Bone Biomarkers and Subsequent Survival in Men with Hormone-sensitive Prostate Cancer: Results from the SWOG S1216 Phase 3 Trial of Androgen Deprivation Therapy with or Without Orteronel.

Nicholas J Vogelzang, 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, Ian Thompson, Neeraj Agarwal

Journal: European urology 2024;85(2):171-176

PMID: 37085425

Free Full Text on PubMed Central View on PubMed

Plain Language Summary

This large prospective biomarker study investigates the role of bone biomarkers in predicting survival for men with prostate cancer undergoing treatment. Bone biomarkers are substances found in the blood that can indicate how quickly bone is being broken down (bone resorption) or built up (bone formation). Bone biomarkers have been prognostic in some advanced forms of prostate cancer but their value in earlier disease had not been fully established.

The results showed that elevated levels of all four bone biomarkers were significantly associated with worse overall survival. After adjusting for other clinical risk factors in the validation set, elevated bone biomarkers remained independently and significantly associated with an increased risk of death. Three risk groups were identified based on combinations of bone biomarkers and clinical variables: low, intermediate, and poor risk, with median overall survival of 8.2, 5.1, and 2.1 years, respectively.

In conclusion, bone turnover biomarkers may be a strong prognostic factor for overall survival in men with newly diagnosed metastatic HSPC initiating androgen deprivation therapy. Healthcare professionals may use these findings to risk-stratify patients with metastatic HSPC at diagnosis, allowing for more tailored intervention planning and patient care, and to incorporate bone biomarkers as stratification or outcome variables in future trial design.

Abstract

BACKGROUND

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).

OBJECTIVE

Bone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.

DESIGN, SETTING, AND PARTICIPANTS

Patients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Bone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.

RESULTS AND LIMITATIONS

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.

CONCLUSIONS

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.

PATIENT SUMMARY

In men with newly diagnosed metastatic prostate cancer, high levels of bone turnover biomarkers are associated with a shorter lifespan.

Address: University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: [email protected].; 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.

DOI: 10.1016/j.eururo.2023.03.036

Patient Centred Factor

Antecedents

Physical Environment

Xenobiotics

Clinical Imbalances

Hormonal Structural Integrity and Musculoskeletal

Laboratory Testing

Blood

Modifiable Lifestyle Factors

Diet Exercise and movement

Jadad Score

Allocation Concealment

Yes

Psychological/Emotional Environment

Life Purpose and Meaning

Nutrition Evidence Keywords

Bone metabolism Bone resorption Bone formation Bone alkaline phosphatase C-telopeptide Pyridinoline C-terminal collagen propeptide

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MeSH Terms: Male, Humans, Prostatic Neoplasms, Androgen Antagonists, Androgens, Biomarkers, Prostatic Neoplasms, Castration-Resistant, Biomarkers, Tumor, Imidazoles, Naphthalenes