “important patient-centric endpoint.”

Do these findings indicate that upfront hormone therapy could be avoided altogether, at least until disease progression?

Tang explained that “many patients come to our clinical already on hormone therapy,” and he worried that asking them to stop might counter “what they were told by their medical oncologist.”

Beth Israel’s Aghdam noted, however, that it’s important to work with medical oncologists and discuss the potential to forgo hormone therapy. But he called for longer follow-up among these patients as well as data comparing combination therapy to radiation alone in the metastatic setting.

“We’re seeing more and more signals that a portion of the population can benefit from local therapy alone for an extended period of time,” Aghdam said.

The study received funding from the National Cancer Institute. No relevant financial relationships were declared.

American Society for Radiation Oncology (ASTRO) Annual Meeting 2022: Abstract LBA 05. Presented October 25.

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