The homologous recombination deficiency (HRD) score integrates three DNA-based measures of genomic instability, and has been understudied in prostate cancer. Given the recent FDA approval of two PARP ...inhibitors for prostate cancer, HRD score analysis could help to refine treatment selection. We assessed HRD score (defined as the sum of loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions) in three cohorts of primary prostate cancer, including a Johns Hopkins University (JHU) cohort with germline mutations in BRCA2, ATM, or CHEK2 (n = 64), the TCGA cohort (n = 391), and the PROGENE cohort (n = 102). In the JHU cohort, tumors with germline BRCA2 mutations had higher HRD scores (median = 27) than those with germline ATM or CHEK2 mutations (median = 16.5 p = 0.029 and 9 p < 0.001, respectively). For TCGA tumors without underlying HR pathway mutations, the median HRD score was 11, significantly lower than ovarian carcinoma lacking BRCA1/2 mutations (median = 28). In the absence of HR gene mutations, the median HRD score was unexpectedly higher among prostate cancers with TP53 mutations versus those without (17 vs. 11; p = 0.015); this finding was confirmed in the PROGENE cohort (24 vs. 16; p = 0.001). Finally, among eight BRCA2-altered patients who received olaparib, progression-free survival trended longer in those with HRD scores above versus below the median (14.9 vs. 9.9 months). We conclude that HRD scores are low in primary prostate cancer and higher in cases with germline BRCA2 or somatic TP53 mutations. Germline BRCA2-altered cases have significantly higher HRD scores than germline ATM-altered or CHEK2-altered cases, consistent with the lower efficacy of PARP inhibitors among the latter.
Urothelial carcinoma of the bladder (UC) has a poor prognosis, partly because of chemotherapy resistance. Molecular classifications have shown their interest and can help to offer personalized ...treatment. In this study, we evaluated the feasibility of an immunohistochemical study to divide advanced UC into clinico-pathological-molecular subgroups and evaluate phenotypic correspondence between primary UC and matched lymph node metastases (LMN). An eight-antibody immunohistochemical panel was performed on UC and matched LMN from patients treated with radical cystectomy. One hundred eighty-seven UCs (100 pN0 tumor and 87 pN+ tumor) were tested. Multiple correspondence analysis showed that UC expressing GATA3 also expressed FOXA1 (
p
= 0.010) and did not stain for CK5/6 (
p
= 0.031) nor CK14 (
p
= 0.003). UC expressing CK14 coexpressed CK5/6 (
p
< 0.0001), had high Ki67 (
p
= 0.010) and no GATA3 (
p
= 0.003) nor FOXA1 (
p
= 0.011) expression. Loss of expression of STAG2 was associated with high Ki67 (
p
= 0.001). Sixty-seven percent of CK5/6 CK14+ GATA3 FOAXA1− patients had high Ki67 expression vs 37% of GATA3 FOXA1+ CK5/6 CK14− patients (
p
= 0.024). The majority of CK5/6 CK14+ GATA3 FOAXA1− patients (92%) had advanced disease (pT3-pT4) whilst 86% of pT1-T2 cases were GATA3 FOXA1+ CK5/6 CK14− (
p
= 0.041). Differential antigen expression between 63 pN+ primary tumors and their corresponding LNM showed the following concordance percentages: p53 (76%), p63 (75%), CK5/6 (65%), CK14 (89%), GATA3 (75%), FOXA1 (68%), STAG2 (65%), and Ki-67 (71%). These results support the interest of immunohistochemistry for subtype profiling in metastatic UC, using CK5/6, CK14, GATA3, and FOXA1, highlighting also few phenotypical modifications when tumor spreads to lymph nodes.
Abstract Context There is an ongoing debate about the factors that influence intravesical recurrence (IVR) after radical nephrouretectomy (RNU) to treat upper tract urothelial carcinoma (UTUC). ...Objective To assess significant predictors of IVR after RNU from a systematic review of the literature and meta-analysis. Evidence acquisition A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all reports that included detailed results of multivariate analyses on the predictors of IVR. According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, we selected 18 retrospective studies that each included more than 100 patients treated exclusively with RNU between 2007 and 2014. Cumulative analyses of available hazard ratios (HRs) and their corresponding 95% confidence intervals were conducted using R software to assess the potential predictors of IVR. Evidence synthesis Among the 8275 patients included, 2402 (29%) were diagnosed with IVR within a median time of 22.2 mo (range 6.7–56.5). Patient-specific predictors were as follows: male gender (HR 1.37; p < 0.001), previous bladder cancer (HR 1.96; p < 0.001), and preoperative chronic kidney disease (HR 1.87; p = 0.002). Tumor-specific predictors were as follows: positive preoperative urinary cytology (HR 1.56; p < 0.001), ureteral location (HR 1.27; p < 0.001), multifocality (HR 1.61; p = 0.002), invasive pT stage (HR 1.38; p < 0.001), and necrosis (HR 2.17; p = 0.02). Treatment-specific predictors were as follows: a laparoscopic approach (HR 1.62; p = 0.003), extravesical bladder cuff removal (HR 1.22; p = 0.02), and positive surgical margins (HR 1.90; p = 0.004). Conclusions A meta-analysis of available data identified significant predictors of IVR that should be systematically assessed to propose a risk-adapted approach to adjuvant intravesical instillation of chemotherapy and cystoscopic surveillance after RNU. Patient summary In this report, we looked at the factors linked to intravesical recurrence after radical nephroureterectomy to treat upper urinary tract urothelial carcinoma. We identified patient-, tumor- and treatment-specific characteristics that should be systematically assessed to guide postoperative decision-making.
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.
Abstract Background Volatiles organic compounds (VOCs) in urine have been proposed as cancer biomarkers. Objective To evaluate the efficacy of prostate cancer (PCa) detection by trained dogs on human ...urine samples. Design, setting, and participants A Belgian Malinois shepherd was trained by the clicker training method (operant conditioning) to scent and recognize urine of people having PCa. All urine samples were frozen for preservation and heated to the same temperature for all tests. After a learning phase and a training period of 24 mo, the dog’s ability to discriminate PCa and control urine was tested in a double-blind procedure. Urine was obtained from 66 patients referred to a urologist for elevated prostate-specific antigen or abnormal digital rectal examination. All patients underwent prostate biopsy and two groups were considered: 33 patients with cancer and 33 controls presenting negative biopsies. Measurements During each “run,” the dog was asked to signal a cancer urine among six samples containing only one cancer urine and five randomly selected controls. Sensitivity and specificity of the test were assessed. Results and limitations The dog completed all the runs and correctly designated the cancer samples in 30 of 33 cases. Of the three cases wrongly classified as cancer, one patient was rebiopsied and a PCa was diagnosed. The sensitivity and specificity were both 91%. Conclusions This study shows that dogs can be trained to detect PCa by smelling urine with a significant success rate. It suggests that PCa gives an odor signature to urine. Identification of the VOCs involved could lead to a potentially useful screening tool for PCa.
Abstract
We aimed to evaluate the impact of prostate-specific membrane antigen ligand labelled with gallium-68 (PSMA-11) PET/CT in restaging patients with castration-resistant nonmetastatic prostate ...cancer (PCa). Thirty patients were included. At least one malignant focus was found in 27/30 patients (90%). The PSMA-11 PET/CT positivity rate in patients whose prostate-specific antigen serum level (PSA) was greater than 2 ng/ml was 100% (20/20), significantly superior to that of patients whose PSA was less than 2 ng/ml (7/10 = 70%). Six patients (20%) were categorized as oligometastatic (≤3 metastatic foci). Based on the 17 patients for whom a standard of truth was feasible, the overall sensitivity and specificity of PSMA-11 PET/CT in detecting residual disease in castration-resistant PCa patients were 87% and 100% respectively. PSMA-11 PET/CT impacted patients’ disease management in 70% of cases, 60% of case when PSA was less than 2 ng/ml. This management was considered as adequate in 91% of patients. PSMA-11 PET/CT appeared to be effective in restaging patients with castration-resistant nonmetastatic PCa. PSMA-11 PET/CT should be considered as a replacement for bone scans under these conditions.
Purpose
To assess the performance of the Xpert Bladder Cancer (BC) Monitor during the follow-up of patients with non-muscle invasive bladder cancer (NMIBC).
Methods
Patients with previously diagnosed ...NMIBC and followed up in clinical practice settings in two French urology departments between September 2017 and July 2019 were consecutively enrolled in this prospective observational study. Patients with a positive cystoscopy or computed tomography urogram underwent subsequent transurethral resection of the bladder, and/or biopsy, and the specimens were pathologically assessed. Cytology and Xpert BC Monitor tests were performed on urine samples. Xpert BC Monitor performance was assessed versus cystoscopy for disease-negative patients or versus histology for disease-positive patients, and was compared to that of cytology.
Results
Overall, 500 patients with a median age of 70.0 years were included. NMIBC recurrence was diagnosed in 44 cases (8.8%). Overall sensitivity, specificity, and negative predictive values (NPVs) were 72.7% (32/44), 73.7% (330/448) and 96.5% (330/342) for the Xpert BC Monitor, and 7.7% (2/26), 97.8% (310/317) and 92.8% (310/334) for cytology, respectively. The Xpert BC Monitor detected 92.3% (12/13) of the high-grade tumours and ruled out their presence in 99.7% (330/331) of cases. Analysis of the areas under the receiver operating characteristic curves demonstrated the superior performance of the Xpert BC Monitor over that of cytology.
Conclusion
Xpert BC Monitor performance was superior to that of cytology in the follow-up of NMIBC. The exclusion of aggressive tumours with a very high NPV (99.7%) supports the use of this urinary test in daily practice.
Abstract Objective Urothelial cell carcinoma of the upper urinary tract (UUT-UCC) is a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. This ...review highlights the main chemotherapy regimens available for UUT-UCCs based on the recent literature. Materials and methods Data on urothelial malignancies and UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; urothelial carcinomas; upper urinary tract; carcinoma; transitional cell; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors; and survival. Results No evidence level 1 information from prospective randomized trials was available. Because of its many similarities with bladder urothelial carcinomas, chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. Most teams have proposed a neoadjuvant or an adjuvant treatment based either on the combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) or on gemcitabine/cisplatin (GC). These regimens have been shown to prolong survival moderately. All recent studies have included limited numbers of patients and have reported poor patient outcomes after both neoadjuvant and adjuvant chemotherapy. Regarding metastatic UUT-UCCs, vinflunine has demonstrated moderate activity in these patients with a manageable toxicity. Interestingly, specific molecular markers microsatellite instability (MSI), E-cadherin, HIF-1α, and RNA levels of the telomerase gene can provide useful information that can help diagnose and determine patient prognosis in patients with UUT-UCC. Conclusion Chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. However, there is no strong evidence that chemotherapy is effective due to the rarity of the disease and the lack of data in the current literature. Thus, physicians must take into account the specific clinical characteristics of each individual patient with regard to renal function, medical comorbidities, tumor location, grade, and stage, and molecular marker status when determining the optimal treatment regimen for their patients. The ongoing identification of the oncologic mechanisms of this type of cancer might pave the way for the development of specific treatments that are targeted to the characteristics of each patient's tumor in the future.
Abstract Context The data describing the urologic extracolonic cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC) are variable. Objective Provide an update about the current ...urologic tumor spectrum in HNPCC. Evidence acquisition Data on HNPCC extracolonic tumor spectrum published in the literature were analysed using MEDLINE with emphasis on urological malignancies, upper tract tumors, clinical criteria, genetic diagnosis and counselling. Evidence synthesis HNPCC is a form of colorectal cancer with a dominant autosomal mode of inheritance. HNPCC is caused by germ-line mutations affecting one or several mismatch repair genes. Cancers other than colorectal cancer are sometimes associated with HNPCC. These include specific urological malignancies, most notably tumors of the upper urinary tract, which have been reported to occur at a rate ×22 higher than the general population. Upper urinary tract tumors rank third (5%) after colon (63%) and endometrial (9%) cancer within the group of HNPCC related tumors. Prostate cancer and testicular germ cell tumors are rarely associated. Due to lack of appreciation of such hereditary associations, some inherited cancers are still misclassified as sporadic and their incidence is underestimated. The biological tests requested in suspected cases of HNPCC are: microsatellite instability (MSI) analysis, immunohistochemistry and DNA sequencing. When gene mutations are detected, the patient and their family will benefit from a multidisciplinary management approach. The presence of other HNPCC-associated cancers is sought and close monitoring of patients is undertaken. Genetic counselling is provided to the patient’s family. Conclusions The recognized urologic tumor spectrum in HNPCC includes upper tract tumors. However, in order not to overlook a hereditary cancer, urologists should be aware of the possible urological malignancies associated with HNPCC (i.e., prostate and testicular carcinomas) and evaluate appropriately anyone they feel are at high risk of underlying HNPCC based on set clinical criteria.
Objective
To assess the influence of patient characteristics, anatomical conditions, and technical factors on radiation exposure during prostatic arteries embolization (PAE) performed for benign ...prostatic hyperplasia.
Materials and methods
Patient characteristics (age, body mass index (BMI)), anatomical conditions (number of prostatic arteries, anastomosis), and technical factors (use of cone beam computed tomography (CBCT), large display monitor (LDM), and magnification) were recorded as well as total air kerma (AK), dose area product (DAP), fluoroscopy time (FT), and number of acquisitions (NAcq). Associations between potential dose-influencing factors and AK using univariate analysis and a multiple linear regression model were assessed.
Results
Forty-one consecutive men (68 ± 8 years, min–max: 40–76) were included. LDM and CBCT decreased the use of small field of view with 13.9 and 3.8% respectively, both
p
< 0.001. The use of a LDM significantly reduced AK (1006.6 ± 471.7 vs. 1412 ± 754.6 mGy,
p
= 0.02), DAP (119.4 ± 64.4 vs. 167.9 ± 99.2,
p
= 0.04), FT (40.4 ± 11.5 vs. 53.6 ± 25.5 min,
p
= 0.01), and NAcq (16.3 ± 6.3 vs. 18.2 ± 7,
p
= 0.04). In multivariate analysis, AK reduction was associated with lower patient BMI (
β
= 0.359,
p
= 0.002), shorter FT (
β
= 0.664,
p
< 0.001) and CBCT use (
β
= − 0.223,
p
= 0.03), and decreased NAcq (
β
= 0.229,
p
= 0.04).
Conclusion
LDM and CBCT are important technical dose-related factors to help reduce radiation exposure during PAE, and should be considered in standard practice.
Key Points
• The use of large display monitor (LDM) and cone beam computed tomography (CBCT) both decreased the need for magnification during prostatic arteries embolization (PAE).
• The use of LDM reduces radiation exposure during PAE.
• Total air kerma is associated with patient’s body mass index, fluoroscopy time, CBCT, and the number of acquisitions.
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