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.

  • Review Article
  • Clinical
  • Published:

Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy

Abstract

Background

While the addition of androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) results in better of overall survival in patients with metastatic hormone-sensitive prostate cancer (mHSPC), information regarding health related quality of life (HR-QoL) is sparse. We aimed at summarizing current evidence on the impact of ARSIs on HR-QoL.

Methods

We performed a systematic review of the published literature on PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane libraries between January 2011 and April 2022. We included only phase III randomized controlled trials (RCT), which were selected according to the PRISMA guidelines. We aimed at evaluating differences in HR-QoL, assessed by validated patient reported outcomes instruments. We analyzed global scores and sub-domains such as sexual functioning, urinary symptoms, bowel symptoms, pain/fatigue, emotional and social/family wellbeing. We reported data descriptively.

Results

Six RCTs were included: two used enzalutamide with ADT as intervention arms (ARCHES, ENZAMET); one used apalutamide with ADT (TITAN); two abiraterone acetate and prednisone (AAP) with ADT (STAMPEDE, LATITUDE); and one darolutamide with ADT (ARASENS). Enzalutamide or AAP with ADT increase overall HR-QoL in comparison with ADT alone, ADT with first generation nonsteroideal anti-androgens or ADT with docetaxel, whereas apalutamide and darolutamide with ADT maintain HR-QoL similarly to ADT alone or ADT with docetaxel, respectively. Time to first deterioration of pain was longer with combination therapy with enzalutamide, AAP or darolutamide, but not with apalutamide. No worsening of emotional wellbeing was reported from the addition of ARSIs to ADT than ADT alone.

Conclusions

The addition of ARSIs to ADT in mHSPC tends to increase overall HR-QoL and prolong time to first deterioration of pain/fatigue compared with ADT alone, ADT with first generation nonsteroideal anti-androgens, and ADT with docetaxel. ARSIs show a complex interaction with remaining HR-QoL domains. We advocate a standardization of HR-QoL measurement and reporting to allow further comparisons.

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

Access options

Buy this article

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

Fig. 1
Fig. 2: Risk of bias assessment.

Similar content being viewed by others

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

References

  1. Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate cancer incidence and survival, by stage and race/ethnicity - United States, 2001-2017. MMWR Morb Mortal Wkly Rep. 2020;69:1473–80.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Desai MM, Cacciamani GE, Gill K, Zhang J, Liu L, Abreu A, et al. Trends in incidence of metastatic prostate cancer in the US. JAMA Netw Open. 2022;5:e222246.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kinsey EN, Zhang T, Armstrong AJ. Metastatic hormone-sensitive prostate cancer: a review of the current treatment landscape. Cancer J. 2020;26:64–75.

    Article  PubMed  Google Scholar 

  4. Ng K, Smith S, Shamash J. Metastatic hormone-sensitive prostate cancer (mHSPC): advances and treatment strategies in the first-line setting. Oncol Ther. 2020;8:209–30.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tagawa ST, Ramaswamy K, Huang A, Mardekian J, Schultz NM, Wang L, et al. Survival outcomes in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone acetate. Prostate Cancer Prostatic Dis. 2021;24:1032–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019;37:2974–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sydes MR, Spears MR, Mason MD, Clarke NW, Dearnaley DP, de Bono JS, et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Ann Oncol. 2018;29:1235–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.

    Article  CAS  PubMed  Google Scholar 

  9. Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381:121–31.

    Article  CAS  PubMed  Google Scholar 

  10. Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386:1132–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019;20:686–700.

    Article  CAS  PubMed  Google Scholar 

  12. Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer. part ii-2020 update: treatment of relapsing and metastatic prostate cancer. Eur Urol. 2021;79:263–82.

    Article  CAS  PubMed  Google Scholar 

  13. Saad F, Bögemann M, Suzuki K, Shore N. Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors. Prostate Cancer Prostatic Dis. 2021;24:323–34.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647.

    Article  PubMed  Google Scholar 

  15. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European organization for research and treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76.

    Article  CAS  PubMed  Google Scholar 

  16. van Andel G, Bottomley A, Fosså SD, Efficace F, Coens C, Guerif S, et al. An international field study of the EORTC QLQ-PR25: a questionnaire for assessing the health-related quality of life of patients with prostate cancer. Eur J Cancer. 2008;44:2418–24.

    Article  PubMed  Google Scholar 

  17. Esper P, Mo F, Chodak G, Sinner M, Cella D, Pienta KJ. Measuring quality of life in men with prostate cancer using the functional assessment of cancer therapy-prostate instrument. Urology. 1997;50:920–8.

    Article  CAS  PubMed  Google Scholar 

  18. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20:1727–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994;23:129–38.

    CAS  PubMed  Google Scholar 

  20. Mendoza TR, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, et al. The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue Inventory. Cancer. 1999;85:1186–96.

    Article  CAS  PubMed  Google Scholar 

  21. Stenzl A, Dunshee C, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, et al. Effect of enzalutamide plus androgen deprivation therapy on health-related quality of life in patients with metastatic hormone-sensitive prostate cancer: an analysis of the ARCHES randomised, placebo-controlled, phase 3 study. Eur Urol. 2020;78:603–14.

    Article  CAS  PubMed  Google Scholar 

  22. Stockler MR, Martin AJ, Davis ID, Dhillon HM, Begbie SD, Chi KN, et al. Health-related quality of life in metastatic, hormone-sensitive prostate cancer: ENZAMET (ANZUP 1304), an international, randomized phase III trial led by ANZUP. J Clin Oncol. 2022;40:837–46.

    Article  CAS  PubMed  Google Scholar 

  23. Agarwal N, McQuarrie K, Bjartell A, Chowdhury S, Pereira de Santana Gomes AJ, Chung BH, et al. Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2019;20:1518–30.

    Article  CAS  PubMed  Google Scholar 

  24. Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018;19:194–206.

    Article  CAS  PubMed  Google Scholar 

  25. Rush HL, Murphy L, Morgans AK, Clarke NW, Cook AD, Attard G, et al. Quality of life in men with prostate cancer randomly allocated to receive docetaxel or abiraterone in the STAMPEDE trial. J Clin Oncol. 2022;40:825–36.

    Article  CAS  PubMed  Google Scholar 

  26. Gupta D, Braun DP, Staren ED. Prognostic value of changes in quality of life scores in prostate cancer. BMC Urol. 2013;13:32.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Koo KC, Park SU, Kim KH, Rha KH, Hong SJ, Yang SC, et al. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels. Prostate Int. 2015;3:10–5.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization: LA, ML, FE; study design: LA, ML, FE, MM, GG, RC; data collection: LA, ML, FE; data analysis: LA, ML; data interpretation: LA, ML; writing: ML, LA; revision: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE; final approval: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE; accountability: ML, LA, MM, GG, AKM, RC, AM, AB, RMS, RP, CDN, FE.

Corresponding author

Correspondence to Luca Afferi.

Ethics declarations

Competing interests

RC: Advisory role for Astellas, Janssen, Bayer, Sanofi, MSD, Roche, BMS, Merck, Pfizer, Ipsen; honoraria from Astellas, Janssen, Merck. The remaining authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afferi, L., Longoni, M., Moschini, M. et al. Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy. Prostate Cancer Prostatic Dis (2023). https://doi.org/10.1038/s41391-023-00668-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41391-023-00668-0

Search

Quick links