Table 1.
Overview of suggested biomarkers for patient selection and as prognostic and predictive tools to assess radium-223 therapy.
| Biomarker | Mechanism | Patient Selection |
Predictive | Prognostic | Ref. |
|---|---|---|---|---|---|
| Molecular markers | |||||
| Mutations in HR genes | Inability of cancer cells to adequately repair dsDNA breaks | x | x | x | [65,66,67,68,69] |
| Classic serum biomarkers | |||||
| Serum PSA levels | Expressed by (metastatic) prostate cancer cells | x | x | [37,70,72,73] | |
| Serum t-ALP levels | Expressed by osteoblasts precursors and liver cells | x | x | x | [37,70,74] |
| Serum LDH levels | Predominantly expressed by cancer cells | x | [37,70] | ||
| Serum biomarkers of bone-turnover | |||||
| Serum b-ALP | Expressed by osteoblasts precursors | x | [75,76] | ||
| Serum CTx, NTx, PYR, and P1NP levels | Collagen degradation product | x | [75,76] | ||
| Liquid biopsies | |||||
| CTC | Prostate cancer cells in peripheral blood | x | x | [59,77,78,79] | |
| γH2AX positive CTC | CTCs with marks of dsDNA damage | x | [59] | ||
| Immune biomarkers | |||||
| Peripheral blood NLR | Occurrence of immune cells | x | [80,81] | ||
| Patient characteristics | |||||
| Previous cabazitaxel | Patient characteristic | x | x | x | [37] |
| Number of Ra-223 cycles | Treatment intensity | x | x | [78,82,83,84,85] | |
| Radiographic imaging | |||||
| Bone only disease | Radiographic assessment | x | x | x | [26,37] |
| Number of bonemetastases | Radiographic assessment | x | x | [26,37] | |
| bone scintigraphyindex | Radiographic estimate of bone metastases burden | x | x | [72,86,87,88] | |
| FDG-PET | Metabolic tumor volume | x | x | [89] | |
| Choline-PET | Tumor volume | x | [90] | ||
| 18F-NaF PET | Tumor volume | x | [91,92,93] | ||
Patient selection: biomarker possibly useful for selection of patients for Ra-223 therapy, Predictive: biomarker possibly useful for Ra-223 response evaluation, Prognostic marker: biomarker possibly useful to estimate survival. HR: Homologous recombination, PSA: Prostate Specific Antigen, t-ALP: Total alkaline phosphatase, LDH: Lactate dehydrogenase, b-ALP: Bone specific alkaline phosphatase, NTx: N-telopeptide, P1NP: amino-terminal procollagen propeptides, CTC: Circulation tumor cells, NLR: Neutrophil to lymphocyte ratio, Ra-223: Radium-223, FDG-PET: fluorodeoxyglucose- positron emission tomography, 18F-NaF PET: positron emission tomography using 18F-sodium fluoride (NaF).