Impact of DNA damage repair defects and aggressive variant features on response to carboplatin-based chemotherapy in metastatic castration-resistant prostate cancer.

Platinum-based chemotherapy is not standard of care for unselected or genetically selected metastatic castration-resistant prostate cancer (mCRPC) patients. A retrospective assessment of 71 patients was performed on platinum use in the Netherlands. Genetically unselected patients yielded low response rates. For a predefined subanalysis of all patients with comprehensive next-generation sequencing, 30 patients were grouped based on the presence of pathogenic aberrations in genes associated with DNA damage repair (DDR) or aggressive variant prostate cancer (AVPC). Fourteen patients (47%) were DDR deficient (DDRd), of which seven with inactivated BRCA2 (BRCA2mut). Six patients classified as AVPC. DDRd patients showed beneficial biochemical response to carboplatin, largely driven by all BRCA2mut patients having >50% prostate-specific antigen (PSA) decline and objective radiographic response. In the wild-type BRCA2 subgroup, 35% had a >50% PSA decline (P = .006) and 16% radiographic response (P < .001). Median overall survival was 21 months for BRCA2mut patients vs 7 months (P = .041) for those with functional BRCA2. AVPC patients demonstrated comparable responses to non-AVPC, including a similar overall survival, despite the poor prognosis for this subgroup. In the scope of the registration of poly-(ADP)-ribose polymerase inhibitors (PARPi) for mCRPC, we provide initial insights on cross-resistance between PARPi and platinum compounds. By combining the literature and our study, we identified 18 patients who received both agents. In this cohort, only BRCA2mut patients treated with platinum first (n = 4), responded to both agents. We confirm that BRCA2 inactivation is associated with meaningful responses to carboplatin, suggesting a role for both PARPi and platinum-based chemotherapy in preselected mCRPC patients.

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

PURPOSE: Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). METHODS: This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. RESULTS: A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5-15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73-3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. CONCLUSION: Early treatment-induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

Real-world outcomes of radium-223 dichloride for metastatic castration resistant prostate cancer.

Aim: Timing of radium-223 (Ra-223) in metastatic castration-resistant prostate cancer (mCRPC) remains challenging due to alternative options and short window of opportunity. Methods: Ra-223 treated patients in the CAPRI-registry were included. Outcomes were evaluated based on treatment line of Ra-223. Results: Out of 285 patients, 49% received Ra-223 in line ≥3. 51% completed six Ra-223 injections and 34% had a symptomatic skeletal event after first Ra-223 without differences between subgroups. After correction of known prognostic factors Ra-223 in line ≥3 (HR: 3.267; 95% CI: 1.689-6.317; p < 0.01) remained associated with worse OS. Conclusion: In the Netherlands, Ra-223 was mainly started as second or third mCRPC-treatment in 2014-2018. Later timing of Ra-223 did affect OS, but not treatment completion and occurrence of symptomatic skeletal events.

A clinically relevant decrease in abiraterone exposure associated with carbamazepine use in a patient with castration-resistant metastatic prostate cancer.

ADVERSE EVENT: Decreased abiraterone exposure after introducing carbamazepine. DRUGS IMPLICATED: Abiraterone acetate and carbamazepine. THE PATIENT: A 65-year-old man with metastatic castration resistant prostate cancer, was treated with abiraterone acetate and prednisolone, and received concomitant carbamazepine for treatment of facial neuropathy. EVIDENCE THAT LINKS THE DRUG TO THE EVENT: The interaction was confirmed by a decrease in abiraterone exposure >2-fold (area-under-the-curve and trough levels). After discontinuation of carbamazepine therapy, the abiraterone exposure normalized. No alternative causes were found that explain the decrease in abiraterone exposure. MECHANISM: Induction of CYP3A and potentially phase I metabolism (SULT2A1) by carbamazepine. IMPLICATIONS FOR THERAPY: Clinicians and pharmacists should be aware of this clinically relevant interaction. The national drug-drug interaction checker does not warn for this interaction, whereas both the Lexicomp® and Micromedex® advice to avoid if possible or to increase the abiraterone dose frequency to twice daily. Carbamazepine should not be combined with abiraterone to avoid underexposure and suboptimal therapy. Therapeutic drug monitoring of abiraterone is useful to guide therapy when drug-drug interactions cannot be avoided.

Results of primary versus recurrent surgery to treat stress urinary incontinence in women.

INTRODUCTION AND HYPOTHESIS: We compared cure rates and complication rates in patients who had undergone primary or recurrent (secondary) surgery for stress urinary incontinence (SUI). METHODS: A retrospective cohort study that included patients who underwent surgery to treat SUI in a tertiary referral center was carried out. All patients had, predominantly, SUI. Exclusion criteria were patients with a neurogenic bladder or a neobladder and patients without postoperative follow-up (FU). The primary objective was to assess the success rate, defined as cured SUI or improved SUI at six weeks and at the latest available moment of FU. The secondary objective was to assess complications. RESULTS: A total of 541 women with SUI underwent surgery for SUI between 2002 and 2010. After exclusion of 102 patients a total of 242 patients with primary SUI and 197 patients with recurrent SUI were identified. The success rate at first FU was 89 %. At last FU (median 205 days) the success rate was 83 % (P < 0.01). There were no significant differences in success rate between primary and recurrent surgery at first FU. The overall success rate of primary surgery was 86 %; for recurrent surgery it was 79 %. During surgery, 27 bladder injuries occurred (6.2 %), with no significant difference between the two groups. At last FU, 11 patients (2.6 %) had persistent residual volume, necessitating prolonged clean intermittent self-catheterization. CONCLUSIONS: The results of recurrent surgery to treat recurrent or persistent SUI are still good in experienced hands and do not significantly differ from results of primary surgery. The complication rates are comparable to those of primary surgery.

The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Tumoral Ki67 and PSMA Expression in Fresh Pre-PSMA-RLT Biopsies and Its Relation With PSMA-PET Imaging and Outcomes of PSMA-RLT in Patients With mCRPC.

INTRODUCTION: Prostate specific membrane antigen (PSMA) directed radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. However, it is still poorly understood why approximately 40% of the patients does not respond to PSMA-RLT. The aims of this study were to evaluate the pretreatment PSMA expression on immunohistochemistry (IHC) and PSMA uptake on PET/CT imaging in mCRPC patients who underwent PSMA-RLT. We correlated these parameters and a cell proliferation marker (Ki67) to the therapeutic efficacy of PSMA-RLT. PATIENTS AND METHODS: In this retrospective study, mCRPC patients who underwent PSMA-RLT were analyzed. Patients biopsies were scored for immunohistochemical Ki67 expression, PSMA staining intensity and percentage of cells with PSMA expression. Moreover, the PSMA tracer uptake of the tumor lesion(s) and healthy organs on PET/CT imaging was assessed. The primary outcome was to evaluate the association between histological PSMA protein expression of tumor in pre-PSMA-RLT biopsies and the PSMA uptake on PSMA PET/CT imaging of the biopsied lesion. Secondary outcomes were to assess the relationship between PSMA expression and Ki67 on IHC and the progression free survival (PFS) and overall survival (OS) following PSMA-RLT. RESULTS: In total, 22 mCRPC patients were included in this study. Nineteen (86%) patients showed a high and homogenous PSMA expression of >80% on IHC. Three (14%) patients had low PSMA expression on IHC. Although there was limited PSMA uptake on PET/CT imaging, these 3 patients had lower PSMA uptake on PET/CT imaging compared to the patients with high PSMA expression on IHC. Yet, no correlation was found between PSMA uptake on PET/CT imaging and PSMA expression on IHC (SUVmax: R2 = 0.046 and SUVavg: R2 = 0.036). The 3 patients had a shorter PFS compared to the patients with high PSMA expression on IHC (HR: 4.76, 95% CI: 1.14-19.99; P = .033). Patients with low Ki67 expression had a longer PFS and OS compared to patients with a high Ki67 expression (HR: 0.40, 95% CI: 0.15-1.06; P = .013) CONCLUSION: The PSMA uptake on PSMA-PET/CT generally followed the PSMA expression on IHC. However, heterogeneity may be missed on PSMA-PET/CT. Immunohistochemical PSMA and Ki67 expression in fresh tumor biopsies, may contribute to predict treatment efficacy of PSMA-RLT in mCRPC patients. This needs to be further explored in prospective cohorts.

Health-related quality of life, psychological distress, and fatigue in metastatic castration-resistant prostate cancer patients treated with radium-223 therapy.

BACKGROUND: Radium-223 is a registered treatment option for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). Aim of this multicenter, prospective observational cohort study was to evaluate health-related quality of life (HR-QoL), psychological distress and fatigue in mCRPC patients treated with radium-223. METHODS: Primary endpoint was cancer-specific and bone metastases-related HR-QoL, as measured by the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints were psychological distress and fatigue, evaluated by the HADS and CIS-Fatigue questionnaires. Outcomes were analyzed for the total cohort and between subgroups (1-3 versus 4-5 versus 6 radium-223 injections). A trajectory analysis was performed to explore HR-QoL patterns over time. RESULTS: In total, 122 patients were included for analysis. Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. Trajectory analysis revealed that HR-QoL deterioration over time was more likely in patients with baseline opioid use, low hemoglobin and high alkaline phosphatase levels. CONCLUSIONS: Patients who discontinued radium-223 therapy showed worse HR-QoL, psychological distress and fatigue at baseline and more frequent deterioration of HR-QoL, psychological distress and fatigue over time when compared to patients who completed therapy. Specific attention with regard to HR-QoL during follow-up is indicated in patients with opioid use, low hemoglobin and high alkaline phosphatase levels before radium-223 therapy initiation. CLINICAL TRIAL REGISTRATION NUMBER: NCT04995614.

Impact of DNA damage repair defects on response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer.

PURPOSE: Prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a novel treatment for castration-resistant prostate cancer (mCRPC). While the majority of patients responds to PSMA-RLT, with 10-15% having an exceptional response, approximately 30% of patients is unresponsive to PSMA-RLT. The molecular underpinning may in part explain these varying responses. This study investigated alterations in DNA damage repair (DDR) genes in tumour biopsies and their association with response to PSMA-RLT. METHODS: A predefined retrospective cohort study was performed in mCRPC patients of whom the tumours had undergone next-generation sequencing of 40 DDR genes and received Lu-177-PSMA and/or Ac-225-PSMA-RLT. The primary outcome of this study was to compare the progression free survival (PFS) after PSMA-RLT for patients with and without pathogenic DDR aberrations in their tumour. Secondary outcomes were prostate-specific antigen (PSA) response and overall survival (OS). RESULTS: A total of 40 patients were included of which seventeen had a tumour with a pathogenic DDR aberration (DDR+), of which eight had defects in BRCA1/2. DDR+ patients had an equal varying response to PSMA-RLT compared to those without pathological DDR anomalies (DDR-) in terms of PFS (5.9 vs. 6.4 months, respectively; HR 1.14; 95% CI 0.58-2.25; p = 0.71), ≥50% PSA response (59% vs. 65%, respectively; p = 0.75) or OS (11.1 vs. 10.7 months, respectively; HR 1.40; 95% CI: 0.68-2.91; p = 0.36). CONCLUSION: In this study of a selected cohort, pathogenic DDR aberrations were not associated with exceptional responsiveness to PSMA-RLT. Translational studies in larger prospective cohorts are warranted to associate DDR gene defects with differential responses to PSMA-RLT.

Clinical outcomes and molecular profiling of advanced metastatic castration-resistant prostate cancer patients treated with 225Ac-PSMA-617 targeted alpha-radiation therapy.

INTRODUCTION: Targeted alpha-radiation therapy (TAT) with 225Ac-labeled prostate-specific membrane antigen (PSMA) ligands is a promising novel treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. However, limited data are available on efficacy, quality of life (QoL), and pretherapeutic biomarkers. The aim of this study was to evaluate the efficacy of 225Ac-PSMA TAT and impact on QoL in advanced mCRPC, and to explore predictive biomarkers on pretherapeutic metastatic tissue biopsies. METHODS: Observational cohort study including consecutive patients treated with 225Ac-PSMA TAT between February 2016 and July 2018. Primary endpoint was overall survival (OS). Furthermore, prostate-specific antigen (PSA) changes, radiological response, safety, QoL, and xerostomia were evaluated. Biopsies were analyzed with immunohistochemistry and next-generation sequencing. RESULTS: Thirteen patients were included. Median OS was 8.5 months for the total cohort and 12.6 months for PSMA radioligand therapy-naïve patients. PSA declines of ≥90% and ≥50% were observed in 46% and 69% of patients, respectively. Six patients were radiologically evaluable; 50% showed partial response. All patients showed >90% total tumor volume reduction on PET imaging. Patients experienced clinically relevant decrease of pain and QoL improvement in physical and role functioning domains. Xerostomia persisted during follow-up. Patients with high baseline immunohistochemical PSMA expression or DNA damage repair alterations tended to have longer OS. CONCLUSIONS: TAT with 225Ac-PSMA resulted in remarkable survival and biochemical responses in advanced mCRPC patients. Patients experienced clinically relevant QoL improvement, although xerostomia was found to be nontransient. Baseline immunohistochemical PSMA expression and DNA damage repair status are potential predictive biomarkers of response to 225Ac-PSMA TAT.

Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: Radium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy. MATERIALS AND METHODS: In this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings. RESULTS: We observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets - the regulatory T cells and the monocytic MDSCs - increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy. CONCLUSION: Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.

Results of the York Mason Procedure with and without Concomitant Graciloplasty to Treat Iatrogenic Rectourethral Fistulas.

BACKGROUND: Rectourethral fistulas (RUFs) are rare but devastating complications after surgery or radiation therapy to the urethra, prostate, or rectum. RUF repair is challenging, especially in irradiated patients. OBJECTIVE: To evaluate the efficacy of the York Mason (YM) procedure with or without concomitant gracilis muscle interposition (graciloplasty) for RUF repair. DESIGN, SETTING, AND PARTICIPANTS: Records of patients with an iatrogenic RUF who underwent the YM procedure between 2008 and 2018 in two university hospitals were reviewed. Data on etiology, diagnostic and operative procedures, urinary and fecal diversion, and postoperative follow-up were collected. INTERVENTION: Twenty-eight patients underwent 33 YM procedures. Concomitant graciloplasty was performed in four (14%) primary repairs and two (7%) repairs for recurrent RUFs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was successful RUF repair, defined as absence of symptoms and no leakage on control urethrocystography. The secondary endpoint was colostomy reversal rate. RESULTS AND LIMITATIONS: Median follow-up was 24 mo. Ten patients (36%) were irradiated previously. The ultimate success rate was 75% after a maximum of three YM procedures. Success rates were 89% and 50% in patients with nonirradiated and irradiated fistulas, respectively. In irradiated patients, the success rates of the first YM procedure with and without graciloplasty were 100% and 29%, respectively. In recurrent cases, concomitant graciloplasty did not result in better outcomes. Colostomy reversal was possible in 15 patients after successful repair. In all patients, fecal continence was intact and no anal stenosis was reported. Limitations of the study include small sample size and the retrospective design. CONCLUSIONS: Combination of the YM procedure with graciloplasty resulted in higher success rates of RUF repair in patients with irradiated fistulas. Fecal continence was preserved, and colostomy reversal is feasible. PATIENT SUMMARY: We analyzed the outcomes, complications, and colostomy reversal rate of the York Mason procedure for the repair of rectourethral fistulas (RUFs). We found that concomitant graciloplasty increases success rates in case of prior radiation therapy. Colostomy reversal is feasible after RUF repair.

Impact of DNA damage repair defects on response to radium-223 and overall survival in metastatic castration-resistant prostate cancer.

PURPOSE: Radium-223 is a targeted alpha radiation therapy for metastatic castration-resistant prostate cancer. DNA damage repair (DDR) defective prostate cancers, specifically genetic aberrations leading to homologous recombination deficiency (HRD), accumulate irreparable DNA damage following genotoxic treatment. This retrospective study assessed DDR mutation status in patients treated with radium-223, investigating their association with efficacy and overall survival (OS). PATIENTS AND METHODS: Included patients were treated with radium-223 and had results from primary or metastatic tumour tissue of a comprehensive next-generation sequencing panel of DDR genes, including canonical HRD genes. Patients were grouped by presence (DDR+) or absence (DDR-) of pathogenic somatic or germline aberrations in DDR genes. We evaluated OS, time to ALP progression (TAP), time to initiation of subsequent systemic therapy (TST) and biochemical responses between DDR groups. RESULTS: Ninety-three patients were included. Twenty-eight (30%) patients had DDR mutations, most frequently in ATM (8.6%), BRCA2 (7.5%) and CDK12 (4.3%) genes. DDR+ patients showed prolonged OS (median 36.3 versus 17.0 months; HR 2.29; P = 0.01). Median TAP and TST in the DDR+ and DDR- patients was 6.9 versus5.8 months (HR = 1.48; P = 0.15), and 8.9 versus7.3 months (HR = 1.58; P = 0.08), respectively. DDR+ patients more frequently completed radium-223 therapy (79% versus 47%; P = 0.05). No difference in biochemical responses were seen. CONCLUSION: Patients harbouring DDR aberrations showed significant OS benefit, and more commonly completed radium-223 therapy. These findings need prospective confirmation and support strategies of genotoxic agents such as radium-223 in patients harbouring DDR defects.

Patient Selection for Radium-223 Therapy in Patients With Bone Metastatic Castration-Resistant Prostate Cancer: New Recommendations and Future Perspectives.

Radium-223 therapy was registered in 2013 as a new life-prolonging therapeutic option for patients with symptomatic bone metastatic castration-resistant prostate cancer after the phase 3 ALSYMPCA study. Postregistration reports on the use of radium-223 in real-world populations demonstrate that appropriate selection of patients for radium-223 therapy is challenging. While primarily retrospective and post hoc studies identified prognostic variables associated with overall survival, validated predictive biomarkers are still lacking. Important pretherapeutic prognostic variables include the number of prior therapies, baseline Eastern Cooperative Oncology Group performance status, baseline extent of bone metastatic disease, and baseline alkaline phosphatase, prostate-specific antigen, and lactate dehydrogenase levels. We reviewed the currently available literature to provide recommendations on patient selection for radium-223 therapy in patients with bone metastatic castration-resistant prostate cancer. In addition, the recent evidence from the report of the European Medicines Agency's Pharmacovigilance Risk Assessment Committee regarding the restricted use of radium-223 after interim data analysis of the ERA-223 trial has been incorporated into our recommendations. Future perspectives are also discussed, including radium-223 re-treatment, the use of concomitant therapies, and the implementation of pretherapeutic molecular analysis for treatment stratification.

223Ra Therapy in Patients With Advanced Castration-Resistant Prostate Cancer With Bone Metastases: Lessons from Daily Practice.

PURPOSE: To identify pre-therapeutic variables associated with overall survival (OS) in patients treated with Ra. METHODS: Data from 45 CRPC patients treated with Ra were retrospectively analyzed. All patients who received at least one Ra injection were included in the study. Cox proportional hazard regression models were used to estimate hazard ratio's (HR) and to test for association. RESULTS: Twenty-one patients (47%) received six Ra injections and 24 patients (53%) received one to five Ra injections. Median OS since start of Ra was 13.0 months (95% confidence interval (CI) 8.2-17.8). Patients who completed Ra therapy had a median OS of 19.7 months (95% CI 14.9-24.6), while patients who received one to five Ra injections had a median OS of 5.9 months (95% CI 3.8-8.1; P < 0.001).Univariable analysis showed poor baseline ECOG performance status (PS), baseline opioid use, lowered baseline hemoglobin, and elevated prostate-specific antigen, alkaline phosphatase and lactate dehydrogenase (LD) levels were significantly associated with OS. Multivariable Cox regression analysis demonstrated that poor baseline ECOG PS (HR 10.6) and high LD levels (HR 7.7) were pre-therapeutic variables that predicted poor OS. CONCLUSIONS: 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.