Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Research

Impact of symptomatic skeletal events on health-care resource utilization and quality of life among patients with castration-resistant prostate cancer and bone metastases

Prostate Cancer and Prostatic Diseases volume 20, pages 276–282 (2017)Cite this article

Subjects

Abstract

Background:

Data regarding the impact of symptomatic skeletal events (SSEs) on health economics and patient-reported outcomes in men with castration-resistant prostate cancer (CRPC) and bone metastases from a clinical setting are lacking. Hence, this study aimed to quantify the effects of SSEs on health-care resource utilization (HRU), health-related quality of life (HRQoL) and pain in men with CRPC metastasized to bone.

Methods:

This cohort study included men with CRPC and bone metastasis treated at a tertiary center during December 1996–July 2015. SSEs, including pathological fracture, radiation to bone, spinal cord compression and bone surgery, as well as HRU were identified retrospectively through medical records and clinical database. A subset of surviving patients completed Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires. The incremental effect of SSEs on HRU was evaluated using multivariable generalized linear regression. Questionnaire scores were compared using effect sizes (ES); ES⩾0.33 indicated meaningful differences between SSE and non-SSE cohorts. Lower scores suggest lower HRQoL and pain.

Results:

Of the 832 patients, 207 developed ⩾1 SSE (mean 1.5±0.8) during follow-up (median 2.1 years). Radiation to bone was the most common SSE (84.1%). SSE cohort had significantly higher emergency room (incidence rate ratio (IRR)=1.48; P=0.006), outpatient (IRR=1.17; P=0.005) and inpatient (IRR=1.74; P<0.001) visits. Of the 107 eligible survey patients, 103 (96.3%) responded. SSE cohort had lower mean FACT-P functional well-being (17.5 vs 19.8; P=0.158; ES=0.36), higher mean pain severity (2.5 vs 1.6; P=0.048; ES=0.47) and worst pain scores (3.6 vs 2.3; P=0.033; ES=0.50) compared with the non-SSE cohort, indicating meaningful differences between cohorts.

Conclusions:

This study demonstrated high economic and HRQoL burden of SSEs. The findings underscore the need for better supportive and disease-modifying treatments for these patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Herrera FG, Tawadros T, Berthold DR . Bone metastases in prostate cancer: pathophysiology, clinical complications, actual treatment, and future directions. In: Heymann D (ed). Bone Cancer: Primary Bone Cancers and Bone Metastases, 2nd edn. Elsevier Inc.: San Diego, CA; Elsevier/Academic Press: Waltham, MA, 2015.

    Google Scholar 

  2. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002; 94: 1458–1468.

    Article  CAS  Google Scholar 

  3. Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D et al. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol 2014; 15: 1147–1156.

    Article  CAS  Google Scholar 

  4. Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN et al. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol 2012; 13: 1210–1217.

    Article  CAS  Google Scholar 

  5. Gartrell BA, Coleman R, Efstathiou E, Fizazi K, Logothetis CJ, Smith MR et al. Metastatic prostate cancer and the bone: significance and therapeutic options. Eur Urol 2015; 68: 850–858.

    Article  Google Scholar 

  6. Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014; 15: 738–746.

    Article  CAS  Google Scholar 

  7. Nilsson S, Cislo P, Sartor O, Vogelzang NJ, Coleman RE, O'Sullivan JM et al. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Ann Oncol 2016; 27: 868–874.

    Article  CAS  Google Scholar 

  8. Rathkopf DE, Smith MR, de Bono JS, Logothetis CJ, Shore ND, de Souza P et al. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302). Eur Urol 2014; 66: 815–825.

    Article  CAS  Google Scholar 

  9. Hagiwara M, Delea TE, Saville MW, Chung K . Healthcare utilization and costs associated with skeletal-related events in prostate cancer patients with bone metastases. Prostate Cancer Prostatic Dis 2013; 16: 23–27.

    Article  CAS  Google Scholar 

  10. Pockett RD, Castellano D, McEwan P, Oglesby A, Barber BL, Chung K . The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. Eur J Cancer Care 2010; 19: 755–760.

    Article  CAS  Google Scholar 

  11. Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008; 26: 1148–1159.

    Article  Google Scholar 

  12. Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A et al. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol 1993; 11: 570–579.

    Article  CAS  Google Scholar 

  13. Cleeland CS, Ryan KM . Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994; 23: 129–138.

    CAS  PubMed  Google Scholar 

  14. Fritz CO, Morris PE, Richler JJ . Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen 2012; 141: 2–18.

    Article  Google Scholar 

  15. Yost KJ, Eton DT . Combining distribution- and anchor-based approaches to determine minimally important differences: the FACIT experience. Eval Health Prof 2005; 28: 172–191.

    Article  Google Scholar 

  16. Graff JN, Beer TM . Reducing skeletal-related events in metastatic castration-resistant prostate cancer. Oncology (Williston Park) 2015; 29: 416–423.

    Google Scholar 

  17. Bourke L, Boorjian SA, Briganti A, Klotz L, Mucci L, Resnick MJ et al. Survivorship and improving quality of life in men with prostate cancer. Eur Urol 2015; 68: 374–383.

    Article  Google Scholar 

  18. Saad F, Clarke N, Colombel M . Natural history and treatment of bone complications in prostate cancer. Eur Urol 2006; 49: 429–440.

    Article  CAS  Google Scholar 

  19. Barlev A, Song X, Ivanov B, Setty V, Chung K . Payer costs for inpatient treatment of pathologic fracture, surgery to bone, and spinal cord compression among patients with multiple myeloma or bone metastasis secondary to prostate or breast cancer. J Manag Care Pharm 2010; 16: 693–702.

    PubMed  Google Scholar 

  20. Hoefeler H, Duran I, Hechmati G, Garzon Rodriguez C, Luftner D, Ashcroft J et al. Health resource utilization associated with skeletal-related events in patients with bone metastases: Results from a multinational retrospective - prospective observational study - a cohort from 4 European countries. J Bone Oncol 2014; 3: 40–48.

    Article  CAS  Google Scholar 

  21. Mahmood A, Ghazal H, Fink M, Patel M, Atchison C, Wei R et al. Health-resource utilization attributable to skeletal-related events in patients with advanced cancers associated with bone metastases: results of the US cohort from a multicenter observational study. Commun Oncol 2012; 9: 148–157.

    Article  Google Scholar 

  22. DePuy V, Anstrom KJ, Castel LD, Schulman KA, Weinfurt KP, Saad F . Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer 2007; 15: 869–876.

    Article  Google Scholar 

  23. Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005; 16: 579–584.

    Article  CAS  Google Scholar 

  24. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004; 96: 879–882.

    Article  CAS  Google Scholar 

  25. Yong C, Onukwugha E, Mullins CD . Clinical and economic burden of bone metastasis and skeletal-related events in prostate cancer. Curr Opin Oncol 2014; 26: 274–283.

    Article  Google Scholar 

  26. Sathiakumar N, Delzell E, Morrisey MA, Falkson C, Yong M, Chia V et al. Mortality following bone metastasis and skeletal-related events among men with prostate cancer: a population-based analysis of US Medicare beneficiaries, 1999-2006. Prostate Cancer Prostatic Dis 2011; 14: 177–183.

    Article  CAS  Google Scholar 

  27. Lage MJ, Barber BL, Harrison DJ, Jun S . The cost of treating skeletal-related events in patients with prostate cancer. Am J Manag Care 2008; 14: 317–322.

    PubMed  Google Scholar 

  28. Abi-Ghanem AS, McGrath MA, Jacene HA . Radionuclide therapy for osseous metastases in prostate cancer. Semin Nucl Med 2015; 45: 66–80.

    Article  Google Scholar 

  29. Sanford M, Green K, Carroll P . The argument for palliative care in prostate cancer. Transl Androl Urol 2013; 2: 278–280.

    PubMed  PubMed Central  Google Scholar 

  30. Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst 2005; 97: 59–69.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank David Kinrich of Analysis Group for his support during the analysis of data. This study was supported by Bayer Healthcare Pharmaceuticals (Bayer).

Author information

Authors and Affiliations

  1. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    R McKay, M Nakabayashi, M Fiorillo & P Kantoff

  2. Division of Hematology/Oncology, University of California, Moores Cancer Center, San Diego, CA, USA

    R McKay

  3. Analysis Group, Inc., Boston, MA, USA

    B Haider, M S Duh & L Ristovska

  4. Bayer Healthcare Pharmaceuticals, Wayne, NJ, USA

    A Valderrama & L Wen

  5. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    P Kantoff

Authors
  1. R McKay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Haider
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M S Duh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Valderrama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Nakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Fiorillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Ristovska
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P Kantoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R McKay.

Ethics declarations

Competing interests

RM, MN and MF were employed by the Dana-Farber Cancer Institute (DFCI) at the time of the study. RM is currently employed by Moores Cancer Center and University of California. PK, currently employed by Memorial Sloan Kettering Cancer Center, was an employee of the DFCI at the time of the study. PK has served as a consultant to Astellas, Bayer, Janssen, Millennium/Prometrika, Pfizer and Sanofi. RM has received institutional research funding from Bayer and Pfizer. MSD and BH are employees of Analysis Group, a consulting company that has received research grants from Bayer, including one for the current study. LR was an employee of the Analysis Group at the time of the study. AV and LW are employees of Bayer Healthcare, and LW owns Bayer stock. The remaining authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McKay, R., Haider, B., Duh, M. et al. Impact of symptomatic skeletal events on health-care resource utilization and quality of life among patients with castration-resistant prostate cancer and bone metastases. Prostate Cancer Prostatic Dis 20, 276–282 (2017). https://doi.org/10.1038/pcan.2017.4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2017.4

This article is cited by

Search

Advanced search

Quick links