Molecular imaging could transform management of people with aggressive cancer

A medical imaging technique known as PSMA PET/CT that provides detailed body scans while detecting levels of a molecule associated with prostate cancer could help doctors better tailor treatments for their patients, by determining the extent of disease spread at the time of diagnosis, a randomised controlled trial involving 300 patients in Australia published in The Lancet journal has found.

Watch The Lancet video abstract here.

The approach combines two imaging technologies – positron emission tomography (PET) and computed tomography (CT) – and is almost one third more accurate than standard imaging at pinpointing the spread of prostate cancer throughout the body. PSMA PET/CT proved to be 92% accurate compared with only 65% accuracy with standard imaging.

Although the study did not assess whether the scans had any effect on patient survival, the researchers say this approach could improve outcomes by helping doctors decide whether to offer a localised treatment, such as surgery or radiotherapy, or to use more advanced treatments to treat the whole body if the cancer has already spread.

Prostate cancer is commonly treated by surgery to remove the prostate or intensive radiotherapy to target the tumour. If there is a high risk the cancer may have spread to other parts of the body, patients may be offered medical imaging – typically CT and bone scans – to help doctors determine if additional treatments are needed.

Study lead Professor Michael Hofman of the Peter MacCallum Cancer Centre, Melbourne, said: “Taken together, our findings indicate that PSMA-PET/CT scans offer greater accuracy than conventional imaging and can better inform treatment decisions. We recommend that clinical guidelines should be updated to include PSMA PET/CT as part of the diagnostic pathway for men with high risk prostate cancer.”

Example from proPSMA trial – on the left, the standard imaging scans appear normal, with no evidence of cancer outside the prostate. On the right (within red box), the PSMA PET/CT confirms cancer in the prostate (shown in blue), and extensive cancer well outside the prostate (in red and green). PSMA PET/CT demonstrated 92% accuracy in the proPSMA trial compared to only 65% with standard imaging. 

Researchers sought to investigate if a molecular imaging approach could help doctors better define the extent of disease at the time of diagnosis. This approach involves giving patients a radioactive substance that detects a molecule called Prostate Specific Membrane Antigen (PSMA), which is found at high levels on prostate cancer cells. They then undergo a PET/CT scan. The CT scan produces detailed images of the body’s organs and structures, while the PET scan lights up areas where PSMA is present at high levels, indicating the presence of prostate cancer cells.

The study involved 300 men recruited to ten sites across Australia. All of the men had been diagnosed with prostate cancer, confirmed by tests on prostate tissue samples, and were deemed to be at high risk of having aggressive disease. The men were randomly assigned to receive either conventional CT and bone scans (152 patients) or PSMA-PET/CT (148 patients). Men then swapped over and were given the scans using the alternative imaging arm unless more than three sites of cancer spread were detected on the initial scans (18 patients). A second round of scans were undertaken at six months if there was any concern about ongoing prostate cancer following treatment. The results of these scans were used to confirm tumour spread, in addition to biopsies and change in blood tests.

Overall, the researchers found the PSMA-PET/CT scans were much more accurate than conventional CT and bone scans at detecting cancer spread (92% vs 65%). This is because the new technique was better at detecting small sites of tumour spread. Conventional imaging failed to detect that the cancer had spread in 29 patients, giving a false negative result. By comparison, PSMA-PET/CT gave false negative results in just six patients. Furthermore, fewer men had false positive results obtained with the new technique (2 with PSMA-PET/CT and 9 with conventional imaging).

Patients who underwent PSMA-PET/CT scans had fewer ambiguous results than conventional imaging (7%, 11/148 patients vs 23%, 35/152 patients).

Both imaging techniques involve exposure to radiation but the dose associated with PSMA-PET/CT was less than half that associated with conventional imaging (8.4mSv vs 19.2mSv).

PSMA-PET/CT scans had greater impact on the way patients’ disease was managed, with 28% having their treatment plans changed after the scans (41/147) compared with 15% following conventional imaging (23/152).

When PSMA-PET/CT was given at the second round of imaging after conventional imaging, disease management plans were still changed in more than a quarter of cases (39/146, 27%). When conventional imaging was used at the second round, however, just 5% of patients had their treatment plans changed (7/135 patients).

A summary of the proPSMA Study and findings

Professor Declan Murphy, senior author, of Peter MacCallum Cancer Centre, Melbourne, said, “Around one in three prostate cancer patients will experience a disease relapse after surgery or radiotherapy. This is partly because current medical imaging techniques often fail to detect when the cancer has spread, which means some men are not given the additional treatments they need. Our findings suggest PSMA-PET/CT could help identify these men sooner, so they get the most appropriate care.”

Associate Professor Roslyn Francis, co-author and scientific Chair of the Australasian Radiopharmaceutical Trials network, said: “Costs associated with PSMA-PET/CT vary in different regions of the world but this approach may offer savings over conventional imaging techniques. A full health-economic analysis will help to determine the cost effectiveness of introducing PSMA-PET/CT, both from a patient and a healthcare perspective”

Dr Stephen Mark, President of the Urological Society of Australia and New Zealand, welcomed the results saying  “he results of this ground-breaking study have been eagerly anticipated and will be of great significance in the treatment of men with aggressive prostate cancer all around the world.”

The trial was conducted at 10 hospitals around Australia who were early adopters of this new technology. The ANZUP Cancer Trials Group supported the trial. ANZUP Chair, Professor Ian Davis, said, “This remarkable clinical trial brought together experts in nuclear medicine, surgery, oncology and clinical trials. This type of co-operative, academic trial is essential to producing the highest quality data leading to global changes in practice.”

The proPSMA study was funded by men’s health charity Movember via a partnership with the Prostate Cancer Foundation of Australia (PCFA). Dr Mark Buzza, Global Director of Prostate Cancer Biomedical Research at Movember said: “The research arising from the proPSMA study represents a really exciting development in novel imaging that will lead to the optimal management of men with high-risk prostate cancer. There is now solid evidence that PSMA PET/CT scans are the gold standard first-line imaging test for staging high-risk prostate cancer. We would like to see PSMA PET/CT scans adopted into clinical practice as soon as possible for this group of men.”

CEO of Prostate Cancer Foundation of Australia, Professor Jeff Dunn AO, hailed the study a game-changer. “These findings will transform the way we manage and treat prostate cancer, providing men around the world with much greater hope of combatting the disease effectively. Today we are one step closer to our vision of a future where no man dies of prostate cancer – standing on the shoulders of research leaders.”

Frequently Asked Questions

What is a PSMA PET/CT scan?

This scan is called PSMA PET/CT (“prostate specific membrane antigen positron emission tomography/computed tomography”) (“PSMA PET” for short). 

This is a full body scan which helps determine if prostate cancer might have spread beyond  the prostate.

PSMA is present on the surface of prostate cancer cells. A radioactive substance which binds to PSMA is injected into a vein. This travels around the body and is taken into prostate cancer cells. The patient then undergoes a PET/CT scan. The PET scan lights up areas where PSMA is present at high levels, indicating the presence of prostate cancer cells. The CT scan produces detailed images of the body’s organs and structures. The combination produces whole body three-dimensional imaging enabling visualisation of prostate cancer. The technology can identify tumour deposits as small as 3-4mm in size.

What happens during a PSMA scan?

The PSMA PET scan includes the following procedures performed in a single visit:  

• The patient has a needle inserted into a hand or arm vein, and a small amount of a radioactive substance called PSMA (68Ga-PSMA-11) is injected.
• This is followed by a wait of around 1 hour, during which time it is possible to walk around can leave the imaging department. During this time, the PSMA travels through the blood stream and is taken up by any prostate cancer. It has a small amount of radioactivity which is detected by the scanner. 
• The patient is positioned on the bed of the scanner to get PET and CT pictures of the body from thighs to head. The total time in the scanner is around 20 minutes.  
• A doctor will check the scan to make sure that the pictures are satisfactory. Occasionally, the doctor will request an additional scan to obtain better pictures. The entire visit takes around 90 minutes.

What are the risks associated with a PSMA scan?

The PSMA radiotracer that is given does not have any known adverse effects. In the proPSMA study, no adverse effects were reported.

It does result in exposure to a small amount of radiation. As part of everyday living, everyone is exposed to naturally occurring background radiation. This can be measured and the average dose is around 2 millisievert (mSv) each year. The proPSMA study showed that the average dose from a PSMA PET/CT scan was 8 mSv. This was half the dose of current imaging with CT and a bone scan. At this dose level, no harmful effects of radiation have been demonstrated.

There are only minor risks associated with the scan. As with other scans:

• it involves an injection which may cause some discomfort or bruising. Sometimes, the blood vessel may swell, or blood may clot in the blood vessel, or the spot from which blood is taken could become inflamed. Rarely, there could be a minor infection or bleeding. If this happens, it can be easily treated.
• and lying in the scanner can cause claustrophobia (anxiety), occurring in about 5% of patients. If you have experienced this before, you should tell the technologist or nurse who is in the room. The scan can be stopped if needed.

How does it differ from a conventional CT or bone scan?

The standard scanning performed for patients with aggressive prostate cancer are two scans - a bone scan and a CT (Computed Tomography) scan.

The bone scan is good for looking at tumour spread to bones, whereas the CT scan is better for looking at tumour spread to lymph nodes and other organs. A bone scan highlights any areas of bone that are damaged and reacting to a tumour deposit. However, it is not specific for prostate cancer as many other causes of bone injury, for example fractures, also appear on these scans. To obtain a bone scan, the process is similar to a PSMA PET scan. A needle is inserted into a vein, and a radioactive substance that is taken up by bone is injected. This is followed by a 2-4 hour wait and then a scan which takes around 45 minute. The entire visit takes around 5 hours.

The CT scan provides detailed pictures of tissues but it is also not specific for prostate cancer. Tumours generally need be larger than 1 to 1.5cm to be identified on a standard CT scan. To obtain a CT scan, you are positioned on the scanner bed. A needle is inserted and a dye is injected to highlight blood vessels. This makes it easier for the radiologist to interpret the images. The scan itself takes less than 5 minutes.

How will PSMA scans change how prostate cancer is diagnosed and treated?

The proPSMA study has demonstrated that PSMA PET/CT scans are significantly more accurate than conventional scans. More accurate information about the location of prostate cancer will allow prostate cancer specialists to advise their patients more appropriately and better personalise care. For example, if there is disease spread outside the prostate gland this might alter the surgical or radiotherapy plan, or even direct treatment towards hormone or other treatments. If the prostate cancer is limited to only the prostate gland, this might provide reassurance that surgery or radiotherapy is likely to be curative.

Could all prostate cancer patients benefit from a PSMA scan?

Not at present. For now, we can say that newly-diagnosed patients with quite aggressive cancer, who are being considered for surgery or radiotherapy, should have a PSMA PET/CT instead of conventional scans such as CT and bone scan. Also, patients who have previously had surgery or radiotherapy for prostate cancer, but who are suspected of having recurrence of their cancer, may benefit from having a PSMA PET/CT as it is more likely to detect any recurrence. Studies are ongoing to determine the value of PSMA PET/CT in patients with earlier and later stages of prostate cancer.

How could the results of this trial change clinical practice?

The proPSMA trial clearly shows that PSMA PET/CT is more accurate than conventional scans, with less uncertain results and less radiation dose for the patient. These results suggest that PSMA PET/CT should replace CT and bone scan in men with newly-diagnosed, aggressive prostate cancer. This trial should help convince funders to support reimbursement of this scan for these patients. Having a “one-stop” scan such as PSMA PET/CT, is also more patient-friendly than having two separate scans, often involving a long day in the imaging centre, or two separate visits.

What are the limitations of this technology?

PSMA PET is a new imaging technology and many centres do not yet have access to it.

The scan can miss sites of tumour spread - false negative results - especially if very small in size such as less than 5mm in size. It’s also possible to misinterpret findings as tumour when no tumour is present - false positive results. As this is a new technology, imaging specialists may have little experience in how to interpret findings.

Whilst no scan is perfect, the proPSMA trial showed that PSMA PET is a significant improvement over current imaging technology, with better accuracy and high agreement amongst different imaging specialists.

Where can I obtain a PSMA PET/CT scan and how much does it cost?

At present, the availability of PSMA PET/CT is quite variable around the world. In some countries such as Australia and Germany, there is a lot of experience and availability, whereas in countries such as the UK and the USA, there is much less access. This is due to different regulations around radioactive substances in different countries. The scan is not yet approved by the Food and Drug Administration (FDA) in the USA.

Also, costs vary considerably depending on local regulatory and reimbursement. Hopefully the proPSMA trial will lead to improved availability and reimbursement around the world. Prostate cancer specialists can advise on local availability.

At Peter Mac, we have extensive experience using PSMA PET/CT since 2014, and continue to run many studies in this area.