Although patients with metastatic hormone-sensitive prostate cancer (mHSPC) undergo androgen deprivation therapy (ADT), the disease can progress to metastatic castration-resistant prostate cancer (mCRPC). There are no reliable biomarkers for predicting this progression. Chromosomal instability resulting in copy number alterations (CNAs) is characteristically observed in patients with various cancers.
To investigate the role of chromosomal instability in patients with mHSPC.
This prospective study analyzed cell-free DNA (cfDNA) in pretreatment plasma samples from 75 patients with elevated prostate-specific antigen. Low-depth whole-genome sequencing of cfDNA was performed to identify CNAs.
The I score (sum of the product of the absolute Z score and the corresponding chromosome length) was used as a measure of chromosomal instability. Kaplan-Meier and Cox proportional-hazard regression analyses were performed to evaluate the association between the I score and time to progression (TTP) and the prognostic value of chromosomal instability in predicting castration resistance, respectively.
Of 22 patients with a positive I score, 86.4% (19/22) had metastatic prostate cancer. Of these 19 cases, 94.7% (18/19) were mHSPC, which was high-volume mHSPC in 83.3% (15/18). None of the patients with localized prostate cancer had a positive I score. TTP in patients with mHSPC was significantly shorter in the positive than in the negative I-score group (16.4 vs 36.9 mo; p = 0.001). Only the I score could independently predict mCRPC development (hazard ratio 10.315, 95% confidence interval 1.141-93.208; p = 0.038).
The I score could be a biomarker for ADT response and progression to mCRPC in patients with mHSPC.
We investigated whether genetic changes in cell-free DNA can predict outcomes for patients with metastatic prostate cancer that still responds to hormone therapy. We found that chromosomal instability could be a potential predictor of the development of metastatic castration-resistant prostate cancer.
European urology focus. 2022 Sep 24 [Epub ahead of print]
Chung Un Lee, Eunhae Cho, Junnam Lee, Joung Eun Lim, Jae Hoon Chung, Wan Song, Minyong Kang, Hyun Hwan Sung, Byong Chang Jeong, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Hwang Gyun Jeon
Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea., GC Genome, Yongin, Republic of Korea., Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea., Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: .