Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases

Abstract

The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.

Alendronate-Grafted Nanoemulsions for Bone-Targeted Vincristine Delivery: Preliminary Studies on Cell and Animal Models

“…Osteolytic metastases, most frequent in the case of breast cancer, are a consequence of increased bone resorption due to tumour cells [32]. Osteoblastic bone metastases occur mostly in prostate cancer [33]. In this case, together with an increase in osteoclastogenesis, osteoblasts are also activated by prostate cancer cells and the tumour microenvironment, leading to the accumulation of newly formed bone.…”

Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer

“…CRPC includes the spectrum of PCa ranging from asymptomatic disease to advanced CRPC (metastatic CRPC or mCRPC), characterized by an over-activation and over-expression of the AR, which results in the transcription of downstream target genes that promote carcinogenesis [ 19 , 20 ]. In patients with mCRPC the cancer cells usually spread to the bones and lymph nodes [ 21 ], ultimately developing therapeutic resistance regardless of the treatment modality applied, whether this is anti-androgen therapy, cytotoxic drugs, or radiopharmaceuticals. These patients have limited treatment options and a very bad prognosis [ 22 ].…”

Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer

“…CRPC includes the spectrum of PCa ranging from asymptomatic disease to advanced CRPC (metastatic CRPC or mCRPC), characterized by an over-activation and over-expression of the AR, which results in the transcription of downstream target genes that promote carcinogenesis [19,20]. In patients with mCRPC the cancer cells usually spread to the bones and lymph nodes [21], ultimately developing therapeutic resistance regardless of the treatment modality applied, whether this is anti-androgen therapy, cytotoxic drugs, or radiopharmaceuticals. These patients have limited treatment options and a very bad prognosis [22].…”