Abstract
Purpose
To evaluate the effectiveness and harms of DES in treating prostate cancer compared to other forms of androgen deprivation therapy (orchiectomy, LHRH agonists, and anti-androgens).
Methods
We included clinical trials comparing DES with other forms of ADT (bicalutamide, flutamide, LHRH agonists, or orchiectomy) in PCa treatment. The primary outcomes were overall survival, cancer-specific survival, and progression-free survival, and secondary outcomes were cardiovascular effects. We searched in MEDLINE, EMBASE, Central, and Lilacs from inception to nowadays and saturated information for unpublished data in other sources. We performed a qualitative analysis of all included studies. It was not possible to perform meta-analysis due to low-quality trials and high heterogeneity.
Results
Overall, 1700 references were scanned and 14 prospective randomized trials with a total of 3986 patients were included in the final analysis. Although trials showed DES as similarly effective to another forms of ADT, evidences about cardiovascular toxicity in out of date high doses have discouraged its use. In doses of 1 mg, DES has been used as secondary line PCa treatment with safety.
Conclusions
DES might be similarly effective to other forms of ADT on advanced PCa patients, with potential important roles. Intriguingly, the burden of severe cardiovascular toxicity is mainly related to old-fashioned doses of 5.0 and 3.0 mg. Modern PCa hormonal knowledge warrants stout high-quality prospective randomized trials in the low-dose 1 mg DES scenario.
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Funding
LOR, CNPq Research Productivity, Brazil—Grant: 302622/2015-2.
Author information
Authors and Affiliations
Contributions
LOR contributed to protocol design, writing and mentoring. ELZ contributed to searching and assessing documents, and writing. HAGP contributed to searching and assessing documents, drafting the final document.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the review reported.
Appendix: Search strategy
Appendix: Search strategy
MEDLINE
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1.
exp Prostatic Neoplasms/
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2.
exp prostatic intraepithelial neoplasia/
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3.
(prostatic adj2 malignanc$).mp
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4.
(prostatic adj2 cancer).mp
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5.
or/
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6.
DES.mp
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7.
Diethylstilbestrol.mp
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8.
or/
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9.
exp randomized controlled trial/
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10.
(randomi*ed adj2 controlled adj2 trial).mp.
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11.
exp clinical trial/
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12.
(clinical adj2 trial).mp.
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13.
exp double-blind method/
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14.
or/
EMBASE
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1.
‘Prostate Tumor’/exp
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2.
‘prostatic intraepithelial neoplasia’/exp
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3.
(prostatic NEXT/2 malignanc*):ti,ab
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4.
(prostatic NEXT/2 cancer):ti,ab
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5.
(organ NEXT/2 confined NEXT/2 disease):ti,ab
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6.
or/
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7.
DES:ti,ab
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8.
Diethylstilbestrol:ti,ab
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9.
or/
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10.
‘randomized controlled trials’/exp
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11.
(randomi*ed NEXT/2 controlled NEXT/2 trial):ti,ab
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12.
‘clinical trials’/exp
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13.
(clinical NEXT/2 trial):ti,ab
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14.
‘double blind procedure’/exp
Central and lilacs
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1.
exp Prostatic Neoplasms/
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2.
exp prostatic intraepithelial neoplasia/
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3.
(prostatic adj2 malignanc$).mp
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4.
(prostatic adj2 cancer).mp
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5.
or/
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6.
DES.mp
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7.
Diethylstilbestrol.mp
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Reis, L.O., Zani, E.L. & García-Perdomo, H.A. Estrogen therapy in patients with prostate cancer: a contemporary systematic review. Int Urol Nephrol 50, 993–1003 (2018). https://doi.org/10.1007/s11255-018-1854-5
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DOI: https://doi.org/10.1007/s11255-018-1854-5