Fluorescence targeted pelvic lymph node dissection allows for the lymphatic drainage of the prostate to be identified with great reliability. Since only the nodes draining the prostate are removed, the absolute number of removed nodes is decreased while diagnostic accuracy is increased.

Due to the urgent need for new prostate cancer (PCa) therapies, the role of androgen receptor (AR)-interacting proteins should be investigated. In this study we aimed to address whether the AR coactivator nuclear receptor coactivator 1 (NCOA1) is involved in PCa progression. Therefore, we tested the effect of long-term NCOA1 knockdown on processes relevant to metastasis formation. [ 3 H]-thymidine incorporation assays revealed a reduced proliferation rate in AR-positive MDA PCa 2b and LNCaP cells upon knockdown of NCOA1, whereas AR-negative PC3 cells were not affected. Furthermore, Boyden chamber assays showed a strong decrease in migration and invasion upon NCOA1 knockdown, independently of the cell line's AR status. In order to understand the mechanistic reasons for these changes, transcriptome analysis using cDNA microarrays was performed. Protein kinase D1 (PRKD1) was found to be prominently up-regulated by NCOA1 knockdown in MDA PCa 2b, but not in PC3 cells. Inhibition of PRKD1 reverted the reduced migratory potential caused by NCOA1 knockdown. Furthermore, PRKD1 was negatively regulated by AR. Immunohistochemical staining of PCa patient samples revealed a strong increase in NCOA1 expression in primary tumors compared with normal prostate tissue, while no final conclusion could be drawn for PRKD1 expression in tumor specimens. Thus, our findings directly associate the AR/NCOA1 complex with PRKD1 regulation and cellular migration and support the concept of therapeutic inhibition of NCOA1 in PCa.

The median follow-up of our cohort was 52.7 months. We found large differences in BCR between all grade groupings based on both the biopsy and surgical grading. The 5-year actuarial BCR for grade groups 1-5 based on the biopsy grade were 94.2%, 89.2%, 73.1%, 63.1%, and 54.7%, respectively (p<0.00001). Similarly, the 5-year actuarial BCR based on the surgical grade was 96.1%, 93.0%, 74.0%, 64.4%, and 49.9% for grade groups 1-5, respectively (p<0.00001). Based on the biopsy grade, the hazard ratios relative to grade group 1 were 2.1, 4.8, 6.9, and 10.6 for groups 2, 3, 4, and 5, respectively, and for surgical grade were 2.3, 7.3, 10.4, and 18.9. When adjusting for T-stage, pre-operative PSA, and year of treatment the new grade grouping system remained highly prognostic. The five-grade group system had a higher prognostic discrimination compared to the commonly used 3-tier system (i.e. Gleason score 6, 7, and 8-10).CONCLUSIONS: In an independent surgical cohort, we have validated the prognostic benefit of the 2015 prostate cancer 5-tier grade grouping system in respect to BCR. The benefits of the new grade groupings are numerous for both patients and clinicians to improve prognostic staging systems and risk stratification systems.

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