Proximal femoral tumor resection followed by joint prosthesis replacement: a systematic review and meta-analysis

Background This study aimed to determine the prognostic outcome of hip joint replacement after resection of proximal femoral tumors by reviewing original studies. Methods Two researchers independently searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to July 17, 2022. Then, the literature was screened by inclusion criteria. The basic information, primary outcomes, and secondary outcomes were extracted for weighted combined analysis. The quality of the included literature was evaluated using the Newcastle–Ottawa scale. Results Twenty-four retrospective cohort studies comprising 2081 patients were included. The limb salvage rate was 98%. The survival rates at 1, 2, 3, 4, and 5 years were 80, 72, 65, 64, and 55% for patients with primary tumors and the rate at 1, 2, 3, 4, and 5 years were 44, 25, 17, 14, and 11% for patients with bone metastases, respectively. Conclusion As chemotherapy and radiotherapy treatment progressed, joint reconstruction after proximal femoral tumor resection improved patients' function and quality of life. Supplementary Information The online version contains supplementary material available at 10.1186/s12891-023-06913-w.


Background
Primary and secondary bone tumors can occur in bone and cartilage tissues [1].Primary bone tumors occur in children and adolescents and are an important contributor to death and disability in this age group [2].Secondary bone tumors, i.e., bone metastases, are 30-40 times more common than primary ones and are characterized by higher prevalence and poor quality of life [3].Except for the spine, the proximal femur is the most frequent site of bone metastases (approximately 10%) and is the most commonly affected long bone [4].The risk of pathologic fracture of the proximal femur metastases is high due to weight bearing and biomechanical conditions [5].
One of the most important objectives in treating proximal femoral tumors is to reduce pain to provide a better quality of life for the patient.Limb-preserving surgery has gradually become the main surgical modality for bone tumors [6].With the advancement of relevant, comprehensive treatments, the goal of treatment for bone tumors requires improving patient survival and preserving good limb function [7].Metal tumor-based artificial joints are currently the first choice for functional reconstruction after limb preservation surgery due to the advantages of immediate postoperative restoration of affected limb function, early mobility, and long-term functional satisfaction [8].
The preferred reconstruction method for patients with proximal femoral tumors is prosthetic replacement after tumor resection.Due to the low incidence and limited follow-up time, reports of clinical outcomes, survival, prosthetic survival, and function of patients after surgery vary widely in original studies.A systematic evaluation meta-analysis published by Thambapillary et al. [9] in 2013 reported a limb preservation rate of over 90%, a 5-year prosthetic survival rate of 84%, and an overall revision rate of 11% without addressing patient survival.In contrast, the systematic evaluation published by Brown et al. [10] in 2018 only qualitatively described the relevant data.Based on the publication of several relevant original studies in recent years, this study intends to update and supplement the analysis of clinical outcomes, complications, survival, prosthetic survival, and function of metal prosthesis replacement after proximal femoral tumor resection and subgroup analysis was according to follow-up time, prosthesis type, and tumor type to bring reference for clinical decision-making.

Literature search
This systematic review was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines.Two investigators independently conducted database searches, and arguments were resolved through discussion.PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to July 17, 2022.The search strategy was "Neoplasms" AND "Arthroplasty, Replacement, Hip" and was limited to English-language papers.

Eligibility criteria
The inclusion criteria were: 1) patients diagnosed with a proximal femoral tumor; 2) hip replacement after tumor resection; 3) cohort study.The exclusion criteria were: 1) number < 10; 2) conference abstracts, and reviews; 3) revision surgery; 4) unavailability of the full text.

Literature screening and data extraction
Two investigators independently screened the literature and extracted data.After literature de-duplication, irrelevant literature was excluded by reading the title and abstract, and the full text of relevant literature was further analyzed.Data were extracted based on a predesigned table, including authors, year of publication, country, total number, gender, age, and follow-up time.The primary outcomes included overall patient survival and limb preservation rate.The secondary outcomes included limb salvage rate (the proportion of patients who avoided amputation at end of follow-up period), prosthesis survival, revision rate, hemi to total hip conversion rate, tumor status, complications, and function based on the Musculoskeletal Tumor Society, 1993, MSTS.

Risk of bias assessment
The quality of the included literature was assessed using the Newcastle-Ottawa scale (NOS).The following characteristics were assessed: representativeness of the exposed cohort, selection of the non-exposed cohort, ascertainment of exposure, the demonstration that the outcome of interest was not present at the start of the study, comparability of cohorts based on the design or analysis, or outcome assessment, whether the follow-up was long enough for outcomes to occur, and adequacy of follow-up of cohorts.

Data synthesis and statistical analysis
Data were analyzed using R software (v.6.0).Individual rates were combined using double inverse sine transformation [11], and the rate and 95% confidence intervals (CIs) were calculated.Cochran-Q test for heterogeneity and I 2 evaluated the magnitude of heterogeneity.An I 2 > 50% was considered high heterogeneity, and a random effects model was used; for I 2 ≤ 50%, a fixed effects model was used.The survival data were captured from Kaplan-Meier (K-M) curves using Engauge Digitizer software.The subgroup analysis was performed according to follow-up time, prosthesis type, and tumor type.The publication bias was assessed using Egger's test, and the sensitivity analysis was performed by excluding individual studies on a case-by-case basis.

Literature search results
A total of 4486 studies were searched.After excluding duplicates (1137), the title and abstract of 3349 studies were analyzed, and 70 studies were selected for full-text screening.Two studies with < 10 patients, three revisionrelated reports, two conference abstracts, 13 with unextractable data, 11 with irrelevant study content, and 15 non-proximal femoral tumors were excluded.Finally, 24 studies were included for analysis.The selection process is shown in Fig. 1.

Studies description
The 24 included papers were retrospective cohort studies (Table 1) comprising 2081 patients, with the number of males ranging from 4-236 in each study and the number of females ranging from 8-468.The age at surgery ranged from 27.8-66.1 years, and the follow-up period ranged from 3-216 months.The year of publication for each study ranged from 1998-2020.The countries with the most published studies were the United States (12), China (3), and the United Kingdom (2).

Methodological quality of included studies
The results of the NOS evaluation form showed that three of the 24 articles scored 8, 12 scored 7, and nine scored 6.There was no literature with a high risk of bias.

Prosthesis revision rate
The overall prosthesis revision rate was 9% (95% CI: 5-15%, I 2 = 86%) (Fig. 2).The subgroup analysis based on follow-up time showed that the revision rates were 2, 8, 21, and 47% at 2, 5, 10, and 20 years, respectively.Moreover, the subgroup analysis based on prosthesis type showed that the revision rate was 11% for    custom-made prostheses and 8% for modular-made prostheses (Additional file 2: Appendix Table 2).Additionally, three studies described the causes of revision, with the main causes being aseptic loosening and infection.

Local recurrence rate of tumors
Moreover, the local recurrence rate was 7% (95% CI: 4-11%, I 2 = 75%) (Fig. 4).Based on the follow-up time subgroup analysis, the local recurrence rates were 6 and Fig. 2 Revision rate of prosthetic Fig. 3 Limb salvage rate 8% at 2-5 and 6-10 years of follow-up, respectively.In the prosthesis type subgroup analysis, the recurrence rate was 13% for custom-made prostheses, 1% for modularmade prostheses, 4% for local hemi hip recurrence, and 5% for local recurrence of the total hip (Additional file 2: Appendix Table 5).

Complications
Forty-six complications, such as infections, dislocations, and visceral injuries, were reported in 2069 patients from 24 cohorts.The five main complications reported were infections, dislocations, acetabular wear, deep vein thrombosis, and aseptic loosening.

Sensitivity analysis and publication bias
The funnel plots and Egger regression presented p > 0.05, suggesting no publication bias.The exclusion of each study did not affect outcome indicators, indicating robust results.

Discussion
Herein, patient clinical and prosthetic outcomes were analyzed using data from 24 studies with 2081 patients with joint prosthesis replacement after proximal femoral tumor resection.The overall patient limb preservation rate was 98%.The total prosthesis revision rate was 9% and gradually increased with increasing follow-up time.
According to the tumor type classification, patients with primary tumors still had more than a 50% survival rate in the fifth year, and the trend of survival rate decreased more slowly.Meanwhile, more than 50% of patients with bone metastases had already died in the first year, and survival rate decreased by almost half in the second year.This finding was consistent with Houdek et al. [19], where the overall patient survival was associated with the presence or absence of tumor metastasis [hazard ratio (HR) 2.96; 95% CI: 2.11-4.20].The prosthesis type analysis showed that patients with total hip replacement had a higher survival rate than those with hemi-hip replacement.The total hip replacement studies in this systematic review [30,32] included mostly patients with primary tumors of the proximal femur or chemotherapy-sensitive proximal femoral malignancies.They have a relatively better prognosis than chemotherapy-insensitive malignant patients with higher requirements for long-term function.The total hip replacement has a better socket-prosthesis head fit, with friction occurring at the prosthesis interface rather than the prosthesis-chondral interface, and has a better long-term postoperative function.The total hip replacement patients in this study used custom prostheses, so the subgroup analysis shown that patients with custom prostheses had a higher survival rate than those with modular-made prostheses.Meanwhile, survival rates for patients with modular tumors were worse may well be because these were used in patients with metastases who were not expected to live so long considering convenience and economy.
Prosthesis survival rates were much higher than patient survival rates at the same follow-up time.This finding suggested that for patients with poor oncologic outcomes, joint prostheses can successfully preserve functional limbs without revision and for long-term survivors for at least 5-10 years.However, implant survival steadily declined over time (mean 20-year implant survival: 39%, 95% CI: 12-66%), while tumor survival declined more slowly and eventually remained stable after 10 years of follow-up.This result is similar to Liang Fig. 7 Rate of aseptic loosening et al. [36] regarding joint reconstruction after resectioning periprosthetic tumors in the knee.
Infection is the main cause of limb salvage failure, with deep infection being a lifelong threat after prosthetic replacement.The subgroup analysis showed a gradual increase in infection rate with increasing follow-up time, but this result should be cautiously interpreted because most studies did not provide the type of infection.The risk factors for periprosthetic infection include prolonged and repeat surgery, malnutrition, and immune compromise during comorbidities such as chemotherapy, radiation therapy, extra-articular resection, poor soft tissue coverage, hematoma formation, and diabetes mellitus [37,38].Various methods are available to control deep periprosthetic infections, such as amputation, level 2 revision, level 1 revision, joint replacement, irrigation, debridement, and conservative antibiotic therapy, with level 2 revision the most likely cure for infection in most infected patients [7,39].
The hemi hip replacement has better stability than the total hip replacement.Hip dislocation was the most common complication of the upper femoral prosthesis.The subgroup analysis showed a gradual increase in dislocation rate with increasing follow-up time and a higher rate of dislocation in total hip replacements than in hemi hip replacements, similar to Thambapillary et al. [9].Aseptic loosening is also a major complication of prosthetic reconstruction.The subgroup analysis showed a gradual increase in aseptic loosening with increasing follow-up time and a higher rate of total hip replacement aseptic loosening than hemi hip replacement.Thambapillary et al. [9] reported a 5.2% aseptic loosening, higher than the 3% reported here, which might be related to the improved prosthesis design and the choice of fixation method, making recent cases reported no aseptic loosening occurred in any of the follow-up cases [40].Aseptic loosening is more frequent in pediatric patients than in adults [41].Thambapillary et al. [9] included pediatric patients, while the present study included only adult patients.The pooled DVT rate was lower than the 8.5% reported by Thambapillary et al. [9].This might be due to the emphasis on prophylactic management of postarthroplasty thrombosis and prophylactic management of thrombosis in oncology patients in the last decade, with all study patients undergoing perioperative and postoperative prophylactic use of anticoagulants.
However, this study also has some limitations.First, due to data limitations, it was not possible to analyze the relevant outcome for specific tumor types, different prosthesis brands, resection methods, margin sizes, radiotherapy types, the combination of adjuvant radiotherapy and fixation types, and compare the impact of each factor on the outcome.Second, due to incidence limitations, the number of cases reported so far is small, and more original studies are still needed to expand the sample size of the analysis.

Conclusion
The use of joint reconstruction after proximal femoral tumor resection to improve patients' function and quality of life has been solidified with advances in chemotherapy and radiotherapy.Proximal femoral arthroplasty has benefits in treating primary or metastatic tumors of the proximal femur.The prosthesis tends to outlive the patient, providing them with a relatively pain-free limb with good functional capacity, with limb salvage rates of 98%.Compared to total hip replacement, hemi-hip offers better stability and reduced dislocation and aseptic loosening rates.

Fig. 1
Fig. 1 Flow diagram of the study selection process

Table 1
Basic characteristics of included studies P Proximal tumor, M Bone metastases, R Retrospective

Table 2
Bleeding volume, operative time and hospital days

Table 3
Subgroup analysis of patient survival rates

Table 4
Subgroup analysis of prosthetic survival