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Association between age and efficacy of combination systemic therapies in patients with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis

Prostate Cancer and Prostatic Diseases volume 26, pages 170–179 (2023)Cite this article

Subjects

Abstract

Background

Combination systemic therapies have become the standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, the effect of age on oncologic outcomes remains unknown. Our aim was to perform a systematic review, meta-analysis, and network meta-analysis (NMA) on the effect of chronological age on overall survival (OS) in patients treated with combination therapies for mHSPC.

Methods

We searched the PubMed®, Web of ScienceTM, and Scopus® databases to identify randomized controlled trials (RCTs) that analyzed the efficacy of combination systemic therapies using ADT plus docetaxel and/or androgen receptor signaling inhibitor (ARSI) in patients with mHSPC. We included studies, which provided separate hazard ratios (HRs) for younger vs. older patients. The selected age cut-off was 70 years (±5 years). Our outcome of interest was OS.

Results

We included nine RCTs with a total of 9183 patients. Younger and older men constituted 51% and 49% of included patients, respectively. Docetaxel plus ADT significantly improved OS among both older (HR 0.79, 95% CI 0.63–0.99, p = 0.04) and younger patients (HR 0.79, 95% CI 0.69–0.90, p < 0.001) with no differences according to age. ARSI plus ADT improved OS in older (HR 0.72, 95% CI 0.64–0.80, p < 0.001) and younger (HR 0.58, 95% CI 0.51–0.66, p < 0.001) patients; younger patients did benefit more (p = 0.02). On NMA treatment ranking, triplet therapy showed the highest probability of OS benefit irrespective of age group; in older patients, the benefit of triplet therapy compared to doublet was less expressed.

Conclusions

Patients with mHSPC benefit from combination systemic therapies irrespective of age; the effect is, however, more evident in younger patients. Chronological age alone seems not to be a selection criteria for the administration of combination systemic therapies.

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Data availability

All the data used for this study are available online on journal sites where the included studies were retrieved from.

Code availability

Example R code used for this analysis is found in a statistical methodology papers by Shim et al. [26, 43].

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Funding

EUSP Scholarship of the European Association of Urology (PR).

EAU-YAU Prostate Cancer Working Party

Pawel Rajwa1,2, Isabel Heidegger4, Fabio Zattoni5, Giancarlo Marra6, Timo F. W. Soeterik7, Roderick C. N. van den Bergh7, Massimo Valerio8, Francesco Ceci9,10, Claudia V. Kesch11, Veeru Kasivisvanathan12, Guillaume Ploussard19, Giorgio Gandaglia20

Author information

Authors and Affiliations

  1. Department of Urology, Medical University of Vienna, Vienna, Austria

    Pawel Rajwa, Takafumi Yanagisawa, Ekaterina Laukhtina, Tatsushi Kawada & Shahrokh F. Shariat

  2. Department of Urology, Medical University of Silesia, Zabrze, Poland

    Pawel Rajwa

  3. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan

    Takafumi Yanagisawa

  4. Department of Urology, Medical University Innsbruck, Innsbruck, Austria

    Isabel Heidegger

  5. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

    Fabio Zattoni

  6. Department of Urology, San Giovanni Battista Hospital, University of Torino, Torino, Italy

    Giancarlo Marra

  7. Department of Urology, St Antonius Hospital, Utrecht, The Netherlands

    Timo F. W. Soeterik, Roderick C. N. van den Bergh & Roderick C. N. van den Bergh

  8. Department of Urology, CHUV Lausanne, Lausanne, Switzerland

    Massimo Valerio

  9. Division of Nuclear Medicine, European Institute of Oncology IRCCS, Milan, Italy

    Francesco Ceci

  10. Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy

    Francesco Ceci

  11. Department of Urology, University Hospital Essen, Essen German Cancer Consortium (DKTK) University Hospital Essen, Essen, Germany

    Claudia V. Kesch

  12. Division of Surgery and Interventional Science, University College London, London, UK

    Veeru Kasivisvanathan

  13. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia

    Ekaterina Laukhtina & Shahrokh F. Shariat

  14. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Tatsushi Kawada

  15. Department of Urology, Semmelweis University, Budapest, Hungary

    Peter Nyiriadi

  16. Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Quoc-Dien Trinh

  17. Department of Urology, Jagiellonian University, Krakow, Poland

    Piotr Chlosta

  18. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada

    Pierre I. Karakiewicz

  19. Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France

    Guillaume Ploussard

  20. Unit of Urology/Division of Oncology, IRCCS San Raffaele, San Raffaele Hospital, Milan, Italy

    Alberto Briganti, Francesco Montorsi & Giorgio Gandaglia

  21. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic

    Shahrokh F. Shariat

  22. Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan

    Shahrokh F. Shariat

  23. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  24. Department of Urology, University of Texas Southwestern, Dallas, TX, USA

    Shahrokh F. Shariat

Authors
  1. Pawel Rajwa
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  2. Takafumi Yanagisawa
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  3. Isabel Heidegger
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  9. Francesco Ceci
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  12. Ekaterina Laukhtina
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  22. Giorgio Gandaglia
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Consortia

EAU-YAU Prostate Cancer Working Party

  • Pawel Rajwa
  • , Isabel Heidegger
  • , Fabio Zattoni
  • , Giancarlo Marra
  • , Timo F. W. Soeterik
  • , Roderick C. N. van den Bergh
  • , Massimo Valerio
  • , Francesco Ceci
  • , Claudia V. Kesch
  • , Veeru Kasivisvanathan
  • , Guillaume Ploussard
  •  & Giorgio Gandaglia

Contributions

Conception and design PR, TY, SFS, GG; Acquisition of data PR, TY, SFS, GG; Analysis and interpretation of data PR, TY, SFS, GG; Drafting of the paper PR, IH, FZ, GM, TFWS, RCNB, CVK, GP, SFS, GG; Critical revision of the paper for important intellectual content MV, FC, CVK, VK, PN, QDT, PC, PIK, AB, FM; Statistical analysis PR, TK.

Corresponding author

Correspondence to Shahrokh F. Shariat.

Ethics declarations

Competing interests

PR and GG served as a speaker and/or consultant and/or advisory board for Janssen, SFS has served as a speaker and/or consultant and/or advisory board for Astellas, Astra Zeneca, BMS, Ferring, Ipsen, Janssen, Lilly, MSD, Olympus, Roche, Sanofi, Takeda, and Urogen. CK has received consultant fees from Apogepha, research funding from AAA/Novartis and Curie Therapeutics and compensation for travel from Janssen.

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

Members of the EAU-YAU Prostate Cancer Working Party are listed below Funding.

Supplementary information

Supplementary legends.

41391_2022_607_MOESM2_ESM.png

Supplementary Figure 1. Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies

41391_2022_607_MOESM3_ESM.png

Supplementary Figure 2. Risk of bias and applicability concerns summary: review authors' judgments about each domain for each included study

41391_2022_607_MOESM4_ESM.tif

Supplementary Figure 3. Network plots show the association between docetaxel- and ARSI-based combination systemic therapies in terms of overall survival in patient with mHSPC.

Supplementary Figure 4. SUCRA treatment ranking probability graph for: A) older patients; B) younger patients

Supplementary Table 1. PRISMA checklist

Supplementary Table 2.

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Rajwa, P., Yanagisawa, T., Heidegger, I. et al. Association between age and efficacy of combination systemic therapies in patients with metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 26, 170–179 (2023). https://doi.org/10.1038/s41391-022-00607-5

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