Positive prostate biopsy following radiotherapy can predict metastasis-free survival in localized prostate cancer.

BACKGROUND/AIMS: To determine the impact of post-treatment biopsy results on 10-year metastasis-free survival (MFS), overall survival (OS) and cause-specific survival (CSS) in localized prostate cancer (PCa) patients treated with high-dose radiotherapy (RT). MATERIALS/METHODS: Retrospective analysis of 232 patients with T1c-T3bN0M0 PCa who underwent a prostate biopsy 24-36 months after high-dose RT. Biopsies were categorized as positive biopsy (PB) if H&E staining showed evidence of residual malignancy and negative biopsy (NB) if no malignant cells were present. Kaplan-Meier estimates of 10-year MFS, OS and CSS rates were calculated for each group and Cox proportional-hazards models were used to estimate the hazard ratios. The median follow-up was 124 months (range 26-267). RESULTS: Sixty-two of 232 (26.7%) patients had post-treatment positive biopsies (PB). A positive post-treatment biopsy was significantly associated with a lower 10-year MFS (78.4% vs. 95.4%, p = 0.001, HR: 3.9, 95% CI: 1.8-8.3). Although patients with PB had worse outcomes that those with NB, we could not show a statistically significant difference in OS (81.0% vs. 87.9%, p = 0.282, HR: 1.3, 95% CI: 0.7-2.3) or CSS (96.2% vs. 99.4% (p = 0.201, HR. 2.4, 95% CI: 0.6-9.7). After multivariate analysis, the strongest predictor of MFS was the post-treatment biopsy status (p < 0.001, HR: 5.4, 95% CI 2.26-12.85) followed by Gleason score (p = 0.002, HR: 2.24, 95% CI 1.33-3.79). CONCLUSION: A positive biopsy following RT can predict MFS in localized prostate cancer. These data highlight the relevance of achieving a local control and support the use of aggressive local therapeutic interventions for PCa.

A high migratory capacity of donor T-cells in response to the lymph node homing receptor CCR7 increases the incidence and severity of GvHD.

The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD. Similarly, the acute GvHD (aGvHD) group received higher percentage of CD4+CCR7+ T-cells, whereas chronic GvHD (cGvHD) patients were transplanted with higher percentages of CD8+CCR7+ T-cells compared with the non-GvHD group. These results were confirmed when patients were subdivided according to degrees of severity. Further, multivariate analysis confirmed that the proportions of CCR7+ CD4+ and CCR7+ CD8+ T-cells are risk factors for the development and severity of aGvHD and cGvHD, respectively. Functional experiments demonstrated that CCR7+ T-cells exhibited higher potential for activation than CCR7- T-cells did. We therefore propose that the selective depletion of CCR7-expressing T-cells may be an effective preventive therapy for GvHD.