Preston Sprenkle

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panels most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Comparison of Open and Minimally Invasive Partial Nephrectomy for Renal Tumors 4-7 Centimeters

BACKGROUND Indications for partial nephrectomy (PN) in the treatment of renal cell carcinoma are evolving, particularly for larger, more complex tumors. OBJECTIVE Compare single-institution outcomes for minimally invasive partial nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors>4-7 cm. DESIGN, SETTING, AND PARTICIPANTS A total of 2290 patients underwent PN from 2002 to 2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4-7 cm renal cortical tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and 37 laparoscopic procedures). Perioperative management was uniform on the clinical pathway. Perioperative data, clinicopathologic variables, complications within 30 d, and oncologic outcomes were reviewed. MEASUREMENTS Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Complications were reported from prospectively collected data based on a modified Clavien system. The Fisher exact and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan-Meier methods were used to estimate survival. RESULTS AND LIMITATIONS Median follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no statistically significant differences in age, gender, preoperative American Society of Anesthesiologists score, laterality, histologic subtype, tumor size, tumor stage, or margin status between procedures. Univariate analysis revealed significantly greater values in the OPN group for preoperative eGFR, renal artery clamp time, estimated blood loss, use of renal hypothermia, and length of stay. Differences in overall survival and recurrence-free survival were not statistically significant; however, short median follow-up times limit comparison. There was no significant difference in the number of complications grade≥3 (p=0.1) or urine leaks requiring intervention (p=0.7). Limitations include the retrospective nature of the study and the possibility of selection bias. CONCLUSIONS OPN and MIPN procedures performed in patients with tumors>4-7 cm offer acceptable and comparable results in terms of operative, functional, and convalescence measures, regardless of approach.

Prognostic Impact of Muscular Venous Branch Invasion in Localized Renal Cell Carcinoma Cases

PURPOSE Beginning with the 2002 American Joint Committee on Cancer staging system, renal sinus muscular venous branch invasion has prognostic equivalence with renal vein invasion in renal cell carcinoma cases. To validate this presumed equivalence we compared patients with isolated muscular venous branch invasion to those with renal vein invasion and those with no confirmed vascular invasion. MATERIALS AND METHODS From routine cataloging at our institution we identified 500 patients who underwent partial or radical nephrectomy from 2003 to 2008. After excluding patients with metastasis or noncortical renal cell carcinoma pathology we identified 85 with positive muscular venous branch invasion (+). The 259 patients with pT1-2 muscular venous branch (-) invasion and the 71 with renal vein (+) invasion served as comparison groups. We used a multivariate Cox model to control for tumor characteristics using the Kattan renal cell carcinoma nomogram. RESULTS On multivariate analysis the risk of recurrence in the pT1-2 muscular venous branch invasion (-) group was lower than in the muscular venous branch invasion (+) group (HR 0.06, 95% CI 0.02-0.18, p < 0.001). Patients with renal vein invasion (+) had a recurrence rate similar to that in those with muscular venous branch invasion (+) (HR 0.80, 95% CI 0.39-1.65, p = 0.6). The overall survival rate was higher in the muscular venous branch invasion (-) group than in the other groups. CONCLUSIONS Patients with muscular venous branch invasion have an outcome inferior to that in patients with pT1-2 disease. This confirms the adverse prognosis of muscular venous branch invasion and supports pathological up-staging. The prognosis of muscular venous branch invasion is similar to that of renal vein invasion, although we cannot exclude the possibility of a difference. Our findings underscore the importance of close patient followup and careful pathological assessment of the nephrectomy specimen.

Urine Neutrophil Gelatinase-Associated Lipocalin as a Marker of Acute Kidney Injury After Kidney Surgery

PURPOSE We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. MATERIALS AND METHODS Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater. RESULTS Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. CONCLUSIONS Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Negative Multiparametric Magnetic Resonance Imaging of the Prostate Predicts Absence of Clinically Significant Prostate Cancer on 12-Core Template Prostate Biopsy

OBJECTIVE To determine the negative predictive value of multiparametric magnetic resonance imaging (mpMRI), we evaluated the frequency of prostate cancer detection by 12-core template mapping biopsy in men whose mpMRI showed no suspicious regions. METHODS Six hundred seventy patients underwent mpMRI followed by transrectal ultrasound (TRUS)-guided systematic prostate biopsy from December 2012 to June 2016. Of this cohort, 100 patients had a negative mpMRI. mpMRI imaging sequences included T2-weighted and diffusion-weighted imaging, and dynamic contrast enhancement sequences. RESULTS The mean age, prostate-specific antigen, and prostate volume of the 100 men included were 64.3 years, 7.2 ng/mL, and 71 mL, respectively. Overall cancer detection was 27% (27 of 100). Prostate cancer was detected in 26.3% (10 of 38) of patients who were biopsy-naïve, 12.1% (4 of 33) of patients who had a prior negative biopsy, and in 44.8% (13 of 29) of patients previously on active surveillance; Gleason grade ≥7 was detected in 3% of patients overall (3 of 100). The negative predictive value of a negative mpMRI was 73% for all prostate cancer and 97% for Gleason ≥7 prostate cancer. CONCLUSION There is an approximately 3% chance of detecting clinically significant prostate cancer with systematic TRUS-guided biopsy in patients with no suspicious findings on mpMRI. This information should help guide recommendations to patients about undergoing systematic TRUS-guided biopsy when mpMRI is negative.

The effect of argon gas pressure on ice ball size and rate of formation.

INTRODUCTION Contemporary cryoablation technology utilizes the Joule-Thomson effect, defined as a change in temperature that results from expansion of a nonideal gas through an orifice or other restriction. We evaluated the effect of initial gas tank pressures on freezing dynamics in a single-probe model and in a multiprobe model using contemporary cryoablation technology. MATERIALS AND METHODS Cryoablation trials were performed in a standardized system of transparent gelatin molds at 25°C. Two sets of trials were performed. The first trial evaluated temperature and ice ball size for a given tank pressure when a single needle was deployed. The second trial recorded ice ball temperatures for each probe when multiple probes were fired simultaneously. RESULTS Trial 1: The rate of temperature change is directly related to the initial pressure of the gas being released, and the group with the highest starting pressures reached the lowest mean temperature and had the largest mean ice ball size (p < 0.01). Trail 2: Multiple-probe ablation did not affect the rate of temperature change or final temperature compared with firing a single probe (p > 0.7). CONCLUSIONS In accordance with the Joule-Thomson effect, higher initial gas pressures used for cryoablation in a transparent gel model demonstrate statistically significant lower temperatures, faster decreases in temperature, and formation of larger ice balls than lower gas pressures do. With contemporary technology, multiple simultaneous cryoprobe deployment does not compromise individual probe efficacy. The use of higher initial tank pressures will theoretically help future cryoprobes be more effective, creating a greater volume of cell necrosis and a smaller indeterminate zone.

Neutrophil gelatinase-associated lipocalin (NGAL) levels in response to unilateral renal ischaemia in a novel pilot two-kidney porcine model

To test a novel porcine two‐kidney model for evaluating the effect of controlled acute kidney injury (AKI) related to induced unilateral ischaemia on both renal units (RUs) To use neutrophil gelatinase‐associated lipocalin (NGAL) and physiological serum and urinary markers to assess AKI and renal function.

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion–targeted biopsy in patients with a solitary PI-RADS v2–scored lesion

PURPOSE To evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS A total of 176 patients underwent MRI/ultrasound fusion-targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location. RESULTS Fusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone. CONCLUSION The PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ.

Learning Non-rigid Deformations for Robust, Constrained Point-based Registration in Image-Guided MR-TRUS Prostate Intervention

HighlightsModel non‐rigid deformations typically encountered when fusing pre‐procedure MR and intra‐procedure TRUS images for image‐guided prostate biopsy.A large database of clinical prostate biopsy interventions is used to train a statistical deformation model (SDM).The SDM prevents the registration process from failing in the presence of prostate gland segmentation errors.Rigorous validation using synthetic data and clinical landmarks demonstrates accurate, reliable, robust, and consistent registration results. Graphical abstract Figure. No Caption available. ABSTRACT Accurate and robust non‐rigid registration of pre‐procedure magnetic resonance (MR) imaging to intra‐procedure trans‐rectal ultrasound (TRUS) is critical for image‐guided biopsies of prostate cancer. Prostate cancer is one of the most prevalent forms of cancer and the second leading cause of cancer‐related death in men in the United States. TRUS‐guided biopsy is the current clinical standard for prostate cancer diagnosis and assessment. State‐of‐the‐art, clinical MR‐TRUS image fusion relies upon semi‐automated segmentations of the prostate in both the MR and the TRUS images to perform non‐rigid surface‐based registration of the gland. Segmentation of the prostate in TRUS imaging is itself a challenging task and prone to high variability. These segmentation errors can lead to poor registration and subsequently poor localization of biopsy targets, which may result in false‐negative cancer detection. In this paper, we present a non‐rigid surface registration approach to MR‐TRUS fusion based on a statistical deformation model (SDM) of intra‐procedural deformations derived from clinical training data. Synthetic validation experiments quantifying registration volume of interest overlaps of the PI‐RADS parcellation standard and tests using clinical landmark data demonstrate that our use of an SDM for registration, with median target registration error of 2.98 mm, is significantly more accurate than the current clinical method. Furthermore, we show that the low‐dimensional SDM registration results are robust to segmentation errors that are not uncommon in clinical TRUS data.

Current Management Strategy for Active Surveillance in Prostate Cancer

Purpose of ReviewActive surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes.Recent FindingsPatient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30–50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer.SummaryThe optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.