Prospective Cohort Study Highlights QOL Benefits of Surgery for Bone Metastases in Advanced Cancer

R. Lor Randall, MD, FACS

For patients with metastatic bone disease stemming from solid tumors, surgical intervention in the setting of realized or impending fractures could serve as a method to improve quality of life for this patient population, according to R. Lor Randall, MD, FACS.

In a prospective cohort study published by Randall and colleagues in the Journal of Surgical Oncology, findings showed that among evaluable patients who underwent surgery for bone metastases (n = 81), 39.5% survived for at least 1 year after surgery and completed 1 year of follow-up, 28.4% died before the 1-year mark, 9.9% dropped out due to ill health, and 22.2% were lost to follow-up. In this population, 63.0% of patients experienced at least a 5-point improvement in physical function, and 72.8% had at least a 5-point improvement in pain interference. The time to achieve a minimal clinically important difference (MCID) was 6 weeks for physical function and 4 weeks for pain interference.

“Patients with metastatic bone disease often don’t live very long, unfortunately; however, many are living longer and longer. Orthopedic interventions [can] get the patient back on their feet and moving around,” Randall said. “If they’re living many months, their quality of life, as reported by subjective patient-reported outcomes, is clinically improved by that [surgical] intervention.”

In an interview with OncLive®, Randall discussed the burden of metastatic bone disease for patients with cancer, shared findings from the prospective cohort study, and expanded on why surgical intervention could play a role in improving quality of life for patients with bone metastases.

Randall is the David Linn Endowed Chair for Orthopedic Surgery, chair of the Department of Orthopedic Surgery, and a professor in the Department of Orthopedic Surgery at the University of California, Davis Comprehensive Cancer Center in Sacramento.

OncLive: In current clinical practice, what are the key considerations for determining whether surgical intervention is appropriate for patients with advanced cancer and skeletal metastases?

Randall: When I use the term metastatic bone disease, I'm talking about secondary involvement of the skeleton or musculoskeletal system by a primary tumor [located] somewhere else that metastasizes to the bone. This study arose out of a question that was asked of me by a very well-intended nurse approximately 15 years ago, when we were rolling a patient with advanced cancer to the operating room. I remember [the nurse] asking, ‘Why would you operate on this patient with advanced cancer?’ It was a very salient, very well-intended point. For me, the indications were clear, but [the nurse] and in her advocacy for the patient, didn't understand [in that moment] why we would put someone [in this clinical scenario] through a procedure.

We [can] operate on patients with metastatic bone disease. There are [approximately] 400,000—if not 500,000—people per year living with metastatic bone disease [in the United States]. Skeletal-related events make up nearly 20% of the cancer care economy in the United States, so this is a big problem within the cancer community. I call it a pandemic within the cancer world. We operate on some [of these patients]; many of them will get radiation and sometimes surgery. The reason is because when these tumors metastasize to the skeleton, they set up a microenvironment that is usually destructive; therefore, they become mechanically weak and cause these bones to break.

Overall mortality increases three-fold when a patient [suffers a] fracture, and the chance of a patient with a realized fracture being alive at 2 years is much lower than if the bone didn't fracture. Without getting into all the criteria for when we prophylactically stabilize, we will often—if we’re on the fence at all—favor doing some sort of prophylactic stabilization of a long bone. The spine is another issue, and we're mostly [discussing] non-spine involvement here, with the femur being the second most common site after the spine. We will prophylactically intervene, but sometimes we don't get that opportunity, a patient goes on to fracture, and then they need the intervention.

In the particular case [from approximately 15 years ago], that was the salient question [from the nurse about the need for surgery]. This patient was [facing] an impending fracture, and it was more clear in [the nurse’s] mind to ask [about the] procedure when the bone hadn’t even broken yet. The risk was so high of the bone breaking that we decided to [go to surgery].

What was the rationale behind the cohort study design, and how were PROMIS scores used to assess outcomes in patients with metastatic bone disease?

We recently published a study of a prospectively collected cohort of 100 patients across 4 institutions: the University of Utah; University of California, Davis; Rush University; and Colorado [Limb Consultants]. We prospectively enrolled patients who had a realized or impending fracture, and we collected PROMIS scores for physical function and pain interference at the time of initial contact.

Patients then had [surgical] intervention, and we followed those patients. We wanted to see the length of time for recovery and look at the maximum effect [of surgery on] pain interference and physical function.

What were the key data reported from this study?

Of the 100 patients enrolled, 81 patients were ultimately included in the [analysis]; 19 patients were lost to follow-up. Thirty-two patients [39.5%] survived and were able to be followed up at 1 year; 23 patients [28.4%] died before the 1-year [mark]. You can see this is a very frail community, and that further emphasizes the question: why would we intervene?

However, the good news with this is that 51 patients [63%] achieved at least a 5-point improvement in physical function, and 59 patients [72.8%] achieved at least a 5-point improvement in pain interference. This minimal clinical improvement was noted by 6 weeks for physical function and 4 weeks for pain interference.

If you take the worst-case scenario where the patient doesn’t make it out to 1 year [following surgery], they’ve really recovered by 4 weeks—if not 6 weeks—from this intervention, and therefore [can] have months of improved quality of life from where they were [prior to surgery]. We think this is a valuable contribution; we do not want to write off patients. There is justification for doing these [surgical] interventions, despite the potentially 1- or 2-week setback from the surgery. These patients go on, for their relatively short lifespan, to have improved quality of life.

How does a PROMIS score inform the benefit of surgical intervention?

Our biostatistician, Amy Morgan Cizik, PhD, MPH, [of the University of Utah], informed us that a 5-point improvement represents the MCID. This means that, based on statistical analysis, a 5-point improvement is unlikely to be due to random chance; instead, it reflects a meaningful clinical improvement.

Is there any ongoing research or upcoming studies in this space that you think are important to highlight?

When tumors from, [for example], breast, prostate, lung, kidney, and thyroid cancers metastasize to the bone, they create a unique tumor microenvironment at these secondary sites. This process may not only result in local bone destruction, but it may also act as a [catalyst] for further disease progression.

There are some data to suggest that early metastasis to the bone is associated with a worse prognosis. The current thinking is that when tumor cells metastasize to bone, the microenvironment may help reactivate the tumor, enabling it to seed additional distant sites.

Our laboratory, along with several others, is actively investigating the tumor microenvironment in bone, including how macrophage polarization and other biological factors may influence both skeletal stability and the potential for further metastatic spread.

Reference

Groundland J, Tokson JH, Hakim A, et al. Length of Time to Clinical Improvement After Orthopedic Oncology Surgery in Patients With Metastatic Cancer: A Multi-Institution Patient-Reported Outcome Study. J Surg Oncol. 2025;131(5):955-964. doi:10.1002/jso.27932