Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.

BACKGROUND: Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant. METHODS: Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record. RESULTS: Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5. CONCLUSIONS: In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.

The impact of genomic biomarkers on a clinical risk prediction model for upgrading/upstaging among men with favorable-risk prostate cancer.

BACKGROUND: The challenge of distinguishing indolent from aggressive prostate cancer (PCa) complicates decision-making for men considering active surveillance (AS). Genomic classifiers (GCs) may improve risk stratification by predicting end points such as upgrading or upstaging (UG/US). The aim of this study was to assess the impact of GCs on UG/US risk prediction in a clinicopathologic model. METHODS: Participants had favorable-risk PCa (cT1-2, prostate-specific antigen [PSA] ≤15 ng/mL, and Gleason grade group 1 [GG1]/low-volume GG2). A prediction model was developed for 864 men at the University of California, San Francisco, with standard clinical variables (cohort 1), and the model was validated for 2267 participants from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (cohort 2). Logistic regression was used to compute the area under the receiver operating characteristic curve (AUC) to develop a prediction model for UG/US at prostatectomy. A GC (Oncotype Dx Genomic Prostate Score [GPS] or Prolaris) was then assessed to improve risk prediction. RESULTS: The prediction model included biopsy GG1 versus GG2 (odds ratio [OR], 5.83; 95% confidence interval [CI], 3.73-9.10); PSA (OR, 1.10; 95% CI, 1.01-1.20; per 1 ng/mL), percent positive cores (OR, 1.01; 95% CI, 1.01-1.02; per 1%), prostate volume (OR, 0.98; 95% CI, 0.97-0.99; per mL), and age (OR, 1.05; 95% CI, 1.02-1.07; per year), with AUC 0.70 (cohort 1) and AUC 0.69 (cohort 2). GPS was associated with UG/US (OR, 1.03; 95% CI, 1.01-1.06; p < .01) and AUC 0.72, which indicates a comparable performance to the prediction model. CONCLUSIONS: GCs did not substantially improve a clinical prediction model for UG/US, a short-term and imperfect surrogate for clinically relevant disease outcomes.

Pharmacokinetic Comparison of Selective Prostatic Arterial and Intravenous PSMA PET/CT Radioligand Infusions in Primary Prostatic Adenocarcinoma.

Background Intravenous prostate-specific membrane antigen (PSMA)-targeted radioligand therapy improves survival in men with metastatic castration-resistant prostate cancer. Yet, the impact of selective prostatic arterial administration on primary tumor uptake is unclear. Purpose To compare gallium 68 (68Ga)-PSMA-11 uptake using dynamic PET/CT in prostatic tumoral volumes of interest (VOIs) during intravenous and selective prostatic arterial infusions for individuals with untreated, high-risk prostate cancer. Materials and Methods In this prospective, intraindividual comparative study conducted at an academic medical center, five men aged 58, 61, 64, 66, and 68 years with treatment-naive prostate cancer were enrolled between January 2022 and February 2023 and underwent two dynamic 68Ga-PSMA-11 PET/CT examinations 1 week apart. During the first examination, the radiotracer was administered intravenously. During the second administration, the radiotracer was delivered into either the right or left prostatic artery through an angiographically placed microcatheter. The primary outcome was maximum standardized uptake value (SUVmax) in prostatic tumoral VOIs. The secondary outcomes included mean SUV (SUVmean) in prostatic tumoral VOIs and area under the SUVmean curves (AUC). Longitudinal mixed-effects models were used to compare dynamic SUVmax and SUVmean time-activity curves (TACs), and paired t tests were used for the remaining data. Results The mean SUVmax within tumoral VOIs was 14 (range, 3-43) for venous sessions and 938 (range, 460-1436) for arterial sessions (P = .008). The SUVmean within VOIs was greater during arterial sessions (P < .001) overall and 46-fold and 19-fold greater at peak uptake and final time points, respectively. The mean AUC was greater on arterial TACs than on venous TACs at 14600 SUV × min (range, 8353-20025 SUV × min) and 240 SUV × min (range, 69-622 SUV × min), respectively (P = .002). Conclusion Selective prostatic arterial infusion resulted in greater 68Ga-PSMA-11 tumoral SUV than intravenous infusion. Further study of local-regional, intra-arterial delivery of a PSMA-targeted theranostic agent is warranted in high-risk prostate cancer. ClinicalTrials.gov identifier: NCT04976257 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Civelek in this issue.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Long-Term Outcomes in Patients Using Protocol-Directed Active Surveillance for Prostate Cancer.

Importance: Outcomes from protocol-directed active surveillance for favorable-risk prostate cancers are needed to support decision-making. Objective: To characterize the long-term oncological outcomes of patients receiving active surveillance in a multicenter, protocol-directed cohort. Design, Setting, and Participants: The Canary Prostate Active Surveillance Study (PASS) is a prospective cohort study initiated in 2008. A cohort of 2155 men with favorable-risk prostate cancer and no prior treatment were enrolled at 10 North American centers through August 2022. Exposure: Active surveillance for prostate cancer. Main Outcomes and Measures: Cumulative incidence of biopsy grade reclassification, treatment, metastasis, prostate cancer mortality, overall mortality, and recurrence after treatment in patients treated after the first or subsequent surveillance biopsies. Results: Among 2155 patients with localized prostate cancer, the median follow-up was 7.2 years, median age was 63 years, 83% were White, 7% were Black, 90% were diagnosed with grade group 1 cancer, and median prostate-specific antigen (PSA) was 5.2 ng/mL. Ten years after diagnosis, the incidence of biopsy grade reclassification and treatment were 43% (95% CI, 40%-45%) and 49% (95% CI, 47%-52%), respectively. There were 425 and 396 patients treated after confirmatory or subsequent surveillance biopsies (median of 1.5 and 4.6 years after diagnosis, respectively) and the 5-year rates of recurrence were 11% (95% CI, 7%-15%) and 8% (95% CI, 5%-11%), respectively. Progression to metastatic cancer occurred in 21 participants and there were 3 prostate cancer-related deaths. The estimated rates of metastasis or prostate cancer-specific mortality at 10 years after diagnosis were 1.4% (95% CI, 0.7%-2%) and 0.1% (95% CI, 0%-0.4%), respectively; overall mortality in the same time period was 5.1% (95% CI, 3.8%-6.4%). Conclusions and Relevance: In this study, 10 years after diagnosis, 49% of men remained free of progression or treatment, less than 2% developed metastatic disease, and less than 1% died of their disease. Later progression and treatment during surveillance were not associated with worse outcomes. These results demonstrate active surveillance as an effective management strategy for patients diagnosed with favorable-risk prostate cancer.

Prostate-Specific Antigen Values in Transgender Women Receiving Estrogen.

This study examines prostate-specific antigen values among transgender women in the Veterans Health Administration receiving estrogen.

Evaluation of URO17® to improve non-invasive detection of bladder cancer.

BACKGROUND: The gold standard for detecting bladder cancer is cystoscopy with biopsy or transurethral resection confirming histologic diagnosis. URO17® employs a chromogenically labeled monoclonal antibody to keratin 17 (k17), an intermediate filament cytoskeleton molecule associated with bladder, pancreatic, and cervical cancers. Preliminary studies evaluating k17 demonstrated a high sensitivity and specificity for the detection of bladder cancer, supporting the need for further study. OBJECTIVE: To evaluate the sensitivity and specificity of URO17. METHODS: This is a cross-sectional study of participants undergoing urologic procedures between July 6, 2018 and July 17, 2019 at a single institution. Patients undergoing cystectomy, endoscopic bladder and/or upper tract procedure for probable urothelial carcinoma comprised cases; patients undergoing urologic procedures for other reasons comprised the control group (i.e. prostatectomy, nephrectomy, etc.). Voided urine samples were at the time of procedure; a minority of participants underwent multiple resections in the study period, thus, as many as three urine samples were taken from any given participant. Samples were distributed for blinded testing with URO17. Sensitivity and specificity were calculated. RESULTS: In 152 participants and 167 samples, URO17 demonstrated an overall sensitivity of 90% and 92% and a specificity of 88% and 87%, respectively. In 76 participants and 91 samples from patients with suspected urothelial carcinoma, the sensitivity was 90% and 92%, and the specificity was 50% and 54%, respectively. No controls demonstrated a positive URO17 result, and URO17 superseded urine cytology detection of low-grade and high-grade Ta. False positive results were associated with inflamed tissue or urothelial atypia on histology; the large majority had a history of intravesical therapy. CONCLUSION: Limitations include cross-sectional design and convenience sampling. URO17 may improve sensitivity of urine cytology in the detection of urothelial cancer, though further study is required to refine the application of this biomarker in clinical practice.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

High expression of Trop2 is associated with aggressive localized prostate cancer and is a candidate urinary biomarker.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Development and evaluation of an interprofessionalstudent-led influenza vaccination clinic for medical, nursingand pharmacy students

Background: Students in their final years of medicine, nursing and pharmacy degrees were invited to participate in an interprofessional influenza vaccination training course and clinic. Twenty-four students (8 from each discipline) were selected to participate. After vaccination training these students administered free influenza vaccines under supervision in two student-led clinics to 546 students in health and allied health programs prior to their clinical placements. Objective: To evaluate the students’ experience of the interprofessional vaccination training and clinic, and to evaluate the experiences of students who received their vaccination in the student-led clinic. Methods: Before and after participating, students completed a questionnaire evaluating their perceived knowledge of influenza vaccinations, and their skills and confidence in administering vaccinations and the Readiness for Interprofessional Learning Scale (RIPLS). Eighteen students completed both the pre- and post-questionnaires. All students who received their flu vaccination were also asked to complete a short patient evaluation survey. Results: The course resulted in significant increases in the students’ perceived knowledge of influenza vaccinations (27.5% increase, p<0.001), skills in managing patients receiving influenza vaccines (23.9% increase, p<0.001) and confidence level to administer influenza vaccines (46.0% increase, p<0.001). While there was no significant change in any subscales of the RIPLS, open-ended responses indicated that the students enjoyed and could see the benefits of meeting and learning with and from students from other health disciplines. Of the students who received their influenza vaccination, 97.7% were very likely or somewhat likely to recommend the clinic to fellow students (AU)

Detection of clinically significant prostate cancer with PI-RADS v2 scores, PSA density, and ADC values in regions with and without mpMRI visible lesions

ABSTRACT Purpose To determine if PSAD, PSADtz, and ADC values improve the accuracy of PI-RADS v2 and identify men whose concurrent systematic biopsy detects clinically significant cancer on areas without mpMRI visible lesions. Materials and methods Single reference-center, cross-sectional, retrospective study of consecutive men with suspected or known low to intermediate-risk prostate cancer who underwent 3T mpMRI and TRUS-MRI fusion biopsy from 07/15/2014 to 02/17/2018. Cluster-corrected logistic regression analyses were utilized to predict clinically significant prostate cancer (Gleason score ≥3+4) at targeted mpMRI lesions and on systematic biopsy. Results 538 men (median age=66 years, median PSA=7.0ng/mL) with 780mpMRI lesions were included. Clinically significant disease was diagnosed in 371 men. PI-RADS v2 scores of 3, 4, and 5 were clinically significant cancer in 8.0% (16/201), 22.8% (90/395), and 59.2% (109/184). ADC values, PSAD, and PI-RADS v2 scores were independent predictors of clinically significant cancer in targeted lesions (OR 2.25-8.78; P values <0.05; AUROC 0.84, 95% CI 0.81-0.87). Increases in PSAD were also associated with upgrade on systematic biopsy (OR 2.39-2.48; P values <0.05; AUROC 0.69, 95% CI 0.64-0.73). Conclusions ADC values and PSAD improve characterization of PI-RADS v2 score 4 or 5 lesions. Upgraded on systematic biopsy is slightly more likely with PSAD ≥0.15 and multiple small PI-RADS v2 score 3 or 4 lesions.

Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer / Impacto da incorporação da espectroscopia por ressonância magnética ao PI-RADS 2 para a predição de câncer de próstata de alto grau e de estágio avançado

Abstract Objective: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging (1H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including 1H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and 1H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2x2 tables for diagnostic accuracies. Results: The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with 1H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with 1H-MRSI (p > 0.05). Conclusion: 1H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE.

Resumo Objetivo: Comparar as predições de tumor com padrão 4 de Gleason dominante ou de tumor com extensão extraprostática utilizando o sistema Prostate Imaging Reporting and Data System (PI-RADS v2), combinado ou não a espectroscopia por ressonância magnética (1H-ERM). Materiais e Métodos: Trinta e nove pacientes submeteram-se a RM de 3 tesla com bobina endorretal, incluindo 1H-ERM, e prostatectomia. Dois radiologistas classificaram as principais lesões identificadas em cada caso utilizando PI-RADS v2 e escores de 1H-ERM. As análises estatísticas incluíram regressões logísticas, curvas receiver operating characteristic (ROC) e tabelas 2x2 para acurácia diagnóstica. Resultados: A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de câncer de próstata de alto grau foram 85,7% (57,1%) e 92,9% (100%), e 56% (68%) e 24% (24%). A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de extensão extraprostática (EEP) foram 64,0% (40%) e 20% (48%), e 50% (57,1%) e 71,4% (64,3%). As áreas das curvas ROC para a predição de câncer de alto grau foram 0,65 e 0,61 para PI-RADS v2 e 0,72 e 0,70 quando combinado com 1H-ERM (radiologistas 1 e 2, p = 0.04 e 0.21). Para a predição de EEP, as áreas das curvas ROC foram 0,54 e 0,60 para PI-RADS v2 e 0,55 e 0,61 quando combinado com 1H-ERM (p > 0.05). Conclusão: É possível que a 1H-ERM melhore a predição de câncer de alto grau quando combinada ao PI-RADS v2, em particular para lesões que recebem um escore PI-RADS v2 4; entretanto, ela não afeta a predição de EEP.

Urovysion™ testing can lead to early identification of intravesical therapy failure in patients with high risk non-muscle invasive bladder cancer

Purpose: In this study, we investigated the ability of UroVysion™ to assess response to intravesical therapy in patients with high risk superficial bladder tumors. Materials and methods: We performed a retrospective review of patients undergoing intravesical therapy for high risk superficial bladder tumors. Urine specimens were collected for UroVysion™ analysis before and immediately after a course of intravesical therapy. Cytology and cystoscopy were performed six weeks after treatment, using either a positive cytology or visible abnormality on cystoscopy as a prompt for biopsy. The operating characteristics of the UroVysion™ test were then determined. Results: 41 patients were identified in whom 47 cycles of induction and 41 cycles of maintenance intravesical therapy were given during the study period. This yielded a total of 88 treatment and evaluation cycles. Median follow-up was 9 months per induction (range 1-21 months) and 13 months per patient (range 1-25 months). A total of 133 urine samples were collected for UroVysion™ of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysion™ testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85 percent, 61 percent, and 71 percent. Conclusions: The use of UroVysion™ following intravesical therapy for high-risk superficial bladder tumors helps to identify patients at high risk of refractory or recurrent disease who should undergo immediate biopsy under anesthesia.