TY - JOUR
T1 - Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer
AU - Fizazi, Karim
AU - Massard, Christophe
AU - Smith, Matthew
AU - Rader, Michael
AU - Brown, Janet
AU - Milecki, Piotr
AU - Shore, Neal
AU - Oudard, Stephane
AU - Karsh, Lawrence
AU - Carducci, Michael
AU - Damiaõ, Ronaldo
AU - Wang, Huei
AU - Ying, Wendy
AU - Goessl, Carsten
N1 - Funding Information:
In conclusion, bone-related parameters were found to be strong predictors of overall survival in addition to established disease stage factors in multivariate analyses using a large contemporary trial population of metastatic CRPC patients. The main utility of these findings is in the stratification of prospective clinical trials, although survival prediction in routine clinical practice is also feasible. Presented at the annual meeting of the American Society of Clinical Oncology 2012. Author contributions: Karim Fizazi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Fizazi, Goessl, Massard, Smith, Brown. Acquisition of data: Fizazi, Goessl, Smith, Shore, Milecki, Karsh, Oudard, Rader, Carducci. Analysis and interpretation of data: Fizazi, Massard, Goessl, Smith, Ying, Shore, Milecki, Karsh, Oudard, Rader, Brown, Carducci. Drafting of the manuscript: Fizazi, Ying, Wang, Goessl. Critical revision of the manuscript for important intellectual content: Massard, Shore, Smith, Milecki, Karsh, Oudard, Rader, Brown, Wang, Carducci. Statistical analysis: Wang, Ying. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Fizazi, Goessl. Other (specify): None. Financial disclosures: Karim Fizazi certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Karim Fizazi reports consultant fees for Amgen and Novartis and honoraria from Amgen. Christophe Massard reports consultant fees from Amgen, Roche, and Janssen. Matthew Smith and Ronaldo Damiao have nothing to disclose. Michael Rader reports research funding, honoraria, and consultant fees from Amgen. Janet Brown reports consultant fees from Amgen, Novartis, and Bristol Myers Squibb, and honoraria from Amgen and Novartis. Piotr Milecki reports honoraria and consultant fees from Amgen. Neal Shore reports research funding and consultant fees from Amgen. Stephane Oudard reports honoraria and consultant fees from Amgen, Ipsen, and Sanofi-Aventis. Lawrence Karsh reports research funding, consultant fees, and honoraria from Amgen. Michael Carducci reports consultant fees from Amgen and Bayer, and research funding to the university from Amgen. Huei Wang and Wendy Ying are employees of Amgen and hold Amgen stock. Carsten Goessl was an employee of Amgen while the work was conducted. Funding/Support and role of the sponsor: Amgen Inc. (Thousand Oaks, CA, USA) sponsored this study/analysis and was involved in the design and conduct of the study; management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript. Acknowledgment statement: Wanda Krall, PhD, on behalf of Amgen, and Geoff Smith, PhD, of Amgen, provided writing assistance. Appendix A
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Background: Previous studies have reported on prognostic factors for castrationresistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≥143 U/l ( p < 0.0001); bone-specific alkaline phosphatase (BSAP) < 146 U/l (p < 0.0001); corrected urinary N-telopeptide (uNTx) ≥50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory- Short Form [BPI-SF] score ≥4) (p < 0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p < 0.0001); and longer time from first bone metastasis to randomization (p < 0.0001). Other significant predictors of improved survival included prostatespecific antigen (PSA) level < 10 ng/ml (p < 0.0001), hemoglobin >128 g/l (p < 0.0001), absence of visceral metastases (p < 0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
AB - Background: Previous studies have reported on prognostic factors for castrationresistant prostate cancer (CRPC); however, most of these studies were conducted before docetaxel chemotherapy was approved for CRPC. Objective: To evaluate the prognostic value of multiple parameters in men with bone metastases due to CRPC using a contemporary dataset. Design, setting, and participants: The analysis included 1901 patients with metastatic CRPC enrolled in an international, multicenter, randomized, double-blind phase 3 trial conducted between May 2006 and October 2009. Outcome measures and statistical analysis: We developed multivariate validated Cox proportional hazards models and nomograms to estimate 12-mo and 24-mo survival probabilities and median survival time. Results and limitations: The median (95% confidence interval) overall survival was 20 (18, 21) mo. The final model included 12 of the 15 potential prognostic variables evaluated (concordance index 0.72). Seven bone-related variables were associated with longer survival in the final model: alkaline phosphatase ≥143 U/l ( p < 0.0001); bone-specific alkaline phosphatase (BSAP) < 146 U/l (p < 0.0001); corrected urinary N-telopeptide (uNTx) ≥50 nmol/mmol (p = 0.0008); mild or no pain (Brief Pain Inventory- Short Form [BPI-SF] score ≥4) (p < 0.0001); no previous skeletal-related event (SRE; p = 0.0002); longer time from initial diagnosis to first bone metastasis (p < 0.0001); and longer time from first bone metastasis to randomization (p < 0.0001). Other significant predictors of improved survival included prostatespecific antigen (PSA) level < 10 ng/ml (p < 0.0001), hemoglobin >128 g/l (p < 0.0001), absence of visceral metastases (p < 0.0001), Eastern Co-operativeOncology Group (ECOG) score ≥1 (p = 0.017), and younger age (p = 0.008). Nomograms were generated based on the parameters included in the final validatedmodels (with/without uNTx and BSAP). One limitation was that lactate dehydrogenase (LDH) levels, a known prognostic factor, were not available in this study. Conclusions: Bone-related parameters are strong prognostic variables for overall survival in patients with bone metastases from CRPC. Patient summary: Survival time is variable in patients with bone metastases from prostate cancer. We found that factors related to bone help to predict how long a patient will live. #2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
KW - Bone metastases
KW - Castration-resistant prostate cancer
KW - Nomogram
KW - Prognostic factors
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84942982616&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2014.10.001
DO - 10.1016/j.eururo.2014.10.001
M3 - Article
C2 - 25449207
AN - SCOPUS:84942982616
SN - 0302-2838
VL - 68
SP - 42
EP - 50
JO - European Urology
JF - European Urology
IS - 1
ER -