Akhil Muthigi

Missing the Mark: Prostate Cancer Upgrading by Systematic Biopsy over Magnetic Resonance Imaging/Transrectal Ultrasound Fusion Biopsy

Purpose: Multiparametric magnetic resonance imaging and fusion biopsy detect more high risk prostate cancer and less low risk prostate cancer than systematic biopsy. However, there remains a small subset of patients in whom systematic biopsy captures higher grade disease than fusion biopsy. We sought to identify potential mechanisms of the failure of fusion biopsy in the detection of clinically significant prostate cancer. Materials and Methods: We reviewed a prospectively maintained database of patients who underwent multiparametric magnetic resonance imaging followed by fusion biopsy and systematic biopsy from 2007 to 2014. In patients in whom disease was upgraded to clinically significant disease (Gleason 7 or greater) by systematic biopsy over fusion biopsy, independent re‐review of magnetic resonance imaging, archived biopsy imaging and whole mount pathology as well as needle coordinate mapping were performed. Multivariate logistic regression analysis was done to determine predictors of upgrading by systematic biopsy. Results: Disease was upgraded based on systematic biopsy over fusion biopsy in 135 of 1,003 patients (13.5%), of whom only 62 (6.2%) were upgraded to intermediate (Gleason 7) and high risk (Gleason 8 or greater) prostate cancer (51 or 5.1% and 11 or 1.1%, respectively). On multivariate analysis lower prostate specific antigen (p <0.001), higher magnetic resonance imaging prostate volume (p <0.001) and a lower number of target cores (p = 0.001) were predictors of upgrading by systematic biopsy. Main mechanisms of under grading by fusion biopsy included multiparametric magnetic resonance imaging reader oversight, presence of magnetic resonance imaging invisible cancer, fusion biopsy technique error and intralesion Gleason heterogeneity. Conclusions: Magnetic resonance imaging and fusion biopsy rarely missed clinically significant prostate cancer as only 62 of 1,003 cases (6.2%) were upgraded to clinically significant disease by systematic biopsy. Imaging and biopsy techniques are continually refined. Further studies will help clarify mechanisms of fusion biopsy failure and the patient populations that benefit from systematic biopsy in addition to fusion biopsy.

Magnetic Resonance Imaging-Transrectal Ultrasound Guided Fusion Biopsy to Detect Progression in Patients with Existing Lesions on Active Surveillance for Low and Intermediate Risk Prostate Cancer

Purpose: Active surveillance is an established option for men with low risk prostate cancer. Multiparametric magnetic resonance imaging with magnetic resonance imaging‐transrectal ultrasound fusion guided biopsy may better identify patients for active surveillance compared to systematic 12‐core biopsy due to improved risk stratification. To our knowledge the performance of multiparametric magnetic resonance imaging in following men on active surveillance with visible lesions is unknown. We evaluated multiparametric magnetic resonance imaging and magnetic resonance imaging‐transrectal ultrasound fusion guided biopsy to monitor men on active surveillance. Materials and Methods: This retrospective review included men from 2007 to 2015 with prostate cancer on active surveillance in whom magnetic resonance imaging visible lesions were monitored by multiparametric magnetic resonance imaging and fusion guided biopsy. Progression was defined by ISUP (International Society of Urological Pathology) grade group 1 to 2 and ISUP grade group 2 to 3. Significance was considered at p ≤0.05. Results: A total of 166 patients on active surveillance with 2 or more fusion guided biopsies were included in analysis. Mean followup was 25.5 months. Of the patients 29.5% had pathological progression. Targeted biopsy alone identified 44.9% of patients who progressed compared to 30.6% identified by systematic 12‐core biopsy alone (p = 0.03). Fusion guided biopsy detected 26% more cases of pathological progression on surveillance biopsy compared to systematic 12‐core biopsy. Progression on multiparametric magnetic resonance imaging was the sole predictor of pathological progression at surveillance biopsy (p = 0.013). Multiparametric magnetic resonance imaging progression in the entire cohort had 81% negative predictive value, 35% positive predictive value, 77.6% sensitivity and 40.5% specificity in detecting pathological progression. Conclusions: Multiparametric magnetic resonance imaging progression predicts the risk of pathological progression. Patients with stable multiparametric magnetic resonance imaging findings have a low rate of progression. Incorporating fusion guided biopsy in active surveillance nearly doubled our detection of pathological progression compared to systematic 12‐core biopsy.

Tumor contact with prostate capsule on magnetic resonance imaging: A potential biomarker for staging and prognosis.

BACKGROUND The high-spatial resolution of multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer. mpMRI characteristics (extraprostatic extension [EPE], number of lesions, etc.) may predict final pathological findings (positive lymph node [pLN] and pathological ECE [pECE]) and biochemical recurrence (BCR). Tumor contact length (TCL) on MRI, defined as the length of a lesion in contact with the prostatic capsule, is a novel marker with promising early results. We aimed to evaluate TCL as a predictor of +pathological EPE (+pEPE),+pathological LN (+pLN), and BCR in patients undergoing robotic-assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS A review was performed of a prospectively maintained single-institution database of men with prostate cancer who underwent prostate mpMRI followed by robotic-assisted laparoscopic radical prostatectomy without prior therapy from 2007 to 2015. TCL was measured using T2-weighted magnetic resonance images. Logistic and Cox regression analysis were used to assess associations of clinical, imaging, and histopathological variables with pEPE, pLN, and BCR. Receiver operating characteristic curves were used to characterize and compare TCL performance with Partin tables. RESULTS There were 87/379 (23.0%)+pEPE, 18/384 (4.7%)+pLN, and 33/371 (8.9%) BCR patients. Patients with adverse pathology/oncologic outcomes had longer TCL compared to those without adverse outcomes (+pEPE: 19.8 vs. 10.1mm, P<0.0001,+pLN: 38.0 vs. 11.7mm, P<0.0001, and BCR: 19.2 vs. 11.2mm, P = 0.001). On multivariate analysis, TCL remained a predictor of+pEPE (odds ratio: 1.04, P = 0.001),+pLN (odds ratio: 1.07, P<0.0001), and BCR (hazard ratio: 1.03, P = 0.02). TCL thresholds for predicting+pEPE and+pLN were 12.5 and 19.7mm, respectively. TCL alone was found to have good predictive ability for+pEPE and+PLN (pEPE:TCLAUC: 0.71 vs. PartinAUC: 0.66, P = 0.21; pLN:TCLAUC: 0.77 vs. PartinAUC: 0.88, P = 0.04). CONCLUSION We demonstrate that TCL is an independent predictor of+pEPE, +pLN, and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.

The significance of anterior prostate lesions on multiparametric magnetic resonance imaging in African-American men

INTRODUCTION African-American (AA) men tend to harbor high-risk prostate cancer (PCa) and exhibit worse outcomes when compared to other groups. It has been postulated that AA men may harbor more anterior prostate lesions (APLs) that are undersampled by the standard transrectal ultrasound guided-biopsy (SBx), potentially resulting in greater degree of Gleason score (GS) upgrading at radical prostatectomy. We aimed to evaluate the detection rate of anterior PCa significance of APLs in AA men on multiparametric magnetic resonance imaging (mpMRI) and compare it to a matched cohort of White/Other (W/O) men. MATERIALS AND METHODS A review of 1,267 men who had an mpMRI with suspicious prostate lesions and who underwent magnetic resonance transrectal ultrasound fusion-guided biopsy (FBx) with concurrent SBx in the same biopsy session was performed. All AA men were matched to a control group of W/O using a 1:1 propensity score-matching algorithm with age, prostate-specific antigen, and prostate volume as matching variables. Logistic regression analysis was used to determine predictors of APLs in AA men. RESULTS Of the 195 AA men who underwent mpMRI, 93 (47.7%) men had a total of 109 APLs. Prior negative SBx was associated with the presence of APLs in AA men (Odds ratio = 1.81; 95% CI: 1.03-3.20; P = 0.04). On multivariate logistic regression analysis, smaller prostate (P = 0.001) and rising prostate-specific antigen (P = 0.007) were independent predictors of cancer-positive APLs in AA men. Comparative analysis of AA (93/195, 47.7%) vs. W/O (100/194, 52%) showed no difference in the rates of APLs (P = 0.44) or in cancer detection rate within those lesions or the distribution of GS within those cancers (P = 0.63) despite an overall higher cancer detection rate in AA men (AA: 124/195 [63.6%] vs. W/O: 97/194 [50.0%], P = 0.007). In cases where APLs were positive for PCa on FBx, the GS of APL was equal to the highest GS of the entire gland in 82.9% (29/35) and 90.9% (30/33) of the time in AA and W/O men, respectively. CONCLUSION Cancer-positive APLs represented the highest risk GS in most cases. AA men with prior negative SBx are twice as likely to harbor a concerning APL. In our cohort, AA and W/O men had comparable rates of APLs on mpMRI. Thus, differences in APLs do not explain the higher risk of AA men for deahth due to PCa. However, targeting of APLs via FBx can clinically improve PCa risk stratification and guide appropriate treatment options.

A urologist’s perspective on prostate cancer imaging: past, present, and future

Prostate cancer is unique in that unlike other solid organ malignancies, only recently has imaging been employed to routinely detect and localize disease. The introduction of transrectal ultrasound was a significant development, transitioning digitally guided prostate biopsies to ultrasound guidance. The arrival of multiparametric MRI has become the next major step, transforming the way Urologist’s diagnose, stage, and treat prostate cancer. Recent recommendations against PSA screening have changed the landscape of urologic oncology with the changing needs being reflected in the initiation of additional robust imaging techniques at different time points in prostate cancer care. The current review aims to provide a clinical perspective in the history, current standard of care, and novel imaging modalities in the evaluation of prostate cancer.

The prostate cancer prevention trial risk calculator 2.0 performs equally for standard biopsy and MRI/US fusion-guided biopsy

Background:The Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC) is a widely used risk-based calculator used to assess a man’s risk of prostate cancer (PCa) before biopsy. This risk calculator was created from data of a patient cohort undergoing a 6-core sextant biopsy, and subsequently validated in men undergoing 12-core systematic biopsy (SBx). The accuracy of the PCPTRC has not been studied in patients undergoing magnetic resonance imaging/ultrasound (MRI/US) fusion-guided biopsy (FBx). We sought to assess the performance of the PCPTRC for straitifying PCa risk in a FBx cohort.Methods:A review of a prospective cohort undergoing MRI and FBx/SBx was conducted. Data from consecutive FBx/SBx were collected between August 2007 and February 2014, and PCPTRC scores using the PCPTRC2.0R-code were calculated. The risk of positive biopsy and high-grade cancer (Gleason ⩾7) on biopsy was calculated and compared with overall and high-grade cancer detection rates (CDRs). Receiver operating characteristic curves were generated and the areas under the curves (AUCs) were compared using DeLong’s test.Results:Of 595 men included in the study, PCa was detected in 39% (232) by SBx compared with 48% (287) on combined FBx/SBx biopsy. The PCPTRC AUCs for the CDR were similar (P=0.70) for SBx (0.69) and combined biopsy (0.70). For high-grade disease, AUCs for SBx (0.71) and combined biopsy (0.70) were slightly higher, but were not statistically different (P=0.55).Conclusions:In an MRI-screened population of men undergoing FBx, PCPTRC continues to represent a practical method of accurately stratifying PCa risk.

Novel immunotherapeutic approaches to the treatment of urothelial carcinoma

Immunotherapy has long played a role in urothelial cancers with the use of bacille Calmette Guérin (BCG) being a mainstay in the treatment of nonmuscle invasive bladder cancer. Novel therapeutic approaches have not significantly impacted mortality in this population and so a renaissance in immunotherapy has resulted. This includes recombinant BCG, oncolytic viruses, monoclonal antibodies, vaccines, and adoptive T-cell therapy. Herein, we provide a review of the current state of the art and future therapies regarding immunotherapeutic strategies for urothelial carcinoma.

Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low dose rate brachytherapy

PURPOSE Prostate multiparametric magnetic resonance imaging (mpMRI) has utility in detecting post-radiotherapy local recurrence. We conducted a multireader study to evaluate the diagnostic performance of mpMRI for local recurrence after low dose rate (LDR) brachytherapy. METHODS A total of 19 patients with biochemical recurrence after LDR brachytherapy underwent 3T endorectal coil mpMRI with T2-weighted imaging, dynamic contrast-enhanced imaging (DCE) and diffusion-weighted imaging (DWI) with pathologic confirmation. Prospective reads by an experienced prostate radiologist were compared with reads from 4 radiologists of varying experience. Readers identified suspicious lesions and rated each MRI detection parameter. MRI-detected lesions were considered true-positive with ipsilateral pathologic confirmation. Inferences for sensitivity, specificity, positive predictive value (PPV), kappa, and index of specific agreement were made with the use of bootstrap resampling. RESULTS Pathologically confirmed recurrence was found in 15 of 19 patients. True positive recurrences identified by mpMRI were frequently located in the transition zone (46.7%) and seminal vesicles (30%). On patient-based analysis, average sensitivity of mpMRI was 88% (standard error [SE], 3.5%). For highly suspicious lesions, specificity of mpMRI was 75% (SE, 16.5%). On lesion-based analysis, the average PPV was 62% (SE, 6.7%) for all lesions and 78.7% (SE, 10.3%) for highly suspicious lesions. The average PPV for lesions invading the seminal vesicles was 88.8% (n=13). The average PPV was 66.6% (SE, 5.8%) for lesions identified with T2-weighted imaging, 64.9% (SE, 7.3%) for DCE, and 70% (SE, 7.3%) for DWI. CONCLUSION This series provides evidence that mpMRI after LDR brachytherapy is feasible with a high patient-based cancer detection rate. Radiologists of varying experience demonstrated moderate agreement in detecting recurrence.

Multiple Recurrent Paraganglioma in a Pediatric Patient with Germline SDH-B Mutation

Magnetic Resonance Imaging (MRI) and fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) are recognized approaches for locating paragangliomas. Recently, gallium-68 DOTA-octreotate (DOTATATE) scans have shown promise detecting neuroendocrine tumors missed by FDG-PET and MRI. 13-year-old male with SDH-B mutation presented with symptoms of paraganglioma and elevated catecholamines. MRI did not demonstrate the T2 hyper intense signal typical of paraganglioma and pheochromocytoma; FDG-PET scan did not reveal increased foci of uptake. DOTATATE scan revealed a signal consistent only with residual adrenal tissue. Resection of the right adrenal bed revealed paraganglioma. Following surgery, no further symptoms were reported and biochemical tests normalized.

Managing Renal Cell Carcinoma Associated Paraneoplastic Syndrome with Nephron-sparing Surgery in a Patient with von Hippel-Lindau

A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.