prostate cancer imaging

Posts Tagged ‘prostate cancer imaging’

Following (or not) the guidelines for use of imaging in management of prostate cancer

Posted in Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Imaging-based Cancer Patient Management, Medical Device Therapies for Altzheimer’s Disease, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, tagged guidlines, health, Imaging-based Cancer Patient Management, management of prostate cancer, Medical imaging, medicine, Personalized medicine, Prostate cancer, prostate cancer imaging, prostate cancer patients on August 29, 2013| 1 Comment »

Following (or not) the guidelines for use of imaging in management of prostate cancer.

Writer and curator: Dror Nir, PhD

Over diagnosis and over treatment is a trend of the last two decades. It leads to increase in health-care costs and human-misery.

The following headline on Medscape; Swedes Show That We Can Improve Imaging in Prostate Cancer elicited my curiosity.

I was expecting “good news” – well, not this time!

In spite the “general language” the study that the above mentioned headline refers to is not addressing the global use of imaging in prostate cancer patients’ pathway but is specific to use of radionuclide bone-scans as part of patients’ staging. The “bad-news” are that realization that the Swedish government had to invest many man-years to achieve “success” in reducing unnecessary use of such imaging in low risk patients. Moreover, the paper reveals under-use of such imaging technology for staging high risk prostate cancer patients.

Based on this paper, one could come to the conclusion that in reality, we are facing long lasting non-conformity with established guidelines related to the use of “full-body” imaging as part of the prostate cancer patients’ pathway in Europe and USA.

Here is a link to the original paper:

Prostate Cancer Imaging Trends After a Nationwide Effort to Discourage Inappropriate Prostate Cancer Imaging, Danil V. Makarov, Stacy Loeb, David Ulmert, Linda Drevin, Mats Lambe and Pär Stattin Correspondence to: Pär Stattin, MD, PhD, Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå University, SE- 901 87 Umeå, Sweden (e-mail:par.stattin@urologi.umu.se).

JNCI J Natl Cancer Inst (2013)doi: 10.1093/jnci/djt175

For convenience, here are the highlights:

Reducing inappropriate use of imaging to stage incident prostate cancer is a challenging problem highlighted recently as a Physician Quality Reporting System quality measure and by the American Society of Clinical Oncology and the American Urological Association in the Choosing Wisely campaign.

Since 2000, the National Prostate Cancer Register (NPCR) of Sweden has led an effort to decrease national rates of inappropriate prostate cancer imaging by disseminating utilization data along with the latest imaging guidelines to urologists in Sweden.

Results Thirty-six percent of men underwent imaging within 6 months of prostate cancer diagnosis. Overall, imaging use decreased over time, particularly in the low-risk category, among whom the imaging rate decreased from 45% to 3% (P < .001), but also in the high-risk category, among whom the rate decreased from 63% to 47% (P < .001). Despite substantial regional variation, all regions experienced clinically and statistically (P < .001) significant decreases in prostate cancer imaging.

These results may inform current efforts to promote guideline-concordant imaging in the United States and internationally.

In 1998, the baseline low-risk prostate cancer imaging rate in Sweden was 45%. Per the NCCN guidelines (7), none of these men should have received bone imaging unless they presented with symptoms suggestive of bone pain (8,24). In the United States, the imaging rate among men with low-risk prostate cancer has been reported to be 19% to 74% in a community cohort and 10% to 48% in a Surveillance Epidemiology and End Results (SEER)–Medicare cohort (10–13,16). It is challenging to compare these rates directly across the two countries because the NPCR aggregates all staging imaging into one variable. However, our sampling revealed that 88% of those undergoing imaging had at least a bone scan, whereas only 11% had any CTs and 10% had any MRI. This suggests that baseline rates of bone scan among low-risk men in Sweden were similar to those among their low-risk counterparts in the United States, whereas rates of axial imaging were likely much lower. During the study period, rates of prostate cancer imaging among low-risk men in Sweden decreased to 3%, substantially lower than those reported in the United States at any time.

Miller et al. describe a decline in imaging associated with a small-scale intervention administered in three urology practices located in the United States participating in a quality-improvement consortium. Our study’s contribution is to demonstrate that a similar strategy can be applied effectively at a national scale with an associated decline in inappropriate imaging rates, a finding of great interest for policy makers in the United States seeking to improve health-care quality.

In 1998, the baseline high-risk prostate cancer imaging rates in Sweden were 63%, and decreased by 43% in 2008 (rising slightly to 47% in 2009). Based on our risk category definitions and the guidelines advocated in Sweden, all of these men should have undergone an imaging evaluation (8,24). Swedish rates of prostate cancer imaging among men with high-risk disease are considerably lower than those reported from the SEER–Medicare cohort, where 70% to 75% underwent bone scan and 57% to 58% underwent CT (13,16). These already low rates of imaging among men with high-risk prostate cancer only decreased further during the NPCR’s effort to promote guideline-concordant imaging. Clearly in both countries, imaging for high-risk prostate cancer remains underused despite the general overuse of imaging and numerous guidelines encouraging its appropriate use (3–9).

Similar items I have covered on this this Open Access Online Scientific Journal:

Not applying evidence-based medicine drives up the costs of screening for breast-cancer in the USA.

Read Full Post »

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Posted in Biomarkers & Medical Diagnostics, Cancer Prevention: Research & Programs, Imaging-based Cancer Patient Management, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Statistical Methods for Research Evaluation, tagged American Urological Association, AUA, cancer management, choice of treatment, CT, Medical guideline, Medical imaging, MRI, Prostate, Prostate biopsy, Prostate cancer, prostate cancer imaging, Prostate cancer screening, Prostate-specific antigen, psa screening, urology on May 21, 2013| 9 Comments »

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Author-Writer: Dror Nir, PhD

When reviewing the DETECTION OF PROSTATE CANCER section on the AUA website , The first thing that catches one’s attention is the image below; clearly showing two “guys” exploring with interest what could be a CT or MRI image…..

But, if you bother to read the review underneath this image regarding EARLY DETECTION OF PROSTATE CANCER: AUA GUIDELINE produced by an independent group that was commissioned by the AUA to conduct a systematic review and meta-analysis of the published literature on prostate cancer detection and screening; Panel Members: H. Ballentine Carter, Peter C. Albertsen, Michael J. Barry, Ruth Etzioni, Stephen J. Freedland, Kirsten Lynn Greene, Lars Holmberg, Philip Kantoff, Badrinath R. Konety, Mohammad Hassan Murad, David F. Penson and Anthony L. Zietman – You are bound to be left with a strong feeling that something is wrong!

The above mentioned literature review was done using rigorous approach.

“The AUA commissioned an independent group to conduct a systematic review and meta-analysis of the published literature on prostate cancer detection and screening. The protocol of the systematic review was developed a priori by the expert panel. The search strategy was developed and executed

by reference librarians and methodologists and spanned across multiple databases including Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials and Scopus. Controlled vocabulary supplemented with keywords was used to search for the relevant concepts of prostate cancer, screening and detection. The search focused on DRE, serum biomarkers (PSA, PSA Isoforms, PSA kinetics, free PSA, complexed PSA, proPSA, prostate health index, PSA velocity, PSA

doubling time), urine biomarkers (PCA3, TMPRSS2:ERG fusion), imaging (TRUS, MRI, MRS, MR-TRUS fusion), genetics (SNPs), shared-decision making and prostate biopsy. The expert panel manually identified additional references that met the same search criteria”

While reading through the document, I was looking for the findings related to the roll of imaging in prostate cancer screening; see highlighted above. The only thing I found: “With the exception of prostate-specific antigen (PSA)-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests.”

This must mean that: Notwithstanding hundreds of men-years and tens of millions of dollars which were invested in studies aiming to assess the contribution of imaging to prostate cancer management, no convincing evidence to include imaging in the screening progress was found by a group of top-experts in a thorough and rigorously managed literature survey! And it actually lead the AUA to declare that “Nothing new in the last 20 years”…..

My interpretation of this: It says-it-all on the quality of the clinical studies that were conducted during these years, aiming to develop an improved prostate cancer workflow based on imaging. I hope that whoever reads this post will agree that this is a point worth considering!

For those who do not want to bother reading the whole AUA guidelines document here is a peer reviewed summary:

“Early Detection of Prostate Cancer: AUA Guideline; Carter HB, Albertsen PC, Barry MJ, Etzioni R, Freedland SJ, Greene KL, Holmberg L, Kantoff P, Konety BR, Murad MH, Penson DF, Zietman AL; Journal of Urology (May 2013)”

It says:

“A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age<40; 40 to 54; 55 to 69; ≥70).

RESULTS: With the exception of prostate-specific antigen (PSA)-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and over treatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.

CONCLUSIONS: The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence. The entire guideline is available at www.AUAnet.org/education/guidelines/prostate-cancer-detection.cfm.”

Other research papers related to the management of Prostate cancer were published on this Scientific Web site:

From AUA2013: “Histoscanning”- aided template biopsies for patients with previous negative TRUS biopsies

Imaging-biomarkers is Imaging-based tissue characterization

On the road to improve prostate biopsy

State of the art in oncologic imaging of Prostate

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

Today’s fundamental challenge in Prostate cancer screening

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Men With Prostate Cancer More Likely to Die from Other Causes

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

New clinical results supports Imaging-guidance for targeted prostate biopsy

Prostate Cancer: Androgen-driven “Pathomechanism” in Early-onset Forms of the Disease

Prostate Cancer and Nanotecnology

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition

Imaging agent to detect Prostate cancer-now a reality

Scientists use natural agents for prostate cancer bone metastasis treatment

ROLE OF VIRAL INFECTION IN PROSTATE CANCER

Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

Read Full Post »

State of the art in oncologic imaging of Prostate.

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Ecosystems & Industrial Concentration in the Medical Device Sector, Health Economics and Outcomes Research, Imaging-based Cancer Patient Management, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Personalized and Precision Medicine & Genomic Research, tagged American Cancer Society, gleason score, imaging modalities, prostate cancer imaging, psa level, tissue characterization on January 28, 2013| 4 Comments »

State of the art in oncologic imaging of Prostate.

Author-Writer: Dror Nir, PhD

This is the third post in a series in which I will address the state of the art in oncologic imaging based on a review paper; Advances in oncologic imaging^†^‡ that provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, colorectal cancers, and lymphoma. This paper is published at CA Cancer J Clin 2012. © 2012 American Cancer Society.

The paper gives a fair description of the use of imaging in interventional oncology based on literature review of more than 200 peer-reviewed publications. In this post I summaries the chapter on prostate cancer imaging.

Although ultrasound is the most frequently used imaging-device in prostate cancer management the authors did not review the related literature. Instead, they focused their review on MRI and PET imaging. To anyone who wishes to learn about ultrasound-imaging’s state of the art in prostate cancer I can offer reading some of my previous posts that are listed below.

My own interpretation (as stated in my summary-note) to the focus by the authors on MRI and PET imaging is that they were mainly looking to highlight the advances in those imaging modalities which provides tissue characterization! Although, this term is not explicitly mentioned by them.

The authors identifies correctly the main issues in Prostate cancer management:

It’s a frequent disease, but not an aggressive killer
It’s highly heterogeneous, therefore it is difficult to predict the clinical outcomes both before and after treatment.
“Although several predictive methods have been developed,72 the treatment decision-making process is complex and requires balancing clinical benefits, life expectancy, comorbidities and potential treatment-related side effects.”
The disease’s staging and related prognosis are determined during diagnosis based on PSA level and the Gleason score of biopsy’s samples. “Although prostate-specific antigen (PSA) screening hsis as resulted in the diagnosis of prostate cancer at earlier stages and with lower Gleason scores, it has also contributed to concerns about over-diagnosis, overtreatment of clinically insignificant disease, associated treatment-related toxicity, and escalating costs”

The following sections summarizes the latest advances in MRI and PET imaging methods for functional and metabolic assessment of prostate cancer.

Advances in MRI of Prostate Cancer

“MRI is potentially an ideal imaging modality for the local staging of prostate cancer, given its ability to depict the prostate and surrounding structures in exquisite detail. Recently, morphologic imaging with conventional MR imaging sequences has been supplemented by a multiparametric imaging approach using new functional and metabolic methods, namely diffusion waited MRI (DW-MRI); dynamic contrast-enhanced MRI (DCE-MRI), which probes tissue micro-vascular and perfusion properties; and MR spectroscopy (Fig. below).”

Representative images from a 3-T multiparametric MRI examination in a 57-year-old man with PSA level of 9.1 ng/mL and Gleason score 7 (3 + 4) prostate cancer (arrow) located in the right anterior prostate and involving the transition and peripheral zones: (A) transverse T2-weighted image, (B) transverse ADC map generated from DW-MRI images, (C) transverse DCE-MRI image, (D) volume transfer constant (Ktrans) parametric map from DCE-MRI overlaid on T2-weighted image.

Diffusion-Weighted MRI

“Because the diffusion of water molecules within tumors is more restricted than in normal tissue, ADCs calculated with DW-MRI tend to be lower in cancer than in normal tissue. A number of studies, using various image acquisition methods and reference standards, have reported the utility of DW-MRI in prostate cancer detection.74-79. More importantly, studies have indicated that the greatest value of DW-MRI as an addition to conventional MRI might lie in its potential to assess prostate cancer aggressiveness noninvasively, because ADC values have been shown to correlate significantly with tumor Gleason scores.77-79 “

“However, the clinical value of DW-MRI in predicting the surgical Gleason score needs to be further studied.”

Dynamic Contrast-Enhanced MRI

“DCE-MRI is based on the repeated acquisition of images of a region of interest during the passage of an intravenously administered contrast agent. DCE-MRI allows malignant tissue to be distinguished from benign tissue by exploiting differences in the distribution of the contrast agent between vascular and extravascular spaces over time. 80 Prostate cancer usually shows early, rapid, and intense enhancement with quick washout of contrast compared to noncancerous prostate tissue. Although DCE-MRI has shown potential in assessing prostate cancer in preliminary studies, further research is necessary to establish its clinical value and indications and address technical challenges, such as standardization of acquisition and analysis methods.”

MR Spectroscopy

“Commercially available acquisition and analysis software packages for MR spectroscopic imaging of the prostate produce 3-dimensional spectral data showing the relative concentrations of tissue metabolites within specified volumes of tissue. In the prostate, the metabolites of interest on in vivo MR spectroscopic imaging are citrate, creatine, choline, and polyamines.87, 88 (choline + creatine)/citrate ratio has traditionally been used to identify prostate cancer on MR spectroscopy. “

“Studies have indicated that MR spectroscopy might have potential for aiding cancer localization, estimating tumor volume, noninvasively assessing prostate cancer aggressiveness and predicting the probability of insignificant cancer.90-92”

the authors found that MRI, especially when acquired with multiparametric techniques (DW-MRI, DCE-MRI, and/or MR spectroscopy), has the potential to add value in prostate cancer diagnosis, eg, by guiding biopsy to the most suspicious areas and eventually reduce the number of systematic/random biopsies.108-110 A specific use-case for MRI guided biopsies is men with elevated PSA and negative systematic/random TRUS-guided biopsy where MRI is used for locating suspicious areas for targeted biopsies.111 MRI, “could potentially improve prostate cancer management especially in the intermediate- and high-risk groups.” 112 They also suggest to use MRI, especially when acquired with multiparametric techniques as a tool for choosing and managing active survailance and focal treatment. These two novel methods of treatment have immerged as an answer to unbearable overdiagnosis and overtreatment in prostate cancer management.113 114

About active surveillance: “Given the risks of morbidity associated with radical treatment (eg, radical prostatectomy or radiation therapy), active surveillance (monitoring of PSA levels, periodic imaging and repeat biopsies) is gaining acceptance as an alternative initial management strategy for carefully selected men with low-risk prostate cancer.115 Active surveillance could be a considerably more cost-effective approach than immediate treatment for prostate cancer, as suggested in a theoretical cohort.116 Furthermore, by preserving quality of life and minimizing the harms from radical treatment of low-risk prostate cancer, active surveillance could mitigate the concerns regarding extensive screening, overdiagnosis, and overtreatment of prostate cancer. Ultimately questions about how to best practice active surveillance will need to be addressed in prospective studies. Currently, the main challenges in active surveillance of prostate cancer are adequate characterization of disease at diagnosis and determination of the risk of progression.”

About focal therapy:, sometime referred to as focused therapy. This approach is frequently used in other cancers; e.g. breast lumpectomies. The idea is to treat only the cancer lesion and preserve the rest of the organ. Such treatment has the potential of offering better quality of life for the patients. 117 An open clinical question in respect to focal treatments is related to the fact that prostate cancer is often multifocal. Some studies suggest that it is enough to treat the index tumor (tumor volume > 0.5 mL) in order to control the disease.118 To date, patients’ selection for focal treatment is based on multiparametric MRI techniques and prostate mapping biopsy (trans-perinea template biopsy) 119

Advances in PET Imaging of Prostate Cancer

The main application for [¹⁸F]FDG PET is in patients with aggressive, metastatic prostate cancer. For these patients it helps detecting metastasis, and assessment on response to treatment.93-97, The authors of this review did not find support to using it for the majority of prostate cancer patients who are diagnosed at early stage due to its low specificity in this population.

Representative images from 3-T MRI and [18F]FDG PET/CT examinations in a 70-year-old man with PSA level of 8.0 ng/mL and Gleason score of 8 (4 + 4) prostate cancer (arrow) located in the left posterolateral prostate within the peripheral zone: (A) transverse T2-weighted image, (B) transverse fused [18F]FDG PET/CT image, (C) transverse fused [18F]FDG PET/CT image overlaid on T2-weighted MRI.

Other tracers such as [¹¹C]choline and radiolabeled acetate ([¹¹C]acetate) have recently been evaluated in clinical studies and found to be more promising than [¹⁸F]FDG for prostate cancer assessment.93, 96, 98

“Currently, the major indication for choline PET/CT is the early localization of recurrence in patients with PSA relapse after primary radical treatment. Potentially, this test may also be useful in radiotherapy planning.99, 100 Acetate participates in cytoplasmic lipid synthesis, and an increased fatty acid synthesis is thought to occur in prostate cancer.101 Similarly to [¹¹C]choline, radiolabeled acetate ([¹¹C]acetate) appears to be more useful than [¹⁸F]FDG in the assessment of prostate cancer before and after treatment.102, 103 “

“In summary, the role of PET imaging in prostate cancer is still evolving, as new and promising tracers are under investigation. Rigorous clinical trials using these new tracers in specific clinical scenarios will be needed before they can be employed routinely.”

On expectations from future screening, diagnosis and pre-treatment staging the authors summarizes: “An imaging modality that could reliably assess prostate cancer would be of great help in selecting from the wide range of management options now available.” and;

“there is a pressing need to improve not only anatomical imaging for tumor detection, localization and staging, but also functional and metabolic imaging for characterization of tumor biology. “

In regards to treatment choice: “active surveillance, focal therapy, radical prostatectomy, and radiation therapy represent a range of treatments with varying degrees of invasiveness for men with different disease grades and stages. Active surveillance and focal therapy, which are relatively new options, are promising but are complicated by uncertainties in risk stratification that affect treatment decision-making, as well as by uncertainties regarding the definition of appropriate outcome measures. Biopsy, which leaves the possibility of under sampling, is not sufficient to resolve these uncertainties. Novel biomarkers and modern imaging are expected to play increasingly important roles in facilitating broader acceptance of both active surveillance and focal therapy. Further research, particularly involving prospective validation, is needed to facilitate standardization and establish the roles of advanced imaging tools in routine prostate cancer management.”

My summary: Prostate cancer is a disease managed by urologists, not radiologists. This disease’s multi-choice of pathways is “craving” for tissue characterization. Nothing could fit the urologist’s work-flow better than ultrasound-based tissue characterization!