The Influence of Male Urinary and Prostatic Microbiota on the Detection and Progression of Prostate Cancer

Prostate cancer is the most common cancer in men and second most common cancer-related death in the United States (Siegel 2023). Chronic inflammation is highly prevalent in areas of the adult prostate and this inflammation has been hypothesized to contribute to prostate cancer development and/or progression, but the etiology of that inflammation has not been defined (Sfanos 2012, Marzo 2007, Sfanos 2013, Hrbacek 2013, Sfanos 2018). Since no specific biomarkers of prostate inflammation exist, establishing an epidemiological link between prostatic inflammation and prostate cancer development has been difficult.Several groups have studied the prostate microbiome. The urinary microbiome is suggested to be different in men with prostate cancer (Shrestha 2018). Prostatic tissue from radical prostatectomy specimens has been shown to be non-sterile, and the microbial differences between benign and malignant tissue has been mixed (Feng 2019, Cavarretta 2017). However, a direct association to cancer has not been established.This gap in knowledge may be related to limitations in the designs of the published studies. These limitations include the use of voided urine and/or transrectal prostate biopsy specimens or of radical prostatectomy specimens obtained from patients having undergone a transrectal prostate biopsy. Transperineal prostate biopsy has gained traction with urologists as it offers advantages compared to the transrectal method. The transperineal method offers equivalent cancer detection rates, but carries a lower risk of post-procedural sepsis compared to the transrectal approach (Shen 2012, Xiang 2019, Pepe 2013, Grummet 2014). This lack of contamination helps avoid the drawback of potential cross contamination in the studies mentioned above.Here, we aim to characterize the prostate microbiome using a novel transperineal biopsy method. We hypothesize that certain prostatic microbiota are enriched within neoplastic prostatic tissue and/or in urinary specimens and that these microbiota may help predict the presence and virulence of prostate cancer. We also sought to determine if microbiota findings correlate with clinical findings at the time of presentation of patients for prostatic biopsy, including PSA levels, digital rectal examination (DRE), and multiparametric MRI findings.

前列腺癌是美国男性最常见的癌症，亦是第二大癌症相关致死病因（Siegel 2023）。成人前列腺区域慢性炎症的患病率极高，该炎症被假说认为可促进前列腺癌的发生与/或进展，但此类炎症的病因迄今尚未明确（Sfanos 2012、Marzo 2007、Sfanos 2013、Hrbacek 2013、Sfanos 2018）。由于目前尚无特异性前列腺炎症生物标志物（biomarker），建立前列腺炎症与前列腺癌发生之间的流行病学关联颇具难度。
已有多个研究团队针对前列腺微生物组（microbiome）开展研究。有研究提示，前列腺癌患者的尿液微生物组存在差异（Shrestha 2018）。已有研究证实，根治性前列腺切除术标本中的前列腺组织并非无菌，且良性与恶性组织间的微生物组差异结果不一（Feng 2019、Cavarretta 2017），但目前尚未明确其与癌症的直接关联。
此类认知空白或与已发表研究的设计局限相关：这些研究多采用排空尿液标本、经直肠前列腺活检（transrectal prostate biopsy）标本，或是取自经直肠前列腺活检术后患者的根治性前列腺切除术标本。经会阴前列腺活检（transperineal prostate biopsy）如今已获得泌尿科医师的广泛认可，相较经直肠途径具有显著优势：其癌症检出率相当，但术后脓毒症风险更低（Shen 2012、Xiang 2019、Pepe 2013、Grummet 2014）。这种低污染特性有助于规避上述研究中潜在的交叉污染弊端。
本研究旨在采用新型经会阴活检方法对前列腺微生物组进行表征。我们提出假设：部分前列腺微生物群（microbiota）会在肿瘤性前列腺组织及/或尿液标本中富集，且此类微生物群可用于预测前列腺癌的存在及其毒力。此外，我们还试图明确微生物组检测结果是否与前列腺活检患者就诊时的临床特征相关，包括前列腺特异性抗原（prostate-specific antigen, PSA）水平、直肠指检（digital rectal examination, DRE）以及多参数磁共振成像（multiparametric MRI）结果。