Last week, I came across an interesting abstract related to work that is carried-out in UCLA for several years now by Prof. Lenny Marks. Lenny participated to the development of “Artemis”. Artemis is a system that is adjunct to ultrasound and performs 3D Imaging and Navigation for Prostate Biopsy by Eigen. I thought that this deserves a complementary post to Imaging-guided biopsies: Is there a preferred strategy to choose? which I posted few weeks ago
When men present with risk parameters for harboring prostate cancer, they are advised to undergo a transrectal ultrasound guided prostate biopsy (TRUS biopsy). Over one million biopsies are carried out in the USA ever year.
The indications for a prostate biopsy in the USA are:
· Raised PSA above 2.5ng/ml
· Raised age-specific PSA
· Family history of prostate cancer
· High PSA density > 0.15ng/ml/cc
· High PSA velocity> 0.75 ng/ml/year or doubling time ❤ years
· Abnormal digital rectal examination
Overall, men undergoing systematic trans-rectal ultrasound (TRUS) guided biopsy of 12 cores of prostatic tissue have approximately 1 in 4 probability of being diagnosed with prostate cancer. Of these, about half are diagnosed with low risk disease. A known problem with the current practice of TRUS biopsy, is that it is performed blind – the operator does not know where the cancer is. Therefore, many low risk cancers that do not need treating are detected and many high risk cancers are missed or incorrectly classified.
The abstract below is reporting the results of a clinical study, aimed to evaluate the potential added value in using Artemis and ultrasound-MRI image fusion when performing TRUS biopsies, as a method and system to allow urologists to progress from blind biopsies to biopsies, which are mapped, targeted and tracked.
Image fusion is the process of combining multiple images from various sources into a single representative image. Ultrasound is the imaging modality used to guide Artemis in performing the biopsies. In this study MRI is used to overcome the “blindness” regarding tumor location. More on MRI’s cancer detection reliability can be found in my posts Imaging-guided biopsies: Is there a preferred strategy to choose? and Today’s fundamental challenge in Prostate cancer screening.
Source
Curr Opin Urol. 2013 Jan;23(1):43-50. doi: 10.1097/MOU.0b013e32835ad3ee.
MRI-ultrasound fusion for guidance of targeted prostate biopsy.
Marks L, Young S, Natarajan S. Department of Urology, David Geffen School of Medicine bCenter for Advanced Surgical and Interventional Technology, University of California, Los Angeles, Los Angeles, California, USA.
Abstract
PURPOSE OF REVIEW:
Prostate cancer (CaP) may be detected on MRI. Fusion of MRI with ultrasound allows urologists to progress from blind, systematic biopsies to biopsies, which are mapped, targeted and tracked. We herein review the current status of prostate biopsy via MRI/ultrasound fusion.
RECENT FINDINGS:
Three methods of fusing MRI for targeted biopsy have been recently described: MRI-ultrasound fusion, MRI-MRI fusion (‘in-bore’ biopsy) and cognitive fusion. Supportive data are emerging for the fusion devices, two of which received US Food and Drug Administration approval in the past 5 years: Artemis (Eigen, USA) and Urostation (Koelis, France). Working with the Artemis device in more than 600 individuals, we found that targeted biopsies are two to three times more sensitive for detection of CaP than nontargeted systematic biopsies; nearly 40% of men with Gleason score of at least 7 CaP are diagnosed only by targeted biopsy; nearly 100% of men with highly suspicious MRI lesions are diagnosed with CaP; ability to return to a prior biopsy site is highly accurate (within 1.2 ± 1.1 mm); and targeted and systematic biopsies are twice as accurate as systematic biopsies alone in predicting whole-organ disease.
SUMMARY:
In the future, MRI-ultrasound fusion for lesion targeting is likely to result in fewer and more accurate prostate biopsies than the present use of systematic biopsies with ultrasound guidance alone.
Written by: Dror Nir, PhD.
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This is unquestionably impressive. I have to point out that men go to the urologist on referral, and I don’t think that the rectal exam has the same status here as in Europe. I was probably misinformed in thinking that ultrasound guided biopsy was more accurate than it is, but the multiple fine needles take skill to interpret.
Of course my view has consistently been to get a good handle on the extent, location, and size. If only 40% of men with Gleason Score of at least 7 are only diagnosed using smart-imaging, how many Gleason Scores of over 5 are missed by US directed fine-needle. A Gleason Score of 7 is, in my view, already metastatic based on the very obsessive study with MM Pinto and Martin Rosman years ago. I wouldn’t take a score of over 5 lightly. I would expect there to be vas deferens involvement at a score of 7.
The PSA over 2.5 appears to be an adjustment to compensate for 2.0 ng/ml used for some time. The PSA velocity is an adjustment to be sure. The problem has been that the PSA is not specific for PCA and is well distributed in prostate tissue, so that it presents with BPH or with benign prostatitis.
This is where visualizing texture would be important.
I reviewed a really fine manuscript on a new method for PSA quite some time ago for Clinical Biochemistry (Elsevier) that sends me only difficult papers. I have waited a reasonable time to bring it up.
It is no wonder now that the presentation by Stamey was so disappointing. People in the audience didn’t want to believe it. It’s a hot button issue. This is where we separate science from strong held belief!
Hi Larry,
A very important correction to: “If only 40% of men with Gleason Score of at least 7 are only diagnosed using smart-imaging,….”
The majority of urologists are not using “smart-imaging” in daily routine. They use conventional B-mode (grey-scale) ultrasound. sometime they use Doppler modes or elastography, which have not proven to be able to improve much the sensitivity and specificity of B-mode ultrasound…
Statistically, we can say that the use of “smart-imaging”; e.g. multi-parametric, functional MRI sequences or ultrasound-based tissue characterization such as HistoScanning, in prostate cancer diagnosis can be considered as anecdotal.
in regards to the other issues you raised in your comment:
you can go on http://www.mayoclinic.com/health/prostate-biopsy/MY00182 to learn more about prostate biopsy practice in the USA..
For your information, PSA screening in the USA is still much more aggressive than in Europe. The cut-off value here is 4.0 ng/ml.
Also, Gleason 5 & 6 diseases are considered indolent. The recommendation for those is active surveillance. Radically treating them can be considered as unwise in view of the sever effects on the patients quality of life. BTW; I’ve seen many cases of Gleason-7 which were still confined. True, if you wait enough time (can be years..) they will probably metastase.
Than You Dr Dror for Your excellent post,the considerations about everydays urologists practice are indeed true(in Portugal we have more of the same)………we have to improve our skill to diagnose with expertise.Yes they are differences in urological atitude between Europe and U.S..I strongly agree with this magnificent post.”Smart-imaging” should be the prefered method because it gives more information(it sees better) to the doctor and of course to the patient.Blindness is sad and not cost effective…….!Once more Congratulations!
I published the cutoff of 4.0 ng/ml in an intensive analysis with Marguerite M Pinto, and I never saw it take hold. I’ll have too check again, but what I have seen not just locally – if California and Florida, and CT are not contiguous, is great anxiety at or near 2.0. The treatment might not be surgical resection with a risk of impotence, but medical treatment and followup. I found that using Kullback-Liebler distance, the entropy decision point had to be 4. Nevertheless, that doesn’t necessarily carry weight.
I know of intelligent, competent physicians who have made personal decisions to have resection at lower values than 4.
“Gleason 5 & 6 diseases are considered indolent. The recommendation for those is active surveillance. Radically treating them can be considered as unwise in view of the sever effects on the patients quality of life.”
Yes, you are probably correct on this because anyone age 70 is likely to develop PCA, and we still find “quiescent” PCA at the fewer and fewer autopsies that are done (the only QA check for medical and surgical outcomes in some cases, but also a generator of fear of litigation). I know a few physicians who spent their remaining time with bone mets on the golf course! What a privilege to die that way.
I would welcome you to review the implications of the significance of a Gleason Score of 5 or 6, which is technically moderate, but 100% for a false borderline call, with no basis for predicting a long quiescence. That is only a prediction you would make when the decision is made based on the “Median”, which is all that you have to go on for a single variable.
I did thousands of autopsies over a period of several years when I was younger. I wanted to redo the way autopsies were done, but they are payed for out of Part A operating expenses. I did intensive study on many cases and heavily referenced my Epicrisis. There was much to learn, and even more if the anatomy were combined with biochemical analysis. They still talk about the autopsy I did at UC San Diego when I didn’t present the heart at the “Organ Recital”.
Why? I froze the normal heart for enzyme purification, which later resulted in the demonstration of the diagnosis of myocardial infarct by a stop flow assay in which the heart type LD is inhibited by a ternary complex of NAD+, pyruvate, and LD in 500 msec. A few years later, Don Finn, President of Aminco sent me a clinical stop flow instrument to evaluate.
I just read an interesting related article. You have opened the door wider.
Novel technology to detect cancer in early stages
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Researchers have developed novel technology to detect the tumors in the body in early stages with the help of nanoparticles that would help to amplify the minute cancerous alarms.
This research has been published in the December 16th issue of the journal Nature Biotechnology.
Cancer cells produce many of the proteins that could be used as biomarkers to detect the cancer in the body but the amount of these proteins is not up to the mark or they may get diluted in the body of the patients making it nearly impossible to detect them in early stages.
Nanoparticles (brown) coated with peptides (blue) cleaved by enzymes (green) at the disease site. Peptides than come into the urine to be detected by mass spectrometry. (Credit: Justin H. Lo/MIT)
This new technology has been developed by the researchers from MIT and led by Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT.
“There’s a desperate search for biomarkers, for early detection or disease prognosis, or looking at how the body responds to therapy,” Bhatia, who is also a member of MIT’s Institute for Integrative Cancer Research, said in a statement.
In this technology, nanoparticles will interact with the tumor proteins helping to make thousands of biomarkers secreted by the cancer cells. Those biomarkers would then easily be detected in the patient’s urine.
“The cell is making biomarkers, but it has limited production capacity,” Bhatia added. “That’s when we had this ‘aha’ moment: What if you could deliver something that could amplify that signal?”
In this research, scientists administered ‘synthetic biomarkers’ having peptides bonded to the nanoparticles. They found that the particles interact with the protease enzymes, which are used to break down proteins. These enzymes are often found in large quantities in cancer cells as they help them to cut the proteins normally holding the cells in place and to spread in other parts of the body.
Researchers found that the proteases break down hundreds of peptides from the nanoparticles and release them in the bloodstream. These peptides are then excreted in the urine, where the process of mass spectrometry could help to detect such peptides.
Researchers wrote, “These protease-sensitive agents (“Synthetic biomarkers”) perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry.”
According to Bhatia, this biomarker amplification technology could also be used to manage the advancement of the disease and to check the response of the tumors to the drugs.
Reference:
Kwong, G., von Maltzahn, G., Murugappan, G., Abudayyeh, O., Mo, S., Papayannopoulos, I., Sverdlov, D., Liu, S., Warren, A., Popov, Y., Schuppan, D., & Bhatia, S. (2012). Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease Nature Biotechnology DOI: 10.1038/nbt.2464
Dr. Nir,
Thank you for this post.
The Goal for efficacy is:
MRI-ultrasound fusion for lesion targeting is likely to result in fewer and more accurate prostate biopsies than the present use of systematic biopsies with ultrasound guidance alone.
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