Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Prostate. 2019 Sep;79(13):1572-1579. doi: 10.1002/pros.23881. Epub 2019 Aug 7.
Isolated pulmonary involvement is uncommon in metastatic hormone-sensitive prostate cancer (mHSPC). To characterize outcomes and molecular alterations of this unique patient subset, we conducted a retrospective review of patients with hormone-naïve prostate cancer presenting with lung-only metastases.
This was a retrospective single-institution study. Medical records of 25 patients presenting with pulmonary-only metastases before receiving androgen deprivation therapy (ADT) were analyzed. Germline and/or somatic genomic results, where available (n = 16), were documented. Tumor tissue was analyzed using clinical-grade next-generation DNA sequencing assays. Clinical endpoints included complete prostate-specific antigen (PSA) response to ADT (<0.1 ng/mL), median overall survival (OS) from time of ADT initiation, median PSA progression-free survival (PSA-PFS), and failure-free survival (FFS) at 4 years.
Baseline characteristics were notable for 48% of men (12 of 25) having first or second-degree relatives with prostate cancer, compared with 20% expected. Complete PSA responses to ADT were noted in 52% of men, with a median PSA-PFS of 66 months, a 4-year FFS rate of 72%, and a median OS that was not reached after 190 months. In evaluable patients, molecular drivers were enriched for mismatch repair mutations (4 of 16, 25%) and homologous-recombination deficiency mutations (4 of 16, 25%). These results are limited by the small sample size and retrospective nature of this analysis.
This exploratory study represents one of the largest cohorts of lung-only mHSPC patients to-date. The prevalence of actionable DNA-repair gene alterations was higher than anticipated (any DNA-repair mutation: 8 of 16, 50%). Compared to historical data, these patients appear to have exceptional and durable responses to first-line ADT. This study suggests that pulmonary-tropic mHSPC biology may be fundamentally different from nonpulmonary mHSPC.
转移性激素敏感型前列腺癌（mHSPC）中孤立性肺部受累并不常见。为了描述这一独特患者亚群的结局和分子改变，我们对接受雄激素剥夺治疗（ADT）前仅出现肺部转移的激素初治前列腺癌患者进行了回顾性研究。
这是一项回顾性单机构研究。分析了 25 例仅出现肺部转移而未接受 ADT 治疗的患者的病历。记录了可获得的胚系和/或体细胞基因组结果（n=16）。使用临床级别的下一代 DNA 测序检测分析肿瘤组织。临床终点包括 ADT 后完全前列腺特异性抗原（PSA）应答（<0.1ng/mL）、ADT 起始时的中位总生存（OS）、中位 PSA 无进展生存（PSA-PFS）和 4 年时无失败生存（FFS）。
基线特征值得注意的是，48%（12/25）的男性有一级或二级亲属患有前列腺癌，而预期为 20%。52%的男性对 ADT 有完全 PSA 应答，PSA-PFS 的中位值为 66 个月，4 年 FFS 率为 72%，190 个月后 OS 未达到。在可评估的患者中，分子驱动因素富集错配修复基因突变（16 例中的 4 例，25%）和同源重组缺陷基因突变（16 例中的 4 例，25%）。这些结果受到本分析中小样本量和回顾性的限制。
这项探索性研究代表了迄今为止最大的肺部 mHSPC 患者队列之一。可操作的 DNA 修复基因突变的发生率高于预期（任何 DNA 修复突变：16 例中的 8 例，50%）。与历史数据相比，这些患者对一线 ADT 似乎有极好且持久的反应。这项研究表明，肺转移 mHSPC 生物学可能与非肺转移 mHSPC 有根本的不同。
