Liselotte M S Boevé1, Maarten C C M Hulshof2, André N Vis3, Aeilko H Zwinderman4, Jos W R Twisk5, Wim P J Witjes6, Karl P J Delaere7, R Jeroen A van Moorselaar3, Paul C M S Verhagen8, George van Andel9. 1. Department of Urology, OLVG, Amsterdam, The Netherlands; Department of Urology, VU university Medical Centre, Amsterdam, The Netherlands. Electronic address: l.boeve@olvg.nl. 2. Department of Radiotherapy, Academic Medical Centre, Amsterdam, The Netherlands. 3. Department of Urology, VU university Medical Centre, Amsterdam, The Netherlands. 4. Department of Epidemiology and Biostatistics, Academic Medical Centre, Amsterdam, The Netherlands. 5. Department of Epidemiology and Biostatistics, VU university Medical Centre, Amsterdam, The Netherlands. 6. CuraTrial SMO & Research BV, Arnhem, The Netherlands. 7. Department of Urology, Zuyderland Medical Centre, Heerlen, The Netherlands. 8. Department of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands. 9. Department of Urology, OLVG, Amsterdam, The Netherlands.
Abstract
BACKGROUND: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. OBJECTIVE: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. DESIGN, SETTING, AND PARTICIPANTS: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20ng/ml and primary bone mPCa on bone scan between 2004 and 2014. INTERVENTION: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. RESULTS AND LIMITATIONS: Median PSA level was 142ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4-49.6) in the radiotherapy group and 43 mo (95% CI: 32.6-53.4) in the control group (p=0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70-1.14; p=0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8-18.2), compared with 12 mo (95% CI: 10.6-13.4) in the control group. The crude HR (0.78; 95% CI: 0.63-0.97) was statistically significant (p=0.02). CONCLUSIONS: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. PATIENT SUMMARY: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. TWITTER SUMMARY: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival.
RCT Entities:
BACKGROUND: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. OBJECTIVE: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. DESIGN, SETTING, AND PARTICIPANTS: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20ng/ml and primary bone mPCa on bone scan between 2004 and 2014. INTERVENTION: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. RESULTS AND LIMITATIONS: Median PSA level was 142ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4-49.6) in the radiotherapy group and 43 mo (95% CI: 32.6-53.4) in the control group (p=0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70-1.14; p=0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8-18.2), compared with 12 mo (95% CI: 10.6-13.4) in the control group. The crude HR (0.78; 95% CI: 0.63-0.97) was statistically significant (p=0.02). CONCLUSIONS: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. PATIENT SUMMARY: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancerpatients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. TWITTER SUMMARY: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival.
Authors: Shawn Malone; Bobby Shayegan; Naveen S Basappa; Kim Chi; Henry J Conter; Robert J Hamilton; Sebastien J Hotte; Fred Saad; Alan I So; Laura Park-Wyllie; Huong Hew; Deanna McLeod; Geoffrey Gotto Journal: Can Urol Assoc J Date: 2019-04-26 Impact factor: 1.862
Authors: E M Kwan; I A Thangasamy; J Teh; O Alghazo; N J Sathianathen; N Lawrentschuk; A A Azad Journal: World J Urol Date: 2020-01-02 Impact factor: 4.226