Survival Benefit From Preventive Radiotherapy for Bone Metastases Draws Major Attention

Many cancers tend to metastasize (spread) to bone in their advanced stages. Giving radiotherapy for painful bone metastases is standard cancer care. However, a new study evaluating radiotherapy for bone metastases produced an unexpected result: in patients with asymptomatic bone metastases (causing no symptoms or complaints), prophylactic (preventive) radiotherapy was shown not only to reduce skeletal-related events and hospitalization but also to prolong survival.

In this first-of-its-kind study, approximately 80 patients with more than five high-risk metastases were randomized to prophylactic radiotherapy or standard care.

Patients receiving radiotherapy had fewer skeletal-related events, and none required hospitalization. Results also showed a 55% improvement in overall survival compared with controls, giving these patients an additional 8 months of life.

Lead author Dr. Erin F. Gillespie, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York City, said, “It is thought-provoking that radiation to prevent pain could potentially prolong life.”

Gillespie added that an overall survival difference from radiotherapy for asymptomatic bone metastases was “unexpected”, but consistent with earlier studies showing that palliative care “can improve overall survival”.

This groundbreaking research was presented on October 23, 2022 at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

These results were enthusiastically welcomed by many cancer professionals worldwide.

Examples of skeletal events associated with bone metastases include “bone fracture,” “spinal cord compression,” “paralysis due to compression” and “severe bone pain.” Preventing skeletal-related events is “really important for patients.” The overall survival benefit from radiotherapy for bone metastases is “unexpected,” but radiotherapy now needs to be considered as a prophylactic (preventive) treatment.

In a patient with features increasing the likelihood of serious conditions such as spinal cord compression, considering radiotherapy earlier “seems intuitive” in light of this study. Treating asymptomatic bone metastases may prolong survival by killing cancer cells at these sites and reducing the body’s tumor burden.

Until now, however, “we had no evidence” that preemptive radiotherapy for asymptomatic bone metastases would be effective. This study is a “really important step” toward providing that evidence.

Given the magnitude of the survival benefit, if a drug had produced this difference, there would be a huge and interested pharmaceutical market pursuing it.

One “advantage” of radiotherapy as the intervention is that it is already standard care and is “widely accessible everywhere.”

“There is no additional cost to society, the payer or the patient,” she said. “This is a big win,” because bringing forward a treatment that would be less effective later does not impose an additional burden on patients or their doctors.

Although this was a relatively small phase 2 trial requiring confirmation in further studies, the results are very promising for patients with asymptomatic bone metastases.

“More studies are needed to optimize appropriate use” of radiotherapy and “avoid overtreatment.” Identifying patients while their bone metastases remain asymptomatic is also a separate issue, because bone metastases may not always be clearly visible.

Study Details

Dr. Gillespie and colleagues randomized patients with high-risk asymptomatic bone metastases to receive radiotherapy or not. Patients were stratified by cancer type and treatment.

Patients had to be at least 18 years old, have ECOG performance status 0-2, a solid (organ-based) tumor and more than five metastatic sites on imaging. At least one metastasis had to be high-risk, defined as bulky disease larger than 2 cm or involving the hip, shoulder or sacroiliac joints, long bones or spine.

The team randomized 78 patients from three institutions. Data were evaluable for 35 patients with 62 lesions in the radiotherapy arm and 36 patients with 49 lesions in the control group.

The median age was 61-65 years, and approximately half were women. The most common cancers were lung, breast and prostate cancer, and systemic treatment was planned for 90%. About half had received a bone-modifying agent, such as a bisphosphonate.

The primary endpoint was skeletal-related events, defined as pathological fracture, spinal cord compression, surgery to a fracture site or radiotherapy for pain.

• A skeletal-related event occurred in only 1.6% of those given prophylactic radiotherapy, versus 29% without radiotherapy (P  < 0.001).
• After a median follow-up of 2.4 years, median overall survival was 1.7 years with radiotherapy versus 1 year without it (P  = 0.011). Radiotherapy was found to reduce the risk of death by 55%.
• There were also no hospitalizations among radiotherapy recipients, compared with 4 in the untreated arm (P  = 0.045), and Brief Pain Inventory scores improved significantly (P  = 0.039).

Regarding safety, grade 2 or higher adverse events were reported in 38% of radiotherapy patients and 21% of controls, with 13% and 3%, respectively, considered potentially treatment-related. The most common events were nausea, vomiting, erythema (rash), fatigue and diarrhea, mostly moderate (grade 2).

In conclusion, oncology professionals will now consider intervening before asymptomatic bone metastases cause problems rather than leaving their course solely to systemic treatments. The question is when radiotherapy should be given to patients with bone metastases. Many have several metastatic sites, but how do we identify lesions most likely to cause problems? If we decide to intervene, how do we ensure that patients who may benefit can access radiotherapy despite workload and other barriers?