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.