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First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH

  • Kagan Griffin
  • Ilona Csizmadi
  • Lauren E. Howard
  • Gina-Maria Pomann
  • William J. Aronson
  • Christopher J. Kane
  • Christopher L. Amling
  • Matthew R. Cooperberg
  • Martha K. Terris
  • Jennifer Beebe-Dimmer
  • Stephen J. FreedlandEmail author
Original Paper

Abstract

Purpose

We aimed to study the associations between androgen-deprivation therapy (ADT)-induced weight changes and prostate cancer (PC) progression and mortality in men who had undergone radical prostatectomy (RP).

Methods

Data from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort were used to study the associations between weight change approximately 1-year post-ADT initiation and metastases, castration-resistant prostate cancer (CRPC), all-cause mortality (ACM), and PC-specific mortality (PCSM) in 357 patients who had undergone RP between 1988 and 2014. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) using covariate-adjusted Cox regression models for associations between weight loss, and weight gains of 2.3 kg or more, and PC progression and mortality post-ADT.

Results

During a median (IQR) follow-up of 81 (46–119) months, 55 men were diagnosed with metastases, 61 with CRPC, 36 died of PC, and 122 died of any cause. In multivariable analysis, weight loss was associated with increases in risks of metastases (HR 3.13; 95% CI 1.40–6.97), PCSM (HR 4.73; 95% CI 1.59–14.0), and ACM (HR 2.16; 95% CI 1.25–3.74) compared with mild weight gains of ≤ 2.2. Results were slightly attenuated but remained statistically significant in analyses that accounted for competing risks of non-PC death. Estimates for the associations between weight gains of ≥ 2.3 kg and metastases (HR 1.58; 95% CI 0.73–3.42), CRPC (HR 1.33; 95% CI 0.66–2.66), and PCSM (HR 2.44; 95% CI 0.84–7.11) were elevated, but not statistically significant.

Conclusions

Our results suggest that weight loss following ADT initiation in men who have undergone RP is a poor prognostic sign. If confirmed in future studies, testing ways to mitigate weight loss post-ADT may be warranted.

Keywords

Prostate cancer Androgen-deprivation therapy Metastases Prostate cancer-specific mortality Weight gain Weight loss 

Notes

Funding

This study was supported by NIH/NCI Grant Nos. P50CA92131 and NIH K24 CA160653.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest.

Supplementary material

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Supplementary Table 1 (RTF 129 KB)
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Supplementary Table 2 (DOCX 14 KB)
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Supplementary Table 3 (DOCX 16 KB)
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Supplementary Table 4 (DOCX 16 KB)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kagan Griffin
    • 1
  • Ilona Csizmadi
    • 2
  • Lauren E. Howard
    • 1
    • 3
  • Gina-Maria Pomann
    • 3
  • William J. Aronson
    • 4
  • Christopher J. Kane
    • 5
  • Christopher L. Amling
    • 6
  • Matthew R. Cooperberg
    • 7
  • Martha K. Terris
    • 8
  • Jennifer Beebe-Dimmer
    • 9
  • Stephen J. Freedland
    • 1
    • 2
    • 10
    Email author
  1. 1.Urology Section, Department of SurgeryVeterans Affairs Medical CentersDurhamUSA
  2. 2.Division of Urology, Department of SurgeryCedars-Sinai Medical CenterLos AngelesUSA
  3. 3.Department of Biostatistics and BioinformaticsDuke University School of MedicineDurhamUSA
  4. 4.Department of UrologyUniversity of California at Los Angeles Medical CenterLos AngelesUSA
  5. 5.Division of Urology, Department of SurgeryUniversity of California at San Diego Medical CenterSan DiegoUSA
  6. 6.Division of Urology, Department of SurgeryOregon Health & Science UniversityPortlandUSA
  7. 7.Department of UrologyUCSF Helen Diller Family Comprehensive Cancer CenterSan FranciscoUSA
  8. 8.Urology Section, Division of Surgery, Veterans Affairs Medical Center and Division of Urologic Surgery, Department of SurgeryMedical College of GeorgiaAugustaUSA
  9. 9.Department of OncologyWayne State University School of MedicineDetroitUSA
  10. 10.Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA

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