Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer.

Knowledge Generated We found that some lung-recurrent metastatic hormone-sensitive prostate cancer has very good clinical outcomes and that lung metastases in these patients lack driver gene alterations associated with aggressive disease including defects in TP53, RB1, or DNA damage repair genes. Localized prostate cancer is treated with surgery or radiation, but 20%-40% of patients experience disease relapse indicated by rising serum prostate-specific antigen (PSA).[1],[2] In recent years, the use of new functional imaging techniques has demonstrated that most patients harbor clinical metastases within lymph nodes or bone at the time of PSA (ie, biochemical) recurrence.[3],[4] Current guidelines for metastatic hormone-sensitive prostate cancer (mHSPC) recommend systemic androgen deprivation therapy (ADT) plus androgen receptor (AR) pathway inhibitors and/or taxane-based chemotherapy.[5] [7] However, patient outcomes are highly variable, and we need to improve disease segmentation and customize treatment plans. Our cohort was also not enriched for DNA damage repair gene alterations, as previously reported in a series of 16 patients with lung-only mHSPC and germline and/or somatic profiling.[11] However, this published series included patients with de novo metastatic presentation and family history of prostate cancer, so is a different population to unselected lung-recurrent mHSPC. However, subgroup analyses of clinical trials in late-stage hormone-resistant prostate cancer suggest that lung metastases may be associated with different clinical outcomes to liver or other patterns of spread.[8],[9] There is limited and retrospective support for this hypothesis in treatment-naive mHSPC,[10] [13] as studies are difficult to perform because of the relative rarity of lung metastases. [Extracted from the article]