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Simple Summary: In our study, we found genetic mutations in the DNA of cancer cells obtained from the blood of many patients with metastatic prostate cancer. These changes were more common in patients whose cancer was progressing and aggressive in nature, often unresponsive to conventional treatment strategies. Additionally, these genetic mutation findings were more sensitive than the conventional method of checking the prostate-specific antigen (PSA) level in the blood for detecting prostate cancer progression. This means a simple blood test could help us track genetic mutations, detect aggressive cancer subtypes, determine the progression of the disease, and manage advanced prostate cancer more effectively. The positivity rate of circulating tumor DNA (ctDNA) next-generation sequencing (NGS) varies among patients with metastatic prostate cancer (mPC), complicating its incorporation into regular practice. This retrospective study analyzed the ctDNA sequencing results of 100 mPC patients from May 2021 to March 2023 to identify the factors associated with positive ctDNA. Three custom gene panels were used for sequencing. Overall, 63% of the patients exhibited tier I/II somatic alterations, while 12% had pathogenic/likely pathogenic germline alterations. The key genes that were altered included AR, TP53, RB1, PTEN, and APC. Mutations in BRCA1/2, either germline or somatic, were observed in 21% of the patients. Among the metastatic castration-resistant prostate cancer (mCRPC) patients, the ctDNA-positive samples generally showed higher median prostate-specific antigen (PSA) levels and were more likely to be at the radiographic and clinical progressive disease stages, although they were not significantly associated with PSA progression. Our results suggest that ctDNA analysis could detect meaningful genetic changes in mPC patients, especially during disease progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating tumor DNA (ctDNA) has emerged as a potential biomarker for clear cell renal cell carcinoma (ccRCC). However, the ctDNA characteristics have not been demonstrated in small ccRCC. The aim of our pilot study is to explore the characteristics of ctDNA in pT1a ccRCC (ccRCC less than 4 cm in diameter). We included 53 patients with pT1a ccRCC, a greater number than in previous studies using next-generation sequencing. We found that the ctDNA detection rate was low in pT1a ccRCC. The relationship between ctDNA and clinicopathological features, such as tumor size, tumor grade, and patient age, was not clear. Increasing the sensitivity and removing background noise in ctDNA analysis may aid in further understanding the characteristics of ctDNA, thereby enhancing its clinical utility in pT1a ccRCC. Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC. [ABSTRACT FROM AUTHOR]