Predicting clinical outcome of therapy-resistant prostate cancer

Abstract

Prostate cancer (PCa) is among the most common malignancies in men and a leading cause of cancer-related death. Due to its high incidence, men generally undergo annual screening for serum levels of prostate-specific antigen (PSA). Those with elevated serum PSA are usually referred to urologists and often undergo multiparametric MRI diagnosis and core needle biopsy of the prostate. Due to PSA’s poor specificity, only a fraction of the men with elevated PSA will be diagnosed with PCa. Tumors diagnosed through PSA screening are biologically heterogeneous and clinical outcomes vary significantly from patient to patient. Many such tumors are indolent, do not impact patients’ quality of life or life expectancy, and require no treatment. Low-grade and low-stage tumors can be cured by surgery or radiation. Unfortunately, many men with high-grade and high-stage tumors will experience tumor recurrence after local treatment. The heterogeneity in the biological behavior of PCa makes this a unique tumor among human malignancies. Over the years, a number of factors have been found useful in predicting the biologic behavior of PCa, such as preoperative PSA levels, findings by multiparametric MRI, Gleason grade of the tumor, and the number of positive biopsy cores. In prostatectomy specimens, tumor grade, tumor stage, and the status of resection margins predict clinical outcome. PCa that cannot be controlled by local therapies is treated with hormonal therapy that blocks androgen production and/or the activity of the androgen receptor (AR). Although hormonal treatment is effective initially, the tumor always recurs and becomes castration resistant (CR). Abiraterone and enzalutamide, which are next-generation AR signaling inhibitors (ARSIs), can extend lives for patients with CR PCa (CRPC), but the tumor will eventually progress. Importantly, at the CRPC stage, the prognosis varies significantly from case to case, with some patients surviving for years and others progressing rapidly. A study … \n\n[↵][1]1To whom correspondence may be addressed. Email: jiaoti.huang{at}duke.edu.\n\n [1]: #xref-corresp-1-1