resident physician, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, Department of Radiology
Improving prostate cancer diagnosis, for applying timely treatment and avoiding unnecessary biopsies
The prostate imaging research team I am part of concentrates its efforts to find ways to improve the current methods of diagnosing prostate cancer in a timely manner, in order to streamline the pathway to proper treatment for the patients that truly have cancer, as well as avoiding invasive diagnostic methods (12-core biopsy, which means the patient will get needle biopsy in 12 different areas within the prostate, to cover all the relevant zones – as it comes out from the above description, this method can still miss the cancer (not 100% accurate) and is invasive and painful for the patient).
Multi-parametric magnetic resonance imaging (mpMRI) has been shown to detect prostate cancer with high diagnostic accuracy. Genomic data such as Prostate Cancer Gene 3 (PCA3) is known to be over-expressed in prostate cancer. However, radio-genomic studies combining the two are lacking. We propose a model combining prostate imaging and genomic PCA3 data for detecting clinically significant prostate cancer – oral presentation. Additionally, the four-kallikrein (4K) blood panel is known to help predict clinically significant prostate cancer. We combined prostate mpMRI and 4K blood panel data into a single radio-genomic statistical model that can accurately detect prostate cancer – first poster presentation. Creating personalized medicine by combining mpMRI and PCA3/mpMRI and 4K panel data into combined radio-genomic models can aid in early detection of prostate cancer and decrease invasive and unnecessary prostate biopsies.
The second poster presentation consists of an educational exhibit related to different endoscopic procedures performed within the upper gastro-intestinal tract. With the increasing use of novel endoscopic procedures to replace conventional surgery, based on minimal-invasiveness and brief recovery for the patient, the radiologist needs to keep pace with the expected normal findings or potential complications and their imaging features, as imaging has a major input within the post-procedural evaluation and follow-up process. We believe this work will add value in guiding radiologists to be up-to-date in the context of evolving minimally-invasive techniques and their capability to leave 'traces' for future imaging evaluations, which need to be properly assessed (the paper was already accepted for publication in Abdominal Radiology). The ultimate goal is, of course, having the patient's safety and best interest at heart.
Abstract: To evaluate the diagnostic performance and inter-reader reliability of the multiparametric magnetic resonance imaging (mpMRI) based prostate imaging reporting and data system (PI-RADS) version 1 and version 2 for the assessment of prostate cancer.A cohort of 82 patients underwent endorectal mpMRI at 1.5T. Patients had at least one lesion with a PI-RADS v1 assessment category of ≥3 and were selected for targeted in-bore MR-guided biopsy in a subsequent session. The results of the histopathological workup were used as reference standard. All lesions were retrospectively evaluated according to PI-RADS v2 by an experienced and unexperienced blinded reader. Diagnostic performance was compared by analyzing the area under the Receiver Operating Characteristics Curve (AUC). The weighted kappa method was used to calculate inter-reader reliability.Targeted MR-guided biopsy was performed in 136 lesions and revealed 39 malignant lesions in 31 patients. AUC values increased for the experienced reader (PI-RADS v1 0.79; PI-RADS v2 0.83) and unexperienced reader (PI-RADS v1 0.70; PI-RADS v2 0.83). When excluding the cases of low grade cancer (Gleason score=3+3), AUC values increased further for the experienced reader (PI-RADS v1 0.88; PI-RADS v2 0.91) and unexperienced reader (PI-RADS v1 0.78; PI-RADS v2 0.90). Specificity at the selected threshold of a PI-RADS v1/v2 assessment category ≥4 improved for both readers. Inter-reader agreement increased from κ=0.55 in PI-RADS v1 to κ=0.68 in v2.PI-RADS v2 improved diagnostic performance for the assessment of suspicious intraprostatic lesions identified in PI-RADS v1 for both readers and led to higher inter-reader reliability. These results suggest that PI-RADS v2 is a reliable and replicable reporting system for the assessment of prostate cancer.
Pub.: 15 Mar '16, Pinned: 30 Jun '17
Abstract: The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011.To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa.A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥ 74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur.Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.
Pub.: 12 Nov '13, Pinned: 30 Jun '17
Abstract: Since there are no effective therapeutic options for advanced prostate cancer, early detection of this tumour is pivotal and can increase the curative success rate. Although the routine use of serum PSA testing has undoubtedly increased prostate cancer detection, one of its main drawbacks has been the lack of specificity that results in a high negative biopsy rate. Since prostate cancer is a heterogeneous disease, it has become clear that a defined set of markers will provide significantly more diagnostic information than any one biomarker. The list of potential prostate cancer biomarkers will continue to grow. Only when research groups use the proposed guidelines for biomarker development, then systematic evaluation and clinical investigation of these biomarkers will gain more insight into their true diagnostic potential.
Pub.: 30 Sep '05, Pinned: 30 Jun '17
Abstract: Potential survival benefits from treating aggressive (Gleason score, ≥7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease.To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs.Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort.Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy.Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes.Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men.Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.
Pub.: 19 May '17, Pinned: 30 Jun '17
Abstract: Analysis of systematic 12-core biopsies (SBx) has shown that African-American (AA) men tend to harbor higher risk prostate cancer (PCa) at presentation relative to other races. Multiparametric magnetic resonance imaging (mpMRI) and MRI-ultrasound fusion-guided biopsy (FBx) have been shown to diagnose more intermediate- and high-risk PCa in the general population; however, the efficacy in AA remains largely uncharacterized. We aim to evaluate the utility of FBx in an AA patient cohort.Men suspected of PCa underwent an mpMRI and FBx with concurrent SBx from 2007 to 2015 in this institutional review board-approved prospective cohort study. Patient demographics, imaging and fusion biopsy variables were collected. χ(2), Mann-Whitney U-test and McNemar's tests were performed to compare proportions, means and paired variables, respectively. Clinically significant PCa (CSPCa) was defined as Gleason score ⩾3+4.Fusion biopsy demonstrated exact agreement with SBx risk categories in 64% of AA men. There was no statistically significant difference in the detection of CSPCa between FBx vs SBx (68 vs 62 cases, P=0.36). However, FBx detected 41% fewer cases of clinically insignificant PCa (CIPCa) compared with SBx (FBx 30 vs SBx 51 cases, P=0.0004). The combined FBx/SBx biopsy approach detected significantly more cases of CSPCa (FBx/SBx 80 vs SBx 62 cases, P=0.004) while detecting comparable number of cases of CIPCa (FBx/SBx 45 vs SBx 51 cases, P=0.37) compared with SBx alone. FBx/SBx also detected more CSPCa in patients with a history of prior negative SBx (FBx/SBx 28 vs 19 cases, P=0.003).FBx when used in combination with SBx detected more cases of CSPCa while not significantly increasing the diagnosis of CIPCa in AA men. Future multicenter studies will be needed to validate ultimately the clinical implications of FBx in AA patients.Prostate Cancer and Prostatic Diseases advance online publication, 25 April 2017; doi:10.1038/pcan.2017.21.
Pub.: 26 Apr '17, Pinned: 30 Jun '17
Abstract: Multi-parametric prostate magnetic resonance imaging (MRI) is considered the current imaging standard for detection and staging of prostate cancer. The combination of anatomical and functional imaging provided in this exam significantly increases the accuracy of prostate cancer detection. Computed tomography (CT) imaging has so far been found to be lacking in this regard, however observations at our academic institution as well as evidence present in the literature support the proposition that CT could indeed be helpful in detecting prostate abnormalities that correspond to neoplasm. The purpose of this study was to prove that areas of focal mass-like enhancement on CT imaging directly correlate with prostate neoplasms as revealed on multi-parametric MRI and follow-up targeted biopsy.This was a single institution retrospective study with 27 male subjects. Inclusion criteria required subjects to have a multi-parametric MRI of the prostate between January 1, 2014 and June 1, 2015 and a pelvic venous phase contrast-enhanced CT study between January 1, 2000 and June 1, 2015. Two blinded Radiologists read subjects' CT scans for any abnormalities of the prostate. CT and multi-parametric MRI results were compared and were considered concordant if focal or mass like enhancement to a greater degree than the background parenchyma was detected in the same areas of the prostate on CT scan as areas of decreased T2 signal, perfusion abnormalities, and restricted diffusion on multi-parametric MRI.CT results were directly compared to multi-parametric MRI findings and biopsy results. The overall agreement of MRI and CT is 85.19% (95% CI: 67.52-94.08%). The positive percent agreement is 78.95% (95% CI: 54.43-93.95%) and the negative percent agreement is 100.0% (95% CL: 63.06-100.0%). When CT results are directly compared to biopsy results, sensitivity and specificity of CT are 63.64% (95% CI: 30.79-89.07%) and 100.0% (95% CI: 47.82-100.0%). The positive predictive value (PPV) is 100.0% (95% CI: 59.04-100.0%) and the negative predictive value (NPV) is 55.56% (95% CI: 21.2-86.3%). When compared to MRI, CT has a lower sensitivity and a higher specificity, as well as a higher PPV and NPV. Logistic regression analysis did not show a significant relationship between concordance of MRI and CT and Gleason score, time between studies, age, and Prostate-specific antigen (PSA) level.Incidental focal areas of mass-like enhancement in the peripheral prostate detected on venous phase contrast-enhanced CT imaging may indeed correlate with prostate neoplasm and it would be prudent to suggest further work-up with PSA and perhaps multi-parametric MRI, especially in high-risk patients.
Pub.: 04 Nov '15, Pinned: 30 Jun '17