Faculty Bibliography

Approximately 15% of men with newly diagnosed prostate cancer have high-risk disease. Imaging is critically important for the diagnosis and staging of these patients, and also for the selection of management. While established prostate cancer staging guidelines have increased the appropriate use of imaging, underuse for high-risk prostate cancer remains substantial. Several factors affect the utility of initial diagnostic imaging, including the variable definition of high-risk prostate cancer, variable guideline recommendations, poor accuracy of existing imaging tests, and the difficulty in validating imaging findings. Conventional imaging modalities, including CT and radionuclide bone scan, have been employed for local and metastatic staging, but their performance characteristics have generally been poor. Emerging modalities including multiparametricMRI, positron emission tomography (PET)-CT, and PET-MRI have shown increased diagnostic accuracy and could improve accuracy in staging patients with high-risk prostate cancer.

PURPOSE OF REVIEW: In recent years, multiparametric magnetic resonance imaging (mpMRI) of the prostate has shown promise as a modality to identify areas of suspicion within the gland which correlate with cancer location and disease extent. However, optimal individualization of prostate biopsy using mpMRI relies on aligning the relative benefits of MRI-targeted approaches with the goals of biopsy. RECENT FINDINGS: For men with prior negative biopsies, mpMRI allows improved detection of occult high-grade cancers missed by repeat systematic biopsy but also has the potential to identify men who will not benefit from repeat biopsy due to a low likelihood of significant disease. For men with prior low-grade cancer diagnosis, the addition of MRI-targeted biopsy may identify those who are poor candidates for active surveillance by detecting high-risk disease without serial biopsies. For men without prior biopsy, mpMRI and targeted biopsy may help improve high-grade cancer diagnosis and significantly limit the detection of low-risk disease. SUMMARY: mpMRI of the prostate is a promising tool to address many of the shortcomings of traditional systematic prostate biopsy. Biopsy history plays a critical role in determining how to assess the potential advantages and disadvantages of prostate mpMRI in the context of each patient. Although these benefits have been suggested by published clinical outcomes data, there is a need for prospective validation of mpMRI and MRI-targeted biopsy in comparison with the current approach of systematic biopsy for all men, to define new paradigms for prostate cancer detection and risk stratification.

OBJECTIVE: To report outcomes of MRI-ultrasound fusion (MRF-TB) and 12-core systematic biopsy (SB) over a 26-month period in men with prior negative prostate biopsy. METHODS: Between 6/12 and 8/14, 210 men presenting to our institution for prostate biopsy with >/=1 prior negative biopsy underwent multiparametric MRI followed by MRF-TB and SB and were entered into a prospective database. Clinical characteristics, MRI suspicion scores (mSS), and biopsy results were queried from the database and the detection rates of Gleason >/=7 prostate cancer (PCa) and overall PCa were compared between biopsy techniques using McNemar's test. RESULTS: Fifty-three (31%) of 172 men meeting inclusion criteria (mean age 65+/-8 years; mean PSA 8.9+/-8.9) were found to have PCa. MRF-TB and SB had overall cancer detection rates (CDR) of 23.8% and 18.0% (p=0.12), respectively, and CDR for Gleason score (GS)>/=7 disease of 16.3% and 9.3% (p=0.01), respectively. Of 31 men with GS>/=7 disease, MRF-TB detected 28 (90.3%) while SB detected 16 (51.6%) (p<0.001). Using UCSF-CAPRA criteria, only one man was re-stratified from low-risk to higher risk based on SB results compared to MRF-TB alone. Among men with mSS<4, 80% of detected cancers were low-risk by UCSF-CAPRA criteria. CONCLUSIONS: In men with previous negative biopsies and persistent suspicion for PCa, SB contributes little to the detection of GS>/=7 disease by MRF-TB, and avoidance of SB bears consideration. Based on the low likelihood of detecting GS>/=7 cancer and overall low-risk features of PCa in men with mSS<4, limiting biopsy to men with mSS>/=4 warrants further investigation.

BACKGROUND: The objectives of the present study were to report the incidence of pathologic T3a upstaging in a contemporary cohort of patients with clinical stage T1 (cT1) renal tumors treated with partial or radical nephrectomy; investigate the clinical outcomes; and identify the predictors associated with pathologic upstaging. MATERIALS AND METHODS: From a single-institution, institutional review board-approved renal tumor database of 945 patients, we identified 610 patients who had undergone surgery for a cT1 renal mass. Data for 494 patients were available for analysis. Of these, 66 lesions had been pathologically upstaged to T3a after surgery and 428 had not. The oncologic follow-up data and clinical and pathologic features were recorded, and multivariable logistic regression analysis was performed to identify the risk factors for pT3a upstaging, controlling for age, gender, body mass index, and nephrectomy type. RESULTS: The cT1 tumors of 66 patients (13.3%) were upstaged to pT3a after surgery. Of these 66 patients, 44 (66.7%) had undergone partial and 22 (33.3%) radical nephrectomy. The median follow-up period was 50 months. No patient with upstaging developed recurrence, and all were disease free at their last follow-up visit. On multivariable analysis, tumor size > 4 cm (odds ratio [OR], 3.766; 95% confidence interval [CI], 1.417-10.011; P < .008), clear cell histologic features (OR, 4.461; 95% CI, 1.498-13.461; P < .007), and positive surgical margins (hazard ratio, 5.118; 95% CI, 2.088-12.547; P < .0001) were associated with upstaging. CONCLUSION: Of the cT1 lesions in 66 patients, 13% were pathologically upstaged after surgery. The patients with larger tumors, clear cell histologic features, and positive surgical margins were at the greatest risk of upstaging. However, after an intermediate follow-up period, pathologic upstaging did not appear to result in worsened oncologic outcomes.

PURPOSE: To evaluate the 6-month effects of the recommended drug and light dosage in focal vascular-targeted photodynamic therapy (VTP) using TOOKAD((R)) Soluble in patients with localized prostate cancer (LPCa). METHODS: We performed a pooled analysis of 117 men with LPCa, PSA <10 ng/mL, and Gleason score /= 1 (N = 67). Mean prostate necroses at week-1 were 76.5 and 86.3 %, respectively. In both groups, PSA levels at month 6 decreased by 2.0 ng/mL. Small changes from baseline for IPSS and IIEF-5 indicated a slight improvement in urinary function and a slight deterioration in sexual function. CONCLUSIONS: Focal VTP treatment with TOOKAD((R)) Soluble at 4 mg/kg and 200 J/cm resulted in a negative 6-month biopsy rate of 68.4 % for the whole population and 80.6 % for patients treated by hemiablation with LDI >/= 1. The treatment was well tolerated. Two phase III studies will reach completion in early 2015.

PURPOSE: In an era of increasing prostate cancer incidence and earlier detection, the assessment of clinical significance of prostate cancer is critical. Minimally invasive therapies are increasingly being investigated in localized prostate cancer. METHODS AND RESULTS: In this review, we discuss the current status of magnetic resonance imaging targeted fusion prostate biopsy and focal therapy for prostate cancer, its rationale, and techniques. CONCLUSION: Focal therapy offers a promising outlook for prostate cancer treatment, with the goal of effectively achieving cancer control while minimizing morbidity. Long term studies are needed.

AIM: To evaluate the performance of normalised apparent diffusion coefficient (ADC) values for prostate cancer assessment when performed by independent observers blinded to histopathology findings. MATERIALS AND METHODS: Fifty-eight patients undergoing 3 T phased-array coil magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI; maximal b-value 1000 s/mm2) before prostatectomy were included. Two radiologists independently evaluated the images, unaware of the histopathology findings. Regions of interest (ROIs) were drawn within areas showing visually low ADC within the peripheral zone (PZ) and transition zone (TZ) bilaterally. ROIs were also placed within regions in both lobes not suspicious for tumour, allowing computation of normalised ADC (nADC) ratios between suspicious and non-suspicious regions. The diagnostic performance of ADC and nADC were compared. RESULTS: For PZ tumour detection, ADC achieved significantly higher area under the receiver operating characteristic curve (AUC; p=0.026) and specificity (p=0.021) than nADC for reader 1, and significantly higher AUC (p=0.025) than nADC for reader 2. For TZ tumour detection, nADC achieved significantly higher specificity (p=0.003) and accuracy (p=0.004) than ADC for reader 2. For PZ Gleason score >3+3 tumour detection, ADC achieved significantly higher AUC (p=0.003) and specificity (p=0.005) than nADC for reader 1, and significantly higher AUC (p=0.023) than nADC for reader 2. For TZ Gleason score >3+3 tumour detection, ADC achieved significantly higher specificity (p=0.019) than nADC for reader 1. CONCLUSION: In contrast to prior studies performing unblinded evaluations, ADC was observed to outperform nADC overall for two independent observers blinded to the histopathology findings. Therefore, although strategies to improve the utility of ADC measurements in prostate cancer assessment merit continued investigation, caution is warranted when applying normalisation to improve diagnostic performance in clinical practice.