CORR Insights®: What Are the Complication Rates and Factors Associated With Total Femur Replacement After Tumor Resection? Findings From the Japanese Musculoskeletal Oncology Group

Where Are We Now?

Even more than many other extensive orthopaedic oncology procedures, a total femur resection and reconstruction has a profound effect on all aspects of patients’ lives and on their survival. Other than an ablative procedure, total femoral endoprosthetic replacement (TFR) is the only option remaining after total femur resection. These operations are rarely performed, so our cumulative knowledge regarding the indications, techniques, and outcomes is sparse. When we have the opportunity to learn about this procedure from the report of a multicenter trial, we should pay attention.

This issue of Clinical Orthopaedics and Related Research® includes a multicenter trial by Mori et al. [7], which involved 42 patients from 32 Japanese institutions who underwent TFR during a 30-year period. The fact that there were so few patients distributed over such a long time period at so many institutions further emphasizes the rarity of the procedure. Other than a report of 58 patients from China focusing on technical aspects of TFR without oncologic outcomes [2], this CORR® paper is the largest series of which I am aware. Prior single-center studies from various institutions worldwide provided their individual experiences with anywhere from 17 to 34 patients [4, 8, 12, 14, 15].

The major findings of Mori et al. [7] emphasize what we already know: TFRs are high-risk procedures with numerous potential complications, most commonly infection, hip dislocation, and local recurrence. The current CORR study identifies these three problems as targets for improvement. Doing so may require a paradigm shift in how we view patients undergoing rare and radical procedures such as TFR. Given their overall poor prognosis, patients undergoing TFR probably deserve the same consideration we grant to patients with advanced disease, by offering them everything we have, even investigational therapy, to help them achieve a better result.

Where Do We Need To Go?

Many of the risk factors affecting outcomes of bone sarcomas are not modifiable. With current practice, the extent of bone and soft tissue involvement after neoadjuvant treatment cannot be changed. Hence, although Mori et al. [7] demonstrated that resection of the abductor muscles and tumors larger than 20 cm were associated with hip dislocation, these are not modifiable risk factors. The only modifiable variables orthopaedic oncologic surgeons can control are the technical aspects of our surgery and perioperative care.

Identifying specific modifiable technical and perioperative variables directed at improving instability, infection, and local recurrence would potentially improve the outcomes for these patients. Thus far, Mori et al. [7] and the earlier single-center studies I mentioned have shown this is a challenge. In large part, this is attributable to the small numbers of patients who underwent this rare procedure in each series as well as the changing adjuvant treatments, numerous orthopaedic oncology surgeons involved, and their favored techniques that are inherent in all studies that span decades of treatment.

Moving forward, to know what details of surgical technique and perioperative care to document, we need to know what questions to ask, and there are quite a few. For instance, will the successful use of synthetic material for reconstruction of the hip capsule, as shown by Du et al. [2], be validated by other centers using the same or similar materials? Would the use of total hip with a dual or tripolar mobility or constrained liner instead of hemiarthroplasty, alone or in combination with soft tissue reconstruction, further reduce instability [5, 16, 18]? Would silver-coated implants, routine wound-VAC closure, and/or staged soft tissue coverage to reduce operative time reduce infection rates [9, 11, 15, 17, 19, 20]? Would intraoperative use of near-infrared (NIR) indocyanine green fluorescence imaging to evaluate surgical margins, as is being evaluated by the Weiss lab at the University of Pittsburg Medical Center and others, decrease local recurrence [3, 6]? Is there a similar advantage to targeted imaging? If we think about these questions, we can prospectively collect key data for future analysis.

How Do We Get There?

To better understand what we’re doing, right or wrong, we need more complete, detailed, and consistent documentation of surgical technique and perioperative care that can be used for meaningful meta-analyses of institutionally based and cooperative multicenter reports alike. Standardized documentation can probably best be achieved through shared databases such as that of the Musculoskeletal Tumor Society. These databases facilitate multicenter study and publications of larger series of patients. Forethought needs to be given to the specific modifiable variables we want to document for evaluation, including prophylactic surgical and perioperative steps used to reduce instability, infection, and local recurrence. More multicenter trials in other countries and in cooperative international groups such as the European Musculoskeletal Tumor Society and Connective Tissue Oncology Society using collaborative databases should be the goal.

Even with such cooperation and detailed reporting, there will likely never be enough total femurs performed during any period to allow meaningful assessment of the effects of the varied interventions we use to minimize complications and improve local control. However, there is surrogate value in evaluating these same interventions on more frequent musculoskeletal oncologic procedures. Proximal femoral replacement gives us the opportunity to evaluate and refine techniques for reducing hip dislocation. Silver-coated implants can and are being studied in other megaprostheses, especially the proximal tibia. There is growing experience with targeted and nontargeted NIR and negative pressure devices in soft tissue sarcomas that may also be relevant for TFR given the need for similar resection of large volumes of surrounding tissue [3, 6, 20]. There is one completed study of fluorescence image–guided surgery with a VEGF-targeted tracer in soft tissue sarcomas (NCT03913806) and another ongoing study of indocyanine green fluorescence imaging to evaluate surgical margins (NCT04719157). Six clinical trials of negative-pressure devices in soft tissue sarcoma are currently registered with clinicaltrials.gov, and the results of these may similarly inform soft tissue management after TFR.

Prospective studies such as those even on more common orthopaedic oncology procedures take time. When the stakes for individual patients are particularly high, we just can’t wait until tomorrow for results of long-term studies when we’re planning a TFR today. If our patients understand that some newer interventions are investigational and are being used under compassionate use institutional review board guidelines, we should enlist their consent to try some of these newer techniques even without high-quality evidence, just as we evaluate new drugs in Phase I investigational clinical trials to help patients with poor survival prognosis. To some extent, we already do this, but the paradigm shift would be to do it more commonly for TFR. Although typical overall survival of patients with TFR may be better than that for the usual patient in a Phase I clinical trial, the complication-free survival is poor, and the surgical and perioperative care interventions being offered are unlikely to adversely affect the patient. The interventions suggested above are unlikely to be worse than current standard of care. The question is simply whether those interventions will improve a dire situation for these unfortunate patients.

Read This Next

• A review summarizing the state of the art in sarcoma margin assessment reported that NIR fluorescence intraoperative imaging may provide surgical benefits in understanding tumor anatomy, perfusion, lymphatic drainage, margins and metastases [1].

• A literature review discussed the positive and negative aspects of both targeted and nontargeted NIR, suggested targets for common pediatric sarcomas, and outlined the experiments that need to be done before widespread implementation of fluorescence-guided surgery [10].

• A status report about the ongoing randomized controlled trial comparing negative-pressure wound therapy versus conventional wound dressing and associated postoperative wound complications after surgical removal of deep-seated, high-malignant soft tissue sarcoma of the extremities or trunk wall indicated that the results may have implications for all major musculoskeletal resections, including total femur resection [20].