Elective Surgical Care Pathways Are Associated With Lower Fracture Rates at Presentation and Contribute to Superior Clinical Outcomes in Metastatic Bone Disease.

Introduction

Metastatic bone disease (MBD) has a substantial impact on quality of life in cancer patients, often leading to pathologic fractures (up to 20%), impaired mobility, pain (up to 75%), and subsequent reduced physical function [ 1 , 2 , 3 ]. With advances in cancer care, patients are living longer with advanced disease and as a result, the prevalence of MBD continues to rise [ 4 , 5 ]. Orthopaedic surgery is indicated to treat an acute or impending pathologic fracture, manage an acute pain crisis, reconstruct mechanical instability, or occasionally for curative resection of solitary and oligometastatic disease [ 6 , 7 ].

Patients with MBD enter surgical care via two mechanisms: emergent or elective referral. Research in other surgical disciplines has demonstrated that for surgical procedures routinely performed via both elective or emergent care pathways, such as coronary artery bypass graft, colectomy, and aortic repair, considerably greater mortality is associated with emergent surgery [ 8 ]. MBD patients referred via emergent mechanisms present acutely with either a pathologic fracture or a pain crisis and are treated with emergent surgical intervention. Patients referred via elective pathways may have an identified, high‐risk bone lesion and are referred to an orthopaedic surgeon for consideration of an urgent, yet scheduled, elective procedure [ 9 ]. Orthopaedic literature has demonstrated improved survival and reduced health care costs with prophylactic fixation of impending pathologic fractures [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. However, fracture status alone does not reliably distinguish care pathways: some patients with impending fractures present emergently with pain crises or failure to thrive, while some with actual fractures may undergo elective surgery. From a health‐services perspective, analyzing outcomes by elective versus emergent referral may therefore provide a more accurate framework for understanding and improving surgical care delivery in MBD.

Patients with MBD requiring orthopaedic surgery continue to have poor post‐operative survival [ 17 , 18 ]. There is a compelling clinical rationale to investigate care delivery in these patients to identify care pathway refinements that may improve outcomes and survivorship in cancer patients living with advanced disease. The purpose of this study was to compare overall survival (OS), length of stay (LOS), and 30‐day re‐admission between patients undergoing elective versus emergent surgery for MBD involving the pelvis and appendicular skeleton. Secondary objectives included comparing demographics, patient factors, and oncologic factors associated with the different care pathways.

Methods

Study Design

A retrospective cohort study was performed including all consecutive patients with MBD of the femur, humerus, tibia, or pelvis treated with orthopaedic surgery in southern Alberta, Canada. Patients were treated at nine centers, including four community hospitals, four academic hospitals, and one quaternary cancer center, and underwent surgery between January 1, 2006 and March 31, 2021. These hospitals comprise three health zones within a universal healthcare system and all patients living in these regions would receive care at one of the nine hospitals. Patients were identified by a search query of all patients with a diagnosis of metastatic cancer who underwent surgery for MBD. Indications for surgery included an impending or actual pathologic fracture, intractable pain, loss of mobility, or bone lesions unlikely to improve with systemic therapy or radiation therapy. Revision surgeries were excluded to avoid additional bias. Elective surgical care was defined as a scheduled surgical event preceded by at least one outpatient consultation by an orthopaedic surgeon. This included general orthopaedic surgeons as well as orthopaedic oncologists. Emergent surgical care was defined as an unscheduled surgical event preceded by (1) an emergency department visit resulting in admission to orthopaedic surgery and subsequent unscheduled surgery, (2) an emergency department visit due to pain or fracture less than 7 days prior to surgery indicating an acute event had occurred, or (3) an inpatient consultation by an orthopaedic surgeon prior to surgery.

Patient data extracted included age, sex, comorbidities according to the Charlson Comorbidity Index (CCI), primary diagnosis, stage at diagnosis, pre‐operative systemic therapy and radiation therapy, anatomic location of the lesion, procedure performed, and post‐operative complications [ 19 ]. Notably, CCI includes points for metastatic cancer; as all patients in this study have a diagnosis of metastatic cancer, this comorbidity was removed from the overall CCI score. Procedures were grouped according to fixation strategy, including intramedullary nails (IMN), conventional joint arthroplasty, joint arthroplasty with tumour endoprosthesis, Harrington reconstruction, and open reduction internal fixation (ORIF). ORIF included plate and screw constructs only. Healthcare resource data collected included the date of surgery, geographic location of the hospital, and the sub‐specialty of the treating surgeon. Indications for surgery were recorded as an acute pain crisis, impending pathologic fracture, or actual pathologic fracture. The primary outcome was the post‐operative OS, and secondary outcomes included hospital LOS, including pre‐operative and post‐operative LOS, and readmissions to hospital within 30 days of discharge following the index surgical event.

Propensity score matching (PSM) analysis was performed in order to balance potential confounders between patients managed with either elective or emergent surgery utilizing PsmPy (Python) [ 20 ]. A linear regression method was used to generate propensity score values, which were matched using a nearest‐neighbor matching method with a 1:1 ratio and a caliper of 0.2 of the standard deviation of the logit of the propensity score. Complete case analysis was used which resulted in exclusion of patients with missing variables. For PSM, the following covariates were included in the model: age, sex (male, female), primary cancer type (including breast, lung, prostate, renal cell, multiple myeloma, other, or unknown primary), Eastern Cooperative Oncology Group Performance Status (ECOG PS, 0–4), and the presence of more than one comorbidity. Comorbidities of interest included any listed in the Charlson Comorbidity Index but did not include the diagnosis of metastatic cancer [ 19 ]. These covariates were selected due to their potential significant impact on study outcomes. The elective group served as the smaller reference group for matching. Matching inclusion and yield is illustrated in Figure 1 .

Statistical Analysis

All patients were followed until March 2022, or until death. Descriptive statistics were used to summarize patient characteristics. Comparison of clinical features between groups was performed with chi‐square tests for categorical variables or Student's t tests for continuous variables. Post‐operative survival was calculated using Kaplan–Meier survival analysis with 95% confidence intervals (CI). Patients who were lost to follow‐up or alive at the time of data collection were censored at the last date of follow‐up. Differences between survival curves were evaluated with log rank tests. A multivariate Cox regression analysis was used to evaluate the association of patient characteristics, including surgical referral pathway, and survival and Hazard Ratios (HRs) with 95% CIs were reported. Several subgroup analyzes were performed. A subgroup of all patients with an impending fracture of either the upper or lower extremity was assessed to explore the impact of referral pathway on patients without a pathologic fracture. Furthermore, location of surgery was also assessed using a subgroup of patients with upper extremity pathologic fractures, as these fractures may be appropriately managed in an urgent, but elective manner. Surgical technique was assessed by evaluating a subgroup of all patients treated with surgical fixation (including IMN and ORIF) as well as a subgroup of patients treated with conventional joint arthroplasty. Patients treated with a tumour endoprosthesis were excluded from these subgroups. All statistical analyzes were performed using Stata (StataCorp. 2019. Release 16. College Station, TX: StataCorp LLC).

Results

A total of 558 patients with MBD of the long bones or pelvis were treated with orthopaedic surgery across nine institutions in southern Alberta, Canada over a 15‐year period. Following propensity matching, 296 patients were included with 148 patients in the emergency care group and 148 in the elective care group. Patient characteristics are summarized in Table 1 . Median age was 64.2 years in the total cohort, 65.6 in the emergent care group and 63.8 in the elective care group ( p = 0.55). Patients were propensity matched according to age, sex, primary cancer type, ECOG PS, and the presence of more than one comorbidity and no significant difference was found between variables following matching (Figure 1 , Table 1 ).

Surgical details are summarized in Table 2 . Notably there were significant differences in the methods of stabilization used, with more intramedullary nails (IMN) performed in the emergent group (52.1% vs . 37.5%, p = 0.91) and tumour endoprostheses were more frequently used in the elective group (8.6% vs. 1.4%, p = 0.01). Furthermore, indications for surgery were different between groups, with more pathologic fractures in the emergent group (77.8% vs. 27.6%, p < 0.001) and more impending fractures in the elective group (73.0% vs. 20.8%). There were 19 pathologic femur fractures treated electively, and all of these fractures were of the lesser trochanter.

Median post‐operative OS for the entire cohort was 7.1 months (95%CI: 5.9–8.2). Post‐operative OS was significantly shorter in the emergent group (5.0 months, 95%CI: 3.0–6.0) compared to the elective group (16.9 months 95%CI: 11.1–21.2) [ p < 0.001, Figure 2 ]. On multivariate analysis, emergent surgical referral was found to be an independent poor prognostic factor of post‐operative OS (HR: 1.60, 95%CI: 1.27–2.03, p < 0.001) [Table 3 ]. A diagnosis of multiple myeloma and renal cell carcinoma were found to be positive prognostic factors (HR: 0.36, 95%CI: 0.18–0.70, p < 0.001; HR: 0.52, 95%CI: 0.28‐0.98, p = 0.04) [Table 3 ].

Median hospital LOS was significantly longer in the emergent group compared to the elective group (13 days, 95%CI: 6–28 vs. 6 days, 95%CI: 3–10, p < 0.001, Figure 3 ). In the emergent group, LOS was longer in the pre‐operative phase of care (2 days, 95%CI: 1–5 vs. 0 days, 95%CI: 0–2, p < 0.001) and substantially longer in the post‐operative phase of care (11 days, 95% CI: 9–13 vs. 5 days, 95%CI: 3–8, p < 0.001). Acute 30‐day hospital readmissions were also significantly higher in the emergent group at 12.2% (95%CI: 10.3–17.6) compared to a rate of 6.1% (95%CI: 3.5–10.2) in the elective group ( p = 0.004). Venous thromboembolism events were additionally more common in the emergent group, with 18 patients presenting with an imaging confirmed diagnosis of either pulmonary embolus or deep vein thrombosis (12.2%) compared to five in the elective group (3.4%, p = 0.009).

A subgroup analysis of patients presenting with impending fractures ( n = 146, n = 36 emergent and n = 114 elective) was performed. Post‐operative OS in this cohort was 12.3 months (95%CI: 9.0–17.5 months). There was significantly reduced median OS in the emergent treatment group compared to the elective group (5.5 months 95%CI: 3.2–13.0 vs. 15.6 months 95%CI: 11.2–26.6, p = 0.01). Furthermore, hospital LOS was significantly longer in the emergent group (17 days 95%CI: 9–31.5 vs. 6 days 95%CI: 5–7, p < 0.001) and there were significantly higher rates of hospital readmission in the emergent group (15.6% 95%CI: 5.3%–32.8% vs. 6.2% 95%CI: 2.7%–13.1%, p = 0.04).

To further assess the role of referral pathway on clinical outcomes, a subgroup analysis was performed on patients with an upper extremity pathologic fracture ( n = 44; n = 25 emergent and n = 19 elective). There was a non‐significant trend towards reduced post‐operative OS in the emergent group compared to the elective group (6.2 months 95%CI: 3.6–12.6 vs . 9.0 months 95%CI: 5.3–30.6, p = 0.88). Hospital LOS was significantly longer in the emergent group at 4 days (95%CI: 3–9.5) compared to 3 days (95%CI: 1–3) in the elective group ( p = 0.02). Only one patient in this subgroup from the elective cohort was readmitted to hospital.

The impact of surgical technique was assessed with two subgroups, a fixation group comprised of patients treated with IMN and ORIF and a conventional joint arthroplasty group. Amongst the fixation subgroup, median OS was 7.8 months (95%CI: 5.7–10.4). There was significantly reduced median OS in the emergent treatment group compared to the elective group (5.5 months 95%CI: 3.8–7.1 vs. 11.3 months 95%CI: 8.6–20.2, p = 0.01, Figure 4A ). Hospital LOS was significantly longer in the emergent treatment group at 15 days (95%CI: 9–19) compared to 5 days (95%CI: 4–6) in the elective group ( p < 0.001). There was no significant difference in hospital readmission rates between groups (emergent group: 12.0%, 95%CI: 6.4–20.2; elective group: 7.4%, 95%CI: 2.8%–15.4%; p = 0.24). The median OS in the arthroplasty subgroup was 8.2 months (95%CI: 5.2–10.3). There was also significantly reduced median OS in the emergent treatment group compared to the elective group (5.5 months 95%CI: 3.0–8.3 vs. 13.6 months 95%CI: 6.8–21.3, p = 0.01, Figure 4B ). Hospital LOS was significantly longer in the emergent treatment group at 12.5 days (95%CI: 9–14.3) compared to 5.5 days (95%CI: 3.0–8.3) in the elective group ( p < 0.001). There was no significant difference in hospital readmission rates between groups (emergent group: 13.0%, 95%CI: 4.9–26.2; elective group: 6.1%, 95%CI: 1.3%–16.9%; p = 0.35).

Discussion

Overall survival for metastatic cancer has steadily improved, due to advances in systemic therapies, earlier detection, and more aggressive management [ 4 , 21 , 22 , 23 , 24 ]. However, these survival gains amongst patients undergoing surgical treatment for metastatic bone disease (MBD) have been slower and less pronounced [ 17 , 18 ]. Thus, survival after MBD surgery may lag behind broader oncologic trends, underscoring the need to examine how surgical care pathways impact postoperative outcomes.

In this study, we examined the impact of surgical referral pathways on post‐operative survival and clinical outcomes in patients with MBD of the long bones or pelvis requiring surgical stabilization. Unlike prior studies that stratified patients by acute versus impending fracture, we classified them according to elective versus emergent care pathways, a framework that more accurately reflects how patients with MBD enter the surgical system [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. In this context, we found that after propensity matching, patients managed emergently experienced markedly worse outcomes, including shorter survival, longer hospitalization, higher 30‐day readmission rates, and greater venous thrombotic events. Notably, when evaluating a subgroup of patients who presented either electively or emergently with an impending fracture, the results were consistent with significantly worse outcomes in the patients managed emergently. Furthermore, outcomes remained inferior in the emergent referral treatment group when evaluating subgroups according to surgical technique. These findings underscore the importance of care delivery models that enable timely identification and elective management of at‐risk patients. Our findings in appendicular and pelvic MBD parallel those reported in metastatic spine surgery. Zeoli et al. similarly demonstrated that patients presenting through the emergency department had worse survival, longer hospitalizations, and were less often discharged home compared with those admitted electively [ 25 ]. Together, these data highlight that care delivery pathway, not just disease severity, influences patient outcomes across both spinal and appendicular MBD.

There are several factors that may influence the reduced survival in the emergent group. Longer pre‐operative LOS in the emergent group may be due to several factors including time to obtain appropriate pre‐operative imaging, pre‐operative anesthesia, and internal medicine consultations, and waiting for operating room time on an emergency trauma list. In hip fracture patients, time from injury to surgery is a known predictor of mortality, with a wait time of greater than 24 h identified as a key threshold risk of mortality [ 26 , 27 , 28 ]. This delay may have implications for patients with MBD, as there was a 48‐h difference in the pre‐operative LOS between groups. Expediting time to surgery in this particularly vulnerable population may be of benefit and requires further investigation. Furthermore, post‐operative LOS was substantially longer in the emergent group, with a difference of 6 days between groups. Several studies have demonstrated that shorter hospital LOS leads to improved functional outcomes and lower mortality in older patients which may additionally contribute to the reduced survival in the emergent group [ 29 , 30 , 31 ].

The results of this study may also be due to a coordinated care approach within elective pathways. Improved care delivery in this population has received growing attention in the literature, with more than 60% of orthopaedic oncologists expressing a need for improved communication along the referral pathway [ 32 ]. An early and proactive response to MBD has been shown to improve clinical outcomes, and is facilitated by a coordinated, multidisciplinary approach to treatment [ 17 , 33 , 34 ]. Similar benefits of structured care coordination have been shown in spinal MBD. Miyazaki et al. reported that implementation of a multidisciplinary Bone Metastasis Cancer Board reduced the proportion of emergency surgeries, improved preoperative status, and shortened hospital stays, suggesting coordinated pathways can shift patients from emergent to elective management, with tangible improvements in outcomes [ 35 ]. Challenges exist in coordinating elective care for these patients, and previous studies have identified delays in referring oncology patients to orthopaedics [ 32 , 36 , 37 ]. Surveillance programs, automated referral pathways, and multidisciplinary MBD clinics have been proposed as efficient methods to improve access to elective care [ 32 , 33 ]. Multiple national societies have published guidelines for the management of MBD recommending early involvement of an orthopaedic surgeon for all at risk bone lesions [ 9 , 38 , 39 , 40 , 41 ].

The presence of an actualized pathologic fracture is a poor prognostic factor, independent of age, comorbidities, or primary cancer histology [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Importantly, in our study, emergent care, not just the presence of pathologic fracture was independently associated with worse outcomes. Furthermore, patients treated for an impending fracture through emergent mechanisms had no significant difference in post‐operative survival than those with a pathologic fracture. This highlights the importance of improving elective referral pathways, so that patients can be identified in the community with high‐risk MBD before an acute event occurs. We hypothesize that this finding is partially reflective of the reduced pre‐operative hospital LOS in the elective group, analogous to the hip fracture population and the importance of reducing time to surgery [ 28 ]. Validation of this finding with other large cohorts will be necessary to ensure these findings are generalizable to other jurisdictions. While unmeasured factors such as more advanced disease burden may contribute to emergent presentations and hospitalizations, we minimized potential confounding by propensity matching on key clinical covariates including primary tumor type, ECOG performance status, and comorbidity burden. The persistence of worse outcomes in the emergent group despite this adjustment suggests that care pathway itself is an important determinant of prognosis.

The financial cost of MBD is significant, with an estimated total cost of $12.6 billion USD annually, comprising 17% of total cancer care [ 42 ]. This value is expected to rise as the incidence of metastatic cancer increases. Reducing LOS and 30‐day readmission, as seen in the elective group in this study, would likely have a profound effect on the total surgical cost of treating MBD. Significant cost savings have been identified with prophylactic fixation of impending pathologic fractures [ 11 ]. Our results indicate that this cost saving could be seen on a broader scale by reducing emergent MBD presentations. However, effective screening and follow‐up would be necessary to reduce the burden of emergent presentations, which could translate to increased cost in elective management of MBD. Economic analyzes evaluating these surgical care pathways, and interventions to reduce emergent surgical management, are necessary to further explore this hypothesis.

As a retrospective study, there are several limitations that may influence the interpretations of the results. We were unable to analyze functional outcomes nor quality of life metrics which may be relevant to this clinical question. Furthermore, factors including socioeconomic status and health literacy were not accounted for in this study and may differ across treatment groups. Despite the universal healthcare system present in Canada, socioeconomic inequalities have been shown to increase mortality and interfere with the ability of patients with advanced cancer to access care [ 43 ]. Interventions that may improve care pathways would need to consider socioeconomic disparities to ensure equitable access. MBD is a heterogeneous disease and there are other patient and tumour‐specific factors that influence post‐operative outcomes that were not included in this analysis. A PSM analysis was performed in an attempt to limit the impact of inherent differences between the treatment groups on outcomes, however, several more known and unknown variables may impact the findings, particularly the presence of pathologic fracture. Fracture status and referral pathway are inherently linked and this contributes to the results. The study findings advocate for improved access to elective surgical care but do not negate the impact of the presence of fracture on outcomes. Lastly, post‐operative complications were not included in this analysis.

Conclusion

Emergent surgical management of MBD of the long bones and pelvis is associated with worse survival, longer hospital stays, and higher re‐admission rates compared to elective care, independent of the presence of pathologic fracture. These findings support the implementation of coordinated, elective surgical pathways to improve outcomes in this vulnerable population. Interventions that reduce the need for emergent surgery, through measures such as enhanced screening and proactive follow‐up, have the potential to substantially improve outcomes in this population.

Ethics Statement

A waiver of consent was granted. This study was approved by the Health Research Ethics Board of Alberta Cancer Committee (HREBA. CC‐20‐0335).

Conflicts of Interest

The authors declare no conflicts of interest.

Synopsis

• Care for patients with metastatic bone disease is highly complex, individualized, and centered on patient goals and expectations. • Surgical management of MBD in an elective setting leads to reduced fracture at presentation, improved post‐operative survival, hospital length of stay, and 30‐day hospital readmission when compared to patients who present through emergent care mechanisms.

Acknowledgments

We would like to acknowledge Dr. Scott Moorman for his contributions to the development of the southern Alberta database. The study was supported by the Section of Orthopaedic Surgery, Department of Surgery, University of Calgary.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon request. The data are not publicly available due to privacy or ethical restrictions.

References

1 K. P. Weinfurt , Y. Li , L. D. Castel , et al., “ The Significance of Skeletal‐Related Events for the Health‐Related Quality of Life of Patients With Metastatic Prostate Cancer ,” Annals of Oncology 16 , no. 4 ( 2005 ): 579 – 584 . 15734776 10.1093/annonc/mdi122

2 A. J. W. M. Brouns , A. van Veelen , G. D. M. Veerman , et al., “ Incidence of Bone Metastases and Skeletal‐Related Events in Patients With EGFR ‐Mutated NSCLC Treated With Osimertinib ,” JTO Clinical and Research Reports 4 , no. 5 ( 2023 ): 100513 . 37168878 10.1016/j.jtocrr.2023.100513 PMC10165134

3 R. U. Ashford , L. Benjamin , S. Pendlebury , and P. D. Stalley , “ The Modern Surgical and Non‐Surgical Management of Appendicular Skeletal Metastases ,” Orthopaedics and Trauma 26 , no. 3 ( 2012 ): 184 – 199 .

4 Surveillance, Epidemiology, and End Results (SEER) Program ( www.seer.cancer.gov ). SEER*Stat Database: Relative Survival by Year of Diagnosis, April 2018 Sub (1975–2016). National Cancer Institute, DCCPS, Surveillance Research Program.

5 K. L. Weber , R. L. Randall , S. Grossman , et al., “ Management of Lower‐Extremity Bone Metastasis ,” Journal of Bone and Joint Surgery 88 ( 2006 ): 11 – 19 . 10.2106/JBJS.F.00635 17142431

6 C. Errani , A. F. Mavrogenis , L. Cevolani , et al., “ Treatment for Long Bone Metastases Based on a Systematic Literature Review ,” European Journal of Orthopaedic Surgery & Traumatology 27 ( 2017 ): 205 – 211 . 27650452 10.1007/s00590-016-1857-9

7 T. J. Wood , A. Racano , H. Yeung , F. Farrokhyar , M. Ghert , and B. M. Deheshi , “ Surgical Management of Bone Metastases: Quality of Evidence and Systematic Review ,” Annals of Surgical Oncology 21 ( 2014 ): 4081 – 4089 . 25223925 10.1245/s10434-014-4002-1

8 A. H. Haider , A. Obirieze , C. G. Velopulos , et al., “ Incremental Cost of Emergency Versus Elective Surgery ,” Annals of Surgery 262 ( 2015 ): 260 – 266 . 25521669 10.1097/SLA.0000000000001080

9 Metastatic Bone Disease: A Guide to Good Practice ( British Orthopaedic Association and British Orthopaedic Oncology Society publication , 2000 ) http://www.boos.org.uk/wp-content/uploads/2016/03/BOOS-MBD-2016BOA.pdf .

10 C. Arvinius , J. L. C. Parra , L. S. Mateo , R. G. Maroto , A. F. Borrego , and L. L. D. Stern , “ Benefits of Early Intramedullary Nailing in Femoral Metastases ,” International Orthopaedics 38 ( 2014 ): 129 – 132 . 24126497 10.1007/s00264-013-2108-x PMC3890135

11 A. T. Blank , D. M. Lerman , N. M. Patel , and T. B. Rapp , “ Is Prophylactic Intervention More Cost‐Effective Than the Treatment of Pathologic Fractures in Metastatic Bone Disease ,” Clinical Orthopaedics & Related Research 474 ( 2016 ): 1563 – 1570 . 27020430 10.1007/s11999-016-4739-x PMC4887361

12 S. A. Edwards , H. G. Pandit , and H. J. Clarke , “ The Treatment of Impending and Existing Pathological Femoral Fractures Using the Long Gamma Nail ,” Injury 32 ( 2001 ): 299 – 306 . 11325366 10.1016/s0020-1383(00)00218-7

13 M. Mickelson and M. Bonfiglio , “ Pathological Fractures in the Proximal Part of the Femur Treated by Zickel‐Nail Fixation ,” Journal of Bone & Joint Surgery 58 ( 1976 ): 1067 – 1070 . 1002746

14 T. C. Philipp , J. D. Mikula , Y.‐C. Doung , and K. R. Gundle , “ Is There an Association Between Prophylactic Femur Stabilization and Survival in Patients With Metastatic Bone Disease? ,” Clinical Orthopaedics & Related Research 478 ( 2020 ): 540 – 546 . 32168065 10.1097/CORR.0000000000000803 PMC7145091

15 D. Weikert and H. Schwartz , “ Intramedullary Nailing for Impending Pathological Subtrochanteric Fractures ,” Journal of Bone and Joint Surgery. British Volume 73 ( 1991 ): 668 – 670 . 2071657 10.1302/0301-620X.73B4.2071657

16 R. Zickel and W. Mouradian , “ Intramedullary Fixation of Pathological Fractures and Lesions of the Subtrochanteric Region of the Femur ,” Journal of Bone & Joint Surgery 58 ( 1976 ): 1061 – 1066 . 1002745

17 D. L. Rogers , M. Raad , J. A. Rivera , et al., “ Life Expectancy After Treatment of Metastatic Bone Disease: An International Trend Analysis ,” Journal of the American Academy of Orthopaedic Surgeons 32 , no. 6 (March 2024 ): e293 – e301 . 38241634 10.5435/JAAOS-D-23-00332

18 A. Abbott , J. K. Kendal , C. Hewison , S. Puloski , and M. Monument , “ Longitudinal Survival Trends of Patients With Cancer With Surgically Managed Appendicular Metastatic Bone Disease: Systematic Review ,” Canadian Journal of Surgery 64 , no. 6 (November 2021 ): E550 – E560 . 10.1503/cjs.015520 PMC8565884 34728520

19 M. E. Charlson , P. Pompei , K. L. Ales , and C. R. MacKenzie , “ A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation ,” Journal of Chronic Diseases 40 ( 1987 ): 373 – 383 . 3558716 10.1016/0021-9681(87)90171-8

20 A. Kline and Y. Luo , “ PsmPy: A Package for Retrospective Cohort Matching in Python ,” in Annual International Conference of the IEEE Engineering in Medicine & Biology Society . ( IEEE , 2022 Jul), 1354 – 1357 . 10.1109/EMBC48229.2022.9871333 36086543

21 S. Dawood , K. Broglio , A. M. Gonzalez‐Angulo , A. U. Buzdar , G. N. Hortobagyi , and S. H. Giordano , “ Trends in Survival Over the Past Two Decades Among White and Black Patients With Newly Diagnosed Stage IV Breast Cancer ,” Journal of Clinical Oncology 26 ( 2008 ): 4891 – 4898 . 18725649 10.1200/JCO.2007.14.1168 PMC2736998

22 A. Jemal , E. M. Ward , C. J. Johnson , et al., “ Annual Report to the Nation on the Status of Cancer, 1975–2014, Featuring Survival ,” JNCI: Journal of the National Cancer Institute 109 , no. 9 ( 2017 ): 1 – 22 . 10.1093/jnci/djx030 PMC5409140 28376154

23 M. Luyendijk , O. Visser , H. M. Blommestein , et al., “ Changes in Survival in De Novo Metastatic Cancer in an Era of New Medicines ,” JNCI: Journal of the National Cancer Institute 115 , no. 6 ( 2023 ): 628 – 635 . 36978244 10.1093/jnci/djad020 PMC10248844

24 R. L. Siegel , T. B. Kratzer , A. N. Giaquinto , H. Sung , and A. Jemal , “ Cancer Statistics, 2025 ,” CA: A Cancer Journal for Clinicians 75 , no. 1 ( 2025 ): 10 – 45 . 39817679 10.3322/caac.21871 PMC11745215

25 T. Zeoli , H. Chanbour , R. Ahluwalia , A. M. Abtahi , B. F. Stephens , and S. L. Zuckerman , “ Does Elective Admission vs. Emergency Department Presentation Affect Surgical Outcomes in Metastatic Spine Surgery? ,” Diagnostics 14 , no. 10 (May 2024 ): 1058 . 38786356 10.3390/diagnostics14101058 PMC11119271

26 C. P. Bretherton and M. J. Parker , “ Early Surgery for Patients With a Fracture of the Hip Decreases 30‐day Mortality ,” Bone & Joint Journal 97–B , no. 1 ( 2015 ): 104 – 108 . 10.1302/0301-620X.97B1.35041 25568422

27 A. M. Nyholm , K. Gromov , H. Palm , M. Brix , T. Kallemose , and A. Troelsen , “ Time to Surgery Is Associated With Thirty‐Day and Ninety‐Day Mortality After Proximal Femoral Fracture: A Retrospective Observational Study on Prospectively Collected Data From the Danish Fracture Database Collaborators ,” Journal of Bone and Joint Surgery 97 , no. 16 ( 2015 ): 1333 – 1339 . 10.2106/JBJS.O.00029 26290084

28 D. Pincus , B. Ravi , D. Wasserstein , et al., “ Association Between Wait Time and 30‐Day Mortality in Adults Undergoing Hip Fracture Surgery ,” Journal of the American Medical Association 318 ( 2017 ): 1994 – 2003 . 29183076 10.1001/jama.2017.17606 PMC5820694

29 M. Van Vliet , M. Huisman , and D. J. H. Deeg , “ Decreasing Hospital Length of Stay: Effects on Daily Functioning in Older Adults ,” Journal of the American Geriatrics Society 65 , no. 6 ( 2017 ): 1214 – 1221 . 28263376 10.1111/jgs.14767

30 C. J. Brown , R. J. Friedkin , and S. K. Inouye , “ Prevalence and Outcomes of Low Mobility in Hospitalized Older Patients ,” Journal of the American Geriatrics Society 52 , no. 8 ( 2004 ): 1263 – 1270 . 15271112 10.1111/j.1532-5415.2004.52354.x

31 N. Hughes , J. Birlingmair , J. Baker , G. Tideman , and K. Sweeney , “ Evaluating Factors Affecting Length of Hospital Stay in Patients With Metastatic Bone Tumors ,” Journal of Orthopaedics 29 ( 2022 ): 28 – 30 . 35125778 10.1016/j.jor.2022.01.001 PMC8792391

32 D. Cumming , J. Cumming , A. Vince , and R. Benson , “ Metastatic Bone Disease: The Requirement for Improvement in a Multidisciplinary Approach ,” International Orthopaedics 33 ( 2009 ): 493 – 496 . 18431570 10.1007/s00264-008-0556-5 PMC2899083

33 K. K. Li , E. Sinclair , J. Pope , et al., “ A Multidisciplinary Bone Metastases Clinic at Toronto Sunnybrook Regional Cancer Centre—A Review of the Experience From 1999 to 2005 ,” Journal of Pain Research 1 ( 2008 ): 43 – 48 . 21197287 10.2147/jpr.s4573 PMC3004611

34 N. Hughes , J. Birlingmair , J. Baker , G. Tideman , and K. Sweeney , “ Evaluating Factors Affecting Length of Hospital Stay in Patients With Metastatic Bone Tumors ,” Journal of Orthopaedics 29 ( 2022 ): 28 – 30 . 35125778 10.1016/j.jor.2022.01.001 PMC8792391

35 K. Miyazaki , Y. Kanda , Y. Sakai , et al., “ Effect of Bone Metastasis Cancer Board on Spinal Surgery Outcomes: A Retrospective Study ,” Medicina 59 , no. 12 ( 2023 ): 2087 . 38138190 10.3390/medicina59122087 PMC10744340

36 B. Ristevski , R. J. Jenkinson , D. J. Stephen , et al., “ Mortality and Complications Following Stabilization of Femoral Metastatic Lesions: A Population‐Based Study of Regional Variation and Outcome ,” Canadian Journal of Surgery 52 ( 2009 ): 302 – 308 . PMC2724796 19680515

37 C. S. B. Galasko , H. E. Norris , and S. Crank , “ Spinal Instability Secondary to Metastatic Cancer ,” Journal of Bone and Joint Surgery‐American Volume 82 ( 2000 ): 570 – 576 . 10761947 10.2106/00004623-200004000-00012

38 S. Lutz , T. Balboni , J. Jones , et al., “ Palliative Radiation Therapy for Bone Metastases: Update of An ASTRO Evidence‐Based Guideline ,” Practical Radiation Oncology 7 ( 2017 ): 4 – 12 . 27663933 10.1016/j.prro.2016.08.001

39 British Association of Surgical Oncology Guidelines . “ The Management of Metastatic Bone Disease in the United Kingdom The Breast Specialty Group of the British Association of Surgical Oncology ,” European Journal of Surgical Oncology 25 , no. 1 ( 1999 ): 3 – 23 . 10188849

40 H. Shibata , S. Kato , I. Sekine , et al., “ Diagnosis and Treatment of Bone Metastasis: Comprehensive Guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology ,” ESMO Open 1 ( 2016 ): e000037 . 27843593 10.1136/esmoopen-2016-000037 PMC5070259

41 Advanced Breast Cancer: Diagnosis and Treatment ( National Institute for Health and Clinical Excellence , 2025 ) https://www.nice.org.uk/guidance/cg81 . 31999418

42 K. L. Schulman and J. Kohles , “ Economic Burden of Metastatic Bone Disease in the U.S ,” Cancer 109 ( 2007 ): 2334 – 2342 . 17450591 10.1002/cncr.22678

43 A. S. Salas , B. LeGuerrier , L. Horvath , et al. “ The Impact of Socioeconomic Inequality on Access to Health Care for Patients With Advanced Cancer: A Qualitative Study ,” Asia‐Pacific Journal of Oncology Nursing 11 , no. 7 ( 2024 ): 100520 . 39027088 10.1016/j.apjon.2024.100520 PMC11255108