Global Survey Outlines Optimal Population for Surgical Treatment of Proximal Femur Metastases

R. Lor Randall, MD, FACS

Findings from a global survey of 76 musculoskeletal oncology surgeons demonstrated that enrollment criteria for the proposed PERFORM trial—which plans to evaluate post-surgical outcomes in patients with RCC that has metastasized to the proximal femur—should consider patient life expectancy, extent of bone loss, and risk for perioperative complications, according to R. Lor Randall, MD, FACS.

Additionally, the survey results showed many respondents expressed interest in participating in the study.

Notably, the survey respondents indicated that select patients with bone loss of no more than 75% and no less than 25% would be eligible to undergo either resection and endoprosthetic reconstruction or internal fixation in the PERFORM trial. Notably, PERFORM will exclude patients with renal cell carcinoma (RCC) with oligometastatic bone disease, as complete resection of the lesion is the standard of care in most of those cases.

“RCC [is] one of the big 5 cancer tumors that metastasize to the musculoskeletal system, the others being breast, prostate, lung, and thyroid,” Randall said. “However, RCC is particularly challenging to treat systemically when it’s advanced overall.”

In an interview with OncLive®, Randall highlighted how the survey outcomes have informed the PERFORM trial design and explained the rationale for excluding patients with advanced RCC and oligometastatic bone disease from the study.

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

OncLive: What disease features do you consider before making treatment decisions for patients with cancer metastases to the proximal femur, and how did these questions lead to the initiation of this trial survey?

Randall: In the orthopedic oncologic treatment of patients with advanced RCC and metastases to the upper femur, [there’s] a dilemma. Do we go in and resect the lesion [from the] proximal femur, which is a big [burden on] the patient and sets them back because the recovery time can be anywhere from 3 to 6 months? Or do we hope that this tumor that won’t progress and that we can put in an intramedullary nail or some other implant to stabilize the bone, but not put the patient through the morbidity of the resection? We are faced with this dilemma all the time, with increasing frequency, as the prevalence of patients with advanced-stage RCC progresses. Therefore, in the orthopedic oncologic world and the musculoskeletal tumor society, we put forward a research proposal.

We had a consensus meeting around [treatment] guidelines and released a survey globally to find a zone of equipoise [for enrollment in the proposed PERFORM trial and gauge surgeons’] interest in [participating in this trial]. There are probably philosophical pockets where some surgeons will say, ‘I’m only going to resect,’ and others will say, ‘I don’t want to put the patient through the resection, so I’m going to do a stabilization procedure.’ Some are open to both.

What were the most notable survey responses?

We surveyed across the globe—in North America, South America, Europe, Asia, and Africa—and asked [surgeons about] their level of interest [in participating in this] prospective, randomized, controlled trial. [We also asked about] some of the [population] parameters they would want [the trial] to consider. [The response rate from self-declared stakeholders was] 70% across the globe, which is good, and there was a definite interest in the study.

Emerging [enrollment] criteria [for PERFORM include a] life expectancy of at least 6 months; bone loss of no more than 75% and no less than 25%; and minimal-to-moderate risk for perioperative complications. [In total], 93% of the responders said they would be willing to enroll [patients] in the PERFORM trial; to get anywhere upward of 75% of consensus on equipoise is hopeful. We are moving forward with designing the trial. Get orthopedic oncologists involved, and this study will hopefully be opened within the next year or so.

What is the challenge of treating patients with advanced RCC that has metastasized to the proximal femur?

Patients are living longer with RCC. [However], the proximal femur [has a] high incidence of metastases. [These metastases] are associated with major morbidity and quality-of-life issues, and there’s not a good solution for local control.[Advanced RCC with metastasis to the proximal femur is] troubling because it tends to be radioiodine-refractory, and these are vascular lesions, so some of the more conventional orthopedic oncologic dogma doesn’t apply.

For example, if a patient has metastasis to the proximal femur from breast or prostate cancer and there’s worry about the bone breaking, you can do prophylactic stabilization and radiation, and that usually addresses the issue. With RCC, unfortunately, because it’s so radioiodine-refractory and locally aggressive, sometimes we have to do cancer resections—take out the tumor en bloc and [do] an upper femur replacement. We’re talking specifically about the upper femur because, beyond the spine, the [upper femur is the] most common site of [bone] metastases, and it’s also mechanically a high-risk subtrochanteric area [because it takes] 6 to 8 times [a person’s] body weight with every step. A radioiodine-refractory tumor that’s destructive and locally aggressive adds morbidity for these patients.

Reference

Fogel J, Ng VY, Schubert T, et al. A survey to determine the zone of equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial. Trials. 2024;25(1):759. doi:10.1186/s13063-024-08590-z