University of California San Francisco, San Francisco, CA, USA.
University of California Santa Cruz, Santa Cruz, CA, USA.
Prostate Cancer Prostatic Dis. 2021 Mar;24(1):81-87. doi: 10.1038/s41391-020-0228-0. Epub 2020 Apr 14.
Metastatic disease burden out of proportion to serum PSA has been used as a marker of aggressive phenotype prostate cancer but is not well defined as a distinct subgroup. We sought to prospectively characterize the molecular features and clinical outcomes of Low PSA Secretors.
Eligible metastatic castration resistant prostate cancer (mCRPC) patients without prior small cell histology underwent metastatic tumor biopsy with molecular characterization. Low PSA secretion was defined as serum PSA < 2, 5, or 10 ng/mL plus >5 metastases with radiographic progression at study entry. Clinical and molecular features were compared between low PSA vs. normal secretors in a post-hoc fashion.
183 patients were enrolled, including 15 (8%) identified as Low PSA Secretors using optimal PSA cut point of 5 ng/mL. Biopsies from Low PSA Secretors demonstrated higher t-SCNC and RB1 loss and lower AR transcriptional signature scores compared with normal secretors. Genomic loss of RB1 and/or TP53 was more common in Low PSA Secretors (80% vs. 41%). Overall survival (OS) was shorter in Low PSA Secretors (median OS = 26.7 vs. 46.0 months, hazard ratio = 2.465 (95% CI: 0.982-6.183). Progression-free survival (PFS) on post-biopsy treatment with AR-targeted therapy was shorter than with chemotherapy (median PFS 6.2 vs. 4.1 months).
Low PSA secretion in relation to metastatic tumor burden may be a readily available clinical selection tool for de-differentiated mCRPC with molecular features consistent with t-SCNC. Prospective validation is warranted.
与血清 PSA 不成比例的转移性疾病负担已被用作侵袭性表型前列腺癌的标志物，但尚未明确界定为一个独特的亚组。我们旨在前瞻性地描述低 PSA 分泌者的分子特征和临床结局。
符合条件的转移性去势抵抗性前列腺癌（mCRPC）患者，无小细胞病史，接受转移性肿瘤活检和分子特征分析。低 PSA 分泌定义为血清 PSA<2、5 或 10ng/mL，且研究入组时影像学进展伴有>5 处转移。以低 PSA 与正常分泌者在回顾性分析中进行比较。
共纳入 183 例患者，其中 15 例（8%）使用最佳 PSA 截断值 5ng/mL 被确定为低 PSA 分泌者。与正常分泌者相比，低 PSA 分泌者的 t-SCNC 和 RB1 缺失以及 AR 转录特征评分较低。低 PSA 分泌者中更常见基因组性 RB1 和/或 TP53 缺失（80% vs. 41%）。低 PSA 分泌者的总生存期（OS）更短（中位 OS=26.7 vs. 46.0 个月，风险比=2.465（95%CI：0.982-6.183））。在接受 AR 靶向治疗的活检后治疗中，无进展生存期（PFS）短于化疗（中位 PFS 6.2 vs. 4.1 个月）。
与转移性肿瘤负担相关的低 PSA 分泌可能是一种易于获得的临床选择工具，用于区分去分化 mCRPC，其分子特征与 t-SCNC 一致。需要前瞻性验证。
