Figueras Marcel, Mengual Lourdes, Ingelmo-Torres Mercedes, Roldán Fiorella L, Padullés Bernat, Alfambra Héctor, Herranz Sandra, Paredes Pilar, Amseian Gary, Mases Joel, Ribal Maria J, Izquierdo Laura, Alcaraz Antonio
Department and Laboratory of Urology, Hospital Clínic Barcelona, 08036 Barcelona, Spain.
Genetics and Urological Tumours, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Diagnostics (Basel). 2024 Oct 16;14(20):2293. doi: 10.3390/diagnostics14202293.
Currently, the prediction of disease recurrence after radical prostatectomy (RP) in localized prostate cancer (PCa) relies on clinicopathological parameters, which lack accuracy in predicting clinical outcomes. This study focused on evaluating the utility of cfDNA levels and fragmentation patterns as prognostic biomarkers in progressive prostate-specific antigen (PSA) patients, including those with persistent PSA and biochemical recurrence (BR), after primary treatment in localized PCa patients. Twenty-nine high-risk localized PCa patients were enrolled in the study between February 2022 and May 2023. Blood samples were obtained before robotic RP. cfDNA concentration and fragment size were quantified using the Quant-it PicoGreen dsDNA Assay kit and Agilent 2200 TapeStation System, respectively. The mean PSA value at diagnosis was 9.4 ng/mL. Seven patients (24.1%) had stage pT2 and 22 (75.9%) pT3. Nine patients (31%) had detectable PSA at the first PSA control six weeks after surgery, and four patients (20%) had BR during a mean follow-up of 18.4 months. No associations were found between cfDNA levels or fragmentation patterns and clinicopathological data. Although not statistically significant, patients with detectable PSA levels post-surgery exhibited higher cfDNA levels and shorter fragments compared with those with undetectable PSA. Our study indicated a tendency toward more fragmented cfDNA levels in PCa patients with persistent PSA. Strikingly, biochemical recurrent PCa patients exhibited similar cfDNA levels and fragmentation patterns compared to non-recurrent patients. Further studies exploring liquid biopsy-derived biomarkers in localized PCa patients are needed to elucidate their clinical utility in predicting PSA persistence.
目前，局限性前列腺癌（PCa）根治性前列腺切除术（RP）后疾病复发的预测依赖于临床病理参数，而这些参数在预测临床结果方面缺乏准确性。本研究聚焦于评估游离DNA（cfDNA）水平和片段化模式作为局限性PCa患者接受初始治疗后进展性前列腺特异性抗原（PSA）患者（包括PSA持续存在和生化复发（BR）的患者）预后生物标志物的效用。2022年2月至2023年5月期间，29例高危局限性PCa患者被纳入研究。在机器人辅助RP术前采集血样。分别使用Quant-it PicoGreen双链DNA检测试剂盒和安捷伦2200 TapeStation系统对cfDNA浓度和片段大小进行定量。诊断时的平均PSA值为9.4 ng/mL。7例患者（24.1%）为pT2期，22例（75.9%）为pT3期。9例患者（31%）在术后6周的首次PSA检查时可检测到PSA，4例患者（20%）在平均18.4个月的随访期间发生BR。未发现cfDNA水平或片段化模式与临床病理数据之间存在关联。虽然无统计学意义，但术后PSA水平可检测的患者与PSA不可检测的患者相比，cfDNA水平更高且片段更短。我们的研究表明，PSA持续存在的PCa患者中cfDNA水平有更碎片化的趋势。令人惊讶的是，生化复发的PCa患者与未复发患者相比，cfDNA水平和片段化模式相似。需要进一步研究探索局限性PCa患者液体活检衍生的生物标志物，以阐明其在预测PSA持续存在方面的临床效用。
