title: Early versus deferred androgen suppression therapy for patients with lymph node-positive prostate cancer after local therapy with curative intent: a systematic review.
abstract: BACKGROUND
  There is currently no consensus regarding the optimal timing for androgen suppression therapy in patients with prostate cancer that have undergone local therapy with curative intent but are proven to have node-positive disease without signs of distant metastases at the time of local therapy. The objective of this systematic review was to determine the benefits and harms of early (at the time of local therapy) versus deferred (at the time of clinical disease progression) androgen suppression therapy for patients with node-positive prostate cancer after local therapy.
  
  
  METHODS
  The protocol was registered prospectively (CRD42011001221; http://www.crd.york.ac.uk/PROSPERO). We searched the MEDLINE, EMBASE, and CENTRAL databases, as well as reference lists, the abstracts of three major conferences, and three trial registers, to identify randomized controlled trials (search update 04/08/2012). Two authors independently screened the identified articles, assessed trial quality, and extracted data.
  
  
  RESULTS
  Four studies including 398 patients were identified for inclusion. Early androgen suppression therapy lead to a significant decrease in overall mortality (HR 0.62, 95% CI 0.46-0.84), cancer-specific mortality (HR 0.34, 95% CI 0.18-0.64), and clinical progression at 3 or 9 years (RR 0.29, 95% CI 0.16-0.52 at 3 years and RR 0.49, 95% CI 0.36-0.67 at 9 years). One study showed an increase of adverse effects with early androgen suppression therapy. All trials had substantial methodological limitations.
  
  
  CONCLUSIONS
  The data available suggest an improvement in survival and delayed disease progression but increased adverse events for patients with node-positive prostate cancer after local therapy treated with early androgen suppression therapy versus deferred androgen suppression therapy. However, quality of data is low. Randomized controlled trials with blinding of outcome assessment, planned to determine the timing of androgen suppression therapy in node-positive prostate cancer using modern diagnostic imaging modalities, biochemical testing, and standardized follow-up schedules should be conducted to confirm these findings.
authors.affiliation: Department of Urology, University Clinic Erlangen, Krankenhausstrasse 12, 91054, Erlangen, Germany. frank.kunath@uk-erlangen.de
authors.forename: Frank
authors.initials: F
authors.lastname: Kunath
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Gerta
authors.initials: G
authors.lastname: Rücker
authors.forename: Edith
authors.initials: E
authors.lastname: Motschall
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Gerd
authors.initials: G
authors.lastname: Antes
authors.forename: Joerg J
authors.initials: JJ
authors.lastname: Meerpohl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal