University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.
SWOG Statistical Center, Seattle, WA, USA.
Prostate Cancer Prostatic Dis. 2024 Sep;27(3):566-570. doi: 10.1038/s41391-024-00813-3. Epub 2024 Feb 29.
Circulating biomarkers of bone metabolism are significantly associated with overall survival (OS) in men with advanced prostate cancer. In the SWOG S1216 phase III trial, we showed that elevated bone biomarkers are significantly associated with an increased risk of death in hormone-sensitive prostate cancer (HSPC) regardless of the status of bone metastases, identifying three risk groups with differential OS outcomes based on bone biomarker status. Here we report the association of bone biomarkers with OS in men with HSPC and documented skeletal metastases as part of a planned subset analysis of S1216.
Bone resorption [C-telopeptide (CTx); Pyridinoline (PYD)] and bone formation markers [C-terminal collagen propeptide (CICP); bone alkaline phosphatase (BAP)] were assessed in blood from men with bone metastatic HSPC. Patients were randomly divided into training (n = 238) and validation (n = 475) sets. In the training set, recursive partitioning that maximizes discrimination of OS was used to identify the dichotomous cut-point for each biomarker and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazards models were used to assess the impact of biomarkers on OS, adjusted for patient and tumor characteristics.
Of 1279 men, 713 had both baseline bone metastases and evaluable bone biomarkers. Patient characteristics were similar between the overall population and the subset with bone metastases. Elevated levels of CICP, CTX, and PYD were strongly prognostic for OS. Hazard ratios (95% CI) for OS adjusted for treatment arm and baseline clinical variables were: BAP-1.31 (0.93, 1.84), p = 0.12; CICP-1.58 (1.09, 2.29), p < 0.02; CTx - 1.55 (1.12, 2.15), p = 0.008; and PYD-1.66 (1.27, 2.217), p = 0.0002. There was no evidence of interaction between elevated biomarkers and treatment (all p > 0.2). Recursive partitioning algorithms identified four groups of patients with differential OS outcomes based on bone biomarkers, adjusted for baseline clinical variables, with median OS ranging from 2.3 years (highest risk group) to 7.5 years (lowest risk group).
In this planned S1216 subset analysis of men with HSPC and bone metastases, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes.
NCT01809691.
循环骨代谢生物标志物与晚期前列腺癌男性的总生存期（OS）显著相关。在 SWOG S1216 期 3 试验中，我们发现升高的骨生物标志物与激素敏感前列腺癌（HSPC）的死亡风险增加显著相关，无论骨转移状态如何，均确定了基于骨生物标志物状态具有不同 OS 结果的三个风险组。在这里，我们报告了骨生物标志物与 HSPC 男性和记录有骨骼转移的骨生物标志物与 OS 的关联，这是 S1216 的计划亚组分析的一部分。
从患有骨转移 HSPC 的男性的血液中评估骨吸收标志物[C-末端肽（CTX）；吡啶啉（PYD）]和骨形成标志物[C 末端胶原前肽（CICP）；骨碱性磷酸酶（BAP）]。患者随机分为训练（n=238）和验证（n=475）组。在训练集中，使用递归分区最大化 OS 区分度的方法确定每个生物标志物的二分类截断点以及生物标志物切点组合来定义预后组。在验证集中，使用 Cox 比例风险模型评估生物标志物对 OS 的影响，调整患者和肿瘤特征。
在 1279 名男性中，有 713 名男性同时具有基线骨转移和可评估的骨生物标志物。总体人群和具有骨转移的亚组患者的特征相似。CICP、CTX 和 PYD 水平升高与 OS 呈强预后关系。经治疗臂和基线临床变量调整后的 OS 调整风险比（95%CI）为：BAP-1.31（0.93，1.84），p=0.12；CICP-1.58（1.09，2.29），p<0.02；CTX-1.55（1.12，2.15），p=0.008；PYD-1.66（1.27，2.217），p=0.0002。所有标志物升高与治疗之间均无交互作用（均 p>0.2）。递归分区算法确定了基于骨生物标志物的、具有不同 OS 结果的 4 组患者，调整了基线临床变量，中位 OS 范围从 2.3 年（风险最高组）到 7.5 年（风险最低组）。
在这项针对 HSPC 和骨转移男性的 S1216 计划亚组分析中，血清骨代谢标志物升高与 OS 显著相关。骨生物标志物水平单独以及与患者和肿瘤特征相结合可识别具有不同 OS 结果的独特男性亚组。
NCT01809691。
