PSMA-PET Reduces Prostate Deaths

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

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 with AI

A homegrown AI algorithm was able to detect clinically significant prostate cancer on MRI scans with the same accuracy as experienced radiologists. In a new study in Radiology, researchers say the algorithm could improve radiologists’ ability to detect prostate cancer on MRI, with fewer false positives.

In past issues of The Imaging Wire, we’ve discussed the need to improve on existing tools like PSA tests to make prostate cancer screening more precise with fewer false positives and less need for patient work-up.

  • Adding MRI to prostate screening protocols is a step forward, but MRI is an expensive technology that requires experienced radiologists to interpret.

Could AI help? In the new study, researchers tested a deep learning algorithm developed at the Mayo Clinic to detect clinically significant prostate cancer on multiparametric (mpMRI) scans.

  • In an interesting wrinkle, the Mayo algorithm does not indicate tumor location, so a second algorithm – called Grad-CAM – was employed to localize tumors.

The Mayo algorithm was trained on a population of 5k patients with a cancer prevalence similar to a screening population, then tested in an external test set of 204 patients, finding …

  • No statistically significant difference in performance between the Mayo algorithm and radiologists based on AUC (0.86 vs. 0.84, p=0.68)
  • The highest AUC was with the combination of AI and radiologists (0.89, p<0.001)
  • The Grad-CAM algorithm was accurate in localizing 56 of 58 true-positive exams

An editorial noted that the study employed the Mayo algorithm on multiparametric MRI exams.

  • Prostate cancer imaging is moving from mpMRI toward biparametric MRI (bpMRI) due to its faster scan times and lack of contrast, and if validated on bpMRI, AI’s impact could be even more dramatic.

The Takeaway
The current study illustrates the exciting developments underway to make prostate imaging more accurate and easier to perform. They also support the technology evolution that could one day make prostate cancer screening a more widely accepted test.

Better Prostate MRI Tools

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

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.

MRI’s Value for Prostate Screening

Among cancer screening tests, prostate screening could be the most problematic. But a new study published this week in JAMA Network Open offers guidance on the role that MRI can play in making prostate screening more effective – and opening the door to population-based screening.

The problem with prostate screening is that PSA tests often discover disease that’s either indolent or slow-growing. 

  • This can lead to a cascade of interventions that are expensive and have harms of their own. 

But prostate cancer remains a common – and deadly – cancer, with 1.5M cases globally in 2022, and it’s the second most commonly occurring cancer in men after lung cancer.

  • Given these statistics, there has to be a way to perform prostate screening more effectively.

MRI offers one such alternative, and a clinical consensus has emerged that performing a single MRI scan after a positive PSA result can help stratify men before biopsy. 

  • In this scenario, men might not be referred to biopsy if their MRI scan is negative, and adoption of this protocol has helped reduce prostate biopsies in PSA-positive men while still detecting clinically significant cancer.   

But if one MRI scan is good, are repeat MRI scans even better? In the new study, Swedish researchers investigated this question in a secondary analysis of the STHLM3-MRI trial, which involved repeat screening of 1.5k men 2-3 years after an original prostate screening.

Of the group who got repeat PSA and MRI screening, 667 men had PSA levels of 3 ng/mL or higher, the threshold for MRI testing, with the repeat scans finding … 

  • 51 men (7.6%) had equivocal lesions (PI-RADS score of 3)
  • 33 men (4.9%) had suspicious lesions (PI-RADS score of 4)
  • Only 10 men (1.5%) had lesions with PI-RADS scores of 4 or greater

The findings led the authors to conclude that cancer detection was “limited” in the second round of PSA and MRI prostate screening, and detection of low-grade tumors was low.

The Takeaway

At first blush, STHLM3-MRI may seem like a negative study, but it actually helps frame the debate over prostate cancer screening and MRI’s role by omitting the need for multiple repeat scans. The results also give clinicians confidence that it’s safe to omit prostate biopsies in men who have a single negative MRI result – a key finding in reducing the downstream costs of any population-based screening program.

Prostate MR AI’s Experience Boost

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.

A Case for Multiparametric Ultrasound

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.).

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