Clinical Management of Intraductal Carcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions.

A Comprehensive National Survey of Prostate-specific Antigen Testing and Prostate Cancer Management in France: Uncovering Regional and Temporal Disparities.

We report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men. All prostate-specific antigen (PSA) blood tests performed between 2006 and 2018 were recorded in a National Health registry, which allowed to identify 692516 men diagnosed with PC and a control population consisting of 3899509 men without PC. PSA tests, age at diagnosis, treatments, and survival were analysed. Their management was analysed by age range and compared in the different French regions. Disparities were found in age at PSA testing and management approaches (surveillance, and local and systemic therapies). We found that 50% of men had received five PSA blood tests, but the first PSA test was taken late in life, with a peak in the decade between 65 and 75 yr of age. Adoption of monitoring was low (12%). Older men appeared to receive a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality, but cautious interpretation of our data is warranted in view of competing morbidities and other causes of death. The incidence of metastases at diagnosis, indicated by the use of systemic therapies, increased progressively from 2011 onwards. PATIENT SUMMARY: In this study, we report nationwide real-life practice in the management of prostate cancer (PC) in France in a population of 4936750 men, including 692516 patients with PC. We found that the first prostate-specific antigen test is taken too late in life, leading to a late diagnosis with reduced chances of curative therapy and a subsequent increase in mortality.

Tumour-based Mutational Profiles Predict Visceral Metastasis Outcome and Early Death in Prostate Cancer Patients.

BACKGROUND: Visceral metastases are known to occur in advanced prostate cancer, usually when the tumour is resistant to androgen deprivation and, have worse outcomes regardless of therapies. OBJECTIVE: To analyse genomic alterations in tumour samples according to their lymphatic, bone, and visceral metastatic stages and overall survival. DESIGN, SETTING, AND PARTICIPANTS: We selected 200 patients with metastatic prostate cancer. Genomic profiling of 111 genes and molecular signatures (homologous recombination deficiency [HRD], microsatellite instability, and tumour burden mutation) was performed with the MyChoice test (Myriad Genetics, Inc, Salt Lake City, UT, USA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between genomic profiles and visceral metastatic evolution was evaluated using logistic regression. Kaplan-Meier and Cox proportional hazard analyses were used for analyses of early death. RESULTS AND LIMITATIONS: A total of 173 (87%) genomic profiles were obtained. Eighty-four (49%) patients died during the follow-up period (median duration = 76 mo). TP53 was the most frequently mutated gene, followed by FANC genes, including BRCA2, and those of the Wnt-pathway (APC/CTNNB1). TP53 gene mutations were more frequent in patients of European (42%) than in those of African (16%) ancestry. An HRD score of >25 was predictive of FANC gene mutations. The mutational status of TP53 (p < 0.001) and APC (p = 0.002) genes were significantly associated with the risk of visceral metastases. The mutational status of CTNNB1 (p = 0.001), TP53 (p = 0.015), BRCA2 (p = 0.027), and FANC (p = 0.005) genes were significantly associated with an earlier age at death. The limitations are the retrospective study design based on a selection of genes and the low frequency of certain molecular events. CONCLUSIONS: Mutations in the TP53 gene and genes (APC/CTNNB1) related to the Wnt pathway are associated with metastatic visceral dissemination and early death. These genomic alterations could be considered as markers to identify prostate cancer patients at a high risk of life-threatening disease who might benefit from more intensified treatment or new targeted therapies. PATIENT SUMMARY: In this report, we evaluated the relationships between genomic profiles (gene mutations and molecular signatures) of tumour samples from patients with metastatic prostate cancer and early death. We found that mutations of specific genes, notably TP53 and APC/CTNNB1 related to the Wnt pathway, are associated with visceral metastatic progression and an earlier age at death.

A multi-center international study to evaluate the safety, functional and oncological outcomes of irreversible electroporation for the ablation of prostate cancer.

BACKGROUND: Irreversible electroporation (IRE) is a novel technique to treat localized prostate cancer with the aim of achieving oncological control while reducing related side effects. We present the outcomes of localized prostate cancer treated with IRE from a multi-center prospective registry. METHODS: Men with histologically confirmed prostate cancer were recruited to receive IRE. All the patients were proposed for prostate biopsy at 1-year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The safety of IRE was graded by the treatment-related adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: 411 patients were recruited in this study from July 2015 to April 2020. The median follow-up time was 24 months (IQR 15-36). 116 patients underwent repeat prostate biopsy during 12-18 months after IRE. Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 24.1% (28/116) of the patients; any grade prostate cancers were found in 59.5% (69/116) of the patients. The IPSS score increased significantly from 7.1 to 8.2 (p = 0.015) at 3 months but decreased to 6.1 at 6 months (p = 0.017). Afterwards, the IPSS level remained stable during follow-up. The IIEF-5 score decreased at 3 months from 16.0 to 12.1 (p < 0.001) and then maintained equable afterwards. The rate of AEs was 1.8% at 3 months and then dropped to less than 1% at 6 months and remained stable until 48 months after IRE. Major AEs (Grade 3 or above) were rare. CONCLUSION: For men with localized prostate cancer, IRE could achieve good urinary and sexual function outcomes and a reasonable oncological result. The real-world data are consistent with earlier studies, including recently published randomized controlled studies. The long-term oncological results need further investigation and follow-up.