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A Systematic Review and a Meta-analysis of Randomized Controlled Trials’ Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
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Abstract

Purpose of Review

Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes.

Recent Findings

Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival.

Summary

Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

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Abbreviations

ADT:

Androgen deprivation treatment

mHSPC:

Metastatic hormone-sensitive prostate cancer

ARTA:

Androgen receptor-targeted agents

RCT:

Randomized controlled trial

PFS:

Progression-free survival

OS:

Overall survival

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cancer Statistics, 2021 - Siegel - 2021 - CA: a cancer journal for clinicians - Wiley Online Library [Internet]. [cited 2022 Feb 1]. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21654.

  2. Huggins C, Hodges CV. Studies on prostatic cancer I The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin. 1972;22:232–40.

    Article  CAS  PubMed  Google Scholar 

  3. James ND, Spears MR, Clarke NW, et al. Survival with newly diagnosed metastatic prostate cancer in the “docetaxel era”: data from 917 patients in the control arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). Eur Urol. 2015;67:1028–38.

    Article  PubMed  Google Scholar 

  4. Maximum androgen blockade in advanced prostate cancer. an overview of the randomised trials. Prostate Cancer Trialists’ Collab Group Lancet. 2000;355:1491–8.

    Google Scholar 

  5. Millikan RE, Wen S, Pagliaro LC, et al. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008;26:5936–42.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.

    Article  CAS  PubMed  Google Scholar 

  7. Tucci M, Zichi C, Buttigliero C, et al. Enzalutamide-resistant castration-resistant prostate cancer: challenges and solutions. Onco Targets Ther. 2018;11:7353–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tucci M, Bertaglia V, Vignani F, et al. Addition of docetaxel to androgen deprivation therapy for patients with hormone-sensitive metastatic prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;69:563–73.

    Article  CAS  PubMed  Google Scholar 

  9. Gravis G, Fizazi K, Joly F, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:149–58.

    Article  CAS  PubMed  Google Scholar 

  10. Kyriakopoulos CE, Chen Y-H, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED Trial. J Clin Oncol. 2018;10:1080–7.

    Article  Google Scholar 

  11. James ND. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vale CL, Burdett S, Rydzewska LHM, et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016;17:243–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Boevé LMS, Hulshof MCCM, Vis AN, et al. Effect on survival of androgen deprivation therapy alone compared to androgen deprivation therapy combined with concurrent radiation therapy to the prostate in patients with primary bone metastatic prostate cancer in a prospective randomised clinical trial: data from the HORRAD Trial. Eur Urol. 2019;75:410–8.

    Article  PubMed  Google Scholar 

  14. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392:2353–66.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) (2015) elaboration and explanation BMJ 2015 349:g7647

  16. Combescure C, Foucher Y, Jackson D. Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects. Stat Med. 2014;33:2521–37.

    Article  PubMed  Google Scholar 

  17. Earle CC, Pham B, Wells GA. An assessment of methods to combine published survival curves. Med Decis Making. 2000;20:104–11.

    Article  CAS  PubMed  Google Scholar 

  18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  19. Cabibbo G, Enea M, Attanasio M, et al. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology. 2010;51:1274–83.

    Article  PubMed  Google Scholar 

  20. Sweeney CJ, Carducci M, Eisenberger M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fizazi K, Matsubara N, Alekseev BY, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352–60.

    Article  CAS  PubMed  Google Scholar 

  22. Fizazi K, Tran N, Fein L, 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 

  23. James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017;377:338–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Agarwal N, Tangen C, Hussain MHA, et al. SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients (pts) with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) (NCT01809691). J Clin Oncol. 2021;39:5001–5001.

    Article  Google Scholar 

  25. • Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019;381:121–31. This is the registrative RCT for enzalutamide for metastatic hormone-sensitive prostate cancer.

    Article  CAS  PubMed  Google Scholar 

  26. Vaishampayan UN, Heilbrun LK, Monk P, et al. Clinical efficacy of enzalutamide vs bicalutamide combined with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer: a randomized clinical trial. JAMA Netw Open. 2021;4:e2034633.

    Article  PubMed  PubMed Central  Google Scholar 

  27. • Armstrong AJ, Szmulewitz RZ, Petrylak DP, 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. This is the registrative RCT for Enzalutamide for metastatic hormone sensitive prostatec cancer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019;381:13–24.

    Article  CAS  PubMed  Google Scholar 

  29. • Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021;39:2294. This is the registrative RCT for apalutamide (ARTA) for metastatic hormone-sensitive prostate cancer.

    Article  CAS  PubMed  Google Scholar 

  30. ZAPCA Study Group, Kamba T, Kamoto T, et al. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial. Int J Clin Oncol. 2017;22:166–73.

    Article  Google Scholar 

  31. Dearnaley DP, Mason MD, Parmar MK, et al. Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials. Lancet Oncol. 2009;10:872–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Smith MR, Halabi S, Ryan CJ, et al. Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (Alliance). J Clin Oncol. 2014;32:1143–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. •• Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on prostate cancer Part II—2020 update: treatment of relapsing and metastatic prostate cancer. European Urology. 2021;79:263–82. This article is the summary of EAU-EANM-ESTRO-ESUR-SIOG Guidelines on prostate cancer.

    Article  CAS  PubMed  Google Scholar 

  34. Montironi R, Cimadamore A, Lopez-Beltran A, et al. Morphologic, molecular and clinical features of aggressive variant prostate cancer. Cells. 2020;9:1073.

    Article  CAS  PubMed Central  Google Scholar 

  35. Nizialek E, Lim SJ, Wang H, et al. Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone-sensitive prostate cancer. Prostate. 2021;81:572–9.

    Article  CAS  PubMed  Google Scholar 

  36. Gundem G, Van Loo P, Kremeyer B, et al. The evolutionary history of lethal metastatic prostate cancer. Nature. 2015;520:353–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. •• Phillips R, Shi WY, Deek M, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncology. 2020;6:650–9. This is the first RCT that described the role of metastasis direct stereotactic radiotherapy in oligometastatic prostate cancer.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): five-year results of a randomized phase II trial. | J Clin Oncol [Internet]. [cited 2022 Feb 5]. Available from: https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.6_suppl.10

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Author notes

  1. Bruno Fionda and Fernando Munoz contributed equally to this work.

Authors and Affiliations

  1. Department of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, Verona, Italy

    Giuseppe Napoli, Umberto Tebano, Marco Muraro, Giulia Rinaldi, Nicoletta Luca & Francesco Fiorica

  2. Department of Radiation Oncology, School of Medicine and Surgery, University of Milan Bicocca, Milan, Italy

    Stefano Arcangeli

  3. U.O.C. Radioterapia Oncologica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy

    Bruno Fionda

  4. Radiation Oncology Unit, Regional Hospital of Aosta, Aosta, Italy

    Fernando Munoz

  5. Department of Medical Oncology, AULSS 9 Scaligera, Verona, Italy

    Emilia Durante

  6. Medical Oncology Unit, Regional Hospital of Aosta, Aosta, Italy

    Marcello Tucci

  7. Department of Radiation Oncology, NCI CRO Aviano, Aviano, Italy

    Roberto Bortolus

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  1. Giuseppe Napoli
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Correspondence to Francesco Fiorica.

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Napoli, G., Arcangeli, S., Fionda, B. et al. A Systematic Review and a Meta-analysis of Randomized Controlled Trials’ Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC). Curr Oncol Rep 24, 1633–1644 (2022). https://doi.org/10.1007/s11912-022-01323-y

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