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PubMed2026

Impact of homologous recombination repair gene mutations on survival in metastatic prostate cancer: A real-world analysis from an observational database.

The prognostic significance of homologous recombination repair gene (HRRg) mutations across the different metastatic prostate cancer stages remains unclear. This retrospective real-world study analyzed 162 metastatic castration-sensitive (mCSPC) and 126 castration-resistant (mCRPC) patients from the ProGène database, stratified by HRRg mutational status. Mutation prevalence was similar in both groups (16.0% in mCSPC vs. 13.5% in mCRPC). HRR-positive mCSPC patients had significantly shorter median overall survival (OS) (24.0months; 95% confidence interval [CI]: 16.0-41.0) compared to HRR-negative patients (45.0months; 95% CI: 34.0-69.0; P=0.04). Notably, BRCA2-mutated patients exhibited a reduced median OS of 24.0months (95% CI: 9.0-40.0; P=0.036) and a faster progression-free survival compared to HRR-negative patients (median PFS=8.0months; 95% CI: 0.0-14.0 vs. 17.0months; 95% CI: 12.0-20.0; P=0.006). These findings suggest that HRRg mutations - especially BRCA2 - are associated with worse prognosis in mCSPC, supporting the value of early genomic screening to guide personalized treatment strategies.

Humans↗
PubMed2026

Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study.

INTRODUCTION: Homologous Recombination Repair (HRR) genes alterations are a resistance mechanism to therapies by taxanes or Androgen Receptor Signalling inhibitors in Metastatic Castration Resistant Prostate Cancer (mCRPC). BRCA-mutated mCRPC patients are eligible to poly adenosine diphosphateribose polymerase inhibitors (PARPi). Therefore, assessing the population-specific prevalence of HRR-related genes alterations is of public healthcare importance. METHODS: This retrospective, non-interventional, multicentric study was conducted across 6 reference French centers in a "real-life" setting. 788 paraffin-embedded mCRPC patient-samples were included and submitted to testing for BRCA1/2 in six different centers; additionally, non-BRCA HRR-related genes were investigated in two different centers. RESULTS: Among the samples, n=602 (76.4%) were contributive for molecular testing. In multivariate analysis by logistic regression and sensitivity analysis, only sample age (P<0.01), sample surface area (P=0.02) and institution (P=0.018) remained statistically significant. BRCA alterations were detected in n=39/602 (6.5%) of contributive samples, with n=35 and n=4 alterations of BRCA2 and BRCA1 respectively. Non-BRCA HRR-related genes alterations were detected in n=12/157 (7.6%) of contributive samples, with alterations of mainly ATM (n=6, 3.8%), CDK12 (n=4, 2.5%) and CHEK2 (n=2, 1.3%). DISCUSSION: In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies. LEVEL OF EVIDENCE: 3 (grade C).

Male↗
PubMed1978

Dihydrotestosterone concentration in prostate cancer tissue as a predictor of tumor differentiation and hormonal dependency.

Tissue dihydrotestosterone and 5alpha-reductase (delta4-3-ketosteroid-5alpha-oxidoreductase) levels have been measured in prostates of patients with cancer and benign prostatic hypertrophy; significant decreases in average values for both of these biochemical parameters were noted in prostate cancer compared to benign prostatic hypertrophy, although individual values overlapped in both groups. Prostate cancer tissue dihydrotestosterone levels appeared to correlate better than did either histological tumor grading or 5alpha-reductase with the ultimate clinical response to antiandrogen therapy. These results suggest that assay of tissue dihydrotestosterone levels in prostate cancer should be further explored as a possible marker for tumor differentiation.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2026

Hereditary cancer: Germline testing practices across ERN GENTURIS member countries.

Germline genetic testing practices for hereditary cancer vary across the European Reference Network on Genetic Tumour Risk Syndromes (ERN GENTURIS) member countries. We surveyed experts in genetic testing from 20 EU member countries and Norway to assess multi-gene panel usage, availability of genome-wide sequencing, first-tier testing approaches, implementation of polygenic risk scores, and the roles of non-genetic healthcare professionals. National experts and members of the ERN GENTURIS completed a structured questionnaire covering founder germline pathogenic variants (gPV) testing, panel testing for common genetic tumour risk syndromes, use of whole-exome sequencing (WES) and whole-genome sequencing, polygenic risk score implementation, use of formalin-fixed paraffin-embedded tumour samples, laboratory accreditation, and the clinical roles of physicians, genetic counselors and nurses. Significant inter-country heterogeneity was observed. Most countries rely on next-generation sequencing (NGS) multi-gene panels. Founder gPV testing is first-line in a few high-prevalence populations (e.g., BRCA1/2 founders). All 21 countries offer NGS panel tests for hereditary breast and ovarian cancer, and &#x2265;19 countries do so for colorectal and prostate cancers. However, NGS panel size and gene composition exhibit substantial variability. WES is available in 12 countries on a routine basis. Most countries implemented genetic testing on stored tumour tissue from deceased patients. In all countries, clinical geneticists can order germline genetic tests, and in 9 countries, any physician can do so. These findings show differences in accessibility to germline genetic testing of hereditary cancer in Europe. We propose EU-wide guidance via pathways, standards of care, and sharing of best practices to further optimize access to hereditary cancer genetic molecular diagnostics.

Humans↗
PubMed2025

Cancer spectrum in Mexican patients with the CHEK2 p.(Leu236Pro) variant: a retrospective study.

This study aimed to characterize, for the first time, the cancer spectrum associated with the most frequent pathogenic CHEK2 variant-NM_007194.4(CHEK2):c.707T&#x2009;>&#x2009;C p.(Leu236Pro)-in Mexican individuals. Although this variant is frequently detected through multi-gene panel testing, limited data on its associated cancer risks complicates genetic counseling and surveillance strategies. We retrospectively analyzed 5,759 patients who underwent multi-gene panel testing between August 2015 and August 2024 due to suspected hereditary cancer syndromes. Among them, 58 CHEK2 p.(Leu236Pro) carriers with confirmed cancer diagnoses were identified. Geographical clustering was observed, with 81% of patients originating from central Mexico, suggesting a possible founder effect. Ten distinct clinical indications for genetic testing were identified, with hereditary breast and ovarian cancer (HBOC) syndrome being the most common (74.1%). The mean age at first diagnosis among carriers was 43.8&#x2009;&#xb1;&#x2009;12 years, and 61.1% of them reported a family history of cancer in first- or second-degree relatives. A second or third primary cancer occurred in 20.7% of cases. Tumors were identified in 12 anatomical sites. Breast cancer predominated (67.6%, including one male case), followed by ovarian (8.1%), prostate (6.7%), gastric (4.1%), thyroid (2.7%), and endometrial (2.7%) cancers. Lymphoma, lung, sacrococcygeal bone, colorectal, and non-melanoma skin cancers each occurred in a single patient. Significant risk association was identified only for breast, ovarian, and gastric cancers. These results highlight the need for personalized surveillance, especially for breast cancer. Incorporating CHEK2 p.(Leu236Pro) into clinical decision-making tools may enhance risk assessment in the Mexican population, but larger studies are needed to refine risk estimates and to clarify the possible founder effect.

Humans↗
PubMed1990

[Epidemiology of cancer of the prostate. Descriptive study].

Although the most frequent tumor of the male genitourinary system is cancer of the prostate, epidemiological studies on this tumor are uncommon in our setting. This study attempts to record the number of patients who were diagnosed as having prostatic cancer at La Paz Hospital (Madrid) during 1981-1987 and to determine the influence of pathological antecedents--personal and familial--in the development of the disease. The present study showed 90 patients had been diagnosed during this period. Most of the patients diagnosed as having this condition were aged 70-79 years. Most of the patients (85.6%) were living in urban areas. Only 2.2% were unmarried and without children. The mean patient age on diagnosis was lower in the group with a higher educational level. A previous history of benign hyperplasia of the prostate was present in 22.22%; tonsillectomy had been performed in 11.11%; only 5.55% had a previous history of rheumatic fever; 26.66% were obese; and 36.66% had a family history of cancer. A previous history of disease did not influence mean patient age at the time of diagnosis.

Aged↗
PubMed1991

[Intraprostatic prostheses].

We evaluated the usefulness of the intraprostatic spiral prosthesis as an alternative to surgical treatment of benign prostatic hyperplasia (BPH) (40 cases), cancer of the prostate (7 cases), and cervico-prostatic sclerosis (2 cases). These 49 prostheses were placed in elderly patients (mean age 79 years) who had a long indwelling urethral catheter (mean 6.2 months) and were at high risk for surgery (ASA IV 83.6%). In 17% of the cases, placement of the prosthesis permitted performing curative surgery subsequently, once patient general condition had improved. Overall, good results were achieved in 63% (53 patients with BPH) of the cases who tolerated the long indwelling prosthesis well (mean 22 months). The results were assessed according to the quality of micturition (normal in 74.3%), correct placement of the stent (80%), no post-micturition residual volume (88.5%), and a flow rate of 6-12 ml/sec. (60%). Poor results (9 cases) owing to migration of the stent (7 cases) and/or complications: perforation of urethra (1 case), secondary stricture (1 case) and partial calcification of the prosthesis (1 case). The advantages and disadvantages of other currently utilized stents (Prostakath, Variospire, Wall-Stent, and Double Pezzer) are discussed.

Aged↗