Nathan Lawrentschuk

Sensitivity, Specificity, and Predictors of Positive 68Ga–Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT Positron emission tomography (PET) of 68Ga-labelled prostate-specific membrane antigen (68Ga-PSMA) is an emerging imaging modality introduced to assess the burden of prostate cancer, typically in biochemically recurrent or advanced disease. 68Ga-PSMA PET provides the ability to selectively identify and localize metastatic prostate cancer cells and subsequently change patient management. Owing to its limited history, robust sensitivity and specificity data are not available for 68Ga-PSMA PET-positive scans. OBJECTIVE A systematic review and meta-analysis of reported predictors of positive 68Ga-PSMA PET and corresponding sensitivity and specificity profiles. EVIDENCE ACQUISITION We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Library, and Web of Science databases in April 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality was assessed using the Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analysis and meta-regression of proportions were performed using a random-effects model with pre-PET prostate-specific antigen (PSA) levels as the dependent variable. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. EVIDENCE SYNTHESIS Sixteen articles involving 1309 patients were analysed. The overall percentage of positive 68Ga-PSMA PET among patients was 40% (95% confidence interval [CI] 19-64%) for primary staging and 76% (95% CI 66-85%) for biochemical recurrence (BCR). Positive 68Ga-PSMA PET scans for BCR patients increased with pre-PET PSA. For the PSA categories 0-0.2, 0.2-1, 1-2, and >2 ng/ml, 42%, 58%, 76%, and 95% scans, respectively, were positive. Shorter PSA doubling time increased 68Ga-PSMA PET positivity. On per-patient analysis, the summary sensitivity and specificity were both 86%. On per-lesion analysis, the summary sensitivity and specificity were 80% and 97%, respectively. CONCLUSIONS In the setting of BCR prostate cancer, pre-PET PSA predicts the risk of positive 68Ga-PSMA PET. Pooled data indicate favourable sensitivity and specificity profiles compared to choline-based PET imaging techniques. PATIENT SUMMARY Positron emission tomography using 68Ga-labelled prostate-specific membrane antigen is an emerging radiological technique developed to improve the characterisation of metastatic prostate cancer. We summarised the data available to date and found that this new test provides excellent rates of detection of cancer spread in late-stage prostate cancer.

The Role of Focal Therapy in the Management of Localised Prostate Cancer: A Systematic Review

Context The incidence of localised prostate cancer is increasing worldwide. In light of recent evidence, current, radical, whole-gland treatments for organ-confined disease have being questioned with respect to their side effects, cancer control, and cost. Focal therapy may be an effective alternative strategy. Objective To systematically review the existing literature on baseline characteristics of the target population; preoperative evaluation to localise disease; and perioperative, functional, and disease control outcomes following focal therapy. Evidence acquisition Medline (through PubMed), Embase, Web of Science, and Cochrane Review databases were searched from inception to 31 October 2012. In addition, registered but not yet published trials were retrieved. Studies evaluating tissue-preserving therapies in men with biopsy-proven prostate cancer in the primary or salvage setting were included. Evidence synthesis A total of 2350 cases were treated to date across 30 studies. Most studies were retrospective with variable standards of reporting, although there was an increasing number of prospective registered trials. Focal therapy was mainly delivered to men with low and intermediate disease, although some high-risk cases were treated that had known, unilateral, significant cancer. In most of the cases, biopsy findings were correlated to specific preoperative imaging, such as multiparametric magnetic resonance imaging or Doppler ultrasound to determine eligibility. Follow-up varied between 0 and 11.1 yr. In treatment-naïve prostates, pad-free continence ranged from 95% to 100%, erectile function ranged from 54% to 100%, and absence of clinically significant cancer ranged from 83% to 100%. In focal salvage cases for radiotherapy failure, the same outcomes were achieved in 87.2–100%, 29–40%, and 92% of cases, respectively. Biochemical disease-free survival was reported using a number of definitions that were not validated in the focal-therapy setting. Conclusions Our systematic review highlights that, when focal therapy is delivered with intention to treat, the perioperative, functional, and disease control outcomes are encouraging within a short- to medium-term follow-up. Focal therapy is a strategy by which the overtreatment burden of the current prostate cancer pathway could be reduced, but robust comparative effectiveness studies are now required.

'Prostatic evasive anterior tumours': the role of magnetic resonance imaging.

Study Type – Diagnosis (case series)
Level of Evidence 4

Impact of Multiparametric Endorectal Coil Prostate Magnetic Resonance Imaging on Disease Reclassification Among Active Surveillance Candidates: A Prospective Cohort Study

PURPOSE We report magnetic resonance imaging findings among unselected men with low risk prostate cancer before active surveillance. MATERIALS AND METHODS We prospectively enrolled men with low grade, low risk, localized prostate cancer. All patients underwent multiparametric endorectal coil magnetic resonance imaging and were offered confirmatory biopsy within 1 year of imaging. The primary outcome was the impact of magnetic resonance imaging on identifying patients who were reclassified by confirmatory biopsy as no longer fulfilling active surveillance criteria. We further identified clinical parameters associated with reclassification. The cohort was stratified as patients with 1) normal magnetic resonance imaging, 2) cancer on magnetic resonance imaging concordant with initial biopsy (less than 1 cm) and 3) cancer on magnetic resonance imaging larger than 1 cm. We performed univariate analysis to assess differences in clinical parameters among the groups. RESULTS Magnetic resonance imaging did not detect cancer in 23 cases (38%) while magnetic resonance imaging and initial biopsy were concordant in 24 (40%). Magnetic resonance imaging detected a 1 cm or larger lesion in 13 patients (22%). Of the cases 18 (32.14%) were reclassified. When no cancer was identified on magnetic resonance imaging, only 2 cases (3.5%) were reclassified. The positive and negative predictive values for magnetic resonance imaging predicting reclassification were 83% (95% CI 73-93) and 81% (95% CI 71-91), respectively. Prostate specific antigen density was increased in patients with lesions larger than 1 cm on magnetic resonance imaging compared to those with no cancer on imaging (median 0.15 vs 0.07 ng/ml/cc, p=0.016). CONCLUSIONS Magnetic resonance imaging appears to have a high yield for predicting reclassification among men who elect active surveillance. Upon confirmation of our results magnetic resonance imaging may be used to better select and guide patients before active surveillance.

The role of magnetic resonance imaging in targeting prostate cancer in patients with previous negative biopsies and elevated prostate-specific antigen levels

In the past 20 years, magnetic resonance imaging (MRI) has developed rapidly, along with the management of localized prostate cancer. We summarize current data on the efficacy of MRI for targeting cancer, compared with biopsies, in patients with previous negative prostate biopsies and persistently elevated prostate‐specific antigen (PSA) levels. The key clinical question is how many men benefit by having had prostate cancer detected purely because of the MRI‐targeted, as opposed to standard scheme, biopsies. We reviewed all available databases for prospective studies in patients having MRI and prostate biopsy with previous negative biopsies and persistently elevated PSA levels. Six studies fulfilled the selection criteria, with 215 patients in all; in these studies, the cancer‐detection rate at repeat biopsy was 21–40%. For MRI or combined MRI/MR spectroscopy, the overall sensitivity for predicting positive biopsies was 57–100%, the specificity 44–96% and the accuracy 67–85%. In five studies, specific MRI‐targeted biopsies and standard cores were taken, with a significant proportion (34/63, 54%) having cancer detected purely because of the MRI‐targeted cores. The value of endorectal MRI and MR spectroscopy in patients with elevated PSA levels and previous negative biopsies to target peripheral zone tumours appears to be significant. Although more data obtained with current technologies are needed, published results to data are encouraging. A comparison study and cost‐benefit analysis of MRI‐targeted vs saturation biopsy in this group of patients would also be ideal, to delineate any advantages.

Focal Laser Ablation for Prostate Cancer Followed by Radical Prostatectomy: Validation of Focal Therapy and Imaging Accuracy

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

Assessing regional hypoxia in human renal tumours using 18F-fluoromisonidazole positron emission tomography

To assess renal tumours for hypoxic regions using 18F‐fluoromisonidazole (18F‐FMISO) positron emission tomography (PET), a recognized noninvasive method for detecting hypoxia in tumours, as renal cell carcinoma (RCC) can be potentially cured with nephrectomy but recurrence develops in most patients, who then respond poorly to treatments such as chemotherapy, and hypoxia is known to confer resistance to radiotherapy and chemotherapy in many solid tumours.

The social media revolution is changing the conference experience: analytics and trends from eight international meetings

To analyse the use of Twitter at urology conferences to enhance the social media conference experience.

Sepsis and 'superbugs': should we favour the transperineal over the transrectal approach for prostate biopsy?

To determine the rate of hospital re‐admission for sepsis after transperineal (TP) biopsy using both local data and worldwide literature, as there is growing interest in TP biopsy as an alternative to transrectal ultrasonography (TRUS)‐guided biopsy for patients undergoing repeat prostate biopsy.

The role of magnetic resonance imaging in the diagnosis and management of prostate cancer

The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that multi‐parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer.