Evaluating functional outcomes and quality of life in musculoskeletal tumor patients with distal femoral megaprostheses: a case-control study

Abstract

Background

Endoprosthetic knee replacement using megaprostheses has become a common strategy for preserving joint function in patients with distal femur tumors. While existing literature has primarily focused on surgical techniques, complications, and implants, recent improvements in patient survival rates have sparked increased interest in the long-term functional outcomes associated with this treatment.

Methods

This case-control study evaluated functional outcomes—Timed Up and Go (TUG), 6-Minute Walk Test (6MWT), knee flexor and extensor muscle strength, and sagittal knee range of motion—and health-related quality of life (SF-36) between patients with distal femoral megaprostheses (n = 31) and healthy controls (n = 48). Participants performed the TUG and 6MWT equipped with an inertial measurement unit. Additionally, bivariate Spearman correlations were calculated within the patient group to assess relationships between Musculoskeletal Tumour Society (MSTS) scores and functional outcomes.

Results

Patients performed significantly worse than controls in the TUG test, with longer completion times (Mean Difference: -3.3 s; 95% CI: -5.7 to -0.9; p = 0.008), reduced rotational speed during the middle turn (Mean Difference: 16°/s; 95% CI: 7 to 25; p < 0.001) and final turn (Mean Difference: 22°/s; 95% CI: 9 to 34; p < 0.001), and lower vertical acceleration during the Sit-to-Stand phase (Mean Difference: 1.3 m/s²; 95% CI: 0.1 to 2.5; p = 0.032). In the 6MWT, patients walked 86 m less on average than controls (95% CI: 35 to 136; p = 0.002). Knee range of motion was significantly reduced, with median flexion of 90.2° (range: 5–125) in patients versus 136.4° (range: 115–150) in controls (p < 0.001, Z = -7.268). Muscle strength was also markedly lower in patients (p < 0.001). The SF-36 revealed significant differences in the Physical Component Summary (Mean Difference 95% CI: 15.5 [10.0 to 20.9]; p < 0.001), while no significant differences were found in the Mental Component Summary (p > 0.05). In patient group, bivariate Spearman correlations indicated a very strong positive association between MSTS scores and knee extension strength (ρ = 0.710; p < 0.001), and strong positive correlations with sagittal knee range of motion (ρ = 0.472; p = 0.015), total walking distance in 6MWT (ρ = 0.474; p = 0.019), and final turn rotational speed in TUG (ρ = 0.439; p = 0.032).

Conclusion

Our findings demonstrate a strong association between knee extensor strength and range of motion with overall functional performance, as reflected in MSTS scores. While nearly 75% of patients achieved scores classified as “good” to “excellent,” objective measures from the TUG and 6MWT revealed significant performance deficits compared to healthy controls, likely due to limitations in knee extensor strength and range of motion. These results highlight the need for targeted rehabilitation strategies focused on enhancing muscle strength and range of motion to optimize long-term functional recovery in these patients.

Introduction

Over the past three decades, significant advancements in chemotherapy, biomechanical engineering, and surgical techniques have established limb salvage as the standard treatment for bone tumors of the distal femur. Endoprosthetic knee replacement using megaprostheses has become a common approach to preserving joint function in these patients [1,2,3,4]. While much of the existing literature has focused on surgical techniques, complications, implant types, and longevity [1, 5], the improvement in patient survival rates has led to a growing interest in understanding the long-term functional outcomes associated with this treatment modality.

Despite these efforts, the current literature presents notable limitations. Studies often exhibit substantial variability in key factors such as prosthesis location, surgical techniques, follow-up durations, and functional outcome measures. These inconsistencies hinder cross-comparison and limit the applicability of findings to clinical practice [1, 6,7,8,9,10,11,12,13,14,15,16]. Furthermore, many studies rely on subjective assessment tools or fail to adopt standardized methodologies, which reduces the reliability and objectivity of the reported outcomes. This lack of consistency underscores the need for studies that employ rigorous and objective evaluation methods to better understand the functional recovery of patients with distal femoral megaprostheses.

Assessing the functional status of patients with lower limb tumors is critical not only for evaluating their overall functional abilities and quality of life [6,7,8] but also for informing targeted postoperative rehabilitation strategies. Previous reviews have examined health and functional outcomes following limb salvage procedures in young adult and adult populations [1, 6,7,8,9,10,11,12,13,14,15,16]. However, the findings from these studies are often inconsistent, as they are influenced by differences in prosthesis location, surgical approaches, follow-up periods, and the tools used to measure functional outcomes.

A comprehensive evaluation of functional outcomes encompasses various dimensions, including strength, range of motion, and overall mobility. Notably, knee extensor strength and range of motion have been identified as key factors influencing functional performance in patients with distal femoral megaprostheses [13, 14]. Several studies have compared muscle strength between patient cohorts and healthy controls, highlighting the significance of muscle integrity preservation during surgery and the necessity of focused rehabilitation to restore strength and mobility.

Traditional functional assessments, such as the Timed Up and Go (TUG) and the 6-Minute Walk Test (6MWT), are valuable tools for evaluating mobility and endurance in clinical settings, providing crucial insights into patients’ functional capabilities and identifying specific deficits [17,18,19,20,21]. However, these tests have been underutilized in patients with distal femoral megaprostheses, limiting our understanding of their functional performance. The integration of inertial measurement units (IMUs) into these assessments offers an innovative approach to capture more detailed and objective data on movement patterns, yet no studies to date have employed IMUs to evaluate functional outcomes in this patient population.

This case-control study was guided by the hypothesis that patients with distal femoral megaprostheses would exhibit inferior functional performance compared to healthy controls across all measured variables. Specifically, we aimed to compare functional outcomes—including results from the TUG and 6MWT, knee flexor and extensor muscle strength, sagittal knee range of motion, and health-related quality of life—between these groups. By employing both traditional assessments alongside IMU technology, we sought to address the limitations of prior research and provide a comprehensive evaluation of functional recovery in this population, thereby informing clinical practice and rehabilitation strategies.

Methods

Study design

This study was designed as a single-center case-control study (ClinicalTrials.gov NCT06282198). The study protocol was approved by both the Hospital La Fe Human Ethics Committee (2017/0336) and the Ethics Committee for Biomedical Research of the CEU Cardenal Herrera University (CEI21/062). All procedures were performed in accordance with the principles outlined in the World Medical Association’s Declaration of Helsinki, and written informed consent was obtained from all participants prior to their inclusion in the study.

We retrospectively identified all distal femoral megaprostheses implanted between January 2013 and February 2024 from our tumor registry. A total of 42 patients were considered eligible for inclusion. Five had passed away. The other 37 were contacted via telephone. Of these, 4 declined to participate and 2 had significant difficulties with ambulation, resulting in a final cohort of 31 patients. The overall participation compliance rate was 73,8%.

Eligibility criteria

The inclusion criteria for the case group were defined as follows: [1] patients aged 16 years or older [2], undergoing distal femur megaprosthesis surgery for tumor-related conditions at Hospital La Fe [3], receiving either a conventional cemented or cementless prosthetic system, or a biological osseointegration system such as the Compress^® implant [4], a minimum postoperative follow-up period of 3 months, and [5] adherence to the same standardized postoperative rehabilitation protocol. Exclusion criteria for the case group included: inability to ambulate at the time of the study due to medical or musculoskeletal complications, presence of terminal illness under palliative care, or a history of neurological or musculoskeletal disorders that could impair gait.

For the control group, inclusion criteria consisted of volunteers aged 16 years or older without lower limb joint prostheses or any prior musculoskeletal or neurological conditions that could affect gait.

Operative technique

All patients were operated on by the same team of surgeons, four surgeons make up the Musculoskeletal Tumor Unit within the Department of Orthopedic Surgery at Hospital la Fe in Valencia, all with more than five years of experience in the treatment of these tumors, using a standardized surgical technique. An anteromedial approach was employed in 24 patients, while an anterolateral approach was used in 7 patients. The procedure involved bone tumor resection followed by joint reconstruction, with the extent of soft tissue resection determined by location, tipe and tumor size. The complete surgical technique has been detailed previously [22]. In 18 patients, a distal femur tumor prosthesis with a conventional intramedullary stem was implanted, while in 13 patients a biological osseointegration system (Compress^®) was used.

Of the 31 patients, at the time of the gait study, 17 had required a single surgery in which the tumor prosthesis was implanted. Nine had undergone a previous surgery (4 due to aseptic loosening of the previous tumor prosthesis, 2 due to tumor recurrence, 2 due to prosthesis infection, and 1 due to a pathological fracture of a giant cell tumor previously treated with curettage and filling). In 3 patients, it was the third surgery performed (2 due to infection of the previous tumor prosthesis and 1 due to tumor recurrence), and in 2 patients, it was the fourth surgery, in both cases due to aseptic loosening of the previous tumor prosthesis.

Postoperative protocol

All operated patients followed a similar postoperative protocol, with no joint immobilization performed postoperatively. In patients with a conventional stem prosthesis, immediate postoperative weight-bearing was permitted. For patients treated with the Compress^® system, weight-bearing was delayed for 6–8 weeks depending on clinical and radiographic assessments (signs of osseointegration). Postoperatively, the rehabilitation program consisted of daily therapy sessions, lasting a minimum of 30 min, continuing until the patient’s discharge. After that, rehabilitation treatment followed a standardized protocol across different centers, structured in five treatment phases. (1) Immediate postoperative phase (0–2 weeks): assisted passive mobilization; quadriceps, hamstring, and gluteal isometrics; early mobilization with a walker or crutches (weight-bearing for patients with a conventional stem and non-weight-bearing for the Compress^® system). (2) Early rehabilitation phase (2–6 weeks): work on knee range of motion; muscle strengthening with isometrics and isotonic exercises for the quadriceps, hamstrings, and gluteals; increased ambulation (weight-bearing for conventional stem patients and non-weight-bearing for the Compress^® system). (3) Intermediate phase (6–12 weeks): progressive weight-bearing for patients with a conventional stem and gradual weight-bearing initiation for the Compress^® system based on clinical and radiographic evaluations; advanced muscle strengthening; balance training; gait correction and coordination; increased knee range of motion. (4) Late phase (from 12 weeks): advanced muscle strengthening; functional training (stair climbing, walking long distances), aerobic exercises, occupational therapy. (5) Maintenance phase (6 months-1 year): regular exercise to maintain muscle strength and cardiovascular conditioning; balance and proprioception exercises. Eight patients underwent chemotherapy pre- and post-operatively, 4 chemotherapy post-operatively, 1 radiotherapy preoperatively and 1 radiotherapy postoperatively. The chemotherapy was performed using a combination of 2–4 chemotherapeutic drugs. Post-operative chemotherapy was started a mean of 7 weeks after surgery.

Outcome measures

The demographic variables collected for all participants included age, height, weight, and body mass index (BMI). For the case group, additional clinical parameters were documented, such as time since surgery (in months), leg length discrepancy (in millimeters), percentage of femur remaining healthy after tumor resection (% bone remnant), and overall functional ability. Overall function ability was assessed using the Musculoskeletal Tumour Society (MSTS) Score [23], which evaluates patients’ subjective functional capabilities. This assessment comprises six subscales: pain, function, emotional acceptance, use of assistive devices for ambulation, walking ability, and gait. Each subscale is rated on a scale from 0 to 5 points, with 5 indicating the most favorable outcome. Total scores are categorized as follows: poor (< 15%), fair (15–17%), moderate (18–20%), good (21–22%), and excellent (23–30%). Higher total scores reflect better functional performance.

All participants underwent two functional tests equipped with a BTS G-Sensor device (BTS Bioengineering, Garbagnate Milanese, Italy). The sensor was securely positioned at the S1 vertebral level using a belt to ensure a non-invasive and pain-free application. This device has been validated in multiple studies and is widely used in clinical motion analysis [18, 19, 24,25,26,27,28,29,30,31]. The functional tests conducted were as follows: (1) Timed Up and Go (TUG) Test [32]: Participants were seated in a chair with their backs against the backrest and their hands resting on their thighs. Upon the verbal command “GO”, they were instructed to stand, walk down a 3-meter pathway, turn around, and return to a seated position as quickly and safely as possible. The recorded parameters included total TUG time (s), rotation speed during the middle and final turns (°/s), and vertical acceleration during the sit-to-stand and stand-to-sit transitions (m/s²). (2) 6-Minute Walk Test (6MWT): This test was conducted in a continuous 30-meter corridor, where participants were instructed to walk for 6 min at their own preferred pace. The primary parameter measured was total walking distance (m). Data captured by the sensor were processed using G-Studio software version 2.8.16.1 for subsequent analysis.

Sagittal knee range of motion (ROM) was assessed using a standard universal goniometer. Measurements were performed with participants in a supine position, ensuring full relaxation of the lower limbs. To assess knee extension, the goniometer was aligned with the greater trochanter of the femur (proximal reference), the lateral epicondyle of the knee (fulcrum), and the lateral malleolus of the fibula (distal reference). Full knee extension was defined as 0º. Any hyperextension was recorded as a positive degree value beyond 0º, whereas a lack of full extension was documented as a negative degree value. For knee flexion, the same anatomical landmarks were used, and participants were instructed to bend their knee as far as possible while keeping the pelvis stable. The maximum degree of knee flexion was recorded. The total sagittal ROM for each knee was calculated as the sum of the degrees of flexion and extension [33]. All measurements were taken three times consecutively to ensure reliability, and the mean value was used for analysis.

Knee flexor and extensor muscle strength were evaluated using the Medical Research Council (MRC) scale, which ranges from 0 to 5 [34].

Participants were positioned in a sitting position with their knees flexed at 90º and feet unsupported to allow for accurate muscle strength assessment. To assess knee extensor strength, the examiner stabilized the thigh just proximal to the knee joint, instructing the participant to extend the knee against resistance applied at the distal part of the lower leg (above the ankle). The strength was graded according to the MRC scale, where 0 indicates no muscle contraction, 1 represents a palpable contraction without movement, 2 denotes active movement with gravity eliminated, 3 reflects active movement against gravity, 4 indicates active movement against gravity with added resistance, and 5 corresponds to normal strength. For knee flexor strength, the examiner positioned the participant’s knee in slight flexion and applied resistance at the posterior aspect of the lower leg while instructing the participant to flex the knee. The same grading criteria of the MRC scale (0–5) were used to document the strength of the knee flexor muscles. Each measurement was repeated three times, and the highest grade achieved was recorded for analysis.

Finally, a health status assessment was conducted for each patient and control participant using the SF-36 questionnaire [35]. This instrument evaluates health-related quality of life and consists of 36 items divided into eight subscales: physical functioning, role functioning—physical, pain, general health, vitality, social functioning, role functioning—emotional, and mental health. Each subscale is scored individually, and aggregate scores for the physical component summary (PCS) and mental component summary (MCS) can also be calculated.

Before the measurements, both patients and control participants were given a 20-minute acclimation period to adjust to the examination conditions. All tests were conducted under identical environmental and procedural conditions. A single investigator (NJ), with over 12 years of clinical experience, performed all clinical assessments for both groups. Two researchers (NJ and PG) trained in IMU handling conducted the two functional tests on the cases and controls.

Statistical analysis

No prospective data comparing functional test performance using IMUs between patients with distal femur tumor prostheses and a healthy control group are currently available. We hypothesized that patients with distal femur tumor prostheses would exhibit inferior functional performance compared to healthy controls across all measured variables. A post-hoc power analysis was conducted using G*Power software version 3.1.9.2 (Heinrich-Heine University, Düsseldorf, Germany), which indicated that the sample size of 68 participants achieved 80% statistical power at a 5% significance level (two-sided test) for detecting a medium effect size (d = 0.7). To account for potential attrition, the final sample size was increased by 10%, yielding a total of 75 participants.

The assumption of normality for each dependent variable within both study groups was assessed using the Kolmogorov-Smirnov test. Group differences across the various dependent variables were analyzed using either the Student’s t-test for independent samples or the Mann-Whitney U test, depending on the satisfaction of normality assumptions. To evaluate differences in the categorization of knee flexor and extensor muscle strength between groups, chi-square tests were employed. In patients with tumors, Spearman’s rank correlation coefficients (ρ) were calculated to assess the strength of the relationship between MSTS categories and the functional outcomes. Relationships between knee extension muscle strength and % bone remnant were also calculated. Additionally, the correlation between residual leg length discrepancy and hamstring strength in the operated limb was analyzed. Spearman’s coefficients were interpreted according to the classification by Dancey and Reidy [36], where ρ values of 0–0.19 indicate no or negligible correlation, 0.20–0.29 indicate a weak correlation, 0.30–0.39 a moderate correlation, 0.40–0.69 a strong correlation, and 0.70–1.0 indicate a very strong correlation. All statistical analyses were performed using SPSS version 29.0 for Windows (SPSS Inc., Chicago, IL, USA), with a P-value of ≤ 0.05 considered the threshold for statistical significance.

Results

A total of 79 participants were enrolled in the study, comprising 31 individuals in the case group and 48 in the control group. Table 1 presents the demographic and clinical characteristics of the study population.

Table 1 Demographic and clinical characteristics of the study population

The primary indications for endoprosthetic replacement were osteosarcoma (20 patients), chondrosarcoma (3 patients), giant cell tumor (4 patients), metastasis (2 patients), plasmacytoma (1 patient), and undifferentiated soft tissue sarcoma with osseous involvement (1 patient). Functional outcomes, evaluated using the MSTS scale (Table 2), demonstrated that nearly half of the patients (46.2%) achieved an excellent score, with a mean MSTS raw score of 22.2 (range, 4–29).

Table 2 Overall function ability: Percentages of cases for the Musculoskeletal Tumour Society Score

In the case group, residual leg length discrepancy (LLD) was observed in all patients. Of these, 45.2% (14/31) exhibited limb shortening, with a mean discrepancy of -25.86 mm (SD 19.22), while 51.6% (16/31) presented limb lengthening, with a mean discrepancy of + 8.14 mm (SD 5.88). Among the affected patients, 5 utilized heel or shoe lifts during functional assessments. The average height of the lifts was 31 mm (SD 14.3), which partially corrected the discrepancy, resulting in a mean corrected discrepancy of -11.47 mm (SD 5.21). Spearman correlation analysis identified a significant positive relationship between residual LLD and hamstring strength in the operated limb (ρ = 0.411, p = 0.041).

Regarding functional performance, statistically significant differences were observed between the case and control groups for all measured variables, except for the vertical acceleration during the stand-to-sit phase of the Timed Up and Go (TUG) test. Specifically, patients with distal femoral tumor prostheses exhibited poorer performance compared to healthy volunteers in the TUG and 6-Minute Walk Test (6MWT) (Table 3).

Table 3 Results of the independent t-tests comparing the case and control groups in functional tests

Knee range of motion was significantly reduced in the case group (p < 0.001, Z = -7.268), with a median knee flexion of 136.4° (115–150) in controls compared to 90.2° (5–125) in the case group. Additionally, eleven patients in the case group exhibited knee flexion contractures ranging from − 5° to -20°.

Muscle strength analysis, as assessed by the Chi-squared test, demonstrated significantly lower knee flexor and extensor muscle strength in patients with distal femoral tumor prostheses compared to healthy controls (p < 0.001) (Table 4).

Table 4 Percentages of cases and controls for knee flexor and extensor muscle strength tests (MRC)

In terms of health-related quality of life, the SF-36 results revealed significant differences between the case and control groups in the Physical Component Summary (PCS), but not in the Mental Component Summary (MCS) scores. Patients reported lower scores in physical functioning, pain, general health, role limitations due to physical health, and social functioning. However, no significant differences were found between groups in the domains of vitality, role limitations due to emotional health, or mental health (Tables 5 and 6).

Table 5 Results of the independent t-tests comparing the case and control groups in the SF-36 questionnaire

Table 6 Results of the Mann-Whitney U tests comparing the case and control group in the SF-36 questionnaire

In the case group, bivariate Spearman correlations indicated a very strong positive association between MSTS scores and knee extension strength (ρ = 0.710, p < 0.001), as well as strong positive correlations with sagittal knee ROM (ρ = 0.472, p = 0.015), total walking distance in the 6MWT (ρ = 0.474, p = 0.019), and final turn rotation speed of the TUG (ρ = 0.439, p = 0.032). Bivariate correlations also revealed significant relationships between knee extension muscle strength and % bone remnant (ρ = 0.481, p = 0.015).

Discussion

With advancements in multimodal therapies extending survival rates and innovations in endoprosthetic technology enhancing lower limb function, the focus on long-term functional outcomes has become increasingly significant alongside survivorship. Historically, assessments for tumor megaprostheses have relied primarily on subjective tools. Among these, the Musculoskeletal Tumor Society (MSTS) score is the most widely used, offering a standardized, clinician-administered evaluation of post-surgical function. In our study, nearly 75% of patients achieved scores classified as “good” to “excellent”, with a mean MSTS score of 22.2. These results align with the findings of Wilson et al. [13], who, in a recent systematic review, reported mean MSTS scores ranging from 21.8 to 27.3 following distal femur megaprosthesis limb salvage.

Although the MSTS score provides valuable insights, its limitations have been well-documented [13]. Notably, the scale may exhibit a ceiling effect, limiting its ability to fully capture the range of functional recovery, particularly in patients with high physical demands. To address these shortcomings and gain a more comprehensive evaluation of functional outcomes, we incorporated two well-established objective functional tests: the Timed Up and Go (TUG) and the 6-Minute Walk Test (6MWT). Despite their extensive use in other clinical populations, these tests have been underutilized in patients with distal femur megaprostheses after limb salvage.

In addition to these traditional tools, we introduced the use of an inertial measurement unit (IMU), a novel approach for this patient population. The IMU allows for a more granular assessment of movement by not only measuring completion times and linear velocities but also capturing rotational speeds and accelerations across multiple axes. This provides a more detailed and objective view of functional performance, complementing traditional assessments.

Our findings revealed significant differences in TUG performance between patients and controls, with patients requiring more time to complete the test. This delay likely stems from reduced rotational speed during the middle and final turns, as well as slower vertical acceleration during the sit-to-stand phase, as captured by the IMU. Previous studies in similar limb salvage populations reported shorter TUG completion times (6.6–7.1 s), compared to the 12.3 s observed in our cohort. This discrepancy can largely be attributed to the older mean age of our cohort (39.3 years) relative to the younger cohorts in other studies [6, 9, 12], where mean ages ranged from 14.5 to 19 years.

The 6MWT results also indicated significantly poorer performance in the patient group compared to controls. Kinematic analyses revealed that patients who had undergone limb salvage or total knee replacement (TKR) exhibited a slower gait and reduced knee flexion during stance, a characteristic pattern referred to as “stiff-legged gait” [37]. This altered gait may result from proprioceptive deficits, quadriceps weakness, mechanical disruptions to the patellar mechanism, instability, pain, or compensatory adaptation. Kinetic analyses further revealed shortened contact phases, decreased peak vertical ground reaction forces, and reduced internal knee moments during stance, reflecting efforts to reduce load on the affected limb and compensate by shifting weight to the unaffected side [38]. Residual leg length discrepancy (LLD) is another factor that likely contributed to these alterations in gait and performance. Observed in all patients in this study, LLD ranged from limb shortening to limb lengthening, with 5 patients using heel or shoe lifts during functional assessments. While these lifts partially corrected the discrepancy, the persistent LLD may have influenced performance during the 6MWT and TUG, as even small discrepancies in limb length can alter gait biomechanics and muscle activation patterns. Additionally, a significant positive correlation was found between LLD and hamstring strength in the operated limb, suggesting that limb lengthening may lead to compensatory adaptations or altered loading patterns, potentially affecting overall functional performance.

Our patient cohort also performed worse in the 6MWT compared to other published studies [2, 8, 9, 12], which is likely attributable to the older average age of our participants. However, among patients younger than 27 years in our study, the mean distance covered during the 6MWT was 438 m (SD 56.4), closely aligning with the 486 m reported in Bekkering’s cohort [2]. This finding is consistent with Morri et al. [12], who reported progressive improvements in 6MWT performance, reaching up to 450 m one year post-surgery. These results suggest that while patients are able to maintain functional walking capacity after distal femoral replacement, younger individuals tend to demonstrate superior performance, highlighting the influence of age on functional recovery.

Among the key factors contributing to poorer performance in both the TUG and 6MWT tests in our patient group, compared to controls, were reduced knee extensor strength and limited knee flexion range of motion. Our findings demonstrated a significant reduction in extensor strength in the patient group, which aligns with previous research. Wilson et al. [13] reported impaired knee extensor strength in the affected limb following limb salvage with proximal femoral, distal femoral, and proximal tibial megaprostheses, with no significant differences based on prosthesis location. Similarly, Bernthal et al. [7] observed a 52.6% deficit in isokinetic knee extensor strength compared to the contralateral side. Carty et al. [14] documented a mean knee extension strength of 4.15 (range: 2–5), significantly reduced compared to controls, and found that this reduction in strength was strongly correlated with the extent of soft tissue and muscle resection. Carty et al. [38] further demonstrated that larger resections result in poorer functional outcomes. Morri et al. [12] reported that resections exceeding 20 cm led to significantly lower muscle strength recovery (mean 3.5, SD 1.9), compared to 4.5 in patients with smaller resections. Guo et al. [39] similarly identified resections of 14 cm or more as a significant negative prognostic factor, while Jefferson [40] emphasized the importance of quadriceps strength in controlling forces during heel strike. Consistent with these studies, our findings revealed a strong positive correlation between knee extensor strength and the extent of bone remnant.

In parallel, our results also demonstrated reduced knee range of motion in the patient group compared to controls, consistent with findings in the literature. Specifically, five studies have evaluated joint range of motion following limb salvage surgery with distal femoral megaprostheses. Reported mean active knee flexion ranged from 94º [10] to 108.38º [11], with Carty et al. [14] documenting an average of 120º (range: 85–140º) on the operated side. Additionally, one study noted a mean active extensor lag of 5º (range: 0–20º) [1], while another reported a knee range of motion of 100º [41].

Taken together, these findings regarding both knee extensor strength and range of motion underscore the critical importance of maximizing quadriceps preservation during surgery and focusing on rehabilitation strategies aimed at restoring both quadriceps strength and knee flexion postoperatively. In this context, Carty et al. [14, 38] concluded that muscular integrity—defined by strength, range of motion, and residual muscle mass—was the most predictive factor for functional outcomes following limb salvage surgery. Our results further supported this, showing a very strong positive association between MSTS scores and knee extension strength, as well as strong correlations with sagittal knee range of motion. Consequently, clinicians and therapists should prioritize the restoration of post-surgical range of motion and muscle strength to optimize functional recovery. In addition to strength and range of motion, addressing LLD during surgical planning and postoperative rehabilitation is crucial for optimizing functional outcomes. While shoe lifts provided partial correction during functional tests, the lack of full adjustment likely contributed to performance deficits, further emphasizing the need for individualized rehabilitation strategies. These findings highlight the importance of integrating LLD management into the care of patients undergoing limb salvage surgery to enhance long-term recovery and functional capacity.

In line with the results obtained from all functional tests (TUG, 6MWT, strength, and knee ROM), the Physical Component Summary (PCS) of the health-related quality of life questionnaire indicated significant differences between the patient group and the control group, with the patient cohort exhibiting notably lower scores. These findings underscore the profound impact of physical impairments—such as reduced mobility, diminished muscle strength, and limited knee range of motion—on the quality of life in this population, particularly in domains related to physical functioning and pain. However, no significant differences were observed in the Mental Component Summary (MCS) between the groups, particularly in the domains of vitality, role limitations due to emotional health, and mental health. Similar findings were reported by Ginsberg et al. [6], who noted a lack of significant differences in mental health outcomes, despite objective functional measures favoring limb salvage surgery over amputation. This suggests that the psychological resilience of patients undergoing limb salvage surgery may play a protective role in maintaining their mental well-being. Additionally, Bekkering et al. [2] conducted a prospective study on quality of life and functional outcomes in children and adolescents following malignant bone tumor surgery, revealing that the mental status of these patients was relatively favorable compared to their healthy peers. The authors suggested that this phenomenon may be attributed to feelings of happiness associated with surviving the disease and completing treatment, along with a swift return to functional independence, which could result in the under-reporting of difficulties. This effect, previously documented in both pediatric and adult populations, is known as “response shift” [42, 43].

This study is subject to several limitations. Firstly, potential selection bias may arise, as patients who are more satisfied with their outcomes may be more inclined to participate in functional assessments. Additionally, there is considerable variability in the extent of muscle resection required during these procedures, as some tumors possess significantly larger soft tissue components. This variability complicates comparisons among patients, particularly since those with more extensive resections—who would likely demonstrate poorer functional outcomes—may be less willing to return for evaluation, thereby biasing results in a more favorable direction. Moreover, the heterogeneity of the patient population adds another layer of complexity. Differences in diagnoses, treatments, and the number of prior surgeries could confound the results. Secondly, the analysis of longitudinal data in musculoskeletal cancer patients is inherently challenging due to the varying disease states they may experience during follow-up, including remission, relapse, complications, or mortality. If both the response rates and the extent of missing data correlate with the disease state, neglecting to account for this factor can lead to biased mean outcomes.

In addition, we did not consider the physical abilities of participants prior to surgery. Variations in factors such as activity level and muscle strength between patients and healthy controls could introduce additional variability in our comparisons. While comparing the operated limb to that of healthy controls establishes an idealized benchmark, it may not adequately reflect patient-specific characteristics or pre-existing conditions that could influence functional outcomes. Nonetheless, we chose to compare the operated limb to those of healthy controls rather than the contralateral limb of the same patient to establish a more reliable functional reference. The non-operated limb in individuals undergoing endoprosthetic reconstruction often displays compensatory adaptations or muscular atrophy due to altered biomechanics and prolonged disuse, thus diminishing its validity as a reference for normal function. By utilizing healthy controls as a comparator, we minimize this confounding effect, allowing for a more accurate assessment of functional restoration and providing clearer insights into the true extent of surgical outcomes and residual deficits. Additionally, the lack of blinding in the assessment process represents another limitation. Due to the physical and functional differences between the groups (patients with megaprostheses and healthy controls), blinding of evaluators was not feasible. However, objective measures such as the use of an inertial measurement unit (IMU), standardized protocols, and the involvement of experienced evaluators were employed to minimize potential bias in the evaluation process. Finally, the retrospective nature of the study and the relatively small sample size further limit the generalizability of the findings. While we accessed all eligible patients with distal femoral megaprostheses over a period of more than 10 years at a national reference center, the rarity of this condition inherently constrained the cohort size. This limitation is compounded by the stringent inclusion criteria, which, while necessary to ensure methodological rigor, further reduced the number of participants. Consequently, the findings of this study should be interpreted with caution, as they may not fully represent the broader population of patients undergoing similar procedures. Future research with larger, multicenter cohorts would be beneficial to validate and extend these results.

In summary, this study underscores the critical role of functional outcomes in patients undergoing limb salvage surgery with distal femoral megaprostheses. Our findings indicate a strong association between knee extensor strength and range of motion with overall functional performance, as reflected in the MSTS scores. While nearly 75% of patients achieved scores classified as “good” to “excellent,” objective measures from the Timed Up and Go and 6-Minute Walk Test revealed significant performance deficits compared to healthy controls, likely due to limitations in knee extensor strength and range of motion. These findings underscore the need for targeted rehabilitation strategies that prioritize muscle strength and range of motion to optimize long-term functional recovery in these patients.