Category: Prostate Cancer Imaging

PSMA-PET Reduces Prostate Deaths

Posted on by Brian Casey

Using PSMA-PET instead of conventional imaging to stage patients with recurrent prostate cancer could reduce deaths by 13% and lead to improved quality of life. The new paper in JAMA Network Open confirms the value of PSMA imaging compared to traditional imaging approaches. 

Recurrent prostate cancer is one of the trickiest cancers to manage, especially as biochemical recurrence can occur in up to half of patients getting local treatment. 

  • PSA tests work well for detecting rising prostate antigen levels that could signify recurrence, but it can be difficult to locate recurrent cancer with existing imaging tools like CT and bone scans.

PET using a new generation of PSMA tracers offers a better solution thanks to tracers that target the PSMA protein that builds up on the surface of prostate cancer cells.

  • Previous studies have shown that PSMA-PET is more sensitive and specific for detecting recurrent prostate cancer, especially at lower PSA levels – but the modality’s long-term effects haven’t been explored. 

In the new study, researchers wanted to investigate the impact of switching to PSMA-PET on mortality and quality of life using statistical modeling to predict outcomes from three imaging approaches …

  • Conventional imaging with CT and bone scan.
  • CT and bone scan followed by PSMA-PET for negative or equivocal cases.
  • PSMA-PET alone.

They then projected outcomes for a hypothetical population of 1k patients with biochemically recurrent prostate cancer, defined as a persistent or rising PSA of 0.20 ng/mL after prostatectomy or PSA 2.0 ng/mL or higher following radiation therapy. They found …

  • PSMA-PET had the lowest number of prostate cancer deaths at 512, compared to conventional imaging plus PSMA-PET (520) or just conventional imaging (587).
  • PSMA-PET diagnosed 611 patients with metastasis compared to 630 with conventional imaging plus PSMA-PET and 297 with only conventional imaging.
  • PSMA-PET yielded 824 more quality-adjusted life years per 1k patients than conventional imaging.

The Takeaway

The findings are not only good news for patients with recurrent prostate cancer, they are also a boon for developers of commercially available PSMA-PET radiotracers like Lantheus Medical Imaging’s Pylarify (approved in 2021), Telix Pharmaceuticals’ Illuccix (approved in 2021), and Blue Earth Diagnostics’ Posluma (approved in 2023). 

MRI Reduces Prostate Biopsies

Posted on by Brian Casey

New research provides additional support for MRI’s role in making prostate screening more effective. In a new study in NEJM, researchers found that MRI can help reduce unnecessary biopsies more than 50%, with a very low chance of missing high-risk disease. 

As we’ve discussed in previous newsletters, prostate cancer screening based on PSA levels is an imprecise test. 

  • Many men with suspiciously high PSA (typically 3-4 ng/mL or higher) undergo biopsies that detect clinically insignificant disease that would never present a health risk during their lifetimes – the classic definition of overdiagnosis. 

Adding MRI can help make prostate screening more precise by directing biopsy-based workup to only those men with clinically significant cancer – but questions still abound about exactly when it should be used. 

In new results from the GÖTEBORG-2 trial in Sweden, researchers compared prostate screening protocols in men with PSA levels 3 ng/mL and higher who got MRI scans:

  • One group automatically got systemic biopsy and then MRI-targeted biopsy based on MRI results.
  • The other group only got MRI-targeted biopsy if they had a suspicious MRI scan.

In 13.2k men who were followed up for a median of four years, researchers found that those in whom systemic biopsy was omitted …

  • Had 57% lower risk of clinically insignificant cancers.
  • Had lower relative risk of clinically insignificant cancers in subsequent screening rounds (RR=0.25 vs. 0.49).
  • Had 16% lower risk of detecting clinically significant cancers.
  • Had 35% lower risk of advanced or high-risk cancers.

On the down side, the protocol eliminating systemic biopsy could lead to later diagnoses for higher-risk disease for 3 in 1k men – but given the slow-growing nature of prostate cancer it’s not clear how significant this is. 

  • Also, the data indicate that “most prostate cancers become visible on MRI” before they are incurable, which increases the likelihood that they would at least be detected on subsequent screening rounds and could be treated effectively.

The Takeaway

The new findings should help clinicians hone in on the best prostate screening protocols for maximizing detection of clinically significant cancer while minimizing unnecessary workup. Hopefully, the addition of new technologies like AI can move this process along.

Better Prostate MRI Tools

Posted on by Brian Casey

In past issues of The Imaging Wire, we’ve discussed some of the challenges to prostate cancer screening that have limited its wider adoption. But researchers continue to develop new tools for prostate imaging – particularly with MRI – that could flip the script. 

Three new studies were published in just the last week focusing on prostate MRI, two involving AI image analysis.

In a new study in The Lancet Oncology, researchers presented results from AI algorithms developed for the Prostate Imaging—Cancer Artificial Intelligence (PI-CAI) Challenge.

  • PI-CAI pitted teams from around the world in a competition to develop the best prostate AI algorithms, with results presented at recent RSNA and ECR conferences. 

Researchers measured the ensemble performance of top-performing PI-CAI algorithms for detecting clinically significant prostate cancer against 62 radiologists who used the PI-RADS system in a population of 400 cases, finding that AI …

  • Had performance superior to radiologists (AUROC=0.91 vs. 0.86)
  • Generated 50% fewer false-positive results
  • Detected 20% fewer low-grade cases 

Broader use of prostate AI could reduce inter-reader variability and need for experienced radiologists to diagnose prostate cancer.

In the next study, in the Journal of Urology, researchers tested Avenda Health’s Unfold AI cancer mapping algorithm to measure the extent of tumors by analyzing their margins on MRI scans, finding that compared to physicians, AI … 

  • Had higher accuracy for defining tumor margins compared to two manual methods (85% vs. 67% and 76%)
  • Reduced underestimations of cancer extent with a significantly higher negative margin rate (73% vs. 1.6%)

AI wasn’t used in the final study, but this one could be the most important of the three due to its potential economic impact on prostate MRI.

  • Canadian researchers in Radiology tested a biparametric prostate MRI protocol that avoids the use of gadolinium contrast against multiparametric contrast-based MRI for guiding prostate biopsy. 

They compared the protocols in 1.5k patients with prostate lesions undergoing biopsy, finding…

  • No statistically significant difference in PPV between bpMRI and mpMRI for all prostate cancer (55% vs. 56%, p=0.61) 
  • No difference for clinically significant prostate cancer (34% vs. 34%, p=0.97). 

They concluded that bpMRI offers lower costs and could improve access to prostate MRI by making the scans easier to perform.

The Takeaway

The advances in AI and MRI protocols shown in the new studies could easily be applied to prostate cancer screening, making it more economical, accessible, and clinically effective.  

MRI Makes Prostate Screening More Precise

Posted on by Brian Casey

Prostate cancer screening isn’t a guideline-directed screening test yet, but this could change with the use of MRI and other tools. A series of papers published in several JAMA journals late last week indicates the progress that’s being made. 

As we’ve discussed in previous issues, prostate screening with PSA tests hasn’t met the threshold for clinical benefit achieved by other population-based screening exams.

  • PSA-based screening has been characterized by lower mortality benefits and relatively high rates of overdiagnosis and complications from follow-up procedures. 

But some researchers believe that PSA screening could be made more effective by using additional diagnostic tools like imaging and blood tests to focus on potentially high-risk disease for biopsy while active surveillance is used for less threatening prostate lesions. 

In the ProScreen trial in Finland, researchers tested the combination of PSA, a kallikrein four-panel blood test, and MRI in selecting patients for biopsy. 

  • Patients were sent to MRI if they had PSA scores of 3.0 ng/mL or higher and kallikrein scores of 7.5% or higher; those with abnormal MRI scans got targeted biopsy. 

The researchers tested the ProScreen protocol in a study of 61.2k men, with 15.3k invited to screening and 7.7k getting screened. Over a preliminary three-year follow-up period, researchers found …

  • 9.7% of men met the PSA threshold for a suspicious lesion; this fell to 6.8% after the kallikrein test and 2.7% after MRI, illustrating the protocol’s ability to reduce biopsies
  • Biopsy yield for high-grade cancer was 1.7%, which an editorial called a “remarkably high yield”
  • Overdetection of low-grade disease was 0.4%, compared to 3.2% in a comparable previous study

In a second study, this one in JAMA Oncology, researchers performed a meta-analysis of 80.1k men from 12 studies in which MRI was used to direct patients to prostate biopsy after PSA testing, finding that MRI-directed protocols had …

  • Higher odds of detecting clinically significant prostate cancer (OR=4.15) compared to PSA screening alone
  • Lower odds ratio for biopsy (OR=0.28)
  • Lower odds ratio for detecting clinically insignificant cancer (OR=0.34)

Finally, a secondary analysis in JAMA of a large UK trial illustrates the challenges of prostate screening without MRI guidance. Researchers reviewed 15-year outcomes of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), a study of 415k men,196k of whom were screened from 2002 to 2009 without the use of MRI, finding … 

  • PSA screening increased detection of low-grade cancer (2.2% vs. 1.6%) but not intermediate or high-grade disease
  • Screening reduced prostate cancer mortality by a small amount (0.69% vs. 0.78%)

The Takeaway

Taken together, new studies offer a roadmap toward making MRI an integral part of prostate screening, such that perhaps in years to come it can join other cancer tests as a population-based screening tool.

A Case for VERDICT MRI

Posted on by Jake Fishman

A new Radiology Journal study showed that VERDICT MRI-based analysis could significantly improve prostate cancer lesion characterization, and might solve PCa screening’s unnecessary biopsy problem.

Before we jump into the study… VERDICT MRI (Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor) is a novel diffusion MRI modeling technique that estimates microstructural tissue properties, and has shown promise for cancer diagnosis and assessments. It can also be performed using standard 3T MRI exams.

The UK-based researchers had 165 men with suspected prostate cancer undergo mpMRI and VERDICT MRI (73 later confirmed w/ significant PCa). Over the 3.5yr study, they found that VERDICT MRI-based ‘lesion fractional intracellular’ volumes (FICs) have significant characterization advantages versus mpMRI-based apparent diffusion coefficient and PSA density measurements (ADC & PSAD):

  • VERDICT MRI-based FICs classified clinically significant prostate cancer lesions far more accurately than ADC and PSAD (AUCs: 0.96 vs. 0.85 & 0.74). 
  • VERDICT-based FICs also clearly differentiated clinically insignificant and significant prostate cancer among the study’s Likert 3 lesions (median FICs: 0.53 & 0.18) and Likert 4 lesions (median FICs: 0.60 & 0.28), while ADC and PSAD measurements couldn’t be used to show which of these lesions would be cancerous. 

The Takeaway

Noting that up to 50% of men with positive PI-RADS scores or >3 Likert scores end up with negative biopsy results, these findings suggest that VERDICT MRI could reduce unnecessary prostate biopsies by a whopping 90%.

That makes this study a “massive leap forward” for prostate cancer diagnostics, and provides enough evidence to make VERDICT MRI just one successful large multi-center trial away from clinical adoption.

Prostate MR AI’s Experience Boost

Posted on by Jake Fishman

A new European Radiology study showed that Siemens Healthineers’ AI-RAD Companion Prostate MR solution can improve radiologists’ lesion assessment accuracy (especially less-experienced rads), while reducing reading times and lesion grading variability. 

The researchers had four radiologists (two experienced, two inexperienced) assess lesions in 172 prostate MRI exams, with and without AI support, finding that AI-RAD Companion Prostate MR improved:

  • The less-experienced radiologists’ performance, significantly (AUCs: 0.66 to 0.80 & 0.68 to 0.80)
  • The experienced rads’ performance, modestly (AUCs: 0.81 to 0.86 & 0.81 to 0.84)
  • Overall PI-RADS category and Gleason score correlations (r = 0.45 to 0.57)
  • Median reading times (157 to 150 seconds)

The study also highlights Siemens Healthineers’ emergence as an AI research leader, leveraging its relationship / funding advantages over AI-only vendors and its (potentially) greater focus on AI research than its OEM peers to become one of imaging AI’s most-published vendors (here are some of its other recent studies).

The Takeaway

Given the role that experience plays in radiologists’ prostate MRI accuracy, and noting prostate MRI’s historical challenges with variability, this study makes a solid case for AI-RAD Companion Prostate MR’s ability to improve rads’ diagnostic performance (without slowing them down). It’s also a reminder that Siemens Healthineers is serious about supporting its homegrown AI portfolio through academic research.

HM-MRI Beats mpMRI

Posted on by Jake Fishman

University of Chicago researchers provided solid evidence that hybrid multidimensional MRI (HM-MRI) might be superior to multiparametric MRI (mpMRI) for diagnosing clinically significant prostate cancer.

That’s a big statement after nearly two decades of prostate MRI exams, but mpMRI’s continued variability challenges still leave room for improvement, and some believe HM-MRI’s quantitative approach could help add objectivity.

To test that theory, the researchers had four radiologists with different career experience (1 to 20yrs) interpret HM-MRI and mpMRI exams from 61 men with biopsy-confirmed prostate cancer, finding that the HM-MRI exams produced:

  • Higher AUCs among three of the four readers (0.61 vs. 0.66; 0.71 vs. 0.60; 0.59 vs. 0.50; 0.64 vs. 0.46), with the least experienced rad achieving the greatest AUC improvement 
  • Higher specificity among all four readers (48% vs. 37%; 78% vs. 26%; 48% vs. 0%; 46% vs. 7%)
  • Significantly greater interobserver agreement rates (Cronbach alpha: 0.88 vs. 0.26; >0.60 indicates reliability)
  • Far shorter average interpretation times (73 vs. 254 seconds)

The Takeaway
As the study’s editorial put it, HM-MRI appears to be a “quantitative step in the right direction” for prostate MRI, and has the potential to address mpMRI’s variability, accuracy, and efficiency challenges.

A Case for Multiparametric Ultrasound

Posted on by Jake Fishman

A new Lancet study out of the UK provided the strongest evidence yet that multiparametric ultrasound might deserve a core role in prostate cancer screening, either as a complement or alternative to multiparametric MRI. That could be a big deal given mpMRI’s cost, time, and accessibility challenges, and makes this study worth a deeper look.

The Study – The researchers performed mpUS and mpMRI exams on 306 patients with signs of prostate cancer (either elevated PSAs or abnormal rectal exams), and then conducted targeted biopsies on the 257 patients who had positive imaging findings. 

The biopsy results revealed cancer in 133 patients, including 83 clinically significant cancers, while showing how mpUS might contribute to prostate cancer diagnosis:

  • mpUS was positive in 272 patients (89%)
  • mpMRI was positive in 238 patients (78%)
  • mpUS identified 66 clinically significant cases (79%)
  • mPMRI identified 77 clinically significant cases (93%)
  • mpMRI and mpUS combined to detect all 83 clinically significant cancers
  • mpUS exclusively detected 6 clinically significant cancers 
  • mpMRI exclusively detected 17 clinically significant cancers

In other words, mpUS was only slightly less accurate than mpMRI for clinically significant cancer detection (-4.3%), but led to far more biopsies (+11.1%), while the combined modalities notably improved clinically significant cancer detection (+7.2%). 

The Takeaway

mpMRI’s role in prostate cancer screening is still secure, but this study shows that mpUS could improve cancer detection if the modalities are used together. Perhaps more importantly, it suggests that mpUS could be a valid prostate cancer detection option for the half of the world that doesn’t have access to advanced imaging or for the many patients who can’t/won’t undergo MRI (orthopedic implants, claustrophobia etc.).

The PSMA PET/CT + mpMRI PCa Effect

Posted on by Jake Fishman

There’s been a growing number of studies comparing 68Ga-PSMA PET/CT and mpMRI’s effectiveness along the prostate cancer pathway, but new research suggests that the modalities might be particularly effective if used together early in the diagnostic process.

The Study – A team of Australian researchers reviewed pre-operative mpMRI and 68Ga-PSMA PET/CT exams from 1,123 men (median PSA = 6), comparing their imaging results and histology findings. Here’s what they discovered:

  • mpMRI identified tumors in 93 men (8%) that were missed by 68Ga-PSMA PET/CT
  • 68Ga-PSMA PET/CT spotted tumors in 117 men (10%) that mpMRI missed
  • The combined modalities identified index tumors with Gleason Scores of ≥3+4 in 92% of men (vs. 80% w/ only mpMRI & 82% w/ only PSMA PET/CT)
  • 68Ga-PSMA PET/CT and mpMRI performed similarly for lesion/tumor detection and localization

Better Assessments and Decisions – In addition to identifying more tumors, mpMRI and 68Ga-PSMA PET/CT’s combined localization accuracy might improve biopsy targeting, leading to more accurate tumor grading and better management decisions.

More Necessary Biopsies – Meanwhile, patients with negative mpMRI and 68Ga-PSMA PET/CT findings would likely have a low risk of clinically significant prostate cancer, making them solid candidates for active PSA monitoring and allowing them to avoid unnecessary biopsies.

The Takeaway – This approach needs a lot more research and PSMA tracers currently only have FDA approval for patients with metastatic prostate cancer or biochemical recurrence, so 68Ga-PSMA PET/CT won’t be combined with mpMRI in early diagnostic exams very soon. That said, this study suggests that we’ll see more future efforts to combine and evaluate mpMRI + 68Ga-PSMA PET/CT as an early diagnostic step.

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