The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.

Intraductal carcinoma of the prostate in prostate biopsy samples: correlation with aggressive pathological features after radical prostatectomy and prognostic value in high-risk prostate cancer

Intraductal carcinoma of the prostate(IDC-P)is an aggressive pathological pattern of prostate cancer(PCa).We investigated the association of IDC-P in prostate biopsy(PBx)with several pathological features after radical prostatectomy(RP)and its prognostic value in high-risk PCa.A total of 418 patients with high-risk PCa after RP were included in this study.IDC-P and its architectural patterns were identified according to the 2016 World Health Organization Classification.Chi-squared test and logistic regression were used to investigate the correlation between IDC-P and post-RP pathological features.Kaplan-Meier curves and Cox regression were applied to explore the prognostic value of IDC-P.IDC-P was identified in PBx in 36/418(8.6%)patients.Logistic regression indicated that IDC-P in PBx was independently associated with several pathological features of RP,including Gleason score 8-10(P<0.001),seminal vesicular invasion(P<0.001),and pathological T(pT)3a(P=0.043).Patients with IDC-P in PBx manifested poorer biochemical-free survival(BFS)than those without IDC-P(37.47 months vs not reached,P<0.001).The addition of IDC-P in several prognostic nomograms could improve the predictive accuracy of these tools.We conclude that IDC-P in PBx is positively associated with several aggressive pathological features after RP in high-risk PCa.In addition,IDC-P in PBx could effectively predict the BFS of high-risk PCa patients after RP.