Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with 223 Radium-dichloride: a national multicenter study

Objective: Radium-223 (223Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting radionuclide has a beneficial effect on pain and is also capable to increase overall survival (OS). Several studies evaluated the prognostic value of different biomarkers at baseline, such as serum values, imaging parameters or pain. To date, however, clinicians lack a validated and simple system to assess which patients will most likely benefit from 223Ra treatment. The 3-variable prognostic score (3-PS), proposed in a single-center study in 2017 classifies patients in five prognostic groups with a specific OS. This study aims to validate the 3-PS in a larger multicenter population. Methods: Four hundred and thirty mCRPC patients treated with 223Ra from six different centers were analyzed. The 3-PS score consists of the collection of baseline hemoglobin, prostatic specific antigen and Eastern cooperative oncology group performance status and was initially applied to the whole population (total group). The score was then validated on the 338 patient's subgroup (clean group) obtained by subtracting the 92 patients enrolled for the original study of the 3-PS score. This purified group served as further validation evidence. Results: Statistical analysis showed that the 3-PS score was valid on the total group as well as in the clean group as the AUC estimated (0.74) falls within the CI of the AUC calculated on the validation sample (95% CI 0.66-0.82). Conclusion: This study confirms the validity of the 3-PS score for mCRPC patients. This score is simple, noninvasive and affordable and can be easily used to select patients that will most probably complete 223Ra treatment. In addition, this tool provides an exact estimate of life expectancy in terms of OS

Limportanza del Data Manager nella stesura, approvazione e gestione dello studio:"Pilot Clinical Study of 64Cu(II)CI2: Efficacy and Safety of a new PET tracer for Urologic Tumors"

AIM To evaluate safety and efficacy of Copper-64(II)Dichloride (Cu-64(II)Cl2) as a new PET tracer for Urological Malignancies (UM). MATERIALS AND METHODS Patients with UM were enrolled in a prospective study. All patients were staged with preoperative CT and Cu-64(II)Cl2-PET/CT. Patient characteristics, anatomical and functional imaging, final histopathology were recorded. Surgical specimens for histopathological examination were collected. To determine time–activity curves for Cu-64(II)Cl2 uptake in UM and normal tissues, standardized uptake values (SUVs) were calculated. The safety of Cu-64(II)Cl2 was assessed. RESULTS 23 patients were included. An administered activity of 174.7MBq (4.72mCi) for Cu-64(II)Cl2 was equal to 9.80mSv of the effective dose. The median SUVmax were 5.7, 0.9, 1.8 and 9.8 for the prostate, bladder, penis and kidney, respectively. Median SUVmax were higher in organs with a malignancy in comparison with healthy tissue [prostate (11.5 vs 5.3,p<0.001), bladder (6.2 vs 0.9,p=0.007) and penis (3.9 vs 1.3,p=0.027)], but not in the kidneys (5.0 vs 10.4,p=0.998). The highest area under curve (AUC) was reported for prostate cancer (AUC=0.978), the lowest for penile cancer (AUC=0.775). The detection rates based on the best suggested cut-off according to the SUVmax were 85.7%(6/7) for prostate and bladder, 83.3%(5/6) for penile cancer. Neither drug-related effects or physiologic responses occurred, nor adverse reactions. CONCLUSIONS Cu-64(II)Cl2 is an effective and well tolerated tracer in patients with UM. Our results show higher SUVmax in cancer patients than in healthy subjects. Our findings suggest that Cu-64(II)Cl2-PET/CT is useful in patients affected by prostate, bladder and penis cancer

Primary radical prostatectomy or ablative radiotherapy as protective factors for patients with mCRPC treated with radium-223 dichloride: an Italian multicenter study

Background. We provide an analysis aiming to investigate, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy (RP) or external beam radiotherapy (EBRT)) in terms of overall survival, in mCRPC patients treated with 223-Ra. Materials and methods In this multicenter retrospective study we enrolled 275 consecutive patients. Demographics and clinical data, as well as mCRPC characteristics, have been obtained and evaluated at baseline and the end of the treatment or progression. 223-Ra has been administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: men previously treated with primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and patient with no prior primary treatment available (NO). Results 128 out of 275 patients (46.5%) are alive and currently on follow-up; 103 patients (37.4%) dropped treatment out for disease progression or onset of comorbidities, and 147 patients died during the follow-up (53.5%). 93 patients underwent RP, 76 patients performed ablative EBRT. 132 patients enrolled in the RP/EBRT group (48%), 143 patients in the NO group (52%). Data showed a clear advantage for patients subjected to RP or EBRT in respect of those without primary treatment performed, with an estimated median survival of 18 months and 11 respectively (p&lt;0.001). The multivariate analysis corroborated this trending results, returning in an HR of 0.7 (pvalue= 0.0443), confirming the best outcome of the RP/EBRT group.Conclusions Previous radical treatment plays a protective role in mCRPC patients who underwent 223-Ra treatment

Overall survival in mCPRC patients treated with Radium-223 in association with bone health agents: a national multicenter study

Radium-223 has demonstrated efficacy in improving overall survival (OS) and in delaying symptomatic skeletal-related events (SREs). Bone Health Agents (BHA), i.e. RANK ligand inhibitor (Denosumab) and bisphosphonate such as zoledronic acid, are indicated to prevent SREs without a clear survival benefit. SREs on patient health have a high impact and it is, therefore, important to consider the role of new therapies with BHA to better understand the involvement of combination therapy. The primary aim of this multicentric study is to assess OS in mCRPC patients treated with Radium-223 in combination with BHA

Radium-223 in mCPRC patients: a large real-life Italian multicenter study

Background: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration. Methods: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided. Results: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression. Conclusions: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile

Radium-223 in mCPRC patients: a large real-life Italian multicenter study

Background: Radium-223 is a targeted alpha-particles therapy approved for the treatment of mCRPC patients with symptomatic bone metastases. To our knowledge we account for the largest cohort of mCRPC patients subjected to Radium-223 treatment in our country. We aim to describe in a real-life setting the largest cohort of mCRPC patients treated with Radium-223 ever taken into consideration. Methods: Four hundred and thirty consecutive mCRPC patients were enrolled. Clinical data have been collected at baseline and at the end of the Radium-223 treatment. Furthermore, the overall survival(OS) of our population has been provided. Results: One hundred fifty-seven patients (36.5%) were still alive at the time of data analysis. A mean number of 4.95±1.6 cycles of Radium-223 was reached by our cohort. 265 patients (61.6%) completed the whole six cycles regimen. The mean follow-up period from the first cycle of Radium-223 to the date of the analysis was 12.7 months. The analysis of patients Annual Incidence Rate (AIR) in relation to the number of Radium-223 cycles received depicting a clear advantage for those patients who completed the whole six administrations planned, with an AIR (AIR=0.32) of much lesser value compared to those that have performed five cycles (AIR =0.98). 165 patients (38.4%) dropped out of treatment for death or disease progression. Conclusions: This study offers a cross-section of the clinical performance of Radium-223 treatment in a real-world context, confirming on a large scale the effectiveness of Radium-223 in improving the OS and quality of life, along with the preservation of an excellent safety profile

A national multicenter study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223

Background Radium-223 prolongs overall survival (OS) and delays time to the rst symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and e cacy of Radium-223 treatment in the very elderly population. Aims Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are di erences between young and elderly, as well as to verify e cacy and safety in patients ≥ 75 years of age. Methods 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients’ parameters. The whole cohort was divided into two groups based on the age of the patients (&lt; 75 years old and ≥ 75 years old). Results 47% of the patients were &lt; 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show signi cant di erences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p &lt; 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no signi cant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic e ects are similar in the two groups. Conclusions Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

Purpose: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). Patients and methods: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. Results: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p &lt; 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p &lt; 0.001 for group 3 vs. 1). Conclusions: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs

Prognostic value of the BIO-Ra Score in metastatic castration-resistant prostate cancer patients treated with Radium-223 after the European Medicines Agency restricted use: secondary investigations of the multicentric BIO-Ra study

The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) theprognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p &lt; 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p &lt; 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value