-
Molecules (Basel, Switzerland) Sep 2022Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate... (Review)
Review
Prostate cancer is one of the malignancies that affects men and significantly contributes to increased mortality rates in men globally. Patients affected with prostate cancer present with either a localized or advanced disease. In this review, we aim to provide a holistic overview of prostate cancer, including the diagnosis of the disease, mutations leading to the onset and progression of the disease, and treatment options. Prostate cancer diagnoses include a digital rectal examination, prostate-specific antigen analysis, and prostate biopsies. Mutations in certain genes are linked to the onset, progression, and metastasis of the cancer. Treatment for localized prostate cancer encompasses active surveillance, ablative radiotherapy, and radical prostatectomy. Men who relapse or present metastatic prostate cancer receive androgen deprivation therapy (ADT), salvage radiotherapy, and chemotherapy. Currently, available treatment options are more effective when used as combination therapy; however, despite available treatment options, prostate cancer remains to be incurable. There has been ongoing research on finding and identifying other treatment approaches such as the use of traditional medicine, the application of nanotechnologies, and gene therapy to combat prostate cancer, drug resistance, as well as to reduce the adverse effects that come with current treatment options. In this article, we summarize the genes involved in prostate cancer, available treatment options, and current research on alternative treatment options.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Salvage Therapy
PubMed: 36080493
DOI: 10.3390/molecules27175730 -
Nature Reviews. Disease Primers Feb 2021Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a... (Review)
Review
Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.
Topics: Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms
PubMed: 33542230
DOI: 10.1038/s41572-020-00243-0 -
Nature Reviews. Urology Feb 2021From a clinical, morphological and molecular perspective, prostate cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having... (Review)
Review
From a clinical, morphological and molecular perspective, prostate cancer is a heterogeneous disease. Primary prostate cancers are often multifocal, having topographically and morphologically distinct tumour foci. Sequencing studies have revealed that individual tumour foci can arise as clonally distinct lesions with no shared driver gene alterations. This finding demonstrates that multiple genomically and phenotypically distinct primary prostate cancers can be present in an individual patient. Lethal metastatic prostate cancer seems to arise from a single clone in the primary tumour but can exhibit subclonal heterogeneity at the genomic, epigenetic and phenotypic levels. Collectively, this complex heterogeneous constellation of molecular alterations poses obstacles for the diagnosis and treatment of prostate cancer. However, advances in our understanding of intra-tumoural heterogeneity and the development of novel technologies will allow us to navigate these challenges, refine approaches for translational research and ultimately improve patient care.
Topics: Biomarkers, Tumor; Epigenesis, Genetic; Genetic Heterogeneity; Genome; Genomics; Humans; Male; Neoplasm Metastasis; Neoplasms, Multiple Primary; Phenotype; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 33328650
DOI: 10.1038/s41585-020-00400-w -
Current Oncology Reports Jan 2021Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism... (Review)
Review
PURPOSE OF REVIEW
Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype of prostate cancer that most commonly arises in later stages of prostate cancer as a mechanism of treatment resistance. The poor prognosis of NEPC is attributed in part to late diagnosis and a lack of effective therapeutic agents. Here, we review the clinical and molecular features of NEPC based on recent studies and outline future strategies and directions.
RECENT FINDINGS
NEPC can arise "de novo" but most commonly develops as a result of lineage plasticity whereby prostate cancer cells adopt alternative lineage programs as a means to bypass therapy. Dependence on androgen receptor (AR) signaling is lost as tumors progress from a prostate adenocarcinoma to a NEPC histology, typically manifested by the downregulation of AR, PSA, and PSMA expression in tumors. Genomic analyses from patient biopsies combined with preclinical modeling have pointed to loss of tumor suppressors RB1 and TP53 as key facilitators of lineage plasticity. Activation of oncogenic drivers combined with significant epigenetic changes (e.g., EZH2 overexpression, DNA methylation) further drives tumor proliferation and expression of downstream neuronal and neuroendocrine lineage pathways controlled in part by pioneer and lineage determinant transcription factors (e.g., SOX2, ASCL1, BRN2). These biologic insights have provided a framework for the study of this subgroup of advanced prostate cancers and have started to provide rationale for the development of biomarker-driven therapeutic strategies. Further study of the dynamic process that leads to NEPC is required for the development of effective strategies to identify and treat patients developing lineage plasticity as a mechanism of treatment resistance.
Topics: Carcinoma, Neuroendocrine; Disease Progression; Drug Resistance, Neoplasm; Humans; Male; Prostatic Neoplasms
PubMed: 33433737
DOI: 10.1007/s11912-020-01003-9 -
International Journal of Molecular... Apr 2021Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary... (Review)
Review
Prostate cancer (PCa) is globally the second most diagnosed cancer type and the most common cause of cancer-related deaths in men. Family history of PCa, hereditary breast and ovarian cancer (HBOC) and Lynch syndromes (LS), are among the most important risk factors compared to age, race, ethnicity and environmental factors for PCa development. Hereditary prostate cancer (HPCa) has the highest heritability of any major cancer in men. The proportion of PCa attributable to hereditary factors has been estimated in the range of 5-15%. To date, the genes more consistently associated to HPCa susceptibility include mismatch repair (MMR) genes (, , , and ) and homologous recombination genes (, , , ). Additional genes are also recommended to be integrated into specific research, including , and . Importantly, and mutated patients potentially benefit from Poly (ADP-ribose) polymerase PARP inhibitors, through a mechanism of synthetic lethality, causing selective tumor cell cytotoxicity in cell lines. Moreover, the detection of germline alterations in MMR genes has therapeutic implications, as it may help to predict immunotherapy benefits. Here, we discuss the current knowledge of the genetic basis for inherited predisposition to PCa, the potential target therapy, and the role of active surveillance as a management strategy for patients with low-risk PCa. Finally, the current PCa guideline recommendations are reviewed.
Topics: Germ-Line Mutation; Humans; Male; Molecular Targeted Therapy; Neoplasm Proteins; Prostatic Neoplasms
PubMed: 33916521
DOI: 10.3390/ijms22073753 -
Critical Reviews in Oncology/hematology Jan 2022Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of... (Review)
Review
Overweight and obese men with prostate cancer are at an increased risk of disease recurrence, exacerbated treatment-related adverse effects, development of obesity-related comorbidities, earlier progression and development of metastatic disease, and higher all-cause and prostate cancer-specific mortality. The physiological mechanisms associating obesity with poor prostate cancer outcomes remain largely unknown; however, an increased inflammatory environment and metabolic irregularities associated with excess fat mass are commonly postulated. Although research is limited, fat loss strategies using exercise and nutrition programmes may slow down prostate cancer progression and improve a patient's prognosis. This review is an overview of: 1) the association between obesity and poor prostate cancer prognosis; 2) potential physiological mechanisms linking obesity and prostate cancer progression; 3) the effect of obesity on treatments for prostate cancer; and 4) the potential for weight loss strategies to improve outcomes in patients with prostate cancer.
Topics: Body Mass Index; Exercise; Humans; Male; Neoplasm Recurrence, Local; Obesity; Overweight; Prostatic Neoplasms
PubMed: 34808374
DOI: 10.1016/j.critrevonc.2021.103543 -
Pathologica Feb 2022In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male... (Review)
Review
In 2022, after a six-year interval, the International Agency for Research on Cancer (IARC) has published the 5th edition of the WHO Classification of Urinary and Male Genital Tumors, which provides a comprehensive update on tumor classification of the genitourinary system. This review article focuses on prostate carcinoma and underscores changes in the prostate chapter as well as those made across the entire series of the 5th edition of WHO Blue Books. Although no major alterations were made to this chapter, some of the most notable updates include restructure of contents and introduction of a new format; standardization of mitotic counts, genomic nomenclatures, and units of length; refined definition for the terms "variant", "subtype", and "histologic pattern"; reclassification of prostatic intraepithelial neoplasia (PIN)-like adenocarcinoma as a subtype of prostatic acinar adenocarcinoma; and recognition of treatment-related neuroendocrine prostatic carcinoma as a distinct tumor type. Evolving and unsettled issues related to grading of intraductal carcinoma of the prostate and reporting of tertiary Gleason pattern, the definition and prognostic significance of cribriform growth pattern, and molecular pathology of prostate cancer will also be covered in this review.
Topics: Humans; Male; Prostate; Prostatic Neoplasms; Adenocarcinoma; Prognosis; World Health Organization; Neoplasm Grading
PubMed: 36645399
DOI: 10.32074/1591-951X-822 -
MMWR. Morbidity and Mortality Weekly... Oct 2020Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since...
Among U.S. men, prostate cancer is the second leading cause of cancer-related death (1). Past studies documented decreasing incidence of prostate cancer overall since 2000 but increasing incidence of distant stage prostate cancer (i.e., signifying spread to parts of the body remote from the primary tumor) starting in 2010 (2,3). Past studies described disparities in prostate cancer survival by stage, age, and race/ethnicity using data covering ≤80% of the U.S. population (4,5). To provide recent data on incidence and survival of prostate cancer in the United States, CDC analyzed data from population-based cancer registries that contribute to U.S. Cancer Statistics (USCS).* Among 3.1 million new cases of prostate cancer recorded during 2003-2017, localized, regional, distant, and unknown stage prostate cancer accounted for 77%, 11%, 5%, and 7% of cases, respectively, but the incidence of distant stage prostate cancer significantly increased during 2010-2017. During 2001-2016, 10-year relative survival for localized stage prostate cancer was 100%. Overall, 5-year survival for distant stage prostate cancer improved from 28.7% during 2001-2005 to 32.3% during 2011-2016; for the period 2001-2016, 5-year survival was highest among Asian/Pacific Islanders (API) (42.0%), followed by Hispanics (37.2%), American Indian/Alaska Natives (AI/AN) (32.2%), Black men (31.6%), and White men (29.1%). Understanding incidence and survival differences by stage, race/ethnicity, and age can guide public health planning related to screening, treatment, and survivor care. Future research into differences by stage, race/ethnicity, and age could inform interventions aimed at improving disparities in outcomes.
Topics: Aged; Aged, 80 and over; Ethnicity; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Racial Groups; Survival Analysis; United States
PubMed: 33056955
DOI: 10.15585/mmwr.mm6941a1 -
European Urology Oncology Dec 2021Imaging techniques are used to identify local recurrence of prostate cancer (PCa) for salvage therapy and to exclude metastases that should be addressed with systemic... (Review)
Review
Prostate Magnetic Resonance Imaging for Local Recurrence Reporting (PI-RR): International Consensus -based Guidelines on Multiparametric Magnetic Resonance Imaging for Prostate Cancer Recurrence after Radiation Therapy and Radical Prostatectomy.
BACKGROUND
Imaging techniques are used to identify local recurrence of prostate cancer (PCa) for salvage therapy and to exclude metastases that should be addressed with systemic therapy. For magnetic resonance imaging (MRI), a reduction in the variability of acquisition, interpretation, and reporting is required to detect local PCa recurrence in men with biochemical relapse after local treatment with curative intent.
OBJECTIVE
To propose a standardised method for image acquisition and assessment of PCa local recurrence using MRI after radiation therapy (RP) and radical prostatectomy (RT).
EVIDENCE ACQUISITION
Prostate Imaging for Recurrence Reporting (PI-RR) was formulated using the existing literature. An international panel of experts conducted a nonsystematic review of the literature. The PI-RR system was created via consensus through a combination of face-to-face and online discussions.
EVIDENCE SYNTHESIS
Similar to with PI-RADS, based on the best available evidence and expert opinion, the minimum acceptable MRI parameters for detection of recurrence after radiation therapy and radical prostatectomy are set. Also, a simplified and standardised terminology and content of the reports that use five assessment categories to summarise the suspicion of local recurrence (PI-RR) are designed. PI-RR scores of 1 and 2 are assigned to lesions with a very low and low likelihood of recurrence, respectively. PI-RR 3 is assigned if the presence of recurrence is uncertain. PI-RR 4 and 5 are assigned for a high and very high likelihood of recurrence, respectively. PI-RR is intended to be used in routine clinical practice and to facilitate data collection and outcome monitoring for research.
CONCLUSIONS
This paper provides a structured reporting system (PI-RR) for MRI evaluation of local recurrence of PCa after RT and RP.
PATIENT SUMMARY
A new method called PI-RR was developed to promote standardisation and reduce variations in the acquisition, interpretation, and reporting of magnetic resonance imaging for evaluating local recurrence of prostate cancer and guiding therapy.
Topics: Consensus; Humans; Magnetic Resonance Imaging; Male; Multiparametric Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms
PubMed: 33582104
DOI: 10.1016/j.euo.2021.01.003 -
Journal of the National Comprehensive... Feb 2021The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and...
The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel's discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.
Topics: Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Risk Assessment
PubMed: 33545689
DOI: 10.6004/jnccn.2021.0008