Faculty Bibliography

INTRODUCTION: Vascular targeted photodynamic therapy (VTP) with WST11 (TOOKAD(R) Soluble; STEBA Biotech, Luxembourg) is a form of tissue ablation that may be used therapeutically for localized prostate cancer (PCa). To study dosing parameters and associated treatment effects we undertook a prospective multicenter phase I/II trial of WST11 VTP for treatment of PCa METHODS: 30 men with unilateral, low volume, Gleason 3+3 PCa were enrolled at 5 centers following local IRB approval. Light energy, fiber number, and WST11 dose were escalated to identify optimal dosing parameters for VTP hemiablation. Men were treated by VTP and evaluated by post-treatment MRI and biopsy. PSA, light dose index (LDI -defined as sum of fiber length/ desired treatment volume), toxicity, and quality of life parameters were recorded. RESULTS: Following dose escalation, 21 men received optimized dosing of 4 mg/kg WST11 200 J energy. On post-treatment biopsy, residual PCa was found in the treated lobe in 10 men, untreated lobe in 4, and both lobes in 1. When LDI>/=1, at optimal dosing, (n=15), 73.3% had a negative biopsy in the treated lobe. Six men undergoing retreatment, with optimal dose and LDI >/=1, had negative post-treatment biopsy. Minimal effects on urinary, sexual function, and overall quality of life, were observed. CONCLUSIONS: Hemiablation of the prostate with WST11 VTP was well-tolerated and resulted in negative biopsy in the treated lobe for the majority of men. Dosing parameters and LDI appear related to tissue response as determined by MRI and biopsy. These parameters may serve as the basis for further prospective studies.

INTRODUCTION: Multiparametric-MRI (mp-MRI) is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of MRI targeted biopsy, thereby enhancing clinical risk assessment, and improving the ability to appropriately counsel patients regarding therapy. MATERIAL AND METHODS: We used MEDLINE/PubMed to conduct a comprehensive search of the English medical literature. Articles were reviewed, data was extracted, analyzed, and summarized. In this review, we discuss the mp-MRI prostate exam, its role in targeted prostate biopsy, along with clinical applications and outcomes of MRI targeted biopsies. RESULTS: Mp-MRI, consisting of T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and possibly MR spectroscopy, has demonstrated improved specificity in prostate cancer detection as compared to conventional T2-weighted images alone. An MRI suspicion score has been developed and is depicted using an institutional Likert or, more recently, a standardized reporting scale (PI-RADS). Techniques of MRI-targeted biopsy include in-gantry MRI guided biopsy, TRUS-guided visual estimation biopsy, and software co-registered MRI-US guided biopsy (MRI-US fusion). Among men with no previous biopsy, MRI-US fusion biopsy demonstrates up to a 20% increase in detection of clinically significant cancers compared to systematic biopsy while avoiding a significant portion of low risk disease. These data suggest a potential role in reducing over-detection and, ultimately, over-treatment. Among men with previous negative biopsy, 72-87% of cancers detected by MRI targeted biopsy are clinically significant. Among men with known low risk cancer, repeat biopsy by MR-targeting improves risk stratification in selecting men appropriate for active surveillance secondarily reducing the need for repetitive biopsy during surveillance. CONCLUSIONS: Use of mp-MRI for targeting prostate biopsies has the potential to reduce the sampling error associated with conventional biopsy by providing better disease localization and sampling. MRI-ultrasound fusion-targeted prostate biopsy may improve the identification of clinically significant prostate cancer while limiting detection of indolent disease, ultimately facilitating more accurate risk stratification. Literature supports the clinical applications of MRI-targeted biopsy in men who have never been biopsied before, those with a prior negative biopsy, and those with low risk disease considering active surveillance.

OBJECTIVE: The purpose of this article is to evaluate the utility of a quality improvement (QI) initiative in achieving long-term adherence to an evolving structured format for reporting the level of suspicion for tumor on prostate MRI examinations. MATERIALS AND METHODS: The original QI initiative occurred over a 4-month period in 2010, before which prostate MRI was reported using free text. The initiative consisted of development of a section-wide macro, an initial group training session, ordering physician input regarding the structured report's value, subsequent weekly sessions for ongoing review, and timely individualized feedback in instances of nonuse. The initial structured report included pick lists for describing the level of suspicion for tumor as negative, low, medium, or high. Pick lists were modified in 2011 to incorporate a 5-point Likert scale and again in 2015 to incorporate Prostate Imaging Data and Reporting System (PI-RADS) version 2. These refinements were implemented after accelerated training periods. The frequency of reports providing an MRI-based suspicion level during these periods was assessed. RESULTS: Fifty-five percent of reports provided an MRI-based level of suspicion for tumor before the initiative. For various cohorts evaluated after the initiative (using structured reports based on the low, medium, or high scheme; a numeric Likert scale; or PI-RADS), this frequency improved to 95-100% (p < 0.001). Among reports without a suspicion level, potential confounding factors included marked artifact from hip prosthesis and overt diffuse tumor. CONCLUSION: The QI initiative achieved excellent adherence in reporting a suspicion level for tumor on prostate MRI examinations. The described components of the initiative were useful for maintaining long-term adherence that persisted after serial modifications to the report lexicon.

RATIONALE AND OBJECTIVES: The aim of this study was to assess prostate cancer detection using a broad range of computed b-values up to 5000 s/mm2. MATERIALS AND METHODS: This retrospective Health Insurance Portability and Accountability Act-compliant study was approved by an institutional review board with consent waiver. Forty-nine patients (63 +/- 8 years) underwent 3T prostate magnetic resonance imaging before prostatectomy. Examinations included diffusion-weighted imaging (DWI) with b-values of 50 and 1000 s/mm2. Seven computed DWI image sets (b-values: 1000, 1500, 2000, 2500, 3000, 4000, and 5000 s/mm2) were generated by mono-exponential fit. Two blinded radiologists (R1 [attending], R2 [fellow]) independently evaluated diffusion weighted image sets for image quality and dominant lesion location. A separate unblinded radiologist placed regions of interest to measure tumor-to-peripheral zone (PZ) contrast. Pathologic findings from prostatectomy served as reference standard. Measures were compared between b-values using the Jonckheere-Terpstra trend test, Spearman correlation coefficient, and generalized estimating equations based on logistic regression for correlated data. RESULTS: As b-value increased, tumor-to-PZ contrast and benign prostate suppression for both readers increased (r = +0.65 to +0.71, P 6 tumor was highest for R1 at b1500-3000 (90%-93%) and for R2 at 1500-2500 (78%-80%). The positive predictive value for tumor for R1 was similar from b1000 to 4000 (93%-98%) and for R2 was similar from b1500 to 4000 (88%-94%). CONCLUSIONS: Computed b-values in the range of 1500-2500 s/mm2 (but not higher) were optimal for prostate cancer detection; b-values of 1000 or 3000-5000 exhibited overall lower performance.