Faculty Bibliography

Advancements in magnetic resonance imaging (MRI) and MRI-ultrasound (US)-fusion targeted biopsy have resulted in a paradigm shift in the diagnosis of prostate cancer by overcoming the limitations of systematic biopsy. Prebiopsy MRI and MRI-US-fusion biopsy results in an increased detection of clinically significant disease, reduction in the detection of indolent disease, and allows for tumor localization during targeted biopsy. With these advantages, we have adopted a prebiopsy MRI and MRI-US-fusion biopsy diagnostic care pathway for all men at risk for prostate cancer and have performed more than 1900 biopsies to date. Herein we present our institutional development of MRI-US-fusion biopsy and highlight our results in those men who have had a previous negative biopsy, no prior biopsy, and those with a prior cancer diagnosis who may be candidate for active surveillance. Risk stratification with biomarkers and nomograms may allow for further counseling on the need for biopsy and the risk of harboring clinically significant disease.

BACKGROUND AND OBJECTIVE: Small kidney cancers are a heterogeneous group with varying malignant potential. Pathologic information obtained from a renal biopsy may guide decision-making for small kidney cancers. We sought to assess the effect of pathologic information from renal biopsy on the nonsurgical management of small kidney cancers in a population-based cohort of patients over 65 years of age. METHODS: In the Surveillance, Epidemiology and End Results-Medicare dataset, we identified patients >/=66 years diagnosed with a kidney cancer<4cm between 2002 and 2011. Diagnostic biopsy was defined by a Medicare claim within 1 month prior through 6 months following cancer diagnosis or before surgery. Nonsurgical management was defined by the absence of a claim for partial or radical nephrectomy or tumor ablation in the first 6 months following diagnosis. The relationship between patient and tumor characteristics and the likelihood of nonsurgical management by receipt of diagnostic biopsy was assessed by multivariable logistic regression models. RESULTS: From 8,933 patients, 2,782 (31%) had a diagnostic renal biopsy of whom 616 (22%) were managed nonsurgically. Controlling for patient, disease, and provider specialty, biopsy was associated with nonsurgical management (adjusted odds ratio = 1.61, 95% Cl: 1.43-1.82) in patients with low-grade tumors but also with more aggressive histology (clear cell renal cell carcinoma). Older age (85+) and geographic region were significantly associated with greater odds of diagnostic biopsy. Patients whose initial renal tumor diagnosis was made by a urologist (vs. other type of provider) were less likely to receive a biopsy (adjust odds ratio = 0.73, 95% Cl: 0.60-0.89). CONCLUSIONS: Although the use of renal biopsy has increased over time and is associated with the use of nonsurgical management of small kidney cancers, the use of the pathologic findings remains limited. Further advances, particularly with prognostic markers, are necessary before renal biopsy can be routinely implemented for treatment decision-making for small kidney cancers.

Active surveillance (AS) has emerged as a beneficial strategy for management of low risk prostate cancer (PCa) and prevention of overtreatment of indolent disease. However, selection of patients for AS using traditional 12-core transrectal prostate biopsy is prone to sampling error and presents a challenge for accurate risk stratification. In fact, around a third of men are upgraded on repeat biopsy which disqualifies them as appropriate AS candidates. This uncertainty affects adoption of AS among patients and physicians, leading to current AS protocols involving repetitive prostate biopsies and unclear triggers for progression to definitive treatment. Prostate magnetic resonance imaging (MRI) has the potential to overcome some of these limitations through localization of significant tumors in the prostate. In conjunction with MRI-targeted prostate biopsy, improved sampling and detection of clinically significant PCa can help streamline the process of selecting suitable men for AS and early exclusion of men who require definitive treatment. MRI can also help minimize the invasive nature of monitoring for disease progression while on AS. Men with stable MRI findings have high negative predictive value for Gleason upgrade on subsequently biopsy, suggesting that men may potentially be monitored by serial MRI examinations with biopsy reserved for significant changes on imaging. Targeted biopsy on AS also allows for specific sampling of concerning lesions, although further data is necessary to evaluate the relative contribution of systematic and targeted biopsy in detecting the 25-30% of men who progress on AS. Further research is also warranted to better understand the nature of clinically significant cancers that are missed on MRI and why certain men have progression of disease that is not visible on prostate MRI. Consensus is also needed over what constitutes progression on MRI, when prostate biopsy can be safely avoided, and how to best utilize this additional information in current AS protocols. Despite these challenges, prostate MRI, either alone or in conjunction with MRI-targeted prostate biopsy, has the potential to significantly improve our current AS paradigm and rates of AS adoption among patients moving forward.

Importance: Potential survival benefits from treating aggressive (Gleason score, >/=7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease. Objective: To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs. Design, Setting, and Participants: Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort. Interventions/Exposures: Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy. Main Outcomes and Measures: Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes. Results: Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men. Conclusions and Relevance: Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.

PURPOSE: The purpose of this review is to summarize the available data about the clinical and economic effectiveness of MRI in the diagnosis and management of prostate cancer and to provide practical recommendations for the use of MRI in the screening, diagnosis, staging and surveillance of prostate cancer. MATERIALS AND METHODS: A panel of clinicians with expertise in the diagnosis and management of prostate cancer evaluated the current published data regarding the use and effectiveness of MRI in the management of prostate cancer. For those clinical scenarios where adequate studies are available for analysis, recommendations are made on the basis of data; where such studies are not available; recommendations are made on the basis of expert consensus. RESULTS: At this time the data support the use of MRI for patients with a previous negative biopsy and ongoing concerns about increased risk of prostate cancer. The data regarding the utility of MRI for initial biopsy suggest a possible role for MRI in an initial biopsy in some circumstances. There is currently insufficient evidence to recommend MRI for screening, staging or surveillance of prostate cancer. CONCLUSION: MRI offers superior anatomic detail, the ability to evaluate cellular density based on water diffusion and blood flow based on contrast enhancement. MRI-targeted biopsy may increase the diagnosis of clinical significant cancers by identifying specific lesions not visible on conventional ultrasound. MRI adds cost to the management of prostate cancer. The clinical indications for the use of MRI in the management of prostate cancer are rapidly evolving.