Dynamic prostate cancer transcriptome analysis delineates the trajectory to disease progression.

Comprehensive genomic studies have delineated key driver mutations linked to disease progression for most cancers. However, corresponding transcriptional changes remain largely elusive because of the bias associated with cross-study analysis. Here, we overcome these hurdles and generate a comprehensive prostate cancer transcriptome atlas that describes the roadmap to tumor progression in a qualitative and quantitative manner. Most cancers follow a uniform trajectory characterized by upregulation of polycomb-repressive-complex-2, G2-M checkpoints, and M2 macrophage polarization. Using patient-derived xenograft models, we functionally validate our observations and add single-cell resolution. Thereby, we show that tumor progression occurs through transcriptional adaption rather than a selection of pre-existing cancer cell clusters. Moreover, we determine at the single-cell level how inhibition of EZH2 - the top upregulated gene along the trajectory - reverts tumor progression and macrophage polarization. Finally, a user-friendly web-resource is provided enabling the investigation of dynamic transcriptional perturbations linked to disease progression.

Percutaneous biopsy of small renal mass: can diagnostic accuracy be affected by hospital volume?

INTRODUCTION: High diagnostic performance and low morbidity for renal tumor biopsy (RTB) have been described in highly experienced centers. Here we present the five-year experience of our institute in performing RTB. The protocol used, the safety profile and the diagnostic accuracy obtained were analyzed. MATERIAL AND METHODS: The study is a retrospective single-institution clinical data review of 84 consecutive RTB of small renal masses. Post-biopsy complications were reported using the Clavien-Dindo system. To measure the concordance between biopsy and nephrectomy specimens regarding histological subtype and International Society of Urological Pathology/World Health Organization (ISUP/WHO) renal cell carcinoma grade, the kappa coefficient of Cohen was used. RESULTS: Median (IQR) follow-up time was 44 (29-58) months. In total, 94% of RTB procedures were free of complications; when complications did occur, 80% were grade I and 20% were grade II. No cases of tumor seeding were observed. Combining the first and repeated biopsies the overall diagnostic rate was 85.8%. Overall, 79.1% of diagnostic RTB were malignant. In 42 surgically treated patients, the concordance between the histological results of biopsies and surgical specimens was very good for histological subtypes (k = 0.87) and moderate for tumor grade (k = 0.51). CONCLUSIONS: RTB resulted in a high safety profile. The overall diagnostic rate was 85% and an unnecessary intervention was avoided in 21% of patients. RTB showed a very good accuracy in determining the histological subtype of renal cancer while it was moderate for the tumor grade. These results are similar to those reported in larger series and support feasibility of this procedure in low-volume centers.

Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.

The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.

Current evidence between hospital volume and perioperative outcome: Prospective assessment of robotic radical prostatectomy safety profile in a regional center of medium annual caseload.

INTRODUCTION: We aimed to present the safety profile of robotic radical prostatectomy (RARP) performed in a single center of medium surgical volume since its introduction and identify predictors of postoperative complications. METHODS: We prospectively collected clinical data from 317 consecutive patients undergoing RARP between August 2011 and November 2019 in a medium-volume center. Surgical procedures were performed by a single experienced surgeon. Complications were collected according to the Martin criteria for reporting and the Clavien-Dindo classification for rating. Preoperative, intraoperative, and postoperative data were analyzed and compared with available literature. RESULTS: A total of 102 complications were observed in 96 (30.3%) patients and were minor in 84.4% of cases (Clavien grade 1 and 2). Transfusion rate was 1.3%. Complications of grade 4b or 5 did not occur. The most frequent complications were urinary retention (7.3%) and anastomotic leak (5.9%). At multivariate analysis, the nerve-sparing technique was an independent predictor of complications (odds ratio [OR] 0.55, p=0.02). CONCLUSIONS: The study shows that a high safety profile may be achieved in a medium-volume hospital. The nerve-sparing technique was a predictor of complications. Further studies are needed to define the current relationship between surgical volume and perioperative outcome for RARP.