223Ra Therapy in Patients With Advanced Castration-Resistant Prostate Cancer With Bone Metastases

Abstract

In a multivariable Cox regression model, good baseline ECOG PS and low LD levels were significantly associated with longer OS in patients treated with Ra. These variables may be used for stratification of CRPC patients for Ra therapy. Prospective studies to evaluate these variables are warranted, to develop a nomogram to select patients properly. In this retrospective study, predictors of overall survival in 45 metastatic castration-resistant prostate cancer patients treated with Ra therapy were evaluated. Baseline ECOG performance status and lactate dehydrogenase levels turned out to be significant in a multivariable prediction model for overall survival.

<p>Population-Based Analysis Of The Use Of Radium-223 For Bone-Metastatic Castration-Resistant Prostate Cancer In Ontario, And Of Factors Associated With Treatment Completion And Outcome</p>

“…Nonetheless, early treatment discontinuation was common, and the median survival of patients receiving less than 6 cycles of Ra223 was 8.1 months only (Figure 4). The median survival in our early discontinuation cohort is numerically superior to ALSYMPCA, the iEAP, and retrospective analyses revealing median survival times between 4.5 and 6.3 months for patients that did not complete Ra223 therapy (ie, that received ≤4–5 cycles of Ra223) 9,15,16,18,19. Similar to other analyses, disease progression was found to be the main cause of early Ra223 discontinuation.…”

“…PSA and ALP-based response parameters were also found to be comparable to both ALSYMPCA and the iEAP (Table 3). When further accounting for other population-based retrospective analyses reporting OS times between 10.5 and 13.0 months, including a population-based study from British Columbia (Canada), altogether our results document encouraging patient outcomes 15–18…”

“…Adding to a growing body of evidence, we found early treatment discontinuation to be a strong predictor of poor OS (Figure 4). 15,16,18,19,21 Furthermore, in a multivariable Cox proportional hazards model of OS excluding the number of Ra223 cycles administered as covariate, surrogate markers of high disease burden (high PSA, anemia), the presence of visceral metastases, and a history of prior SRE were all significant predictors of poor survival. Intriguingly, patients referred for Ra223 therapy as opposed to local patients also did worse, which merits further investigation.…”

“…On the other hand, mCRPC patients with visceral metastases were purposely excluded from Ra223 trials, and our analysis supports this decision. Although available analyses have identified multiple demographic (age), patient (baseline pain, performance status), disease (biochemical markers of disease burden), and treatment-related (early Ra223 discontinuation, concurrent therapies) factors predicting survival in men subjected to Ra223 therapy, they all await prospective validation 9,15,17,18…”

Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

“…Although the implication of baseline ALP levels on outcome has been studied, studies on ALP dynamics during and after radium-223 treatment are limited, and the utility of changes in ALP as a biomarker has to be explored [5]. In the ALSYMPCA trial, 47% of the patients experienced ≥30% ALP reduction during therapy, and real-world studies have described ≥25% ALP decrease in 50-62% of patients after initiation of radium-223 treatment [10,[12][13][14]. Post hoc analyses from the ALSYMPCA trial suggested that an ALP response of >30% at week 12 of therapy is associated with prolonged survival and longer time to first symptomatic skeletal event [9,15].…”