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

Abstract 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 < 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 < 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.

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Safety and activity of radium-223 in metastatic castration-resistant prostate cancer: the experience of Istituto Nazionale dei Tumori

Tumori Journal ◽

10.1177/0300891620905646 ◽

2020 ◽

Vol 106 (5) ◽

pp. 406-412

Author(s):

Alessandra Raimondi ◽

Pierangela Sepe ◽

Melanie Claps ◽

Marco Maccauro ◽

Gianluca Aliberti ◽

...

Keyword(s):

Prostate Cancer ◽

Real World ◽

Group Performance ◽

Interquartile Range ◽

World Population ◽

Treatment Schedule ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Radium 223 ◽

Ecog Ps

Introduction: Therapeutic decision-making in metastatic castration-resistant prostate cancer (mCRPC) represents an open challenge. Radium-223 is approved for patients with symptomatic bone metastases, no visceral involvement, progressing after at least 2 lines of systemic therapy, or ineligible for any other systemic treatment. Methods: We performed a retrospective, observational study on patients with mCRPC treated with radium-223 at our institution outside of clinical trials, to assess the safety and activity in a real-world population. Data regarding baseline patient/disease characteristics and treatment outcomes (number of cycles, treatment-related adverse events [AEs], cause of discontinuation, and best response) were collected. Results: Overall, 41 patients were treated from September 2015 to September 2018. Median age was 73 years; baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0, 1, or 2 in 15%, 80%, and 5% of cases, respectively; and 3%, 41%, 44%, and 12% of patients had <6, 6–20, >20, and superscan bone lesions, respectively. A median number of 5 cycles (interquartile range 3–6) with median dose 19.52 MBq (interquartile range 12.87–24.83) was received. Treatment schedule was completed in 49% of cases; discontinuations due to AEs, disease-related death, or disease progression occurred in 24%, 33%, and 43% of patients, respectively. Any-grade AEs occurred in 73% and grade 3/4 treatment-related AEs occurred in 29% of patients, mainly anemia, decreased platelet count, and fatigue. No skeletal-related events or treatment-related deaths were recorded. After treatment, 66%, 2%, and 32% of patients had a stable, improved, or deteriorated ECOG PS versus baseline, respectively, and 24%, 61%, and 15% reported a stable, improved, or worsened pain symptom control. Post-treatment versus baseline alkaline phosphatase was reduced or stable in 46% and increased in 54% of patients, whereas prostate-specific antigen was decreased or stable in 83% and increased in 17% of patients. Conclusions: Our study provides clinically useful real-world data on radium-223, highlighting the importance of multidisciplinary patient management to guarantee the best continuum of care for patients with mCRPC.

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Radium-223 in metastatic castration-resistant prostate cancer: Effect of performance score and albumin levels.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.e594 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. e594-e594

Author(s):

Amarnath Challapalli ◽

Sue Cowley ◽

Dorothy Griffiths ◽

Eleanor Compton ◽

Rajendra Persad ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Serum Alkaline Phosphatase ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

Performance Score ◽

Castration Resistant ◽

Pain Scores ◽

Radium 223 ◽

Ecog Ps

e594 Background: Radium-223 (Ra223) is a novel alpha-emitting radiopharmaceutical agent approved for use in patients with metastatic castration resistant prostate cancer (mCRPC) and bone metastases based on ALSYMPCA results. However, its optimal sequencing in the treatment of mCRPC remains unclear. We evaluated the relevance of albumin (A) levels to aid in optimal selection and timing for Ra223 treatment. Methods: Eighty-eight patients had completed treatment with Ra223 from Feb 2014 - Sep 2016. The patients were planned to receive 6 injections at a dose of 55 kBq/kg every 4 weeks. Visual analogue score (VAS) was used to assess pain. The effect of serum alkaline phosphatase (SAP), docetaxel chemotherapy, A levels and performance score (ECOG-PS) on progression free survival (PFS) and overall survival (OS) were evaluated. Results: At baseline (BL) median age was 74.5years; 68% of patients were ECOG-PS-0/1; median VAS was 4.5 & median A level was 34g/dL. 48% had received prior docetaxel. 45 patients (51%) received all the scheduled 6 cycles with significant reduction in the pain scores after 6 cycles compared to the BL score (p < 0.05). The reduction in pain scores was independent of the PSA response and ECOG-PS. A 34% reduction in the SAP levels was seen (p = 0.003). The treatment was well tolerated with no grade 3,4 toxicity. Discontinuation rate was 49% (43/88) due to disease progression. In PS-0/1 patients who completed 6 cycles, PFS & OS were significantly longer compared to those who didn't (7.8vs.4.2& 21vs.7.6 months, respectively). Patients with SAP ≤ 220 U/L & A ≥ 34 g/dL also had significantly prolonged OS (16.2vs.8.6 & 16.1vs.9.5 months, respectively). Patients with PS-2/3 also had significantly longer PFS and OS with completion of 6 cycles and prolonged OS with SAP ≤ 220 U/L, but not with A levels. Conclusions: Ra223 is a safe and effective treatment for mCRPC with bone metastases. Completion of 6 cycles improved outcome. Lower SAP and high A levels significantly prolonged OS in PS-1/2 patients. Whilst the level of SAP can be a reflection of disease activity, monitoring A levels and ensuring that Ra223 is started before A level goes below 34, especially in PS-1/2 patients will aid in the benefit from this treatment in mCRPC.

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