Outcomes after precision prostatectomy: safety, efficacy and transference of skills.

PURPOSE: Precision Prostatectomy (PP) is a viable treatment option for men with unilateral dominant cancer who are interested in preserving functional outcomes. To date, the data published about the outcomes of this technique has come from a single center only (Henry Ford - HF). We present the surgical, functional, and oncological outcomes of the first series of patients to undergo PP outside of HF, to demonstrate the safety and reproducibility of the technique. METHODS: Between 2022 and 2023, PP was offered to select patients who were interested in preserving their functional status. Men who underwent PP were followed at 3 monthly intervals; information regarding their functional status was simultaneously obtained. Men who had biochemical recurrence were advised to undergo remnant biopsy. If residual cancer was detected, then remnant removal was performed. RESULTS: The median age and median PSA of the study group was 63 years and 6.89 ng/ml respectively. The median operative and console times were 196.5 and 154 minutes. No intra-operative complications were noted. Three patients had a total of three post-operative complications. Three patients had biochemical recurrence; cancer was not detected in any of these patients on postoperative biopsies of the prostatic remnant. At 12 months, 91% of patients reported using 0 pads/day and 90.9% of pre-operatively potent patients were potent at 12 months. CONCLUSION: PP is a safe and reproducible technique that can ensure cancer control and preservation of functional status in select patients. Further studies with large sample sizes and longer follow-up are required to ascertain the long-term outcomes of this surgical technique.

The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.

Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. SIGNIFICANCE: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.