BACKGROUND: The timing of endocrine treatment (ET) for prostate cancer (PCa) remains controversial. The issue is addressed in European Organisation for the Research and Treatment of Cancer (EORTC) protocol 30846 for patients with lymph node-positive (pN1-3) cancer without local treatment of the primary tumour. OBJECTIVE: To evaluate the effect of early versus delayed treatment in pN1-3 PCa. DESIGN, SETTING, AND PARTICIPANTS: Two hundred thirty-four patients with histologically proven PCa and nodal metastases (pN1-3) were randomized to immediate versus delayed ET without treatment of the primary tumour. ET consisted of a depot luteinising hormone-releasing hormone (LHRH) agonist and 1 mo of an anti-androgen or surgical castration. The trial's main objective was to show non-inferiority of delayed ET to immediate ET by ruling out a hazard ratio (HR) of 1.50 for overall survival (OS), with 85% power at one-sided alpha=5%. MEASUREMENTS: All but three patients were treated as randomized. The median follow-up is 13 yr. The median protocol treatment duration was 2.7 yr in the delayed and 3.2 yr in the immediate ET groups. RESULTS AND LIMITATIONS: Overall, 193 patients (82.5%) have died (97 on delayed ET and 96 on immediate ET), 59.4% of them as a result of PCa. The intention-to-treat analysis shows a 22% increase in the hazard of death of those randomized to delayed treatment (HR=1.22, 95% confidence interval [CI]: 0.92, 1.62). The difference is not statistically significant, but non-inferiority is also not proved. The median OS on immediate ET is 7.6 yr (95% CI, 6.3-8.3 yr) versus 6.1 yr (95% CI, 5.7-7.3 yr) in the delayed ET group. The 10-yr cumulative incidence of death resulting from PCa was 55.6% in the delayed ET group versus 52.1% with immediate ET group. Similar conclusions hold for PCa-specific survival. CONCLUSIONS: After 13 years of follow-up, survival or PCa-specific survival between immediate and delayed ET appear similar, but the trial is underpowered to reach its goal of showing non-inferiority.
RCT Entities:
BACKGROUND: The timing of endocrine treatment (ET) for prostate cancer (PCa) remains controversial. The issue is addressed in European Organisation for the Research and Treatment of Cancer (EORTC) protocol 30846 for patients with lymph node-positive (pN1-3) cancer without local treatment of the primary tumour. OBJECTIVE: To evaluate the effect of early versus delayed treatment in pN1-3 PCa. DESIGN, SETTING, AND PARTICIPANTS: Two hundred thirty-four patients with histologically proven PCa and nodal metastases (pN1-3) were randomized to immediate versus delayed ET without treatment of the primary tumour. ET consisted of a depot luteinising hormone-releasing hormone (LHRH) agonist and 1 mo of an anti-androgen or surgical castration. The trial's main objective was to show non-inferiority of delayed ET to immediate ET by ruling out a hazard ratio (HR) of 1.50 for overall survival (OS), with 85% power at one-sided alpha=5%. MEASUREMENTS: All but three patients were treated as randomized. The median follow-up is 13 yr. The median protocol treatment duration was 2.7 yr in the delayed and 3.2 yr in the immediate ET groups. RESULTS AND LIMITATIONS: Overall, 193 patients (82.5%) have died (97 on delayed ET and 96 on immediate ET), 59.4% of them as a result of PCa. The intention-to-treat analysis shows a 22% increase in the hazard of death of those randomized to delayed treatment (HR=1.22, 95% confidence interval [CI]: 0.92, 1.62). The difference is not statistically significant, but non-inferiority is also not proved. The median OS on immediate ET is 7.6 yr (95% CI, 6.3-8.3 yr) versus 6.1 yr (95% CI, 5.7-7.3 yr) in the delayed ET group. The 10-yr cumulative incidence of death resulting from PCa was 55.6% in the delayed ET group versus 52.1% with immediate ET group. Similar conclusions hold for PCa-specific survival. CONCLUSIONS: After 13 years of follow-up, survival or PCa-specific survival between immediate and delayed ET appear similar, but the trial is underpowered to reach its goal of showing non-inferiority.
Authors: Christian von Bodman; Guilherme Godoy; Daher C Chade; Angel Cronin; Laura J Tafe; Samson W Fine; Vincent Laudone; Peter T Scardino; James A Eastham Journal: J Urol Date: 2010-05-15 Impact factor: 7.450
Authors: A J Zurita; L L Pisters; X Wang; P Troncoso; P Dieringer; J F Ward; J W Davis; C A Pettaway; C J Logothetis; L C Pagliaro Journal: Prostate Cancer Prostatic Dis Date: 2015-05-26 Impact factor: 5.554
Authors: Pirus Ghadjar; Alberto Briganti; Peter J L De Visschere; Jurgen J Fütterer; Gianluca Giannarini; Hendrik Isbarn; Piet Ost; Prasanna Sooriakumaran; Christian I Surcel; Roderick C N van den Bergh; Inge M van Oort; Ofer Yossepowitch; Guillaume Ploussard Journal: World J Urol Date: 2014-07-05 Impact factor: 4.226
Authors: Vincenzo Pagliarulo; Sergio Bracarda; Mario A Eisenberger; Nicolas Mottet; Fritz H Schröder; Cora N Sternberg; Urs E Studer Journal: Eur Urol Date: 2011-08-19 Impact factor: 20.096