Long-term outcome and antitumor immune activation response in prostate cancer treated with low-dose-rate brachytherapy

To evaluate the long-term clinical outcomes of iodine-125 low dose-rate brachytherapy (LDR-BT)-based treatment approaches for <= cT3 prostate cancer (PC) patients in China, as well as the effects on the PC immune microenvironment. Data was retrospectively collected from 237 patients with <= cT3 PC who were treated with radical prostatectomy (RP) or LDR-BT alone or in combination with androgen deprivation therapy (ADT), and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS) and overall survival (OS) rates were compared. In 63 cases, PC patients received RP after biopsy, received at least 6 months of ADT before RP, or received LDR-BT and deferred limited transurethral resection of the prostate (TURP). Immunohistological analyses and expression comparisons of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs, expressing CD3, CD4, CD8, and PD-1) on tissue sections from archival prostate biopsy samples with corresponding TURP or RP history were performed by paired t test. The 8-year bPFS, PCSS, and OS rates for LDR-BT and RP were 53.4% and 63.6%, 84.9% and 86.8%, and 63.8% and 70.2%, respectively, although these differences were not statistically significant. PD-L1 was expressed in 35 of 63 cases. The average infiltration scores of TILs (expressing CD3, CD4, and CD8) were 3.6 (1-5), 2.90 (1-5), and 2.46 (1-5), respectively. PD-1 + T cells were seen in 55.6% of cases, with an average score of 0.89 (range: 0-3). In TURP tissue samples from 23 patients, CD3+, CD4+, and CD8 + T cells increased significantly. PD-1 + T cells exhibited a moderate increase, with conversion to positive PD-1 expression in T cells observed in 13 out of 14 cases. The PD-L1 expression score of PC cells was significantly elevated, with conversion to positive in 8 of 9 cases. LDR-BT monotherapy and combination therapy with external beam radiotherapy (EBRT) and ADT are suitable treatment approaches for low-risk and intermediate- or high-risk PC, respectively. Most TILs in PC are not tumor antigen-specific T-cells. LDR-BT can stimulate anti-tumor immunity during a narrow time window and should be combined with immunotherapy as an auxiliary therapy.