The primacy of multiparametric MRI in men with suspected prostate cancer

Background: Multiparametric MRI (mpMRI) became recognised in investigating those with suspected prostate cancer between 2010 and 2012; in the USA, the preventative task force moratorium on PSA screening was a strong catalyst. In a few short years, it has been adopted into daily urological and oncological practice. The pace of clinical uptake, born along by countless papers proclaiming high accuracy in detecting clinically significant prostate cancer, has sparked much debate about the timing of mpMRI within the traditional biopsy-driven clinical pathways. There are strongly held opposing views on using mpMRI as a triage test regarding the need for biopsy and/or guiding the biopsy pattern. Objective: To review the evidence base and present a position paper on the role of mpMRI in the diagnosis and management of prostate cancer. Methods: A subgroup of experts from the ESUR Prostate MRI Working Group conducted literature review and face to face and electronic exchanges to draw up a position statement. Results: This paper considers diagnostic strategies for clinically significant prostate cancer; current national and international guidance; the impact of pre-biopsy mpMRI in detection of clinically significant and clinically insignificant neoplasms; the impact of pre-biopsy mpMRI on biopsy strategies and targeting; the notion of mpMRI within a wider risk evaluation on a patient by patient basis; the problems that beset mpMRI including inter-observer variability. Conclusions: The paper concludes with a set of suggestions for using mpMRI to influence who to biopsy and who not to biopsy at diagnosis. Key Points: • Adopt mpMRI as the first, and primary, investigation in the workup of men with suspected prostate cancer. • PI-RADS assessment categories 1 and 2 have a high negative predictive value in excluding significant disease, and systematic biopsy may be postponed, especially in men with low-risk of disease following additional risk stratification. • PI-RADS assessment category lesions 4 and 5 should be targeted; PI-RADS assessment category lesion 3 may be biopsied as a target, as part of systematic biopsies or may be observed depending on risk stratification

Prostate Indeterminate Lesions on Magnetic Resonance Imaging-Biopsy Versus Surveillance: A Literature Review

CONTEXT: The indeterminate multiparametric prostate magnetic resonance image (mpMRI) lesion is one which cannot be classified as "positive" or "negative" for suspected cancer. Currently, there is no consensus on how to manage patients with indeterminate mpMRIs where areas cannot be classified as positives or negatives (Prostate Imaging Reporting and Data System [PI-RADS] 3 or Likert 3). OBJECTIVE: To define the concept of indeterminate lesion and describe the management strategies that may be adopted for these patients. EVIDENCE ACQUISITION: A literature search of the PubMed database was performed including the search terms "prostate indeterminate lesions", "PI-RADS 3", "Likert 3", "magnetic resonance imaging", and "prostate cancer". EVIDENCE SYNTHESIS: There is no universally accepted definition of what constitutes an indeterminate lesion on mpMRI. This is partly due to the experience of the reporting radiologist and their willingness to call a lesion indeterminate, knowing that this may have consequences for biopsy decisions. This is also partly due to the significant variation in mpMRI acquisition parameters used between different sites. Strategies for managing the indeterminate lesion include: (1) biopsy, where there is a highly variable prevalence of prostate cancer (PCa), reflecting the differences in clinically significant PCa definitions, mpMRI protocols and interobserver variability in characterization of indeterminate lesions and (2) surveillance, where early results suggest that this strategy may be of value for some selected patients with prostate-specific antigen (PSA) monitoring and/or interval mpMRI. The use of prebiopsy MRI, in conjunction with traditional clinical parameters and secondary biomarkers-nomograms, may allow a more accurate selection of patients who can avoid biopsy. CONCLUSIONS: A strategy of close surveillance based on PSA monitoring and interval mpMRI is a feasible management option for motivated patients with indeterminate mpMRI. This surveillance strategy could result in fewer men needing to undergo biopsy, and although early results are promising, long-term results for such a strategy are awaited. PATIENT SUMMARY: In some patients who have an MRI scan of their prostate, the scan may identify an area which may or may not contain cancer. This area is typically called the "indeterminate" lesion. In this report, we attempted to define the concept of indeterminate lesion on multiparametric magnetic resonance (mpMRI) and described the strategies that may be performed for these patients. The use of mpMRI in conjunction with traditional clinical parameters may allow more accurate risk stratification and assessment of the need for prostate biopsy

Comparative Analysis of PSA Density and an MRI-Based Predictive Model to Improve the Selection of Candidates for Prostate Biopsy

Clinically significant prostate cancer; Predictive model; Prostate-specific antigenCàncer de pròstata clínicament significatiu; Model predictiu; Antigen específic de la pròstataCáncer de próstata clínicamente significativo; Modelo predictivo; Antígeno específico de la próstataThis study is a head-to-head comparison between mPSAD and MRI-PMbdex. The MRI-PMbdex was created from 2432 men with suspected PCa; this cohort comprised the development and external validation cohorts of the Barcelona MRI predictive model. Pre-biopsy 3-Tesla multiparametric MRI (mpMRI) and 2 to 4-core transrectal ultrasound (TRUS)-guided biopsies for suspicious lesions and/or 12-core TRUS systematic biopsies were scheduled. Clinically significant PCa (csPCa), defined as Gleason-based Grade Group 2 or higher, was detected in 934 men (38.4%). The area under the curve was 0.893 (95% confidence interval [CI]: 0.880–0.906) for MRI-PMbdex and 0.764 (95% CI: 0.774–0.783) for mPSAD, with p < 0.001. MRI-PMbdex showed net benefit over biopsy in all men when the probability of csPCa was greater than 2%, while mPSAD did the same when the probability of csPCa was greater than 18%. Thresholds of 13.5% for MRI-PMbdex and 0.628 ng/mL2 for mPSAD had 95% sensitivity for csPCa and presented 51.1% specificity for MRI-PMbdex and 19.6% specificity for mPSAD, with p < 0.001. MRI-PMbdex exhibited net benefit over mPSAD in men with prostate imaging report and data system (PI-RADS) <4, while neither exhibited any benefit in men with PI-RADS 5. Hence, we can conclude that MRI-PMbdex is more accurate than mPSAD for the proper selection of candidates for prostate biopsy among men with suspected PCa, with the exception of men with a PI-RAD S 5 score, for whom neither tool exhibited clinical guidance to determine the need for biopsy.This research was funded by Instituto de Salut Carlos III (ESP), grant number PI20/01666

The Barcelona Predictive Model of Clinically Significant Prostate Cancer

Clinically significant prostate cancer; Magnetic resonance imaging; Predictive modelCáncer de próstata clínicamente significativo; Imagen de resonancia magnética; Modelo predictivoCàncer de pròstata clínicament significatiu; Imatge per ressonància magnètica; Model predictiuA new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories.This research was funded by the Instituto de Salud Carlos III (ESP), grant number PI20/01666

Nomogram for predicting survival in patients treated with liposomal irinotecan plus fluorouracil and leucovorin in metastatic pancreatic cancer

NAPOLI-1; Liposomal irinotecan; Survival outcomesNAPOLI-1; Irinotecan liposòmic; Resultats de supervivènciaNAPOLI-1; Irinotecan liposomal; Resultados de supervivenciaNAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m2). The nomogram was used to predict the 6- and 12-month survival probability. The mean absolute errors between the observed and predicted probabilities for OS at 3, 6, and 9 months were 0.07, 0.08, and 0.07, respectively. This nomogram, based on NAPOLI-1, provides additional insight to aid decision-making for patients with mPDAC after previous gemcitabine-based therapy.This study (NCT01494506) was supported by Merrimack Pharmaceuticals, Inc., Cambridge, MA, USA. Analysis sponsored by Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA

Overdiagnosis and overuse of diagnostic and screening tests in low-income and middle-income countries: a scoping review

OBJECTIVE: Overdiagnosis and overuse of healthcare services harm individuals, take resources that could be used to address underuse, and threaten the sustainability of health systems. These problems are attracting increasing attention in low-income and middle-income countries (LMICs). Unaware of any review of relevant evidence, we conducted a scoping review of the evidence around overdiagnosis and overuse of diagnostic and screening tests in LMICs. DESIGN: Scoping review. METHODS: We searched PubMed, Embase, PsycINFO, Global Index Medicus for relevant studies published until 24 May 2021, with no restrictions on date or language. We categorised included studies by major focus (overdiagnosis, overuse of tests, or both) and main themes (presence or estimates of extent; drivers; consequences and solutions). RESULTS: We identified 2763 unique records and included 162 articles reporting on 154 studies across 55 countries, involving over 2.8 million participants and/or requests for tests. Almost half the studies focused on overdiagnosis (70; 45.5%), one-third on overuse of tests (61; 39.6%) and one-fifth on both (23; 14.9%). Common overdiagnosed conditions included malaria (61; 39.6%) and thyroid cancer (25; 16.2%), estimated to be >70% in China. Overused tests included imaging (n=25 studies) such as CT and MRI; laboratory investigations (n=18) such as serological tests and tumour markers; and procedures (n=14) such as colonoscopy. Drivers included fear of conflict with patients and expanding disease definitions. Common consequences included unnecessary treatments such as antimalarials, and wasted resources, with costs of malaria overdiagnosis estimated at US$86 million in Sudan in 1 year alone. Only 9% of studies discussed solutions, which included addressing inappropriately lowered diagnostic thresholds and reforming test-ordering processes. CONCLUSIONS: Overdiagnosis and overuse of tests are widespread in LMICs and generate significant harm and waste. Better understanding of the problems and robust evaluation of solutions is needed, informed by a new global alliance of researchers and policy-makers

The HBP1 tumor suppressor is a negative epigenetic regulator of MYCN driven neuroblastoma through interaction with the PRC2 complex

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