Faculty Bibliography

PURPOSE:We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center. MATERIALS AND METHODS:A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. RESULTS:Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9). CONCLUSIONS:Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.

CONTEXT:A noninvasive multiparametric magnetic resonance imaging (MRI)-based scoring system for predicting muscle-invasive bladder cancer (MIBC), the "Vesical Imaging Reporting and Data System" (VI-RADS), was recently developed by an international multidisciplinary panel. Since then, a few studies evaluating the value of VI-RADS for predicting MIBC have been published. OBJECTIVE:To review the diagnostic performance of VI-RADS for the prediction of MIBC. EVIDENCE ACQUISITION:PubMed and EMBASE databases were searched up to November 10, 2019. We included diagnostic accuracy studies using VI-RADS to predict MIBC using cystectomy or transurethral resection as the reference standard. Methodological quality was evaluated with Quality Assessment of Diagnostic Accuracy Studies-2. Sensitivity and specificity were pooled and plotted using hierarchical summary receiver operating characteristics (HSROC) modeling. Meta-regression analyses were done to explore heterogeneity. EVIDENCE SYNTHESIS: = 87.93%, and 90.99% for sensitivity and specificity). Meta-regression analyses showed that the number of patients (>205 vs ≤205), magnetic field strength (3 vs 1.5 T), T2-weighted image slice thickness (3 vs 4 mm), and VI-RADS cutoff score (≥3 vs ≥4) were significant factors affecting heterogeneity (p ≤  0.03). CONCLUSIONS:VI-RADS shows good sensitivity and specificity for determining MIBC. Technical factors associated with MRI acquisition and cutoff scores need to be taken into consideration as they may affect performance. PATIENT SUMMARY:A recently established noninvasive magnetic resonance imaging-based scoring system shows good diagnostic performance in detecting muscle-invasive bladder cancer.

Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. The advancement of UTUC research is hampered by the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell line models that reflect the genomic and biological heterogeneity of the human disease. Models demonstrate high genomic concordance with the corresponding patient tumors, with invasive tumors more likely to successfully engraft. Treatment of PDX models with chemotherapy recapitulates responses observed in patients. Analysis of a HER2 S310F-mutant PDX suggests that an antibody drug conjugate targeting HER2 would have superior efficacy versus selective HER2 kinase inhibitors. In sum, the biological and phenotypic concordance between patient and PDXs suggest that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.

PURPOSE/OBJECTIVE:F-FDG PET/CT for detecting nodal metastases in patients with muscle-invasive urothelial bladder cancer prior to radical cystectomy. MATERIALS AND METHODS/METHODS:F-FDG PET/CT was assessed according to sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS:F-FDG PET/CT was useful in ruling out lymph node metastases (sensitivity 92-100%). This study was limited by its mixed population and focus on pelvic nodal metastases only. CONCLUSIONS:F-FDG PET/CT has limited utility in clinically node-negative patients.

OBJECTIVE:To examine a set of proposed eligibility factors for hemi-ablative focal therapy in prostate cancer and to determine the likelihood of residual extensive disease. METHODS:We retrospectively analyzed data from 98 patients with unilateral prostate cancer on biopsy with detailed tumor maps from whole-mount slides and preoperative magnetic resonance imaging data. These patients met the focal therapy consensus meeting inclusion criteria (prostate-specific antigen <15 ng/mL, clinical stage T1c-T2a and Gleason score 3 + 3 or 3 + 4 on needle biopsy), and underwent radical prostatectomy between 2000 and 2014. Extensive disease was defined as having Gleason pattern 4/5 in bilateral lobes, any extraprostatic extension, seminal vesicle invasion or lymph node invasion. Both lobes of the prostate were scored on magnetic resonance imaging. Preoperative characteristics including biopsy and magnetic resonance imaging data were used to predict extensive disease. RESULTS:, 17 patients had pathological tumor stage ≥3 and one patient had lymph node invasion. CONCLUSIONS:An important number of patients meeting the focal therapy consensus meeting inclusion criteria can present extensive disease. Further studies using targeted biopsies might provide more accurate information about the selection of focal therapy candidates.

PURPOSE/OBJECTIVE:Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS:An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS:A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS/CONCLUSIONS:One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.