Discussion
The impact of the disease on patients’ QoL, has become an important
consideration in health care and a weighty factor in clinical management
of cancer patients22. In recent years, the
investigation whether baseline QoL-assessment, in addition to
clinic-pathological factors, may improve prognostic stratification, has
aroused a growing interest, and focused the attention on the development
of reliable QoL-assessment questionnaires, designed to capture
information directly from the respondent. The European Organization for
Research and Treatment of Cancer Quality of Life Questionnaire C30
(EORTC QLQ-C30), is considered to be a valid self-completion
questionnaire to reliably and accurately assess QoL in cancer patients
and is to date one of the most widely adopted instruments in cancer
research and clinical practice23. In several studies
among patients with different cancer histologies, the EORTC QLQ-C30,
often associated with disease-specific questionnaires, has proved to be
a valid and reliable tool for the assessment of the correlation between
QoL and OS. In a quality of life study among patients with
gastro-esophageal cancer, the appetite-loss item of the EORTC QLQ-C30,
resulted to be a significant independent predictor of survival,
highlighting the significant prognostic role of QoL measures in this
patient population24. A study involving patients with
Platinum-resistant Ovarian Cancer (PROC) reported a median OS extension
of 6.3 months and 6.0 months, in patients with better physical function
score and lower abdominal/gastrointestinal symptom scores
respectively25. The reported significant correlation
of the abdominal/gastrointestinal domain of the ovarian specific
questionnaire (OV28)26 with OS, confirmed the
importance of using a disease-specific instrument in the assessment of
QoL, in order to better evaluate QoL aspects more strictly correlated
with each particular type of cancer, exceeding the limits of a general
questionnaire for all cancer patients. Similar findings are reported in
a recent study among patients with nasopharyngeal carcinoma treated with
intensity modulated radiation therapy. In this study QoL was assessed by
asking patients to answer the EORTC QLQ Head and Neck Cancer-Specific
Module (H&N35)27 in addition to the EORTC QLQ-C30
(version 3.0). A high pretreatment cognitive functioning score in
QLQ-C30 was associated with longer local recurrence-free survival, while
H&N35 pretreatment teeth-ill and felt-ill were significantly correlated
with progression-free survival and distant-free survival
respectively28. For patients with bone metastases,
particularly occurring in advanced breast, prostate, lung and renal cell
cancers29, pain represents a heavy burden, often
responsible for a significant worsening of QoL. The pain-centered
questionnaire EORTC Bone Metastases Module (EORTC QLQ-BM22) was
specifically designed as a supplement to the EORTC QLQ-C30 to evaluate
the specific aspects of QoL impairment associated with bone
metastases30. The present study is the first analysis
of the prognostic value of baseline QoL measures in mCRPC patients with
symptomatic bone metastases treated with 223Ra and was
performed by submitting to patients both the EORTC QLQ-C30 and the EORTC
QLQ-BM22. In accordance with the above studies among patients with
different advanced cancers, baseline QoL showed a significant
correlation with OS in our patient population. The resulting model of
the multivariate analysis performed after PCA, showed that among
patients with the same clinical condition in terms of baseline Hb and
tALP values, those with better self-reported QoL, are more suitable to
obtain a greater survival benefit from 223Ra. In
particular, as shown in the OS analysis stratified by score of baseline
QoL, the median OS is significantly longer in patients with higher
baseline QoL scores as compared to patients with lower scores,
specifically 16 and 8 months of median OS respectively. A recent paper
proposed a three-variable predictive score as a reliable and helpful
tool for stratifying the expected OS of mCRPC patients treated with
223Ra, by taking into account the baseline arrangement
of ECOG-PS, PSA and Hb13. Our analysis, underlining
the significant correlation between baseline QoL and OS, suggest as
including the baseline QoL assessment in a multi-variable model of
baseline clinicopathological factors, may add prognostic potential, thus
improving mCRPC patients’ stratification about prognosis. Considering
that the effect of 223Ra on OS is known to be obtained
only after at least five cycles, stratifying patients’ expected OS is of
fundamental importance31. The EORTC QLQ-C30,
represents a valid and complete instrument, provides significant
results, as reported in previous systematic reviews and allows QoL
assessment at a minimal cost32,33. In a previous
paper, the QLQ-BM22 demonstrated to be a sensitive instrument for
assessing palliative-radiotherapy benefits in patients with symptomatic
bone metastases, by evaluating responders’ QoL, before treatment and two
months after treatment34. The pain domain of the
QLQ-C30 and three out four domains of the QLQ-BM22, specifically painful
sites, pain characteristics and functional interference, showed a
significant improvement after treatment. This study confirmed the
importance of using QLQ-BM22 as a bone metastases-specific tool when
assessing QoL and evaluating response to palliative treatments in
patients with symptomatic bone metastases. Our evaluation of QoL trend
during 223Ra-therapy and follow-up period, performed
through both the QLQ-C30 and the QLQ-BM22 questionnaire showed a global
deterioration of QoL. These findings might be partially attributed to
the inclusion of both responders and non-responders to
223Ra in terms of bone-pain relief, in the statistical
analysis. Moreover, as we included all patients who had received at
least one cycle of 223Ra, patients still in treatment
were also evaluated, as well as patients with ”flare phenomenon” in
pain35,36, meaning that potential responders to
treatment were included in the study before they obtained a significant
benefit from all the 6 scheduled cycles of therapy. A patient-reported
QoL analysis from the ALSYMPCA study, performed with the general EuroQoL
5D (EQ-5D) questionnaire37 and the disease-specific
Functional Assessment of Cancer Therapy-Prostate (FACT-P)
questionnaire38,39, demonstrated that in
patients undergoing 223Ra-therapy, improved survival
is associated with a slower decline in QoL over time as compared to
placebo40. Despite our study showed similar results
and confirmed QoL deterioration over time in mCRPC patients treated with
223Ra from baseline during both therapy and follow-up
period, different instruments have been employed for QoL evaluation.
These considerations might put the attention on the development of a
standardized method to be applied in QoL assessment, in order to
optimize the sharing of comparable data on patients’ QoL outcomes
between different centers, thus improving both research and clinical
practice. A possible limitation of the present study is the analysis
conducted only in a single center among a limited sample of patients.