The utility of prostate MRI within active surveillance: description of the evidence

Purpose We present an overview of the literature regarding the use of MRI in active surveillance of prostate cancer. Methods Both MEDLINE® and Cochrane Library were queried up to May 2020 for studies of men on active surveillance with MRI and later confirmatory biopsy. The terms studied were ‘prostate cancer’ as the anchor followed by two of the following: active surveillance, surveillance, active monitoring, MRI, NMR, magnetic resonance imaging, MRI, and multiparametric MRI. Studies were excluded if pathologic reclassification (GG1 → ≥ GG2) and PI-RADS or equivalent was not reported. Results Within active surveillance, baseline MRI is effective for identifying clinically significant prostate cancer and thus associated with fewer reclassification events. A positive initial MRI (≥ PI-RADS 3) with GG1 identified at biopsy has a positive predictive value (PPV) of 35–40% for reclassification by 3 years. MRI possessed a stronger negative predictive value, with a negative MRI (≤ PI-RADS 2) yielding a negative predictive value of up to 85% at 3 years. Surveillance MRI, obtained after initial biopsy, yielded a PPV of 11–65% and NPV of 85–95% for reclassification. Conclusion MRI is useful for initial risk stratification of prostate cancer in men on active surveillance, especially if MRI is negative when imaging is obtained during surveillance. While useful, MRI cannot replace biopsy and further research is necessary to fully integrate MRI into active surveillance.

Anti-phospholipase A2 receptor in Non-lupus Patients with Membranous Nephropathy and Crescents

Introduction: Anti-phospholipase A2 receptor (PLA2R) is detected in approximately 70% of biopsies of “primary” membranous nephropathy (MN). Crescents in MN in non-lupus patients suggest additional injury, such as antineutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (anti-GBM)-associated glomerulonephritis and is postulated to reflect injury by a mechanism that unmasks cryptic epitopes leading to the second autoantibody. Methods: We studied PLA2R staining in non-lupus patients with MN and crescents. Native renal biopsies in 16 non-lupus patients with MN and crescents were stained for PLA2R. Results: The patients included 5 women and 11 men, with mean age 61 yrs and elevated serum creatinine (mean 4.68 mg/dL). Hematuria and proteinuria (mean 4.97 g/d) were documented in 13 patients. Two patients had positive serum anti-GBM antibody. Nine of eleven patients tested for ANCA were positive, with p-ANCA (n=4), c-ANCA (n=2), or both (n=1), with two not specified. On average, 27% of glomeruli had crescents. One patient had an initial biopsy with MN, 4 years later had MN with crescent, and 7 years later had rebiopsy with persistent MN with crescents. One patient had ANCA-associated vasculitis, and 5 years later had MN and crescent. The remaining 14 patients had concurrent diagnoses of MN and crescents. PLA2R was positive in 5 cases, 3 with ANCA positivity, 2 with unknown ANCA status, and none with anti-GBM disease. The patient with initial MN preceding crescent was PLA2R positive; the patient with initial ANCA-associated vasculitis preceding MN was PLA2R negative. Conclusions: Most patients (64%) presented with concomitant MN and crescents, with rare occurrence of an initial disease process followed later by the second injury. PLA2R was positive in 31% of patients, suggesting most are secondary MN. Further study to determine the cryptic epitopes may shed light on the triggering mechanisms for these rare but unlikely coincidental glomerular injuries.

The Role of Prostate Combination Biopsy Consisting of Targeted and Additional Systematic Biopsy

Background: To identify the role of combination biopsy, which consists of both targeted and additional systematic cores, in the diagnosis of clinically significant prostate cancer (csPCa). Methods: We retrospectively reviewed patients with PSA levels 2.5–15 ng/mL who have a suspicious prostate lesion (with the Prostate Imaging Reporting and Data System (PI-RADS) ≥ 3) on multiparametric MRI (mpMRI) between January 2016 and December 2018. We analyzed biopsy results by PI-RADS score and biopsy methods (systematic, targeted, and combination biopsy). Results: Of the 711 total patients, an average of 4.0 ± 1.8 targeted and 8.6 ± 3.1 additional systematic biopsies were performed. The additional systematic biopsies were sampled outside the targeted biopsy area. The combination biopsies detected more csPCa (201 patients, 28.3%) than did the targeted (175 patients, 24.6%) or systematic (124 patients, 17.4%) biopsies alone (p < 0.001). In the initial biopsy samples, there was a 7% increase in the detection of csPCa than in targeted biopsy (62% to 69%). It increased by 11% in repeat biopsy (46% to 57%). There was no statistical significance in both groups (p = 0.3174). Conclusions: Combination biopsy has the benefit of detecting csPCa in both initial and repeat biopsy when there is a suspicious lesion on mpMRI.

Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies

Background The ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision. Methods Pooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology. Results The combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of “unnecessary” (benign or Gleason 6/GG1) biopsies, with an NPV of 90%. Conclusions EPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.

C3 Glomerulopathy and Related Disorders in Children

Background and objectives: Membranoproliferative Glomerulonephritis (MPGN) and C3 Glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific aetiological data for paediatric MPGN/C3 glomerulopathy are lacking, and outcome data are based upon retrospective studies without aetiological data. Design, setting, participants, and measurements: Eighty prevalent pediatric patients with MPGN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using COX proportional hazards model. Kidney and transplant graft survival was determined using Kaplan-Meier method. Results: Central histology review determined 39 C3 glomerulopathy, 31 immune-complex MPGN and 10 immune-complex glomerulonephritis (GN) cases. Patients were aged 2-15 (median 9 (IQR 7-11) years. Median complement C3 and C4 levels were 0.31g/L and 0.14g/L respectively; acquired (anti-complement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% patients respectively, across all groups including immune-complex GN. Median follow-up was 5.18 (IQR 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure with 9 transplants performed in 8 patients, 2 of which failed due to recurrent disease. Presence of >50% crescents on initial biopsy was the sole variable associated with kidney failure in multivariable analysis (Hazard Ratio 6.2, p = 0.045; 95% CI 1.05 to 36.6). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on initial biopsy. Conclusions: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric MPGN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

A Case of Laryngeal Mucosa Associated Lymphoid Tissue Lymphoma Mimicking Laryngeal Amyloidosis

Laryngeal amyloidosis is a rare disorder characterized by localized amyloid deposition and carries an excellent prognosis. On the other hand, mucosa associated lymphoid tissue (MALT) lymphoma is the most common type of marginal zone lymphoma. MALT lymphoma has a poorer prognosis compared to laryngeal amyloidosis due to more frequent local recurrence, distant metastasis and malignant changes. Despite the differences, as both are found in the form of benign mass and have slow progression, accurate diagnosis is necessary. This report deals with the case of a patient with voice change accompanied by a mass, in which the initial biopsy did not include enough specimen for an accurate diagnosis. However, in the second attempt, an adequate sample was obtained, hence the final diagnosis of laryngeal MALT lymphoma. Based on our recent experience and a review of related literature, we report a case of laryngeal MALT lymphoma mimicking laryngeal amyloidosis.

Utility of interval kidney biopsy in ANCA-associated vasculitis

Objectives ANCA-associated vasculitis (AAV) is a rare autoimmune disorder that commonly involves the kidney. Early identification of kidney involvement, assessing treatment-response and predicting outcome are important clinical challenges. Here, we assessed the potential utility of interval kidney biopsy in AAV. Methods In a tertiary referral centre with a dedicated vasculitis service, we identified patients with AAV who had undergone interval kidney biopsy, defined as a repeat kidney biopsy (following an initial biopsy showing active AAV) undertaken to determine the histological response in the kidney following induction immunosuppression. We analysed biochemical, histological and outcome data, including times to kidney failure and death for all patients. Results We identified 57 patients with AAV who underwent at least one interval kidney biopsy (59 interval biopsies in total; median time to interval biopsy ∼130 days). Of the 59 interval biopsies performed, 24 (41%) patients had clinically suspected active disease at time of biopsy which was confirmed histologically in only 42% of cases; 35 (59%) patients were in clinical disease-remission, and this was correct in 97% of cases. The clinician’s impression was incorrect in one in four patients. Hematuria at interval biopsy did not correlate with histological activity. Interval biopsy showed fewer acute lesions and more chronic damage compared with initial biopsy and led to immunosuppressive treatment-change in 75% (44/59) of patients. Clinical risk prediction tools tended to operate better using interval biopsy data. Conclusion Interval kidney biopsy is useful for determining treatment-response and subsequent disease management in AAV. It may provide better prognostic information than initial kidney biopsy and should be considered for inclusion into future clinical trials and treatment protocols for patients with AAV.

Risk of tract recurrence with stereotactic biopsy of brain metastases: an 18-year cancer center experience

OBJECTIVE Stereotactic biopsy is increasingly performed on brain metastases (BrMs) as improving cancer outcomes drive aggressive multimodality treatment, including laser interstitial thermal therapy (LITT). However, the tract recurrence (TR) risk is poorly defined in an era defined by focused-irradiation paradigms. As such, the authors aimed to define indications and adjuvant therapies for this procedure and evaluate the BrM-biopsy TR rate. METHODS In a single-center retrospective review, the authors identified stereotactic BrM biopsies performed from 2002 to 2020. Surgical indications, radiographic characteristics, stereotactic planning, dosimetry, pre- and postoperative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM (Response Assessment in Neuro-Oncology Brain Metastases) criteria. RESULTS In total, 499 patients underwent stereotactic intracranial biopsy for any diagnosis, of whom 25 patients (5.0%) underwent biopsy for pathologically confirmed viable BrM, a proportion that increased over the time period studied. Twelve of the 25 BrM patients had ≥ 3 months of radiographic follow-up, of whom 6 patients (50%) developed new metastatic growth along the tract at a median of 5.0 months post-biopsy (range 2.3–17.1 months). All of the TR cases had undergone pre- or early post-biopsy stereotactic radiosurgery (SRS), and 3 had also undergone LITT at the time of initial biopsy. TRs were treated with resection, reirradiation, or observation/systemic therapy. CONCLUSIONS In this study the authors identified a nontrivial, higher than previously described rate of BrM-biopsy tract recurrence, which often required additional surgery or radiation and justified close radiographic surveillance. As BrMs are commonly treated with SRS limited to enhancing tumor margins, consideration should be made, in cases lacking CNS-active systemic treatments, to include biopsy tracts in adjuvant radiation plans where feasible.