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Purpose: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or ≥5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients.
Methods And Materials: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men.
Results: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10-year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05).
Conclusions: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents.
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http://dx.doi.org/10.1016/j.ijrobp.2015.10.056 | DOI Listing |
J Natl Compr Canc Netw
September 2025
1Harvard Medical School, Boston, MA.
Background: Previous studies have operationalized the NCCN list of high-risk medications in older adults into a measurable tool known as the Geriatric Oncology Potentially Inappropriate Medications (GO-PIMs) scale. The current study aims to evaluate the ability of GO-PIMs to identify high-risk medications and their impact on patients with both solid and liquid tumors managed in a large national health care system.
Methods: We performed a retrospective cohort study using data from the national Veterans Affairs (VA) Cancer Registry and electronic health records, including all veterans newly diagnosed with a solid or liquid malignancy from 2000 to 2022.
BJUI Compass
September 2025
Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine Kyoto University Kyoto Kyoto Japan.
Objectives: To develop a novel risk score (RS) model to predict the probability of progression to castration-resistant prostate cancer (PCa) (CRPC) after intensity-modulated radiation therapy (IMRT) for patients with high- and very high-risk PCa according to the National Comprehensive Cancer Network (NCCN) risk classification, since accurate prediction of the clinical outcome of definitive radiation therapy for patients with high- and very high-risk PCa remains challenging due to its heterogeneity.
Materials And Methods: We conducted a retrospective review of 600 patients with high- and very high-risk PCa treated with IMRT at our institution. They were randomly divided into discovery (n = 300) and validation (n = 300) cohorts.
Breast Cancer Res
September 2025
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Background: Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS) in women undergoing clinical sequencing for hereditary breast cancer.
Findings: We integrated PRS into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women.
Front Immunol
August 2025
Department of Hematology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, National Health Commission Key Laboratory of Nuclear Technology Medical Transformation, Mianyang, Sichuan, China.
Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and carries a poor prognosis when it involves the central nervous system (CNS), a condition known as secondary CNS lymphoma (SCNSL). Although the CNS International Prognostic Index (CNS-IPI) is used to estimate SCNSL risk, its limited sensitivity highlights the need for more reliable biomarkers to improve risk stratification and enable earlier intervention.
Methods: We evaluated pretreatment levels of interleukin-10 (IL-10) and interleukin-6 (IL-6) in both peripheral blood (PB) and cerebrospinal fluid (CSF), and compared clinical characteristics between DLBCL patients with and without SCNSL.
Biomedicines
August 2025
Department of Medicine, Faculty of Medicine, Health and Sports, European University of Madrid, 28108 Madrid, Spain.
This study evaluates the combined prognostic value of the apparent diffusion coefficient (ADC) from multiparametric MRI (mpMRI) and prostate-specific antigen (PSA) levels at 6 months post-radiotherapy (RT) in assessing treatment response in prostate cancer patients treated with RT and androgen deprivation therapy (ADT). All prostate cancer patients classified as unfavorable intermediate-risk, high-risk, or very high-risk, according to NCCN criteria, who received ADT and RT between 2008 and 2019 and underwent mpMRI and PSA testing 6 months after RT were included. Patients were stratified into three profiles based on threshold PSA (≤ vs.
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