Salami, Simpa S

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

PURPOSE Pretreatment estimates of seminal vesicle invasion (SVI) are challenging and significantly influence the management of prostate cancer. We sought to improve current models to predict SVI through the development of an SVI prediction genomic signature. PATIENTS AND METHODS A total of 15,889 patients who underwent radical prostatectomy (RP) with available baseline clinical, pathology, and transcriptome data were retrieved from the GRID registry (ClinicalTrials.gov identifier: NCT02609269 ) and other retrospective cohorts. These data were divided into a training (n = 6,766), test (n = 3,363), and two validation (n = 5,062 and 698) cohorts. Multivariable logistic regression was performed to assess the predictive effect of the genomic SVI (gSVI) classifier in the presence of established nomograms (Partin Tables and Memorial Sloan Kettering Cancer Center [MSKCC]). RESULTS In the training cohort, univariable filtering identified 2,132 genes that were differentially expressed between RP tumors with and without SVI. Model parameters were tuned to maximize the area under the curve (AUC) in the testing cohort, resulting in a logistic generalized linear model with 581 genes. The gSVI model scores range from 0 to 1. In the first validation set, gSVI showed superior discrimination of patients with and without SVI at RP compared with other prognostic signatures trained to predict distant metastasis or clinical recurrence. Of the 698 patients in the second validation set, gSVI combined with the MSKCC nomogram had a superior AUC (0.86) compared with either nomogram individually (0.81). CONCLUSION The gSVI represents a novel and validated expression signature to predict the presence of SVI before treatment with surgery. This genomic tool adds discriminatory power to existing clinical predictive nomograms and may help with pretreatment counseling and decision making.

PURPOSE Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis. METHODS Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort. RESULTS The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05). CONCLUSION Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.

Objective To evaluate whether elective off‐clamp laparoscopic partial nephrectomy ( LPN ) affords long‐term renal functional benefit compared with the on‐clamp approach. Patients and Methods This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal‐appearing contralateral kidney underwent elective LPN ; 209 were performed on‐clamp vs 106 off‐clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on‐clamp cohort who underwent subsequent radical nephrectomy for local‐regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate ( eGFR ) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency ( eGFR <60 mL/min/1.73m 2 ). Risk of developing worsened or new‐onset renal insufficiency was also compared. Results The mean preoperative eGFR was similar between the on‐clamp and off‐clamp cohorts (80.7 vs 84.1 mL/min/1.73m 2 , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all‐comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off‐clamp approach with up to 5 years of follow‐up. Conclusions Progressive recovery of renal function after hilar clamping in the elective setting eclipses short‐term functional benefit achieved with off‐clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on‐clamp and off‐clamp cohorts with up to 5 years follow‐up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.