Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

Parikh, Sameer A.; Murray, Louise; Kenning, L.; Bottomley, David; Din, Omar; Dixit, Sanjay; Ferguson, Catherine; Handforth, C.; Joseph, Lisa; Mokhtar, D.; White, Lillian; Wright, Graham A.; Henry, Ann

doi:10.1016/j.clon.2018.06.004

Cited by 44 publications

(57 citation statements)

References 14 publications

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“…Recent studies have shown that patients with 1-4 doses of Ra-223 are more likely to have shorter OS than those with 5-6 doses. [15][16][17][18][19] The cessation of Ra-223 was associated with poor PS, severe pain, and a higher PSA level at baseline and a lower hemoglobin level at baseline. Likewise, the present study demonstrated that patients with PSA values of >100 ng/mL at baseline and PS ≥2 were more likely to have worse PFS with Ra-223.…”

Section: Discussionmentioning

confidence: 96%

Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

et al. 2020

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Section: Discussionmentioning

confidence: 96%

Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

et al. 2020

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“…As evidenced by several reports on the use of 223-Ra in the real world populations, accurate and careful selection of candidates for 223-Ra therapy has revealed to be as complex as strongly relevant 27 . Previous retrospective studies identified various prognostic variables associated with overall survival outcomes 28 , but the presence of validated therapy predictive factors is still lacking until now. In this context, there is a strong rationale to collect multicenter real-world data about patients treated with 223-Ra in clinical practice to assess the best modalities of application of this radiopharmaceutical agent and to test its tolerability and long-term outcomes in a selected range of mCRPC patients.…”

Section: Management Of Mcrpcmentioning

confidence: 99%

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Frantellizzi

Costa

Mascia

et al. 2020

Clinical Genitourinary Cancer

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MicroabstractThis study investigates the impact on the overall survival of previous radical primary treatment in mCRPC patients treated with 223-Ra. In this multicenter retrospective study, we enrolled 275 consecutive patients. Results obtained showed a clear advantage for patients subjected to radical primary treatment in respect of those without, with an estimated median survival of 18 months and 11, respectively. AbstractBackground. 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 methodsIn 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). Results128 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<0.001). The multivariate analysis corroborated this trending results, returning in an HR of 0.7 (p-value= 0.0443), confirming the best outcome of the RP/EBRT group. 3 Conclusions Previous radical treatment plays a protective role in mCRPC patients who underwent 223-Ra treatment.

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“…Besides documenting its effect on pain palliation, the pivotal phase 3 Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial demonstrated the prognostic benefit that is induced by this radio-metabolic approach that prolonged overall survival (OS) and delayed time to the first symptomatic skeletal event with respect to the placebo arm [1]. However, in the last few years, some retrospective studies suggested that the OS benefit in real-life patients might be lower than that reported in the ALSYMPCA study [2][3][4][5]. These evidences might be explained either by the suboptimal sequence of Ra223 use in the castrate-resistant phase or as the result of a suboptimal selection of patients with poorer prognostic clinical characteristics.…”

Section: Introductionmentioning

confidence: 99%

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223

Bauckneht

Capitanio

Donegani

et al. 2019

Cancers

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Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients’ selection or identifying responders’ after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhanced in advanced and chemotherapy-refractory mCRPC, providing prognostic insights. Moreover, this tool showed high potential for the evaluation of response in cancer patients with bone involvement. For these reasons, FDG Positron Emission Tomography (FDG-PET) might represent an effective tool that is able to provide prognostic stratification (improving patients selection) at baseline and assessing the treatment response to Ra223. We conducted a retrospective analysis of 28 mCRPC patients that were treated with Ra223 and submitted to bone scan and FDG-PET/CT for prognostic purposes at baseline and within two months after therapy completion. The following parameters were measured: number of bone lesions at bone scan, SUVmax of the hottest bone lesion, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). In patients who underwent post-therapy 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), (20/28), PET Response Criteria in Solid Tumors (PERCIST), and European Organization for Research and Treatment of Cancer (EORTC) criteria were applied to evaluate the metabolic treatment response. The difference between end of therapy and baseline values was also calculated for Metabolic Tumor Volume (MTV), TLG, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH) (termed deltaMTV, deltaTLG, deltaPSA, deltaAP and deltaLDH, respectively). Predictive power of baseline and post-therapy PET- and biochemical-derived parameters on OS were assessed by Kaplan–Meier, univariate and multivariate analyses. At baseline, PSA, LDH, and MTV significantly predicted OS. However, MTV (but not PSA nor LDH) was able to identify a subgroup of patients with worse prognosis, even after adjusting for the number of lesions at bone scan (which, in turn, was not an independent predictor of OS). After therapy, PERCIST criteria were able to capture the response to Ra223 by demonstrating longer OS in patients with partial metabolic response. Moreover, the biochemical parameters were outperformed by PERCIST in the post-treatment setting, as their variation after therapy was not informative on long term OS. The present study supports the role of FDG-PET as a tool for patient’s selection and response assessment in mCRPC patients undergoing Ra223 administration.

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Real-world Outcomes and Factors Predicting Survival and Completion of Radium 223 in Metastatic Castrate-resistant Prostate Cancer

Cited by 44 publications

References 14 publications

Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

Dynamic changes of bone metastasis predict bone‐predominant status to benefit from radium‐223 dichloride for patients with castration‐resistant prostate cancer

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223

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