Introduction
Bone metastases represent the end-stage of the disease for many patients with metastatic Castration Resistant Prostate Cancer (mCRPC)1. Such patients, dealing with disabling bone pain, hypercalcemia, spinal cord or nerve root compression, pathological fractures, and marrow failure, have poor prognosis and experience a significant worsening of their quality of life (QoL)2,3.
223Ra-dichloride (223Ra), a bone-targeting alpha-particle emitter with low bone-marrow toxicity4, was safety5 and approved for treatment of mCRPC patients with symptomatic bone metastases and no evidence of visceral metastatic involvement6, after the randomized phase III clinical trial (ALSYMPCA), showed palliative effect on bone pain and significant improvement of overall survival (OS) in treated patients7. Survival gain represents the distinctive feature of 223Ra-therapy, as compared to other palliative bone-targeting therapies, such as local radiation, ⁸⁹Sr and ¹⁵³Sm-EDTMP, Zoledronic acid and Denosumab, which have no impact on survival8.  Although the role of 223Ra in improving OS is well established, with a reported median survival extension of 3.6 months as compared with placebo, few reliable and validated prognostic factors have been currently identified9. Several baseline variables commonly used in clinical practice10, such as Eastern Cooperative Oncology Group Performance Status (ECOG-PS), total Alkaline Phosphatase (tALP), hemoglobin (Hb) and number of prior systemic treatments, have been proposed. To date, tALP is considered to be the most reliable marker of response during 223Ra-treatment, but the prognostic value of pretreatment levels is still under investigation11,12. A recent study proposed a three variable prognostic score as a valid multidimensional approach for predicting the survival prolonging effect of 223Ra, by taking into account baseline patients’ Hb, ECOG-PS and Prostate Specific Antigen (PSA)13. In such scenario, identifying further reliable prognostic factors, results of primary importance. Patient-reported QoL, intended as ”patients’ appraisal of and satisfaction with their current level of functioning compared to what they perceive to be possible or ideal”14, has become an important consideration in clinical management of cancer patients and is known to be a significant prognostic factor for patients with different cancers, such as lung cancer15, colorectal cancer16, cholangio and hepatocellular carcinoma17, and head and neck cancer18. Nevertheless, little is known about the prognostic value of pretreatment baseline-QoL in patients with mCRPC prostate cancer undergoing palliative therapies, and no study has investigated the potential value of QoL-assessment in identifying subjects who are more suitable to receive the maximum survival benefit from 223Ra-therapy. The primary endpoint of this study was to evaluate the impact of pretreatment baseline QoL on OS, in mCRPC patients with symptomatic bone metastases receiving 223Ra-therapy. The present study also evaluated the trend of patient-reported QoL during both 223Ra-treatment and post-therapy follow-up.