Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

Is apparent diffusion coefficient associated with clinical risk scores for prostate cancers that are visible on 3-T MR images?

PURPOSE: To investigate whether apparent diffusion coefficients (ADCs) derived from diffusion-weighted (DW) magnetic resonance (MR) imaging at 3 T correlate with the clinical risk of prostate cancer in patients with tumors that are visible on MR images, with MR imaging/transrectal ultrasonography (US) fusion-guided biopsy as a reference. MATERIALS AND METHODS: Forty-eight consecutive patients (median age, 60 years; median serum prostate-specific antigen value, 6.3 ng/mL) who underwent DW imaging during 3-T MR imaging with an endorectal coil were included in this retrospective institutional review board-approved study, and informed consent was obtained from each patient. Patients underwent targeted MR imaging/transrectal US fusion-guided prostate biopsy. Mean ADCs of cancerous target tumors were correlated with Gleason and D'Amico clinical risk scores. The true risk group rate and predictive value of the mean ADC for classifying a tumor by its D'Amico clinical risk score was determined by using linear discriminant and receiver operating characteristic analyses. RESULTS: A significant negative correlation was found between mean ADCs of tumors in the peripheral zone and their Gleason scores (P = .003; Spearman ρ = -0.60) and D'Amico clinical risk scores (P < .0001; Spearman ρ = -0.69). ADC was found to distinguish tumors in the peripheral zone with intermediate to high clinical risk from those with low clinical risk with a correct classification rate of 0.73. CONCLUSION: There is a significant negative correlation between ADCs and Gleason and D'Amico clinical risk scores. ADCs may therefore be useful in predicting the aggressiveness of prostate cancer. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100667/-/DC1.

D'Amico risk stratification correlates with degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging.

PURPOSE: We determined whether there is a correlation between D'Amico risk stratification and the degree of suspicion of prostate cancer on multiparametric magnetic resonance imaging based on targeted biopsies done with our electromagnetically tracked magnetic resonance imaging/ultrasound fusion platform. MATERIALS AND METHODS: A total of 101 patients underwent 3 Tesla multiparametric magnetic resonance imaging of the prostate, consisting of T2, dynamic contrast enhanced, diffusion weighted and spectroscopy images in cases suspicious for or with a diagnosis of prostate cancer. All prostate magnetic resonance imaging lesions were then identified and graded by the number of positive modalities, including low-2 or fewer, moderate-3 and high-4 showing suspicion on multiparametric magnetic resonance imaging. The biopsy protocol included standard 12-core biopsy, followed by real-time magnetic resonance imaging/ultrasound fusion targeted biopsies of the suspicious magnetic resonance lesions. Cases and lesions were stratified by the D'Amico risk stratification. RESULTS: In this screening population 90.1% of men had a negative digital rectal examination. Mean±SD age was 62.7±8.3 years and median prostate specific antigen was 5.8 ng/ml. Of the cases 54.5% were positive for cancer on protocol biopsy. Chi-square analysis revealed a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification (p<0.0001). Within cluster resampling demonstrated a statistically significant correlation between magnetic resonance suspicion and D'Amico risk stratification for magnetic resonance targeted core biopsies and magnetic resonance lesions (p<0.01) CONCLUSIONS: Our data support the notion that using multiparametric magnetic resonance prostate imaging one may assess the degree of risk associated with magnetic resonance visible lesions in the prostate.

Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging.

PURPOSE: A novel platform was developed that fuses pre-biopsy magnetic resonance imaging with real-time transrectal ultrasound imaging to identify and biopsy lesions suspicious for prostate cancer. The cancer detection rates for the first 101 patients are reported. MATERIALS AND METHODS: This prospective, single institution study was approved by the institutional review board. Patients underwent 3.0 T multiparametric magnetic resonance imaging with endorectal coil, which included T2-weighted, spectroscopic, dynamic contrast enhanced and diffusion weighted magnetic resonance imaging sequences. Lesions suspicious for cancer were graded according to the number of sequences suspicious for cancer as low (2 or less), moderate (3) and high (4) suspicion. Patients underwent standard 12-core transrectal ultrasound biopsy and magnetic resonance imaging/ultrasound fusion guided biopsy with electromagnetic tracking of magnetic resonance imaging lesions. Chi-square and within cluster resampling analyses were used to correlate suspicion on magnetic resonance imaging and the incidence of cancer detected on biopsy. RESULTS: Mean patient age was 63 years old. Median prostate specific antigen at biopsy was 5.8 ng/ml and 90.1% of patients had a negative digital rectal examination. Of patients with low, moderate and high suspicion on magnetic resonance imaging 27.9%, 66.7% and 89.5% were diagnosed with cancer, respectively (p <0.0001). Magnetic resonance imaging/ultrasound fusion guided biopsy detected more cancer per core than standard 12-core transrectal ultrasound biopsy for all levels of suspicion on magnetic resonance imaging. CONCLUSIONS: Prostate cancer localized on magnetic resonance imaging may be targeted using this novel magnetic resonance imaging/ultrasound fusion guided biopsy platform. Further research is needed to determine the role of this platform in cancer detection, active surveillance and focal therapy, and to determine which patients may benefit.

Case report of metastatic prostate cancer masquerading as squamous cell carcinoma on the tip of the penis.

We present a 76-year old man with a two year history of Gleason 9 prostate cancer (PCa) presenting with penile pain, erythema, and a fungating mass on the glans. Imaging at initial PCa diagnosis revealed confined disease. His prostate cancer was previously treated with radiation and androgen deprivation therapy (ADT) with initial laboratory response via prostate specific antigen (PSA) levels, however his PSA began to rise six months following cessation of ADT. Shared decision making resulted in partial penectomy for symptomatic management. Computed tomography (CT) and bone scan performed after surgery were not definitive for metastatic disease.

Laparoscopic partial nephrectomy for tumour in the presence of nephrolithiasis or pelvi-ureteric junction obstruction.

OBJECTIVE: To report on patients with a small renal mass and concomitant calculus or pelvi-ureteric junction obstruction (PUJO), and to propose an algorithm for minimally invasive management when these conditions coexist, as the success of laparoscopic partial nephrectomy (LPN) depends greatly on the absence after surgery of ureteric obstruction. PATIENTS AND METHODS: Fifteen (3%) of 548 patients undergoing LPN (November 1999 to May 2005) had concomitant calculus/PUJO; the calculus/PUJO was treated in six, either before (one), during (three) or after (two) LPN, depending on the presence of obstruction. The remaining nine patients were monitored as they had a punctate and unobstructing stone burden. RESULTS; The mean (range) tumour size was 2.7 (1.4-4) cm, the operative duration 3.8 (2-6) h, the warm ischaemia time 34.8 (22-53) min, and blood loss 237 (50-600) mL. Two patients with concomitant PUJO had a single-session dismembered Anderson-Hynes pyeloplasty and LPN. Three patients with smaller stones (5-12 mm) had extracorporeal shock wave lithotripsy, percutaneous nephrolithotomy or or ureteroscopic removal before (one) or after (two) LPN. One patient with a larger 1.6 cm obstructing renal pelvic calculus had laparoscopic flexible pyeloscopy, but the stone was not visualized. At the end of all treatments, the 6-month tumour-free and stone-free rates were 15/15 and 11/13, respectively. CONCLUSION: Patients with a concomitant small renal mass and calculus/PUJO can be successfully managed in a simultaneous or staged manner using minimally invasive techniques. A management algorithm is presented.

Partial adrenalectomy minimizes the need for long-term hormone replacement in pediatric patients with pheochromocytoma and von Hippel-Lindau syndrome.

PURPOSE: Children with von Hippel-Lindau syndrome (VHL) are at an increased risk for developing bilateral pheochromocytomas. In an effort to illustrate the advantage of partial adrenalectomy (PA) over total adrenalectomy in children with VHL, we report the largest single series on PA for pediatric patients with VHL, demonstrating a balance between tumor removal and preservation of adrenocortical function. METHODS: From 1994 to 2011, a prospectively maintained database was reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for PA. Surgery was performed if there was clinical evidence of pheochromocytoma and if normal adrenocortical tissue was evident on preoperative imaging and/or intraoperative ultrasonography. Perioperative data were collected, and patients were observed for postoperative steroid use and tumor recurrence. RESULTS: Ten pediatric patients with a diagnosis of VHL underwent 18 successful partial adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6 cm (range, 1.2-6.5 cm). Over a median follow-up of 7.2 years (range, 2.6-15.8 years), additional tumors in the ipsilateral adrenal gland were found in 2 patients. One patient underwent completion adrenalectomy, and 1 underwent a salvage PA with resection of the ipsilateral lesion. One patient required short-term steroid replacement therapy. At last follow-up, 7 patients had no radiographic or laboratory evidence of pheochromocytoma. CONCLUSION: At our institution, PA is the preferred form of management for pheochromocytoma in the (VHL) pediatric population. This surgical approach allows for removal of tumor while preserving adrenocortical function and minimizing the adverse effects of long-term steroid replacement on puberty and quality of life.

Documenting the location of systematic transrectal ultrasound-guided prostate biopsies: correlation with multi-parametric MRI.

During transrectal ultrasound (TRUS)-guided prostate biopsies, the actual location of the biopsy site is rarely documented. Here, we demonstrate the capability of TRUS-magnetic resonance imaging (MRI) image fusion to document the biopsy site and correlate biopsy results with multi-parametric MRI findings. Fifty consecutive patients (median age 61 years) with a median prostate-specific antigen (PSA) level of 5.8 ng/ml underwent 12-core TRUS-guided biopsy of the prostate. Pre-procedural T2-weighted magnetic resonance images were fused to TRUS. A disposable needle guide with miniature tracking sensors was attached to the TRUS probe to enable fusion with MRI. Real-time TRUS images during biopsy and the corresponding tracking information were recorded. Each biopsy site was superimposed onto the MRI. Each biopsy site was classified as positive or negative for cancer based on the results of each MRI sequence. Sensitivity, specificity, and receiver operating curve (ROC) area under the curve (AUC) values were calculated for multi-parametric MRI. Gleason scores for each multi-parametric MRI pattern were also evaluated. Six hundred and 5 systemic biopsy cores were analyzed in 50 patients, of whom 20 patients had 56 positive cores. MRI identified 34 of 56 positive cores. Overall, sensitivity, specificity, and ROC area values for multi-parametric MRI were 0.607, 0.727, 0.667, respectively. TRUS-MRI fusion after biopsy can be used to document the location of each biopsy site, which can then be correlated with MRI findings. Based on correlation with tracked biopsies, T2-weighted MRI and apparent diffusion coefficient maps derived from diffusion-weighted MRI are the most sensitive sequences, whereas the addition of delayed contrast enhancement MRI and three-dimensional magnetic resonance spectroscopy demonstrated higher specificity consistent with results obtained using radical prostatectomy specimens.

Expression of prostate-specific membrane antigen in tumor-associated neovasculature of renal neoplasms.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Recently, PSMA has been found in the neovasculature in association with other solid malignant tumors, including clear cell renal carcinoma (RCC). We studied the expression of PSMA in different primary renal tumors. METHODS: A tissue microarray was constructed from 60 normal kidney, 21 clear cell RCC (CCRCC), 20 papillary RCC (PRCC), 16 chromophobe RCC, 19 oncocytoma, 14 transitional cell carcinoma, and 19 angiomyolipoma (AML) specimens. This tissue microarray was then immunostained for a vascular endothelial marker CD34 and PSMA. PSMA expression in CD34-positive tumor-associated neovasculature was scored according to the staining intensity and the percentage of vessels. Only diffuse strong or weak, or focal strong PSMA staining was graded as positive. RESULTS: PSMA was expressed in the proximal tubules of the normal kidney and in the tumor-associated vasculature in the renal tumors. Positive PSMA staining was detected in 76.2% of CCRCC, 31.2% of chromophobe RCC, 52.6% of oncocytoma, 21.4% of transitional cell carcinoma, and 0% of PRCC and AML specimens. Its expression was greater in CCRCC than PRCC, chromophobe RCC, transitional cell carcinoma, and AML (P <0.001), but was not significantly different from the expression in oncocytoma (P = 0.79). PSMA expression did not correlate with the pathologic stage in CCRCC. CONCLUSIONS: PSMA is differentially expressed in the tumor-associated neovasculature in different renal tumors. It is most commonly detected in CCRCC and rarely detectable in PRCC and AML. This finding suggests that antibodies against PSMA may potentially be used as a diagnostic marker and therapeutic target for renal neoplasms.

Pathological evidence of necrosis in recurrent renal mass following treatment with sunitinib.

Sunitinib is a highly potent, selective vascular endothelial growth factor-receptor types 1 to 3, platelet-derived growth factor (PDGF)-R-alpha, and PDGF-R-ss. Preclinical data suggest that sunitinib (SU11248) has antitumor activity that may result from both inhibition of angiogenesis and direct antiproliferative effects on certain tumor cell types. Sunitinib resulted in tumor shrinkage in 80% of patients who had failed treatment with Bevacizumab and 13% of patients demonstrated an objective Response Evaluation Criteria in solid Tumors (RECIST) in a study presented at the 2006 American Society of Clinical Oncology (ASCO) meeting. We report the first published pathological evidence of sunitinib's effect on recurrent renal cell carcinoma. This was seen in a patient with renal cell carcinoma who developed a renal fossa recurrence 2 years following radical nephrectomy. Tumor shrinkage was evident in the nephrectomy bed after treatment with sunitinib. The pathology of the resected retroperitoneal mass and its implications are discussed.

Complete resection of seminal vesicles at radical prostatectomy results in substantial long-term disease-free survival: multi-institutional study of 6740 patients.

OBJECTIVES: To estimate the disease-specific survival of patients with complete removal of the seminal vesicles (SVs) at radical prostatectomy and to develop a nomogram for the prediction of SV invasion (SVI). METHODS: An analysis of 6740 patients from three institutions was performed. The primary outcome was biochemical failure analyzed according to the presence or absence of SVI using the Kaplan-Meier method and Cox proportional hazards model. The variables analyzed included age, biopsy Gleason score, clinical T stage, margin status, extracapsular extension, SVI, surgical Gleason score, initial prostate-specific antigen level, and institution. Logistic regression analysis was used to determine the preoperative factors predicting for SVI and create the model for the nomogram. RESULTS: Of the 6740 patients, 566 (8.4%) had positive SVs. The median follow-up was 33.4 months (range 1 to 239). The 5 and 10-year biochemical relapse-free survival rate was 38.0% and 25.6%, respectively, for patients with positive SVs and 85.7% and 77.2%, respectively, for patients with negative SVs (P <0.0001). In the multivariate model, all variables, except for biopsy Gleason score and T stage, were significant predictors of biochemical failure (P <0.05), and all variables, except for age, were predictors of SVI. The nomogram achieved an area under the curve of 0.80. CONCLUSIONS: These results have demonstrated that a substantial number of patients with SVI are disease free at 5 and 10 years after complete excision without adjuvant therapy. These findings suggest the therapeutic efficacy of complete SV excision and can identify those with a nomogram-predicted increased risk of SVI who might benefit from complete excision.

Modified tubularized incised plate urethroplasty (Snodgrass) procedure for hypospadias repair.

OBJECTIVES: To report the outcomes in a large series using a modified tubularized incised plate (TIP) urethroplasty (Snodgrass) technique with a local de-epithelialized skin flap to cover the urethroplasty. The use of the TIP urethroplasty (Snodgrass) technique has gained wide acceptance among pediatric urologists for the correction of hypospadias repair because of its good cosmesis, low complication rate, and reliability in creating a vertically oriented meatus. METHODS: A total of 101 boys, aged 6 months to 3 years, with distal (n = 85), mid-shaft (n = 8), or proximal (n = 8) hypospadias underwent one-stage repair using a modified TIP repair with a local de-epithelialized skin flap to cover the urethroplasty. Charts were reviewed for each patient to determine the complications, reoperations, cosmesis, and functional results after surgery. RESULTS: With at least 6 months of follow-up, all patients had achieved excellent functional and cosmetic results, with the meatus at the tip of the penis on follow-up. Three repairs for meatal stenosis and two for fistula were needed. CONCLUSIONS: The modified TIP procedure is a safe and reliable technique. It provides excellent cosmesis with a low reoperation rate.