Clinical Value Of Iodine-125 Brachytherapy In Prostate Cancer And The Effect On Immune Microenvironment

Objective:To evaluate the outcomes of iodine-125 LDR-BT for ?cT3 prostate cancer,and investigate the prognostic factors of biochemical relapse and overall survival after LDR-BT with iodine-125;to assess the immune status in PCa patients before and at different time points after iodine-125 LDR-BT(1,3,6,and 12 months);to evaluate the effects of iodine-125 permanent brachytherapy on prostate cancer immune microenvironment.Methods:116 patients with?cT3 prostate cancer treated with iodine-125 LDR-BT as monotherapy or combined with homonal therapy,were retrospectively collected.BCR rate and overall survival(OS)were estimated using Kaplan-Meier method.Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates(PSA,Clinical stage,prostate volume,et al)with outcomes.Blood was collected from 32 patients with low and intermediate risk PCa and 12 healthy volunteers,as well as after iodine-125 permanent brachytherapy,the frequency of immunocompetent cells was identified by flow cytometry,PSA was obtained at different time points after brachytherapy treatment(1,3,6,and 12 months).Sixty-three PCa patients were retrospectively studied,in which 20 cases received prostatectomy(RP)after biopsy,20 cases received at least six-month hormone therapy before RP,23 cases received iodine-125 permanent brachytherapy and received deferred limited TURP for treating urinary retention.Immunohistological analyses of CD3,CD4,CD8,PD-1,Foxp3,granzyme B and pd-L1 were performed on tissue sections from archival prostate biopsy samples and TURP and RP.Result:5-and 8-year BCR rate and OS were 25% and 44%,80.2%and 62.1%,respectively;at multivariate analysis,pathological Gleason score,the percentage of positive biopsy cores(%PC),clinical T stage and PV were correlated with BCR rate;Gleason score and clinical T stage were correlated with OS;for patients with ?cT3a prostate cancer,Gleason score,(%PC),PV and risk group were correlated with BCR rate;only Gleason score was independent predictor of death.Various immunocompetent cells were dysregulated in PCa patients compared with healthy volunteers;peripheral serum prostate-specific antigen(PSA)decreased rapidly at the first month after brachytherapy,and the peripheral serum PSA became very low at 6 months after the treatment.CD3+ T cells,CD4+ T cells,CD3?CD16+/56+ natural killer(NK)cells were increased significantly at certain time points after the treatment,although the percentage of the CD8+ T cells did not change markedly,the ratio of CD4/CD8 increased significantly at 3 months.35 of 63 cases expressed PD-L1(55.6%);tumor-infiltrating T lymphocytes were seen in all cases;73% cases had Foxp3+ T cells expression,but slightly;PD-1+ and granzyme B+ T cells were seen in 55.6%,42.9% cases,respectively,but with very small density;after brachytherapy,CD3+,CD4+,CD8+T cells were increased significantly;PD-1+ and Foxp3+T cells had a moderate raise;the expression of PD-L1 on PCa cell significantly raised.Conclusions: Low-risk PCa are the most suitable candidates for iodine-125 LDRBT;the intermediate-or high-risk PCa,specially for stage cT3a-cT3 b or Gleason score?8,LDR-BT combined with external radiotherapy and hormone therapy may be considered,very large PV does not influence BCR rate and OS,the PCa with high(%PC)should pay more attention on BCR,even biopsy when necessary,to clarify the cause of BCR for definite therapy.The immunocompetent cells are dysregulated in PCa patients,Iodine-125 permanent brachytherapy treatment could effectively kill tumor cells and then stimulate cellular immunity in PCa patients.All PCa had TILs expression in cancer immune microenvironment,but may be not tumour antigen-specific Tcell;Iodine-125 permanent brachytherapy can stimulate anti-tumor immunity,and when combined with immunotherapy(Immune Checkpoint Inhibitors),it's reasonable,even necessary.