Bone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).
Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.
Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.
Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.
Of 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p < 0.05) that were associated with worse OS. After adjusting for clinical risk factors in the validation set, elevated bone biomarkers were statistically significantly associated with an increased risk of death (hazard ratios ranging from 1.37 to 1.92). Recursive partitioning algorithms applied to the training set identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 yr, respectively) based on combinations of bone biomarkers. These results were confirmed in the validation set.
In men with HSPC initiating androgen deprivation therapy, bone biomarkers are strongly and independently prognostic for OS. Bone biomarker levels alone or in combination with clinical covariates identify unique subsets of men with differential OS outcomes. These results validate the clinical value of bone biomarker assessment in the HSPC state, extending bone biomarker utility beyond the castration-resistant state.
In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan.
European urology. 2023 Apr 19 [Epub ahead of print]
Primo N Lara, Edward Mayerson, Erik Gertz, Catherine Tangen, Amir Goldkorn, Marta van Loan, Maha Hussain, Shilpa Gupta, Jingsong Zhang, Mamta Parikh, Przemyslaw Twardowski, David I Quinn, Michael LeBlanc, Nicholas J Vogelzang, Ian Thompson, Neeraj Agarwal
University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: ., SWOG Statistical Center, Seattle, WA, USA., US Department of Agriculture, Western Human Nutrition Research Center, University of California Davis, Davis, CA, USA., USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA., Northwestern University, Chicago, IL, USA., Cleveland Clinic, Cleveland, OH, USA., Moffit Cancer Institute, Tampa Bay, FL, USA., University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA., St. John's Cancer Institute, Providence Health, Santa Monica, CA, USA., Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA., Christus Santa Rosa Health System, San Antonio, TX Health, San Antonio, TX, USA., Huntsman Cancer Institute, Salt Lake City, UT, USA.