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 Panel's 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.

Background Conventional biopsy fails to detect the presence of some prostate cancers (PCas). Men with a prior negative biopsy but persistently elevated prostate-specific antigen (PSA) pose a diagnostic dilemma, as some harbor elusive cancer. Objective To determine whether use of magnetic resonance–ultrasound (MR-US) fusion biopsy results in improved detection of PCa compared to repeat conventional biopsy. Design, setting, and participants In a consecutive-case series, 105 subjects with prior negative biopsy and elevated PSA values underwent multiparametric magnetic resonance imaging (MRI) and fusion biopsy in an outpatient setting. Intervention Suspicious areas on multiparametric MRI were delineated and graded by a radiologist; MR–US fusion biopsy was performed by a urologist using the Artemis device; targeted and systematic biopsies were obtained regardless of MRI result. Outcome measurements and statistical analysis Detection rates of all PCa and clinically significant PCa (Gleason ≥3 + 4 or Gleason 6 with maximal cancer core length ≥4 mm) were determined. The yield of targeted biopsy was compared to systematic biopsy. The ability of an MRI grading system to predict clinically significant cancer was investigated. Stepwise multivariate logistic regression analysis was performed to determine predictors of significant cancer on biopsy. Results and limitations Fusion biopsy revealed PCa in 36 of 105 men (34%; 95% confidence interval [CI], 25–45). Seventy-two percent of men with PCa had clinically significant disease; 21 of 23 men (91%) with PCa on targeted biopsy had significant cancer compared to 15 of 28 (54%) with systematic biopsy. Degree of suspicion on MRI was the most powerful predictor of significant cancer on multivariate analysis. Twelve of 14 (86%) subjects with a highly suspicious MRI target were diagnosed with clinically significant cancer. Conclusions MR-US fusion biopsy provides improved detection of PCa in men with prior negative biopsies and elevated PSA values. Most cancers found were clinically significant.

Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.prostate cancer | Krebs cycle | metabolism | desorption electrospray ionization | mass spectrometry P rostate cancer (PCa) is the most commonly diagnosed solidorgan cancer and the second leading cause of cancer death in men in the United States (1). Because of prostate-specific antigen (PSA) screening in the United States, most PCas are discovered when they are confined to the prostate (2). Many of these localized PCas are treated by surgical removal of the entire prostate (radical prostatectomy). The presence of cancer cells at the edge of the surgical resection, or positive surgical margins, is associated with higher rates of recurrence and death from PCa (3, 4). Therefore, an important clinical challenge in PCa management is to devise a rapid and highly accurate method to detect cancerous cells in real time to allow resection of additional periprostatic tissues and reduce cancer recurrence after surgery. Over the last decade, several innovative analytical techniques (5-12) have been developed to distinguish cancer from benign tissue in various organs. However, none has achieved wide clinical adoption for various reasons including inconvenience, narrow information content, unavailability, poor sensitivity, slowness of adoption, and operating room workflow incompatibility. In PCa, intraoperative frozen sections have been used to attempt to identify PCa at the margin based on analysis of histology. However, frozen sections h...

Purpose Targeted biopsy of lesions identified on MRI may enhance detection of clinically relevant prostate cancers (CaP). We evaluate CaP detection rates in 171 consecutive men using MR-US fusion prostate biopsy. Materials and Methods Subjects underwent targeted biopsy either for active surveillance (N=106) or persistently elevated PSA but negative prior conventional biopsy (N=65). Before biopsy, each man had a multiparametric MRI at 3.0-Tesla. Lesions on MRI were outlined in 3D and assigned increasing cancer suspicion levels (image grade 1–5) by a uroradiologist. The Artemis biopsy tracking system was used to fuse the stored MRI with real-time ultrasound (US), generating a 3D prostate model on-the-fly. Working from the 3D model, transrectal biopsy of target lesions and 12 systematic biopsies were performed under local anesthesia in the clinic. Results 171 subjects (median age 65) underwent targeted biopsy. At biopsy, median PSA = 4.9 ng/ml and prostate volume = 48 cc. A targeted biopsy was three times more likely to identify cancer than a systematic biopsy (21% vs. 7%). CaP was found in 53% of men, 38% of whom had Gleason ≥7. 38% of men with Gleason ≥7 cancers were detected only on targeted biopsies. Targeted biopsy findings correlated with level of suspicion on MRI. 15 of 16 men (94%) with an image grade 5 target (highest suspicion) had CaP, including 7 with Gleason ≥7. Conclusions Prostate lesions identified on MRI can be accurately targeted using MR-US fusion biopsy by a urologist in clinic. Biopsy findings correlate with level of suspicion on MRI.

Patients receiving a PI-RADS assessment category of 3 to 5 warrant repeat biopsy with image guided targeting. While transrectal ultrasound guided magnetic resonance imaging fusion or in-bore magnetic resonance imaging targeting may be valuable for more reliable targeting, especially for lesions that are small or in difficult locations, in the absence of such targeting technologies cognitive (visual) targeting remains a reasonable approach in skilled hands. At least 2 targeted cores should be obtained from each magnetic resonance imaging defined target. Given the number of studies showing a proportion of missed clinically significant cancers by magnetic resonance imaging targeted cores, a case specific decision must be made whether to also perform concurrent systematic sampling. However, performing solely targeted biopsy should only be considered once quality assurance efforts have validated the performance of prostate magnetic resonance imaging interpretations with results consistent with the published literature. In patients with negative or low suspicion magnetic resonance imaging (PI-RADS assessment category of 1 or 2, respectively), other ancillary markers (ie PSA, PSAD, PSAV, PCA3, PHI, 4K) may be of value in identifying patients warranting repeat systematic biopsy, although further data are needed on this topic. If a repeat biopsy is deferred on the basis of magnetic resonance imaging findings, then continued clinical and laboratory followup is advised and consideration should be given to incorporating repeat magnetic resonance imaging in this diagnostic surveillance regimen.