Automated Bone Scan Index as an Imaging Biomarker to Predict Overall Survival in the Zometa European Study/SPCG11.

BACKGROUND: Owing to the large variation in treatment response among patients with high-risk prostate cancer, it would be of value to use objective tools to monitor the status of bone metastases during clinical trials. Automated Bone Scan Index (aBSI) based on artificial intelligence has been proposed as an imaging biomarker for the quantification of skeletal metastases from bone scintigraphy. OBJECTIVE: To investigate how an increase in aBSI during treatment may predict clinical outcome in a randomised controlled clinical trial including patients with high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively selected all patients from the Zometa European Study (ZEUS)/SPCG11 study with image data of sufficient quality to allow for aBSI assessment at baseline and at 48-mo follow-up. Data on aBSI were obtained using EXINIboneBSI software, blinded for clinical data and randomisation of zoledronic acid treatment. Data on age, overall survival (OS), and prostate-specific antigen (PSA) at baseline and upon follow-up were available from the study database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association between clinical parameters and aBSI increase during treatment was evaluated using Cox proportional-hazards regression models, Kaplan-Meier estimates, and log-rank test. Discrimination between prognostic variables was assessed using the concordance index (C-index). RESULTS AND LIMITATIONS: In this cohort, 176 patients with bone metastases and a change in aBSI from baseline to follow-up of ≤0.3 had a significantly longer median survival time than patients with an aBSI change of >0.3 (p<0.0001). The increase in aBSI was significantly associated with OS (p<0.01 and C-index=0.65), while age and PSA change were not. CONCLUSIONS: The aBSI used as an objective imaging biomarker predicted outcome in prostate cancer patients in the ZEUS/SPCG11 study. An analysis of the change in aBSI from baseline to 48-mo follow-up represents a valuable tool for prognostication and monitoring of prostate cancer patients with bone metastases. PATIENT SUMMARY: The increase in the burden of skeletal metastases, as measured by the automated Bone Scan Index (aBSI), during treatment was associated with overall survival in patients from the Zometa European Study/SPCG11 study. The aBSI may be a useful tool also in monitoring prostate cancer patients with newly developed bone metastases.

Prevention of bone metastases in patients with high-risk nonmetastatic prostate cancer treated with zoledronic acid: efficacy and safety results of the Zometa European Study (ZEUS).

BACKGROUND: Patients with high-risk localised prostate cancer (PCa) are at risk of developing bone metastases (BMs). Zoledronic acid (ZA) significantly reduces the incidence of skeletal complications in castration-resistant metastatic PCa versus placebo. OBJECTIVE: To investigate ZA for the prevention of BMs in high-risk localised PCa. DESIGN, SETTING, AND PARTICIPANTS: Randomised open-label multinational study with patients having at least one of the following: prostate-specific antigen ≥20 ng/ml, node-positive disease, or Gleason score 8-10. INTERVENTION: Standard PCa therapy alone or combined with 4mg ZA intravenously every 3 mo for ≤4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BMs were assessed using locally evaluated bone-imaging procedures (BIPs), with subsequent blinded central review. Patients with BMs, time to BMs, overall survival, and adverse events were compared between treatment groups. RESULTS AND LIMITATIONS: A total of 1393 of 1433 randomised patients were used for intention-to-treat (ITT) efficacy analyses, with 1040 patients with BIP-BM outcome status at 4±0.5 yr. The local urologist/radiologist diagnosed BIP-BMs in 88 of 515 patients (17.1%) in the ZA group and 89 of 525 patients (17.0%) in the control group (chi-square test: p=0.95), with a difference between proportions of 0.1% (95% confidence interval [CI], -4.4 to 4.7) in favour of the control group. In the ITT population (n=1393), the Kaplan-Meier estimated proportion of BMs after a median follow-up of 4.8 yr was 14.7% in the ZA group versus 13.2% in the control group (log-rank: p=0.65). Low hot spot numbers on bone scans were confirmed as metastases with additional imaging. Central reviews of BIPs were possible only on a subset of patients. CONCLUSIONS: ZA administered every 3 mo was demonstrated to be ineffective for the prevention of BMs in high-risk localised PCa patients at 4 yr. PATIENT SUMMARY: Zoledronic acid administered every 3 mo was demonstrated to be ineffective for the prevention of bone metastases in high-risk nonmetastatic PCa patients at 4 yr. TRIAL REGISTRATION: The ZEUS trial is registered in the Dutch trial register www.trialregister.nl and the ISRCTN register at http://www.controlled-trials.com/ISRCTN66626762.

Prostate cancer metastases to bone: observational study for the evaluation of clinical presentation, course and treatment patterns. Presentation of the METAURO protocol and of patient baseline features.

AIM: The aim of the present study is to describe the research protocol and preliminary results of an observational survey on presentation patterns of prostate cancer metastasis to bone (METAURO), involving urology departments in several Italian hospitals. MATERIALS AND METHODS: The study design was observational and inclusion criteria required subjects with prostate cancer patients who were first diagnosed with metastatic bone disease not more than 18 months before. For each patient recruited to the study, a retrospective evaluation and a prospective surveillance were undertaken. RESULTS: One hundred and ninety-nine patients were enrolled at 32 urological centers in Italy. The median age of participants at first visit was 72.7 years (SD = 7.8). Mean PSA at onset was 323.6 (SD = 1058.3) and these values strongly correlated with Gleason score (Spearman r = 0.228; p = 0.003). The main cause for suspicion of bone metastasis was routine follow up (53%), followed by pathological fracture (31%). Main metastasis sites were located at femur (43.2%), lumbar sacral spine (39.7%), cervical spine (38.2%) and ribs (33.7%). With regard to the main types of bone metastases identified, 27.6% were sclerotic, 5% were lytic and 21.1% were mixed. The specialist who most frequently suspected bone metastasis and referred patients for diagnostic assessment was an urologist (84.9%). CONCLUSIONS: The present survey is a multicentric study with the main aim to identify features of prostate cancer patients with bone metastases. This survey confirmed that suspicion of bone metastasis is motivated by pain symptoms only in a small percentage of patients with prostate cancer, which testifies to both the difficulty of diagnosis and the need and usefulness of accurate regular follow up.

Quality of life evaluation by the EORTC QLQ-C30 questionnaire in patients treated with hormonal treatment in Italy. A QuABIOS group study.

OBJECTIVES: An observational study was planned by the QuABIOS group, to survey the hormonal treatment administered to prostate cancer patients in Italy within a time window of 12 months. We report here a prospective quality of life (QOL) evaluation over time and by hormonal treatment modalities. METHODS: Patients with diagnosis of prostate cancer and treated with hormonal therapy were eligible for this study. The EORTC QLQ-C30 v.3 questionnaire was administered at enrolment, after 6 months and after 12 months from enrolment. RESULTS: 587 patients were enrolled by 33 urological centers. When 1518 visits were considered together independently of time, antiandrogen monotherapy was associated with a significantly better QOL than LHRH-analogue containing treatment modalities in almost all functional scales; cyproterone acetate demonstrated a better physical function and general health status than bicalutamide. When QOL was analyzed in a prospective 12-month window, a worsening of physical function and general health status was observed, notwithstanding, antiandrogens remained significantly associated to a better QOL than LHRH-analogue therapies also over time: a favourable physical function and general health status appeared again to be related to cyproterone acetate than bicalutamide. CONCLUSIONS: Androgen deprivation therapy is associated with decline in QOL, particularly in the domains of physical function, energy, and general health status. This survey demonstrated that antiandrogens had a better QOL profile than LHRH-analogue containing therapies;furthermore, a more favourable tolerability for cyproterone acetate as compared to bicalutamide is suggested.