Intermittent Androgen Suppression for Rising PSA Level After Radiotherapy
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Notice bibliographique
Résumé
Androgen deprivation with medical castration has been the mainstay treatment for metastatic prostate cancer. However, there are several drawbacks to prolonged androgen deprivation, including development of tolerance (loss of androgen dependence) and adverse effects on the quality of life. In mice tumor models of androgen dependence, castration followed by re-exposure to androgens before tumor progression preserved androgen dependence. The possible value of this treatment strategy has been studied in human prostate cancer. Several phases 2 and 3 clinical studies suggest that intermittent androgen deprivation can delay hormone resistance and provide a quality-of-life benefit. This noninferiority randomized trial compared overall survival of prostate cancer patients with use of intermittent and continuous androgen deprivation. Enrolled patients had prostatic adenocarcinoma but no metastatic disease and a rising prostate-specific antigen (PSA) level greater than 3 ng/mL after primary or salvage radiotherapy for localized prostate cancer more than 12 months before enrollment. Intermittent androgen-deprivation therapy consisted of 8-month treatment cycles, with nontreatment periods based on the PSA level. The primary study end point was overall survival. Secondary end points included time to castration-resistant disease, quality of life, and duration of nontreatment intervals. Participants were randomly assigned to intermittent therapy (n = 690) or continuous therapy (n = 696). The median follow-up was 6.9 years. No significant between-group differences in adverse events were found. With intermittent therapy, there was full testosterone recovery in 35% of patients and recovery to the trial-entry threshold in 79%. Intermittent therapy was associated with improvements in physical function and other quality-of-life measurements for hot flashes, urinary problems, fatigue, libido, and erectile function. A total of 524 patients died: 268 in the intermittent-therapy group and 256 in the continuous-therapy group. There was no difference between groups in median overall survival: 8.8 years in the intermittent-therapy group and 9.1 years in the continuous-therapy group; the hazard ratio for death was 1.02, with a 95% confidence interval of 0.86 to 1.21. With respect to the disease-specific survival, the estimated 7-year cumulative disease-related death rates were 18% in the intermittent group and 15% in the continuous group (P = 0.24). These findings show that, for overall survival, intermittent androgen deprivation is not noninferior to continuous therapy. Improvements in some quality-of-life factors are observed with intermittent therapy.
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Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle