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.
Similar content being viewed by others
References
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
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
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
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
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
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
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
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
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
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
Mirels H (1989) Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res (249):256–264
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Acknowledgments
The authors thank all patients and their families.
Author information
Authors and Affiliations
Corresponding author
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
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00264-020-04921-2