Faculty Bibliography

OBJECTIVES: To determine whether a combination of PCA3 and MRI suspicion score (mSS) could further optimize detection of prostate cancer on MRF-TB among men with no previous history of biopsy. MATERIALS AND METHODS: 187 men presenting to our institution between 6/12 and 8/14 who underwent multiparametric MRI and PCA3 prior to MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics (ROC) curves and multivariable logistic regressions were utilized to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS: PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (AUC = 0.67, 95% CI 0.59-0.76). Using a cutoff of >/=35, PCA3 was associated with cancer risk among men with mSS 2-3 (p=0.004), but not among those with mSS 4-5 (p=0.340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (AUC: 0.83 vs. 0.79, p=0.0434). CONCLUSIONS: Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.

Significant differences, including epidemiologic, clinical, pathologic and genetic, exist between Asian and Caucasian prostate cancer. Detailed pathologic data are, however, scarce. We studied in detail and compared the pathological features of prostate cancer in radical prostatectomy specimens in 228 patients (117 Japan, 111 US). Japanese prostate cancer had a higher Gleason grade group (mean 2.67 vs. 2.42 US, P < 0.05), but lower pathological stage (72 % pT2 and 28 % pT3 vs 55 % pT2 and 45 % pT3 US, P < 0.05). Japanese cancer showed significantly more tumor foci (3.8 vs 2.9 US, P < 0.05), and higher incidence of bilateral significant disease (81.3 % vs. 66.7 % US, P < 0.05). The dominant tumor nodules in Japanese cases had higher Gleason grade group (mean 2.73 vs. 2.40 US, P < 0.05). The incidence of intraductal carcinoma was significantly higher in Japanese patients (35.3 % vs. 12.6 % US, P < 0.01), which was independent of Gleason score (7: 30.9 % Japan vs 11.8 % US, P < 0.01; >/= 8: 87.5 % Japan vs 28.6 % US, P < 0.01) and tumor stage (pT2: 24.1 % Japan vs 6.6 % US, P < 0.01; pT3: 62.9 % Japan vs 20 % US, P < 0.01). These findings demonstrate distinct pathological features in prostate cancer between Japanese and Caucasian patients, and may have important diagnostic and therapeutic implications.

Squamous cell carcinoma (SCC) and keratoacanthoma (KA; SCC/KA) research has been hampered mainly by our lack of understanding the underlying genetic and epigenetic alterations associated with SCC/KA development, as well as the lack of animal models that faithfully recapitulate histopathologic features of human SCC/KA. Here, we show that TPL2 overexpression induced both cell transformation in immortalized human keratinocytes and SCC and KA-like cutaneous SCC (cSCC) development in mice. Mechanistically, activation of TPL2 downstream signaling pathways such as MEK/ERK MAPK, mTOR, NF-kappaB, and p38 MAPK leads to TPL2-mediated cell transformation in immortalized human keratinocytes and tumorigenesis in mice. Most importantly, TPL2 overexpression is required for iTPL2 TG-driven SCC and KA-like cSCC tumor maintenance, validating TPL2 as a possible drug target for the treatment of SCC/KA. Finally, we verified that TPL2 is overexpressed in human cutaneous metastatic SCC and KA clinical specimens compared with normal skin. Taken together, our results establish TPL2 as an oncogenic driver in SCC/KA development. Cancer Res; 76(22); 1-11. (c)2016 AACR.

The current substage classification of pT2 prostate cancer (AJCC, 7th edition, 2010) into pT2a (unilateral tumors <1/2 of lobe), pT2b (unilateral tumors >/=1/2 of lobe) and pT2c (bilateral tumors) is of questionable relevance. Many studies show no difference in prognosis between substages, and incidence of pT2b prostate cancer is low. Other classification systems have been proposed based on tumor volume, as measured by dominant nodule size or tumor percentage. We characterized pT2b tumors and assessed utility of current pT2 substaging in predicting biochemical recurrence-free survival after radical prostatectomy and compared with different substaging methods based on tumor volume. Patients with pT2 tumors were selected among patients who underwent radical prostatectomy from 1998 to 2008. Dominant nodule size was dichotomized as <1.6 cm vs. >/=1.6 cm. Tumor percentage was dichotomized as 25%. Kaplan-Meier analysis and multivariate Cox proportional hazard regression models were used to evaluate pathological parameters predictive of biochemical recurrence-free survival. 785 patients met criteria, of which 145 (18.5%) were pT2a, 15 (1.9%) were pT2b and 625 (79.6%) were pT2c. The pT2 substages were not significant predictors of biochemical recurrence-free survival on univariate or multivariate analysis. In a multivariate model, tumor percentage>25% (p=0.002) was associated with decreased biochemical recurrence-free survival. In patients with stage pT2 prostate cancer, the current substaging method lacks predictive value for biochemical recurrence-free survival after accounting for other pathologic and clinical predictors. However, tumor percentage (25%) is a promising approach to substaging of pT2 prostate cancer.

BACKGROUND: The risk of biochemical recurrence (BCR) following radical prostatectomy for pathologic Gleason 7 prostate cancer varies according to the proportion of Gleason 4 component. OBJECTIVE: We sought to explore the value of several novel quantitative metrics of Gleason 4 disease for the prediction of BCR in men with Gleason 7 disease. DESIGN, SETTING, AND PARTICIPANTS: We analyzed a cohort of 2630 radical prostatectomy cases from 1990-2007. All pathologic Gleason 7 cases were identified and assessed for quantity of Gleason pattern 4. Three methods were used to quantify the extent of Gleason 4: a quantitative Gleason score (qGS) based on the proportion of tumor composed of Gleason pattern 4, a size-weighted score (swGS) incorporating the overall quantity of Gleason 4, and a size index (siGS) incorporating the quantity of Gleason 4 based on the index lesion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations between the above metrics and BCR were evaluated using Cox proportional hazards regression analysis. RESULTS AND LIMITATIONS: qGS, swGS, and siGS were significantly associated with BCR on multivariate analysis when adjusted for traditional Gleason score, age, prostate specific antigen, surgical margin, and stage. Using Harrell's c-index to compare the scoring systems, qGS (0.83), swGS (0.84), and siGS (0.84) all performed better than the traditional Gleason score (0.82). CONCLUSIONS: Quantitative measures of Gleason pattern 4 predict BCR better than the traditional Gleason score. PATIENT SUMMARY: In men with Gleason 7 prostate cancer, quantitative analysis of the proportion of Gleason pattern 4 (quantitative Gleason score), as well as size-weighted measurement of Gleason 4 (size-weighted Gleason score), and a size-weighted measurement of Gleason 4 based on the largest tumor nodule significantly improve the predicted risk of biochemical recurrence compared with the traditional Gleason score.

Inflammatory myofibroblastic tumor (IMT), previously referred to as 'inflammatory pseudotumor', is a rare spindle cell neoplasm which typically affects young patients. The lesion has a tendency to recur following resection and has a low metastatic potential1 . Initially described in the lung, IMT have since been recognized in a wide variety of anatomic sites

PURPOSE: The aim of this study was to evaluate multisequence magnetic resonance imaging (MRI) in detecting local recurrence after transurethral resection for bladder cancer. METHODS: Thirty-six patients with bladder cancer with previous transurethral resection underwent bladder MRI incorporating T2-weighted imaging, diffusion-weighted imaging, and delayed contrast-enhanced T1-weighted imaging, followed by cystoscopy. Two radiologists (R1 and R2) evaluated examinations for suspicious findings. RESULTS: Forty-seven percent of patients had recurrent tumor at cystoscopy and biopsy. Using multisequence MRI, sensitivity and specificity were 67% and 81% for R1 and 73% and 62% for R2. Both readers missed 1 high-grade pathologic stage T1 recurrent tumor; otherwise, all missed tumors were low-grade pathologic stage Ta lesions. All false positives for R1 and 7 of 9 false positives for R2 were in patients receiving previous bacillus Calmette-Guerin therapy. Furthermore, 40% to 50% of solitary abnormalities and 83% to 100% of multifocal abnormalities were tumor recurrences; 12% to 20% of smooth wall thickening, 50% to 75% of irregular wall thickening, and 88% to 100% of papillary masses were tumor recurrences. CONCLUSIONS: Although multisequence MRI exhibited moderate performance for detecting recurrent tumor, nearly all missed tumors were low grade and noninvasive.

BACKGROUND: Increasing evidence supports the use of magnetic resonance imaging (MRI)-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). OBJECTIVE: To compare MRF-TB and SB results and investigate the relationship between biopsy outcomes and prebiopsy MRI. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-mo period. A total of 601 of 803 consecutively eligible men were included. INTERVENTIONS: All men were offered prebiopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. OUTCOMES: Detection rates for all PCa and high-grade PCa (Gleason score [GS] >/=7) were compared using the McNemar test. RESULTS AND LIMITATIONS: MRF-TB detected fewer GS 6 PCas (75 vs 121; p<0.001) and more GS >/=7 PCas (158 vs 117; p<0.001) than SB. Higher mSS was associated with higher detection of GS >/=7 PCa (p<0.001) but was not correlated with detection of GS 6 PCa. Prediction of GS >/=7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS >/=7 PCas in men with no prior biopsy (88 vs 72; p=0.012), in men with a prior negative biopsy (28 vs 16; p=0.010), and in men with a prior cancer diagnosis (42 vs 29; p=0.043). MRF-TB detected fewer GS 6 PCas in men with no prior biopsy (32 vs 60; p<0.001) and men with prior cancer (30 vs 46; p=0.034). Limitations include the retrospective design and the potential for selection bias given a referral population. CONCLUSIONS: MRF-TB detects more high-grade PCas than SB while limiting detection of GS 6 PCa in men presenting for prostate biopsy. These findings suggest that prebiopsy multiparametric MRI and MRF-TB should be considered for all men undergoing prostate biopsy. In addition, mSS in conjunction with biopsy indications may ultimately help in identifying men at low risk of high-grade cancer for whom prostate biopsy may not be warranted. PATIENT SUMMARY: We examined how magnetic resonance imaging (MRI)-targeted prostate biopsy compares to traditional systematic biopsy in detecting prostate cancer among men with suspicion of prostate cancer. We found that MRI-targeted biopsy detected more high-grade cancers than systematic biopsy, and that MRI performed before biopsy can predict the risk of high-grade cancer.

BACKGROUND: To assess associations between whole-lesion apparent diffusion coefficient (ADC) metrics and pathologic findings of Likert score 3 prostate lesions at MRI/ultrasound fusion targeted biopsy. METHODS: This retrospective Institutional Review Board-approved study received a waiver of consent. We identified patients receiving a highest lesion score of 3 on 3 Tesla multiparametric MRI reviewed by a single experienced radiologist using a 5-point Likert scale and who underwent fusion biopsy. A total of 188 score 3 lesions in 158 patients were included. Three-dimensional volumes-of-interest encompassing each lesion were traced on ADC maps. Logistic regression was used to predict biopsy results based on whole-lesion ADC metrics and patient biopsy history. Biopsy yield was compared between metrics. RESULTS: By lesion, targeted biopsy identified tumor in 22.3% and Gleason score (GS) > 6 tumor in 8.5%, although results varied by biopsy history: biopsy-naive (n = 80), 20.0%/8.8%; prior negative biopsy (n = 53), 9.4%/1.9%; prior positive biopsy (n = 55): 40.0%/14.5%. Biopsy history, whole-lesion mean ADC, whole-lesion ADC10-25 , and whole-lesion ADC25-50 were each significantly associated with tumor or GS > 6 tumor at fusion biopsy (P 6 tumor, which was significantly higher (P < 0.001) than specificity of PSA (17.5%) at identical sensitivity. CONCLUSION: For score 3 lesions in patients without prior negative biopsy, whole-lesion ADC metrics help detect GS > 6 cancer while avoiding negative biopsies. However, deferral of fusion biopsy may be considered for score 3 lesions in patients with prior negative biopsy (without applying whole-lesion ADC metrics) given exceedingly low ( approximately 2%) frequency of GS > 6 tumor in this group. J. Magn. Reson. Imaging 2015.

INTRODUCTION: There is increasing interest in using imaging in the detection and localization of prostate cancer (PCa). Both multiparametric magnetic resonance imaging (mpMRI) and HistoScanning (HS) have been independently evaluated in the detection and localization of PCa. We undertook a prospective, blinded comparison of mpMRI and HS for cancer localization among men undergoing radical prostatectomy. METHODS: Following approval by the institutional review board, men scheduled to undergo radical prostatectomy, who had previously undergone mpMRI at our institution, were offered inclusion in the study. Those consenting underwent preoperative HS following induction of anesthesia; mpMRI, HS, and surgical step-section pathology were independently read by a single radiologist, urologist, and pathologist, respectively, in a blinded fashion. Disease maps created by each independent reader were compared and evaluated for concordance by a 5 persons committee consisting of 2 urologists, 2 pathologists, and 1 radiologist. Logistic regression for correlated data was used to assess and compare mpMRI and HS in terms of diagnostic accuracy for cancer detection. Generalized estimating equations based on binary logistic regression were used to model concordance between reader opinion and the reference standard assessment of the same lesion site or region as a function of imaging modality. RESULTS: Data from 31/35 men enrolled in the trial were deemed to be evaluable. On evaluation of cancer localization, HS identified cancer in 36/78 (46.2%) regions of interest, as compared with 41/78 (52.6%) on mpMRI (P = 0.3968). The overall accuracy, positive predictive value, negative predictive value, and specificity for detection of disease within a region of interest were significantly better with mpMRI as compared with HS. HS detected 36/84 (42.9%) cancer foci as compared with 42/84 (50%) detected by mpMRI (P = 0.3678). Among tumors with Gleason score>6, mpMRI detected 19/22 (86.4%) whereas HS detected only 11/22 (50%, P = 0.0078). Similarly, among tumors>10mm in maximal diameter, mpMRI detected 28/34 (82.4%) whereas HS detected only 19/34 (55.9%, P = 0.0352). CONCLUSION: In our institution, the diagnostic accuracy of HS was inferior to that of mpMRI in PCa for PCa detection and localization. Although our study warrants validation from larger cohorts, it would suggest that the HS protocol requires further refinement before clinical implementation.