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Radiation for Asymptomatic Bone Metastases May Improve Cancer Survival

— Fewer skeletal events, less pain unexpectedly followed by longer life

MedpageToday

SAN ANTONIO -- Prophylactic radiotherapy (RT) for asymptomatic bone metastases significantly reduced the rate of skeletal-related events (SREs) in patients with cancer, according to a small randomized trial reported here.

Patients who received RT had an SRE rate of 1.6% as compared with 29% among patients randomized to standard care. Pain and hospitalization for SREs were also significantly lower in the RT arm.

Perhaps more important, prophylactic RT was associated with significant improvement in overall survival (OS), reported Erin Gillespie, MD, of Memorial Sloan Kettering Cancer Center in New York City, at the (ASTRO) annual meeting.

"It was somewhat unexpected that patients do appear to live longer," she said during an ASTRO press briefing. "However, there is a good rationale for this. There have been prior randomized trials, looking at purely palliative interventions, [showing that] by keeping patients healthy, more active, and potentially staying out of the hospital, they live longer. Even more recently some of the work with active symptom monitoring with patient-reported outcomes has shown similar findings, but the exact mechanism will need to be ... evaluated in future studies."

"Future research is needed to confirm the overall survival benefit, to really optimize the patients that are treated," Gillespie added. "Only 30% of patients had events. So, there is this question of potentially overtreating patients that don't go on to have events, whether they all need radiation. And then for those that are most likely to have events, how will we see them in the radiation oncology clinic and make sure that they get timely treatment?"

Palliative RT is standard practice for symptomatic bone metastases. However, the benefits of prophylactic RT for asymptomatic lesions in critical skeletal locations remained unclear. Bone metastases can cause substantial pain and lead to hospitalization. Retrospective reviews have identified the presence of bone lesions on prior imaging.

"We saw from a retrospective study that at least 60% of our inpatients treated for bone pain had [prior] evidence, so the question became can radiation to these lesions before they become painful actually prevent complications, such as cord compression, fracture, hospitalization, and also improve patient quality of life," said Gillespie.

To address the question, the investigators enrolled 78 patients with a total of 122 high-risk (because of size, depth, or anatomic location) asymptomatic bone metastases. The primary tumor type was lung in 27% of patients, breast in 24%, and prostate in 22%.

Patients received either planned standard of care (SOC) for symptomatic bone metastases (systemic therapy or observation) or SOC plus RT. The primary endpoint was the 1-year rate of SREs, defined as cancer-related bone fracture or spinal cord compression, surgery, surgery for bone instability, or RT for pain. OS was a secondary endpoint.

The 27.4% absolute difference in SRE represented almost a 95% reduction in the risk of all SREs (P<0.0001). SRE-associated hospitalizations occurred in 11% of patients randomized to SOC versus none of the patients who received prophylactic RT. Patients randomized to RT also had better pain-related quality of life at 1 year.

"When you look at pain-related quality of life over time, you actually see that radiation is preventing future pain, which is a bit of a paradigm shift," said Gillespie. "In the palliative setting we're using radiation only [when] patients develop pain, and we've had some hesitation to use radiation when patients don't have pain because we don't want to cause more harm than good."

The data showed that patients who received only SOC had a median OS of 1 year, whereas those randomized to prophylactic RT had a median OS of 1.7 years (P=0.02). The survival difference persisted after a multivariable analysis adjusted for differences in patient characteristics.

In response to a question about the applicability of the results to clinical practice, Gillespie noted that the patients in the trial were identified in radiation oncologic clinics because the planned treatment for their primary tumors included radiation therapy. Whether the results apply to asymptomatic patients seen in medical oncology clinics, "we really can't answer that question yet," she said.

Without minimizing the clinical benefits of the study, press briefing moderator Iris Gibbs, MD, of Stanford Medicine in California, said the findings reflect the broader role of radiation oncology in the healthcare delivery system, and that in addition to preventing hospitalizations and reducing morbidity, prophylactic RT has the potential to reduce the cost of care for patients with cancer.

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    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007.

Disclosures

Gillespie and Gibbs disclosed no relevant relationships with industry.

Primary Source

American Society for Radiation Oncology

Gillespie EF, et al "Prophylactic radiation therapy vs standard of care for patients with high-risk, asymptomatic bone metastases: A multicenter, randomized phase II trial" ASTRO 2022; Abstract LBA 04.