Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis.
BACKGROUND
Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.


METHODS
Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).


RESULTS
The final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26).


CONCLUSIONS
Overall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.
Evidencias Scientific Credibility, Campinas, São Paulo, Brazil. tobias.engel@evidencias.com.br.
Tobias Engel Ayer
TE
Botrel
Otávio
O
Clark
Rodolfo Borges
RB
dos Reis
Antônio Carlos Lima
AC
Pompeo
Ubirajara
U
Ferreira
Marcus Vinicius
MV
Sadi
Francisco Flávio Horta
FF
Bretas
D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects*; D015984:Causality; D015897:Comorbidity; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D011788:Quality of Life; D012307:Risk Factors; D012735:Sexual Dysfunction, Physiological / Q000209:etiology* / Q000401:mortality*; D016896:Treatment Outcome
D000726:Androgen Antagonists