Jamil S. Syed

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.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test

Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer.

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.

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.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI

OBJECTIVE The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. MATERIALS AND METHODS Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. RESULTS Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. CONCLUSION Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

Genetic testing for hereditary prostate cancer: Current status and limitations

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single‐gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single‐gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1‐interacting protein C‐terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next‐generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM‐mutated, metastatic, castrate‐resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018.

End-stage renal disease secondary to renal malignancy: Epidemiologic trends and survival outcomes

OBJECTIVES Loss of renal parenchyma after surgery may contribute to chronic kidney disease; however, the long-term consequences of chronic kidney disease may differ by cause. We analyzed the outcomes of patients with end-stage renal disease (ESRD) based on various medical and surgical causes. MATERIALS AND METHODS In the United States Renal Data System from the period 1983 to 2007, patients with renal tumors, traumatic surgical loss, diabetes, or other known causes were identified. The annual incidence, prevalence, and influence of age, race, sex, and primary cause on survival were evaluated. RESULTS Of 1.3 million patients, 6,812 (0.49%) had renal malignancy-related ESRD (RM-ESRD). An increased over time was noted in the standardized incidence rates of patients with RM-ESRD (R2 = 0.973, P<0.0001). Patients with RM-ESRD had a worse median survival (1.9 vs. 3.4 y, P<0.0001), whereas those with ESRD related to nonmalignant surgical loss had improved survival (3.8 y) compared to diabetic ESRD (P<0.0001). The 5-year cancer-specific mortality was higher for RM-ESRD (30.9% vs. 5.5%, P<0.0001) compared to ESRD from other known causes; however, the non-cancer-specific mortality was improved compared to patients with ESRD with diabetic causes (P<0.0001). Limitations include retrospective analysis and lack of specific clinical data, such as cancer grade. CONCLUSIONS The incidence of RM-ESRD is increasing, possibly owing to the increased rate of renal cell carcinoma treatment. Although overall survival for RM-ESRD was worse than either that of nonmalignant surgical loss or other known causes, non-cancer-specific mortality was decreased compared to diabetic causes, likely due to systemic effects by cause of ESRD.

Hereditary Kidney Cancer Syndromes and Surgical Management of the Small Renal Mass

The management of patients with hereditary kidney cancers presents unique challenges to clinicians. In addition to an earlier age of onset compared with patients with sporadic kidney cancer, those with hereditary kidney cancer syndromes often present with bilateral and/or multifocal renal tumors and are at risk for multiple de novo lesions. This population of patients may also present with extrarenal manifestations, which adds an additional layer of complexity. Physicians who manage these patients should be familiar with the underlying clinical characteristics of each hereditary kidney cancer syndrome and the suggested surgical approaches and recommendations of genetic testing for at-risk individuals.

Distinguishing pediatric and adolescent renal cell carcinoma from other renal malignancies

Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors.

Optimizing waiting duration for renal transplants in the setting of renal malignancy: is 2 years too long to wait?

Background For potential transplant recipients with a prior history of renal malignancy, no evidence-based recommendations currently exist with regard to waiting duration on dialysis. We aim to improve decision making by evaluating the impact of waiting duration on the outcomes of kidney cancer patients awaiting renal transplantation. Methods The United States Renal Data System was used to identify patients with a known cause of end-stage renal disease (ESRD) from 1983 to 2007. Evaluation of overall survival (OS) was performed with Kaplan-Meier estimates and Cox proportional hazards models. Fine-Gray competing risk models were used to assess cancer-specific mortality (CSM) and non-cancer-specific mortality (NCSM). Results Of 1 374 175 patients with ESRD, 228 984 (16.7%) received transplantation. Transplant recipients with renal malignancy-associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 versus 1.3 years; P < 0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better OS than those who waited longer (2+ years) (10-year OS 69.0 versus 46.7%, respectively; P < 0.0001), with similar CSM (10-year CSM 10.3 versus 10.2%, respectively; P = 0.883), whereas NCSM was worse for those with longer waiting durations (10-year NCSM 20.7 versus 44.3%, respectively; P < 0.0001). On Cox modeling, the status of RM-ESRD was not a significant predictor (P = 0.07), while longer waiting duration remained significant (P < 0.0001). Conclusion We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait times. These findings suggest that the OS of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration.