Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019.

PURPOSE: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

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.

Detection of clinically signifi cant prostate cancer with PIRADS v2 scores, PSA density, and ADC values in regions with and without mpMRI visible lesions.

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.

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.

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.

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.

Endorectal MRI of prostate cancer: incremental prognostic importance of gross locally advanced disease.

OBJECTIVE: The purpose of this study was to determine the frequency and incremental prognostic importance of gross locally advanced disease seen at endorectal MRI in patients with prostate cancer. MATERIALS AND METHODS: We retrospectively identified the cases of all patients with biopsy-proven prostate cancer who underwent pretreatment endorectal MRI over a 6-year period (n = 1777). Three experienced radiologists identified by consensus patients with gross locally advanced disease, defined as unequivocal extracapsular extension or unequivocal seminal vesicle invasion. Outcome among these patients was compared with that in a control group without gross locally advanced disease matched by D'Amico risk stratification. RESULTS: Sixty-six of 1777 (3.7%) patients had gross locally advanced disease. One of 1085 (0.1%) patients had low-risk disease, 25 of 489 (5.1%) had intermediate-risk disease, and 40 of 203 (19.7%) had high-risk disease. Follow-up data were available for 44 of these 66 patients. During a median follow-up period of 79 months, biochemical failure and metastasis had developed in 17 and 6 of these 44 patients compared with 9 and none of the 65 patients in the control group (p < 0.001). CONCLUSION: Almost 4% of patients with prostate cancer, particularly those with intermediate- and high-risk disease, have gross locally advanced disease at endorectal MRI and have a significantly worse prognosis than matched controls. These patients may be candidates for more aggressive treatment.

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 UroVysionTM of which 40 were positive. Based upon standard clinical evaluation, 41 biopsies were performed which detected 20 recurrences. UroVysionTM testing performed immediately upon completion of therapy for the 41 patients undergoing biopsy yielded a sensitivity, specificity, and accuracy of 85%, 61%, and 71%. CONCLUSIONS: The use of UroVysionTM 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.

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.