Srinivas Vourganti

Magnetic Resonance Imaging/Ultrasound–Fusion Biopsy Significantly Upgrades Prostate Cancer Versus Systematic 12-core Transrectal Ultrasound Biopsy

BACKGROUNDnGleason scores from standard, 12-core prostate biopsies are upgraded historically in 25-33% of patients. Multiparametric prostate magnetic resonance imaging (MP-MRI) with ultrasound (US)-targeted fusion biopsy may better sample the true gland pathology.nnnOBJECTIVEnThe rate of Gleason score upgrading from an MRI/US-fusion-guided prostate-biopsy platform is compared with a standard 12-core biopsy regimen alone.nnnDESIGN, SETTING, AND PARTICIPANTSnThere were 582 subjects enrolled from August 2007 through August 2012 in a prospective trial comparing systematic, extended 12-core transrectal ultrasound biopsies to targeted MRI/US-fusion-guided prostate biopsies performed during the same biopsy session.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnThe highest Gleason score from each biopsy method was compared.nnnINTERVENTIONSnAn MRI/US-fusion-guided platform with electromagnetic tracking was used for the performance of the fusion-guided biopsies.nnnRESULTS AND LIMITATIONSnA diagnosis of prostate cancer (PCa) was made in 315 (54%) of the patients. Addition of targeted biopsy led to Gleason upgrading in 81 (32%) cases. Targeted biopsy detected 67% more Gleason ≥4+3 tumors than 12-core biopsy alone and missed 36% of Gleason ≤3+4 tumors, thus mitigating the detection of lower-grade disease. Conversely, 12-core biopsy led to upgrading in 67 (26%) cases over targeted biopsy alone but only detected 8% more Gleason ≥4+3 tumors. On multivariate analysis, MP-MRI suspicion was associated with Gleason score upgrading in the targeted lesions (p<0.001). The main limitation of this study was that definitive pathology from radical prostatectomy was not available.nnnCONCLUSIONSnMRI/US-fusion-guided biopsy upgrades and detects PCa of higher Gleason score in 32% of patients compared with traditional 12-core biopsy alone. Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors.

Multiparametric Magnetic Resonance Imaging and Ultrasound Fusion Biopsy Detect Prostate Cancer in Patients with Prior Negative Transrectal Ultrasound Biopsies

PURPOSEnPatients with negative transrectal ultrasound biopsies and a persistent clinical suspicion are at risk for occult but significant prostate cancer. The ability of multiparametric magnetic resonance imaging/ultrasound fusion biopsy to detect these occult prostate lesions may make it an effective tool in this challenging scenario.nnnMATERIALS AND METHODSnBetween March 2007 and November 2011 all men underwent prostate 3 T endorectal coil magnetic resonance imaging. All concerning lesions were targeted with magnetic resonance imaging/ultrasound fusion biopsy. In addition, all patients underwent standard 12-core transrectal ultrasound biopsy. Men with 1 or more negative systematic prostate biopsies were included in our cohort.nnnRESULTSnOf the 195 men with previous negative biopsies, 73 (37%) were found to have cancer using the magnetic resonance imaging/ultrasound fusion biopsy combined with 12-core transrectal ultrasound biopsy. High grade cancer (Gleason score 8+) was discovered in 21 men (11%), all of whom had disease detected with magnetic resonance imaging/ultrasound fusion biopsy. However, standard transrectal ultrasound biopsy missed 12 of these high grade cancers (55%). Pathological upgrading occurred in 28 men (38.9%) as a result of magnetic resonance imaging/ultrasound fusion targeting vs standard transrectal ultrasound biopsy. The diagnostic yield of combined magnetic resonance imaging/ultrasound fusion platform was unrelated to the number of previous negative biopsies and persisted despite increasing the number of previous biopsy sessions. On multivariate analysis only prostate specific antigen density and magnetic resonance imaging suspicion level remained significant predictors of cancer.nnnCONCLUSIONSnMultiparametric magnetic resonance imaging with a magnetic resonance imaging/ultrasound fusion biopsy platform is a novel diagnostic tool for detecting prostate cancer and may be ideally suited for patients with negative transrectal ultrasound biopsies in the face of a persistent clinical suspicion for cancer.

Accuracy of multiparametric magnetic resonance imaging in confirming eligibility for active surveillance for men with prostate cancer.

Active surveillance (AS) is an attempt to avoid overtreatment of clinically insignificant prostate cancer (PCa); however, patient selection remains controversial. Multiparametric prostate magnetic resonance imaging (MP‐MRI) may help better select AS candidates.

Utility of Multiparametric Magnetic Resonance Imaging Suspicion Levels for Detecting Prostate Cancer

PURPOSEnWe determine the usefulness of multiparametric magnetic resonance imaging in detecting prostate cancer, with a specific focus on detecting higher grade prostate cancer.nnnMATERIALS AND METHODSnProspectively 583 patients who underwent multiparametric magnetic resonance imaging and subsequent prostate biopsy at a single institution were evaluated. On multiparametric magnetic resonance imaging, lesions were identified and scored as low, moderate or high suspicion for prostate cancer based on a validated scoring system. Magnetic resonance/ultrasound fusion guided biopsies of magnetic resonance imaging lesions in addition to systematic 12-core biopsies were performed. Correlations between the highest assigned multiparametric magnetic resonance imaging suspicion score and presence of cancer and biopsy Gleason score on the first fusion biopsy session were assessed using univariate and multivariate logistic regression models. Sensitivity, specificity, negative predictive value and positive predictive value were calculated and ROC curves were developed to assess the discriminative ability of multiparametric magnetic resonance imaging as a diagnostic tool for various biopsy Gleason score cohorts.nnnRESULTSnSignificant correlations were found between age, prostate specific antigen, prostate volume, and multiparametric magnetic resonance imaging suspicion score and the presence of prostate cancer (p<0.0001). On multivariate analyses controlling for age, prostate specific antigen and prostate volume, increasing multiparametric magnetic resonance imaging suspicion was an independent prognosticator of prostate cancer detection (OR 2.2, p<0.0001). Also, incremental increases in multiparametric magnetic resonance imaging suspicion score demonstrated stronger associations with cancer detection in patients with Gleason 7 or greater (OR 3.3, p<0.001) and Gleason 8 or greater (OR 4.2, p<0.0001) prostate cancer. Assessing multiparametric magnetic resonance imaging as a diagnostic tool for all prostate cancer, biopsy Gleason score 7 or greater, and biopsy Gleason score 8 or greater separately via ROC analyses demonstrated increasing accuracy of multiparametric magnetic resonance imaging for higher grade disease (AUC 0.64, 0.69, and 0.72, respectively).nnnCONCLUSIONSnMultiparametric magnetic resonance imaging is a clinically useful modality to detect and characterize prostate cancer, particularly in men with higher grade disease.

Threonine 22 Phosphorylation Attenuates Hsp90 Interaction with Cochaperones and Affects Its Chaperone Activity

Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in α helix-1 of the yeast Hsp90 N-domain both inxa0vitro and inxa0vivo. This α helix participates inxa0a hydrophobic interaction with the catalytic loop in Hsp90s middle domain, helping to stabilize the chaperones ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants.

Low Suspicion Lesions on Multiparametric Magnetic Resonance Imaging Predict for the Absence of High Risk Prostate Cancer

Study Type – Diagnostic (case series) Level of Evidenceu20034 Whats known on the subject? and What does the study add? Over‐treatment of indolent prostate cancer lesions is a problem which can result in increased human and medical costs. Lesions with a low suspician level at mpMRI of the prostate have low risk of including high risk prostate cancer.

Diagnostic value of biparametric magnetic resonance imaging (MRI) as an adjunct to prostate-specific antigen (PSA)-based detection of prostate cancer in men without prior biopsies.

To determine the diagnostic yield of analysing biparametric (T2‐ and diffusion‐weighted) magnetic resonance imaging (B‐MRI) for prostate cancer detection compared with standard digital rectal examination (DRE) and prostate‐specific antigen (PSA)‐based screening.

Overall Survival Advantage with Partial Nephrectomy: A Bias of Observational Data?

Partial nephrectomy (PN) and radical nephrectomy (RN) are standard treatments for a small renal mass. Retrospective studies suggest an overall survival (OS) advantage, however a randomized phase 3 trial suggests otherwise. The effects of both surgical modalities on OS were evaluated compared with controls.

Defining Early-Onset Kidney Cancer: Implications for Germline and Somatic Mutation Testing and Clinical Management

PURPOSEnApproximately 5% to 8% of renal cell carcinoma (RCC) is hereditary. No guidelines exist for patient selection for RCC germline mutation testing. We evaluate how age of onset could indicate the need for germline mutation testing for detection of inherited forms of kidney cancer.nnnPATIENTS AND METHODSnWe analyzed the age distribution of RCC cases in the SEER-17 program and in our institutional hereditary kidney cancer population. The age distributions were compared by sex, race, histology, and hereditary cancer syndrome. Models were established to evaluate the specific age thresholds for genetic testing.nnnRESULTSnThe median age of patients with RCC in SEER-17 was 64 years, with the distribution closely approaching normalcy. Statistical differences were observed by race, sex, and subtype (P < .05). The bottom decile cutoff was ≤ 46 years of age and slightly differed by sex, race, and histology. The mean and median ages at presentation of 608 patients with hereditary kidney cancer were 39.3 years and 37 years, respectively. Although age varied by specific syndrome, 70% of these cases were found to lie at or below the bottom age decile. Modeling age-based genetic testing thresholds demonstrated that the 10th percentile maximized sensitivity and specificity.nnnCONCLUSIONnEarly age of onset might be a sign of hereditary RCC. Even in the absence of clinical manifestations and personal/family history, an age of onset of 46 years or younger should trigger consideration for genetic counseling/germline mutation testing and may serve as a useful cutoff when establishing genetic testing guidelines.

Can Magnetic Resonance-Ultrasound Fusion Biopsy Improve Cancer Detection in Enlarged Prostates?

PURPOSEnPatients with an enlarged prostate and suspicion of prostate cancer pose a diagnostic dilemma. The prostate cancer detection rate of systematic 12-core transrectal ultrasound guided biopsy is between 30% and 40%. For prostates greater than 40 cc this decreases to 30% or less. Magnetic resonance-ultrasound fusion biopsy has shown superior prostate cancer detection rates. We defined the detection rate of magnetic resonance-ultrasound fusion biopsy in men with an enlarged prostate gland.nnnMATERIALS AND METHODSnWe retrospectively analyzed the records of patients who underwent multiparametric prostate magnetic resonance imaging followed by magnetic resonance-ultrasound fusion biopsy at our institution. Whole prostate volumes were calculated using magnetic resonance imaging reconstructions. Detection rates were analyzed with respect to age, prostate specific antigen and whole prostate volumes. Multivariable logistic regression was used to assess these parameters as independent predictors of prostate cancer detection.nnnRESULTSnWe analyzed 649 patients with a mean±SD age of 61.8±7.9 years and a median prostate specific antigen of 6.65 ng/ml (IQR 4.35-11.0). Mean whole prostate volume was 58.7±34.3 cc. The overall detection rate of the magnetic resonance-ultrasound fusion platform was 55%. For prostates less than 40 cc the detection rate was 71.1% compared to 57.5%, 46.9%, 46.9% 33.3%, 36.4% and 30.4% for glands 40 to 54.9, 55 to 69.9, 70 to 84.9, 85 to 99.9, 100 to 114.9 and 115 cc or greater, respectively (p<0.0001). Multivariable logistic regression showed a significant inverse association of magnetic resonance imaging volume with prostate cancer detection, controlling for age and prostate specific antigen.nnnCONCLUSIONSnTransrectal ultrasound guided and fusion biopsy cancer detection rates decreased with increasing prostate volume. However, magnetic resonance-ultrasound fusion biopsy had a higher prostate cancer detection rate compared to that of transrectal ultrasound guided biopsy in the literature. Magnetic resonance-ultrasound fusion biopsy represents a promising solution for patients with suspicion of prostate cancer and an enlarged prostate.