前列腺癌低剂量率近距离放射治疗后的长期结局和抗肿瘤免疫激活反应

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.