Skip to main content

Advertisement

Log in

C-reactive protein and tumour diagnosis predict survival in patients treated surgically for long bone metastases

  • Original Paper
  • Published:
International Orthopaedics Aims and scope Submit manuscript

Abstract

Purpose

Surgical options for long bone metastases include intramedullary nail fixation or prosthetic reconstruction. Patients with a short life expectancy may benefit from less invasive surgery such as intramedullary nail fixation, while patients with a long life expectancy could be treated with more invasive surgery such as prosthetic reconstruction. The purpose of our study was to analyze the survival of patients treated surgically for long bone metastases, determining the prognostic factors affecting survival and analyzing the surgical complications and reoperation rates. Based on our results, we developed a prognostic score that helps to choose the best treatment for these patients. In addition, we compared the performance of our prognostic score with other previous prognostic models.

Method

We investigated prospectively potential clinical and laboratory prognostic factors in 159 patients with metastatic bone disease who underwent surgery with intramedullary nail fixation or prosthetic reconstruction. Clinical data were collected, recording the following data: age and sex of patients, primary tumour and time of diagnosis, number (single or multiple) and presentation (synchronous or metachronous) of bone metastases, presence of visceral metastases. The following laboratory data were analyzed: hemoglobin, leukocyte counts, lymphocyte counts, platelets count, alkaline phosphatase, and C-reactive protein.

Results

Our study showed that pathological C-reactive protein and primary tumour diagnosis were significant negative independent prognostic factors at 12-month survival. Based on our results, we created a score using C-reactive protein and primary tumour diagnosis, creating three different prognostic groups: (A) good prognosis primary tumour and physiological CRP with probability of survival at 12 months of 88.9 [80.1–98.5]; (B) bad prognosis primary tumour and physiological CRP or good prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 56.7 [45.4–70.7]; (C) bad prognosis primary tumour and pathological CRP with a probability of survival at 12 months of 12.5 [5.0–28.3]. Using ROC multiple analysis, our score (AUC = 0.816) was the most accurate in predicting a 12-month survival compared to previous prognostic models.

Discussion

Patients treated surgically for long bone metastases with a life expectancy over 12 months should be treated with more durable reconstruction, while patients with a life expectancy less than 12 months should be treated with less invasive surgery. The diagnosis of primary cancer and C-reactive protein are two very simple data which every orthopaedic surgeon in any community hospital can easily rely on for any decision-making in the surgical treatment of a complex patient as with a patient with skeletal metastases.

Conclusion

Our prognostic score based on only two simple variables (C-reactive protein and primary tumour diagnosis) was able to predict the 12-month survival of patients treated surgically for long bone metastases and could be helpful in choosing the best treatment for these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Harvey N, Ahlmann ER, Allison DC et al (2012) Endoprostheses last longer than intramedullary devices in proximal femur metastases. Clin Orthop Relat Res 470:684–691. https://doi.org/10.1007/s11999-011-2038-0

    Article  PubMed  Google Scholar 

  2. Weiss RJ, Ekström W, Hansen BH et al (2013) Pathological subtrochanteric fractures in 194 patients: a comparison of outcome after surgical treatment of pathological and non-pathological fractures. J Surg Oncol 107:498–504. https://doi.org/10.1002/jso.23277

    Article  PubMed  Google Scholar 

  3. Meares C, Badran A, Dewar D (2019) Prediction of survival after surgical management of femoral metastatic bone disease - a comparison of prognostic models. J Bone Oncol 15:100225. https://doi.org/10.1016/j.jbo.2019.100225

    Article  PubMed  PubMed Central  Google Scholar 

  4. Errani C, Mavrogenis AF, Cevolani L et al (2016) Treatment for long bone metastases based on a systematic literature review. Eur J Orthop Surg Traumatol. https://doi.org/10.1007/s00590-016-1857-9

  5. Willeumier JJ, van der Linden YM, van der Wal CWPG et al (2018) An easy-to-use prognostic model for survival estimation for patients with symptomatic long bone metastases. J Bone Joint Surg Am 100:196–204. https://doi.org/10.2106/JBJS.16.01514

    Article  CAS  PubMed  Google Scholar 

  6. Forsberg JA, Eberhardt J, Boland PJ et al (2011) Estimating survival in patients with operable skeletal metastases: an application of a bayesian belief network. PLoS One 6:e19956. https://doi.org/10.1371/journal.pone.0019956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ratasvuori M, Wedin R, Keller J et al (2013) Insight opinion to surgically treated metastatic bone disease: Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal metastasis. Surg Oncol 22:132–138. https://doi.org/10.1016/j.suronc.2013.02.008

    Article  PubMed  Google Scholar 

  8. Katagiri H, Okada R, Takagi T et al (2014) New prognostic factors and scoring system for patients with skeletal metastasis. Cancer Med 3:1359–1367. https://doi.org/10.1002/cam4.292

    Article  PubMed  PubMed Central  Google Scholar 

  9. Katagiri H, Takahashi M, Wakai K et al (2005) Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg (Br) 87:698–703. https://doi.org/10.1302/0301-620X.87B5.15185

    Article  CAS  Google Scholar 

  10. Nathan SS, Healey JH, Mellano D et al (2005) Survival in patients operated on for pathologic fracture: implications for end-of-life orthopedic care. J Clin Oncol Off J Am Soc Clin Oncol 23:6072–6082. https://doi.org/10.1200/JCO.2005.08.104

    Article  Google Scholar 

  11. Mirels H (1989) Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res (249):256–264

  12. Nakamura T, Matsumine A, Asanuma K et al (2015) The role of C-reactive protein in predicting post-metastatic survival of patients with metastatic bone and soft tissue sarcoma. Tumour Biol 36:7515–7520. https://doi.org/10.1007/s13277-015-3464-5

    Article  CAS  PubMed  Google Scholar 

  13. Hobusch GM, Bodner F, Walzer S et al (2016) C-reactive protein as a prognostic factor in patients with chordoma of lumbar spine and sacrum--a single center pilot study. World J Surg Oncol 14:111. https://doi.org/10.1186/s12957-016-0875-8

    Article  PubMed  PubMed Central  Google Scholar 

  14. Panotopoulos J, Posch F, Alici B et al (2015) Hemoglobin, alkalic phosphatase, and C-reactive protein predict the outcome in patients with liposarcoma. J Orthop Res 33:765–770. https://doi.org/10.1002/jor.22827

    Article  CAS  PubMed  Google Scholar 

  15. Li X, Tian F, Wang F, Li Y (2015) Serum C-reactive protein and overall survival of patients with osteosarcoma. Tumour Biol 36:5663–5666. https://doi.org/10.1007/s13277-015-3240-6

    Article  CAS  PubMed  Google Scholar 

  16. Aggerholm-Pedersen N, Maretty-Kongstad K, Keller J et al (2016) The prognostic value of serum biomarkers in localized bone sarcoma. Transl Oncol 9:322–328. https://doi.org/10.1016/j.tranon.2016.05.006

    Article  PubMed  PubMed Central  Google Scholar 

  17. Li W, Luo X, Liu Z et al (2018) Prognostic value of C-reactive protein levels in patients with bone neoplasms: a meta-analysis. PLoS One 13:e0195769. https://doi.org/10.1371/journal.pone.0195769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shrotriya S, Walsh D, Nowacki AS et al (2018) Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumours. PLoS One 13:e0202555. https://doi.org/10.1371/journal.pone.0202555

  19. Prost S, Bouthors C, Fuentes S et al (2020) Influence of preoperative biological parameters on postoperative complications and survival in spinal bone metastasis. A multicenter prospective study. Orthop Traumatol Surg Res 106:1033–1038. https://doi.org/10.1016/j.otsr.2019.11.031

    Article  PubMed  Google Scholar 

  20. Kaur RP, Rubal, Banipal RPS et al (2019) Association of elevated levels of C-reactive protein with breast cancer, breast cancer subtypes, and poor outcome. Curr Probl Cancer 43:123–129. https://doi.org/10.1016/j.currproblcancer.2018.05.003

    Article  PubMed  Google Scholar 

  21. Nemecek E, Funovics PT, Hobusch GM et al (2018) C-reactive protein: an independent predictor for dedifferentiated chondrosarcoma. J Orthop Res 36:2797–2801. https://doi.org/10.1002/jor.24030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Willeumier JJ, Kaynak M, van der Zwaal P et al (2018) What factors are associated with implant breakage and revision after intramedullary nailing for femoral metastases? Clin Orthop Relat Res 476:1823–1833. https://doi.org/10.1007/s11999.0000000000000201

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bollen L, van der Linden YM, Pondaag W et al (2014) Prognostic factors associated with survival in patients with symptomatic spinal bone metastases: a retrospective cohort study of 1,043 patients. Neuro-Oncology 16:991–998. https://doi.org/10.1093/neuonc/not318

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ma Y, He S, Liu T et al (2017) Quality of life of patients with spinal metastasis from cancer of unknown primary origin: a longitudinal study of surgical management combined with postoperative radiation therapy. J Bone Joint Surg Am 99:1629–1639. https://doi.org/10.2106/JBJS.16.00286

    Article  PubMed  Google Scholar 

  25. Takagi T, Katagiri H, Kim Y et al (2015) Skeletal metastasis of unknown primary origin at the initial visit: a retrospective analysis of 286 cases. PLoS One 10:e0129428. https://doi.org/10.1371/journal.pone.0129428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nakamura T, Grimer R, Gaston C et al (2013) The value of C-reactive protein and comorbidity in predicting survival of patients with high grade soft tissue sarcoma. Eur J Cancer 49:377–385. https://doi.org/10.1016/j.ejca.2012.09.004

    Article  CAS  PubMed  Google Scholar 

  27. Nakamura T, Grimer RJ, Gaston CL et al (2013) The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone. Bone Joint J 95-B:411–418. https://doi.org/10.1302/0301-620X.95B3.30344

    Article  CAS  PubMed  Google Scholar 

  28. Avnet S, Di Pompo G, Lemma S, Baldini N (2019) Cause and effect of microenvironmental acidosis on bone metastases. Cancer Metastasis Rev 38:133–147. https://doi.org/10.1007/s10555-019-09790-9

    Article  PubMed  PubMed Central  Google Scholar 

  29. Proctor MJ, Morrison DS, Talwar D et al (2011) An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study. Br J Cancer 104:726–734. https://doi.org/10.1038/sj.bjc.6606087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Qian B-Z (2017) Inflammation fires up cancer metastasis. Semin Cancer Biol 47:170–176. https://doi.org/10.1016/j.semcancer.2017.08.006

    Article  CAS  PubMed  Google Scholar 

  31. Lehrer S, Diamond EJ, Mamkine B et al (2005) C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer. BJU Int 95:961–962. https://doi.org/10.1111/j.1464-410X.2005.05447.x

    Article  CAS  PubMed  Google Scholar 

  32. Zacherl M, Gruber G, Glehr M et al (2011) Surgery for pathological proximal femoral fractures, excluding femoral head and neck fractures: resection vs. stabilisation. Int Orthop 35:1537–1543. https://doi.org/10.1007/s00264-010-1160-z

    Article  PubMed  Google Scholar 

  33. van Doorn R, Stapert JW (2000) Treatment of impending and actual pathological femoral fractures with the long Gamma nail in The Netherlands. Eur J Surg 166:247–254. https://doi.org/10.1080/110241500750009366

    Article  PubMed  Google Scholar 

  34. Wedin R, Bauer HCF (2005) Surgical treatment of skeletal metastatic lesions of the proximal femur: endoprosthesis or reconstruction nail? J Bone Joint Surg (Br) 87:1653–1657. https://doi.org/10.1302/0301-620X.87B12.16629

    Article  CAS  Google Scholar 

  35. Hunt KJ, Gollogly S, Randall RL (2006) Surgical fixation of pathologic fractures: an evaluation of evolving treatment methods. Bull Hosp Jt Dis 63:77–82

    PubMed  Google Scholar 

  36. Mavrogenis AF, Pala E, Romagnoli C et al (2012) Survival analysis of patients with femoral metastases. J Surg Oncol 105:135–141. https://doi.org/10.1002/jso.22061

    Article  PubMed  Google Scholar 

  37. Alvi HM, Damron TA (2013) Prophylactic stabilization for bone metastases, myeloma, or lymphoma: do we need to protect the entire bone? Clin Orthop Relat Res 471:706–714. https://doi.org/10.1007/s11999-012-2656-1

    Article  PubMed  Google Scholar 

  38. Willeumier JJ, van der Linden YM, Dijkstra PDS (2016) Lack of clinical evidence for postoperative radiotherapy after surgical fixation of impending or actual pathologic fractures in the long bones in patients with cancer; a systematic review. Radiother Oncol 121:138–142. https://doi.org/10.1016/j.radonc.2016.07.009

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank all patients and their families.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Costantino Errani.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Errani, C., Cosentino, M., Ciani, G. et al. C-reactive protein and tumour diagnosis predict survival in patients treated surgically for long bone metastases. International Orthopaedics (SICOT) 45, 1337–1346 (2021). https://doi.org/10.1007/s00264-020-04921-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00264-020-04921-2

Keywords

Navigation