Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in AR -altered lethal prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor (AR)-targeted agents is often lethal. Unfortunately, biomarkers for this deadly disease remain under investigation, and underpinning mechanisms are ill-understood. Here, we applied deep sequencing to ∼100 mCRPC patients prior to the initiation of first-line AR-targeted therapy, which detected AR /enhancer alterations in over a third of patients, which correlated with lethality. To delve into the mechanism underlying why these patients with cell-free AR /enhancer alterations developed more lethal prostate cancer, we next performed genome-wide cell-free DNA epigenomics. Strikingly, we found that binding sites for transcription factors associated with developmental stemness were nucleosomally more accessible. These results were corroborated using cell-free DNA methylation data, as well as tumor RNA sequencing from a held-out cohort of mCRPC patients. Thus, we validated the importance of AR /enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness.

Comparison of single-port and multi-port Retzius-sparing robot-assisted laparoscopic prostatectomy.

Dissemination of robotic surgical technology for robot-assisted laparoscopic prostatectomy (RALP) has yielded advancements including the Retzius-sparing (RS) approach and the single-port (SP) platform. The safety and feasibility of each individual advancement have been evaluated, yet there is a lack of literature comparing SP RS-RALP to conventional multi-port (MP) RS-RALP. All patients who underwent RS-RALP at our institution between January 2019 and February 2021 were retrospectively reviewed. Data regarding baseline patient and tumor characteristics, operative characteristics, and surgical outcomes were collected and analyzed using the Fisher's exact test and two-tailed unpaired t tests. 62 patients were evaluated: 31 received SP RS-RALP and 31 received MP RS-RALP. Differences in patient age, BMI, and initial PSA were not observed. Lower median lymph node yield (SP: 4 vs MP: 12, p < 0.01), lower estimated blood loss (SP: 111.2 vs. MP 157.8 mL, p < 0.01), shorter operative time (SP: 207.7 vs. MP: 255.9 min, p < 0.01) and decreased length of stay (SP: 0.39 vs. MP: 1.23 days, p < 0.01) were observed in the SP RS-RALP cohort. No differences in positive surgical margins, complications, or biochemical recurrence rates were observed. SP RS-RALP is non-inferior to MP RS-RALP in terms of both perioperative and early oncologic outcomes. Despite the small sample size, the SP platform is a safe and feasible option for RS-RALP and confers potential benefits in the form of shorter operative time and reduced length of stay.