Risk Factors for Early Postoperative Morbidity and Mortality following Extremity Metastatic Pathologic or Impending Fracture Fixation.

1. Introduction

The incidence of metastatic bone disease is expected to continue to rise as the life expectancy of cancer patients continues to increase resulting from advances in screening techniques as well as local and systemic treatments. However, despite the progress in cancer care, reaching the stage of metastasis generally signifies irreversible disease course [ 1 – 4 ]. Currently, up to 80% of patients with advanced disease will experience bone metastases and 10–29% will suffer from pathologic fracture(s) [ 1 , 5 – 7 ]. Unfortunately, these skeletal events carry significant consequences with debilitating pain, loss of independence, impaired quality of life, and decreased survival time, in addition to the emotional burden for patients and family members [ 1 , 3 , 8 , 9 ].

The reported one-year survival rate following a pathologic fracture is between 30% and 70%, while the 2-year survival rate is less than 30%, all cancer aetiologies included [ 2 , 6 , 10 – 14 ]. Therefore, the aim of surgical intervention is immediate pain relief, restoration of function, and improved quality of life often in the setting of end-of-life care, while minimizing perioperative complications [ 1 , 3 , 5 , 14 – 16 ]. At present, increased emphasis has been placed on creating models to predict symptomatic skeletal events from the time of cancer diagnosis and to identify prognostic factors for overall survival. However, there are limited data exploring the risk factors for early postoperative morbidity and mortality from the time of impending or pathologic fracture diagnosis, which is usually when patients are seen by an orthopaedic surgeon for the first time. This has great implications in clinical decision-making, perioperative risk assessment, as well as patient and family counselling [ 1 , 6 , 8 , 12 , 17 , 18 ].

The objective of this study is to identify risk factors for short-term complications and mortality in the surgical treatment of extremity metastatic bone disease. Ultimately, the aim is to provide decision-making guidance and to enhance perioperative risk assessment.

2. Methods

A retrospective review of consecutive patients who underwent surgical treatment for impending and/or pathologic fractures related to extremity metastatic bone disease from January 1, 2005, to December 31, 2020, was performed. Primary bone neoplasm, revision surgeries, nonsurgical management, and treatment of skull, spine, pelvis, or nonskeletal metastatic disease were excluded. All patient consultation and surgical interventions were performed at a single tertiary centre with regional cancer care designations.

The data were independently collected by two authors (PQW, BPC) from the institution's electronic medical record. Discrepancies were reviewed until consensus was reached. Primary endpoints were 30-day postoperative complications and mortality. A complication was defined as a new or worsening condition requiring additional medical or surgical treatment. An impending fracture was defined as a metastatic bone lesion without a visible fracture line, with intact height and bone alignment, and which underwent prophylactic fixation [ 19 ]. For risk factor assessment, variables of interest included age, sex, primary cancer, time (in months) between cancer diagnosis and surgery, chemotherapy and radiation therapy history, fracture location, prophylactic versus fracture stabilization, type of fixation, type of anesthesia, surgical duration, metastatic burden, medical comorbidities, smoking history, preoperative (or prefracture) ambulatory status, and transfusion requirements. Metastatic burden was dichotomized into either bone metastasis alone or presence of extra-skeletal metastases. Surgical location was categorized as upper extremity, lower extremity, and multiple limbs given the propensity to metastasize to both the humerus and femur, and less frequently to other bones [ 12 , 19 ]. Medical comorbidities needed to be preexisting conditions and unrelated to the cancer diagnosis and/or treatment. The smoking history and blood transfusion requirements were assessed using categorical values (yes/no) as well as continuous variables (pack-year smoking history and number of blood product units transfused, respectively). Where patients underwent multiple separate surgeries for different limbs within 30 days and sustained a complication or incurred death, these data were linked only to the most recent surgery and not the previous interventions as the patient would have been expected to be optimized for surgery.

Patient demographics, clinical characteristics, 30-day morbidity, and mortality were summarized using descriptive statistics. Categorical variables were presented as frequencies and percentages, whereas continuous independent variables were reported as mean, standard deviation, and range. Postoperative morbidity and mortality were assessed separately using univariate and multivariate analyses. Associations between each variable and outcome were identified using chi-squared or Fischer's exact test for categorical values. A binary logistic regression model was used for continuous independent variables. A multivariate regression analysis was subsequently performed to identify independent risk factors for postoperative complications and mortality. Variables that were statistically significant in the univariate analysis were included in the multivariate model and were reported as odds ratio (OR) with 95% confidence interval (CI). An additional subgroup analysis was performed to identify specific risk factors for local surgical and systemic complications separately. Complications occurring outside the surgical field were considered systemic. Statistical significance was set at p value less than 0.05. Statistical analysis was performed using GraphPad Prism 10 (San Diego, California, USA).

Approval from the institution's research ethics committee was obtained prior to initiating data collection. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines [ 20 ].

3. Results

Of the 185 patients included in the study, 30 underwent multiple surgeries on separate occasions for different extremities leading to a total of 226 surgeries. See Table 1 for patient demographics and clinical characteristics and Table 2 for surgical details. The most common primary cancer was lung cancer ( n = 41) followed by breast cancer ( n = 36), multiple myeloma ( n = 35), prostate cancer ( n = 16), lymphoma ( n = 11), and renal cell carcinoma ( n = 10). The remaining cancers were combined as other ( n = 36) as the number of each individual pathology was insufficient for statistical analysis, see Table 1 . Fifty patients (27.03%) only had skeletal metastatic lesions at the time of surgery, while 135 (72.97%) had both bone and extra-skeletal metastases.

The 30-day postoperative complication and mortality rates were 32.30% ( n = 73) and 17.26% ( n = 39), respectively. The most common morbidity was respiratory-related complications ( n = 26). Amongst them, 15 sustained new or worsening pleural effusions, six were treated for pneumonia, and five had new onset of pulmonary embolism. Other complications observed include superficial wound infection ( n = 8), cardiac event ( n = 7), deep surgical infection ( n = 6), urosepsis ( n = 6), deep vein thrombosis without pulmonary embolism ( n = 4), gastrointestinal bleed ( n = 3), failure of fixation ( n = 3), acute renal failure ( n = 3), symptomatic hyponatremia ( n = 2), Clostridioides difficile infection ( n = 1), febrile neutropenia ( n = 1), hypercalcemia of malignancy ( n = 1), seizure ( n = 1), and hepatic encephalopathy ( n = 1).

Univariate analysis showed that pathologic fracture ( p =0.0064), presence of extra-skeletal metastases ( p =0.046), longer surgical duration ( p =0.021), and blood transfusion (yes/no, p =0.03) were associated with 30-day postoperative complications. Predictors for 30-day mortality were lung cancer ( p =0.046), pathologic fracture ( p =0.0071), presence of extra-skeletal metastases ( p =0.022), and blood transfusion (yes/no, p =0.031). When patients received increasing amounts of blood transfusion units, this also significantly influenced both morbidity and mortality ( p =0.045 and p =0.015, respectively). Although smoking status (ever-smoking versus nonsmoker) was not correlated with mortality, the pack-year smoking history significantly affected the deceased group ( p =0.033), see Tables 3 and 4 .

A multiple logistic regression analysis of statistically significant factors on univariate analysis was performed. The model showed pathologic fracture (OR: 2.14, 95% CI: 1.16 to 4.00, p =0.016) and presence of extra-skeletal metastases (OR: 2.12, 95% CI: 1.14 to 4.37, p =0.029) as independent predictors for 30-day postoperative complications. For 30-day mortality, independent risk factors were pathologic fracture (OR: 2.84, 95% CI: 1.27 to 6.86, p =0.014), presence of extra-skeletal metastases (OR: 4.14, 95% CI: 1.56 to 13.44, p =0.0085), and increasing amounts of blood transfusion units required (OR: 1.27, 95% CI: 1.00 to 1.62, p =0.048), see Table 5 .

The subgroup analysis assessing risk factors stratified by local ( n = 17) and systemic ( n = 56) complications showed that pathologic fracture ( p =0.012), presence of extra-skeletal metastases ( p =0.0051), cardiac medical history ( p =0.049), and increasing amounts of blood transfusion units ( p =0.032) were associated with systemic complications. However, no statistically significant risk factors were identified for local surgical complications alone.

4. Discussion

The objective of this study was to identify the risk factors for short-term postoperative morbidity and mortality to guide clinical decision-making and enhance perioperative risk assessment in the treatment of impending and pathologic fractures of the extremity due to metastatic bone disease. Several risk factors were identified, of which pathologic fractures, presence of extra-skeletal metastases, and increased blood product requirements were independently associated with morbidity and/or mortality. A cardiac past medical history was also a significant risk factor for systemic complications in the subgroup analysis. The most common complications included pulmonary-related morbidity, cardiac events, surgical site infections, sepsis, and thromboembolism.

The treatment of pathologic fractures, similarly reported in previous studies, has significantly worse outcomes compared to prophylactic stabilization and is an independent negative prognostic factor in the treatment of extremity metastatic disease [ 11 , 12 , 21 , 22 ]. Previous studies demonstrated that long bone pathologic fracture fixation compared to prophylactic stabilization resulted in a significantly higher rate of 30-day major medical complications, longer hospital stays, and higher likelihood of patient discharge into a secondary health care facility rather than home discharge [ 19 , 23 ] and is associated with an increased 1-year mortality rate [ 19 , 24 ]. Consequently, identifying patients at a higher risk of pathologic fracture and advocating for treatment of impending rather than completed fractures, all factors considered, is becoming increasingly important. At present, assessment tools quantifying true risks of pathologic fractures are still limited. Mirel's scoring system is still the most widely used screening tool for predicting the risk of pathologic fracture. However, its low specificity rate (35%) leads to a high false-positive rate, thereby leading to overtreatment of extremity metastatic bone disease if decisions were made solely based on Mirel's score. Additionally, previous studies have demonstrated a moderate interobserver agreement only. Computed tomography-based bone assessment models have shown promising results in predicting the risks of pathologic fractures. However, given its complexity, it is still limited in availability and lacks standardization [ 22 , 23 , 25 – 28 ].

Prognostic predictive models such as PATHFx, 2013-SPRING, Optimodel, and SORG (the Skeletal Oncology Research Group) have been developed over the years to assess overall survival prognosis following treatment of metastatic bone disease. However, they do not quantify the risk of completed pathologic fracture. While helpful, these clinical algorithms have not been validated as stand-alone decision-making tools for management of patients with metastatic bone disease, rather, a multidisciplinary approach remains the gold standard. Furthermore, these tools are not yet used routinely, even amongst orthopaedic oncologists. As a result, emphasis should be placed on developing precise and accurate clinical prognostic tools both in quantifying risks of pathologic fracture as well as prognosis to make better informed decisions. These tools should be simple to apply and available, not only for clinicians in tertiary oncology referral centres, but also for secondary centres who also treat these patients. This is ever-more important now that patients survive longer and an increasing number of symptomatic skeletal events are expected to occur [ 22 , 26 , 29 – 32 ].

Similar to this study, reported acute postoperative complications and mortality are observed in up to 31% and 19%, respectively [ 12 , 19 , 21 , 29 ]. The most common reported postoperative complications are respiratory complications, cardiac events, surgical site infections, sepsis, and thromboembolism [ 18 , 19 , 23 ]. Common prognostic factors for morbidity and/or mortality previously published include rapidly growing primary tumours, lung cancer, disseminated disease, age (older), blood transfusion requirements, lower extremity location, and several laboratory values [ 18 , 19 , 29 ]. Unlike previous articles, in the current study, tumours were not differentiated by slow, moderate, and rapid growth, although lung cancer, known for its aggressive potential, was a risk factor in the univariate analysis for mortality, and metastatic burden (advanced disease) was an independent factor for both morbidity and mortality. Laboratory values were categorized as a complication only if they required additional treatment, thus accounting for the discrepancies from previous data. In addition, perioperative albumin levels were not routinely performed. It has been postulated that blood transfusion alone may not be a prognostic factor, rather it is the low preoperative hemoglobin level and perioperative anemia that affect patient outcomes, hence potentially why transfusion requirement (yes/no) was not an independent risk factor in this study, but mortality was affected by the increasing amount of blood transfusion requirements [ 11 , 18 ]. A cardiac medical history as a risk factor for systemic complications was identified in the subgroup analysis but not in the univariate analysis, although it did trend towards, but did not reach significance. Thus, cardiac disease likely has a certain effect on patient morbidity, and the discrepancy could be explained by the low sample size and heterogeneity in data.

This study did not show an increased risk of morbidity for lower extremity compared to upper extremity surgery, unlike observations made from previous studies. First, this could be explained by differences in patient demographics, cancer status, type of surgery, and how complications were defined. Additionally, lower extremity surgeries often require longer hospital stays and more intense rehabilitation compared to the upper extremity. However, most studies assess long-term morbidity, likewise with implant-related failures and complications. Consequently, morbidity related to lower extremity surgery and implant failures likely become more significant beyond the initial 30-day period [ 19 , 33 – 36 ].

There is conflicting evidence as to whether older age is an independent risk factor in long-term outcome studies. Previous pooled analyses proposed some studies showing age as an independent risk factor, while other studies did not reproduce the same results [ 11 ]. Differences can be influenced by the cancer types and whether they are assessed separately or together. For example, age affects survival in breast, prostate, renal cell, and thyroid cancers when analyzed independently [ 11 , 37 – 41 ]. However, studies with pooled primary cancer diagnoses, often do not demonstrate age as a prognostic factor [ 12 , 42 ].

The current study did not demonstrate associations between prior chemotherapy and prior radiation with short-term morbidity or mortality. Similarly, Bindels [ 19 ] did not find correlations between 30-day complications and previous systemic therapies or radiation to the affected bone [ 19 ]. However, given that disease dissemination and metastatic burden affect outcomes, it is more likely that the actual response to systemic treatment will have a greater impact on overall survival, especially if it can delay disease progression [ 7 , 43 ].

This study has several limitations stemming from its retrospective design, heterogenous patient demographics and characteristics, and its reliance on electronic medical record. With a relatively small sample size, not all variables could be independently analyzed. As a result, cancer types and complications were pooled together instead to increase power. Furthermore, in the literature, there is no uniform definition and data collection method for complications, thereby making direct comparisons difficult [ 19 ]. Certain types of surgical procedures from different locations were also combined to increase subgroup sample size, notably for joint reconstruction surgeries. Total joint replacements and megaprosthetic reconstructions were pooled with hemiarthroplasties of the shoulders, hips, and knees although their risk profiles differ, thereby increasing the risk of bias. Other potential confounding factors such as nutritional status, albumin levels, and various laboratory bloodwork could not be independently analyzed due to lack of data. Rather, only the reported abnormal laboratory values that required additional treatment were categorized as a complication. Additionally, information regarding oncology-related patient performance status, an important prognostic factor for survival, was not available in the chart review. Therefore, this study assessed ambulatory status as a surrogate measure. While preoperative ambulatory status did not appear to affect the short-term results, ambulatory status alone is not an adequate representation of functional status [ 29 ].

5. Conclusions

This study highlights the various complications and risk factors associated with early postoperative morbidity and mortality following surgery for extremity metastatic bone disease. After adjusting for potential confounders, pathologic fractures and the presence of extra-skeletal metastases were independent risk factors for morbidity and mortality. Meanwhile, increased blood transfusion requirement was a negative prognostic factor for mortality. Finally, as patient survivorship continues to improve, there is an increasing role for prophylactic treatment given their superior clinical outcomes and the morbidity associated with pathologic fracture surgery. Accurately identifying patients at a risk for pathologic fracture is paramount.

Data Availability

The data supporting the results of this study are available within the results' section and tables.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

1. Hill T., D’Alessandro P., Murray K., Yates P. Prognostic factors following pathological fractures. ANZ Journal of Surgery . 2015;85(3):159–163. doi: 10.1111/ans.12830.

2. Bonnevialle P., Baron-Trocellier T., Niglis L., et al. Functional results and survival after surgery for peripheral skeletal metastasis: a 434-case multicenter retrospective series. Orthopaedics and Traumatology: Surgery & Research . 2020;106(6):997–1003. doi: 10.1016/j.otsr.2019.10.024.

3. Errani C. Treatment of bone metastasis. Current Oncology . 2022;29(8):5195–5197. doi: 10.3390/curroncol29080411.

4. Jawad M. U., Pollock B. H., Wise B. L., et al. Sex, racial/ethnic and socioeconomic disparities in patients with metastatic bone disease. Journal of Surgical Oncology . 2022;125(4):766–774. doi: 10.1002/jso.26765.

5. Ruggieri P., Mavrogenis A. F., Casadei R., et al. Protocol of surgical treatment of long bone pathological fractures. Injury . 2010;41(11):1161–1167. doi: 10.1016/j.injury.2010.09.018.

6. Behnke N. K., Baker D. K., Xu S., Niemeier T. E., Watson S. L., Ponce B. A. Risk factors for same-admission mortality after pathologic fracture secondary to metastatic cancer. Supportive Care in Cancer . 2017;25(2):513–521. doi: 10.1007/s00520-016-3431-8.

7. Costa L., Badia X., Chow E., Lipton A., Wardley A. Impact of skeletal complications on patients’ quality of life, mobility, and functional independence. Supportive Care in Cancer . 2008;16(8):879–889. doi: 10.1007/s00520-008-0418-0.

8. Nakata E., Sugihara S., Osumi S., Yamashita N. Risk stratification for predicting symptomatic skeletal events (SSEs) in breast cancer patients with bone metastases. Journal of Orthopaedic Science . 2017;22(4):743–748. doi: 10.1016/j.jos.2017.03.014.

9. Saad F., Lipton A., Cook R., Chen Y., Smith M., Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer . 2007;110(8):1860–1867. doi: 10.1002/cncr.22991.

10. Skovlund Sørensen M., Hindsø K., Frederik Horstmann P., et al. Incidence of surgical interventions for metastatic bone disease in the extremities: a population-based cohort study. Acta Oncologica . 2019;58(4):456–462. doi: 10.1080/0284186X.2018.1549368.

11. Kirkinis M. N., Lyne C. J., Wilson M. D., Choong P. F. M. Metastatic bone disease: a review of survival, prognostic factors and outcomes following surgical treatment of the appendicular skeleton. European Journal of Surgical Oncology . 2016;42(12):1787–1797. doi: 10.1016/j.ejso.2016.03.036.

12. Hansen B. H., Keller J., Laitinen M., et al. The Scandinavian Sarcoma Group skeletal metastasis register. Survival after surgery for bone metastases in the pelvis and extremities. Acta Orthopaedica Scandinavica . 2004;75(sup311):11–15. doi: 10.1080/00016470410001708270.

13. Sørensen M. S., Gregersen K. G., Grum-Schwensen T., Hovgaard D., Petersen M. M. Patient and implant survival following joint replacement because of metastatic bone disease: a cross-sectional study of 130 patients with 140 joint replacements. Acta Orthopaedica . 2013;84(3):301–306. doi: 10.3109/17453674.2013.788437.

14. Harvey N., Ahlmann E. R., Allison D. C., Wang L., Menendez L. R. Endoprostheses last longer than intramedullary devices in proximal femur metastases. Clinical Orthopaedics and Related Research . 2012;470(3):684–691. doi: 10.1007/s11999-011-2038-0.

15. Axelrod D., Gazendam A. M., Ghert M. The surgical management of proximal femoral metastases: a narrative review. Current Oncology . 2021;28(5):3748–3757. doi: 10.3390/curroncol28050320.

16. Wedin R., Hansen B. H., Laitinen M., et al. Complications and survival after surgical treatment of 214 metastatic lesions of the humerus. Journal of Shoulder and Elbow Surgery . 2012;21(8):1049–1055. doi: 10.1016/j.jse.2011.06.019.

17. Forsberg J. A., Eberhardt J., Boland P. J., Wedin R., Healey J. H. El-Deiry W. S., editor. Estimating survival in patients with operable skeletal metastases: an application of a bayesian belief network. PLoS One . 2011;6(5) doi: 10.1371/journal.pone.0019956.e19956

18. Tsuda Y., Yasunaga H., Horiguchi H., Fushimi K., Kawano H., Tanaka S. Complications and postoperative mortality rate after surgery for pathological femur fracture related to bone metastasis: analysis of a nationwide database. Annals of Surgical Oncology . 2016;23(3):801–810. doi: 10.1245/s10434-015-4881-9.

19. Bindels B. J. J., Thio Q. C. B. S., Raskin K. A., Ferrone M. L., Lozano-Calderon S. A., Schwab J. H. Thirty-day postoperative complications after surgery for metastatic long bone disease are associated with higher mortality at 1 year. Clinical Orthopaedics and Related Research . 2020;478(2):306–318. doi: 10.1097/CORR.0000000000001036.

20. Von Elm E., Altman D. G., Egger M., Pocock S. J., Gøtzsche P. C., Vandenbroucke J. P. The strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies. The Lancet . 2007;370(9596):1453–1457. doi: 10.1016/S0140-6736(07)61602-X.

21. Raschka T., Weiss S., Reiter A., et al. Outcomes and prognostic factors after surgery for bone metastases in the extremities and pelvis: a retrospective analysis of 140 patients. Journal of Bone Oncology . 2022;34 doi: 10.1016/j.jbo.2022.100427.100427

22. Groot O. Q., Lans A., Twining P. K., et al. Clinical outcome differences in the treatment of impending versus completed pathological long-bone fractures. Journal of Bone and Joint Surgery . 2022;104(4):307–315. doi: 10.2106/JBJS.21.00711.

23. El Abiad J. M., Raad M., Puvanesarajah V., Rao S. S., Morris C. D., Levin A. S. Prophylactic versus postfracture stabilization for metastatic lesions of the long bones: a comparison of 30-day postoperative outcomes. Journal of the American Academy of Orthopaedic Surgeons . 2019;27(15):e709–e716. doi: 10.5435/JAAOS-D-18-00345.

24. Ristevski B., Jenkinson R. J., Stephen D. J., et al. Mortality and complications following stabilization of femoral metastatic lesions: a population-based study of regional variation and outcome. Canadian journal of surgery. Journal canadien de chirurgie . 2009;52(4):302–308.

25. Sternheim A., Traub F., Trabelsi N., et al. When and where do patients with bone metastases actually break their femurs?: a CT-based finite element analysis. The Bone & Joint Journal . 2020;102(5):638–645. doi: 10.1302/0301-620X.102B5.BJJ-2019-1328.R2.

26. Nguyễn M. V., Carlier C., Nich C., Gouin F., Crenn V. Fracture risk of long bone metastases: a review of current and new decision-making tools for prophylactic surgery. Cancers . 2021;13(15):p. 3662. doi: 10.3390/cancers13153662.

27. Crenn V., Carlier C., Gouin F., Sailhan F., Bonnevialle P. High rate of fracture in long-bone metastasis: proposal for an improved Mirels predictive score. Orthopaedics and Traumatology: Surgery & Research . 2020;106(6):1005–1011. doi: 10.1016/j.otsr.2020.03.034.

28. Howard E. L., Shepherd K. L., Cribb G., Cool P. The validity of the Mirels score for predicting impending pathological fractures of the lower limb. The Bone & Joint Journal . 2018;100(8):1100–1105. doi: 10.1302/0301-620X.100B8.BJJ-2018-0300.R1.

29. Ladegaard T. H., Sørensen M. S., Petersen M. M. Major surgery for metastatic bone disease is not a risk for 30-day mortality: a population-based study from Denmark. Acta Orthopaedica . 2023;94:447–452. doi: 10.2340/17453674.2023.18394.

30. De Groot T. M., Ramsey D., Groot O. Q., et al. Does the sorg machine-learning algorithm for extremity metastases generalize to a contemporary cohort of patients? Temporal validation from 2016 to 2020. Clinical Orthopaedics and Related Research . 2023;481(12):2419–2430. doi: 10.1097/CORR.0000000000002698.

31. Ladegaard T. H., Sørensen C. L., Nielsen R., et al. Surgical treatment of metastatic bone disease in the appendicular skeleton: a population-based study. Cancers . 2022;14(5):p. 1258. doi: 10.3390/cancers14051258.

32. Ben Gal O., Soh T. C. F., Vaughan S., Jayasanker V., Mahendra A., Gupta S. The prediction of survival after surgical management of bone metastases of the extremities—a comparison of prognostic models. Current Oncology . 2022;29(7):4703–4716. doi: 10.3390/curroncol29070373.

33. Mavrogenis A. F., Pala E., Romagnoli C., Romantini M., Calabro T., Ruggieri P. Survival analysis of patients with femoral metastases: femoral Metastases. Journal of Surgical Oncology . 2012;105(2):135–141. doi: 10.1002/jso.22061.

34. Nilsson J., Gustafson P. Surgery for metastatic lesions of the femur: good outcome after 245 operations in 216 patients. Injury . 2008;39(4):404–410. doi: 10.1016/j.injury.2007.07.006.

35. Wedin R., Bauer H. C. F. Surgical treatment of skeletal metastatic lesions of the proximal femur: endoprosthesis or reconstruction nail? Journal of Bone and Joint Surgery British Volume . 2005;87(12):1653–1657. doi: 10.1302/0301-620X.87B12.16629.

36. Zacherl M., Gruber G., Glehr M., et al. Surgery for pathological proximal femoral fractures, excluding femoral head and neck fractures: resection vs. stabilisation. International Orthopaedics . 2011;35(10):1537–1543. doi: 10.1007/s00264-010-1160-z.

37. Weiss R. J., Tullberg E., Forsberg J. A., Bauer H. C., Wedin R. Skeletal metastases in 301 breast cancer patients: patient survival and complications after surgery. The Breast . 2014;23(3):286–290. doi: 10.1016/j.breast.2014.02.012.

38. Ratasvuori M., Wedin R., Hansen B. H., et al. Prognostic role of en-bloc resection and late onset of bone metastasis in patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate: SSG study on 672 operated skeletal metastases: surgery of Bone Metastases. Journal of Surgical Oncology . 2014;110(4):360–365. doi: 10.1002/jso.23654.

39. Satcher R. L., Lin P., Harun N., Feng L., Moon B. S., Lewis V. O. Surgical management of appendicular skeletal metastases in thyroid carcinoma. International Journal of Surgical Oncology . 2012;2012:12. doi: 10.1155/2012/417086.417086

40. Weiss R. J., Forsberg J. A., Wedin R. Surgery of skeletal metastases in 306 patients with prostate cancer. Acta Orthopaedica . 2012;83(1):74–79. doi: 10.3109/17453674.2011.645197.

41. Fottner A., Szalantzy M., Wirthmann L., et al. Bone metastases from renal cell carcinoma: patient survival after surgical treatment. BMC Musculoskeletal Disorders . 2010;11(1):p. 145. doi: 10.1186/1471-2474-11-145.

42. Nathan S. S., Healey J. H., Mellano D., et al. Survival in patients operated on for pathologic fracture: implications for end-of-life orthopedic care. Journal of Clinical Oncology . 2005;23(25):6072–6082. doi: 10.1200/JCO.2005.08.104.

43. Tsukamoto S., Kido A., Tanaka Y., et al. Current overview of treatment for metastatic bone disease. Current Oncology . 2021;28(5):3347–3372. doi: 10.3390/curroncol28050290.

Associated Data

Data Availability Statement

The data supporting the results of this study are available within the results' section and tables.