Prostate cancer is the second most common cancer in American men, with over 200,000 new cases diagnosed annually in the US. While localized treatment modalities often cure patients with localized disease, approximately 30% demonstrate evidence of biochemical relapse at 10 years. Often, these patients are without evidence of metastatic disease on scans, a setting referred to as BRPC MO. The natural history of patients with BRPC MO is quite heterogeneous in terms of future development of metastatic disease on scans, and their optimal management is controversial. Some of the patients with BRPC MO are treated with androgen deprivation therapy, despite the lack of metastases on scans. Eventually most of them will develop a state of castrate resistant with rising PSA under androgen deprivation therapy. Often, these patients are without evidence of metastatic disease on scans, a setting referred to as CRPC MO, but eventually many will develop a metastatic disease on scans.
An important prognostic factor in patients with rising PSA in the setting of BRPC MO and CRPC MO is the PSA doubling time (PSADT). Over the past decade, understanding of fundamental tumorigenesis mechanisms of prostate cancer led to development of new potent therapies in patients with non-metastatic castrate resistant prostate cancer, The androgen receptor is central in prostate cancer progression. In the castrate resistant state, there are multiple mechanisms leading to activation of the androgen receptor despite a low level of testosterone, e.g. amplification of the androgen receptor. Apalutamide, enzalutamide, and darolutamide are potent inhibitors of the androgen receptor. They act by inhibiting the following steps of the androgen receptor activation: binding of androgens to the androgen receptor, translocation of the complex of androgen-androgen receptor to the cell nucleus, and binding of the complex androgen-androgen receptor to the DNA. In patients with CRPC MO and a PSA doubling time is < 10 months, standard of care with level 1 evidence include the new potent androgen receptor inhibitors apalutamide, enzalutamide, and darolutamide, that were shown in phase 3 randomized clinical trials to improve disease outcomes including overall survival.
The aim of this Research Topic is to focus on various aspects of the settings of BRPC MO and CRPC MO. We welcome Original Research Article, Review Articles, and Systematic Reviews. This Research Topic focuses on the following topics but are not limited to:
-Non-metastatic biochemically relapsed prostate cancer with rising PSA after surgery and/or radiation, including description of the natural history and prognostic factors, salvage therapies, and potentially new systemic therapies.
-Non-metastatic castrate resistant prostate cancer, including analysis of the natural history and prognostic factors, and novel androgen receptors inhibitors.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Prostate cancer is the second most common cancer in American men, with over 200,000 new cases diagnosed annually in the US. While localized treatment modalities often cure patients with localized disease, approximately 30% demonstrate evidence of biochemical relapse at 10 years. Often, these patients are without evidence of metastatic disease on scans, a setting referred to as BRPC MO. The natural history of patients with BRPC MO is quite heterogeneous in terms of future development of metastatic disease on scans, and their optimal management is controversial. Some of the patients with BRPC MO are treated with androgen deprivation therapy, despite the lack of metastases on scans. Eventually most of them will develop a state of castrate resistant with rising PSA under androgen deprivation therapy. Often, these patients are without evidence of metastatic disease on scans, a setting referred to as CRPC MO, but eventually many will develop a metastatic disease on scans.
An important prognostic factor in patients with rising PSA in the setting of BRPC MO and CRPC MO is the PSA doubling time (PSADT). Over the past decade, understanding of fundamental tumorigenesis mechanisms of prostate cancer led to development of new potent therapies in patients with non-metastatic castrate resistant prostate cancer, The androgen receptor is central in prostate cancer progression. In the castrate resistant state, there are multiple mechanisms leading to activation of the androgen receptor despite a low level of testosterone, e.g. amplification of the androgen receptor. Apalutamide, enzalutamide, and darolutamide are potent inhibitors of the androgen receptor. They act by inhibiting the following steps of the androgen receptor activation: binding of androgens to the androgen receptor, translocation of the complex of androgen-androgen receptor to the cell nucleus, and binding of the complex androgen-androgen receptor to the DNA. In patients with CRPC MO and a PSA doubling time is < 10 months, standard of care with level 1 evidence include the new potent androgen receptor inhibitors apalutamide, enzalutamide, and darolutamide, that were shown in phase 3 randomized clinical trials to improve disease outcomes including overall survival.
The aim of this Research Topic is to focus on various aspects of the settings of BRPC MO and CRPC MO. We welcome Original Research Article, Review Articles, and Systematic Reviews. This Research Topic focuses on the following topics but are not limited to:
-Non-metastatic biochemically relapsed prostate cancer with rising PSA after surgery and/or radiation, including description of the natural history and prognostic factors, salvage therapies, and potentially new systemic therapies.
-Non-metastatic castrate resistant prostate cancer, including analysis of the natural history and prognostic factors, and novel androgen receptors inhibitors.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.