The PSMA PET was negative, but my PSA keeps rising

A negative scan is not ‘no cancer’

A PET-CT can only show what is big enough to see. At a low PSA, most of the cancer that is present is below that size, so a negative result is expected in many men.

In pooled studies of men with a rising PSA, a PSMA PET was positive in about 33 in 100 at a PSA below 0.2, and about 45 in 100 at 0.2 to 0.49.[1] In a prospective study of 635 men, it found the recurrence in 38% when the PSA was below 0.5.[2] The American guideline gives a range of 31% to 42% below that level.[3]

So below a PSA of 0.5, more scans are negative than positive. The PSMA PET guideline says plainly that a negative scan cannot exclude microscopic disease.[5]

Why a scan can be negative

• The deposits are too small. This is by far the most common reason. PET has a limit, and early recurrence is often below it.[5]
• Tracer in the bladder. Most PSMA tracers leave the body in urine, and the bladder sits right next to the prostate bed, the area left after the prostate was removed. The guideline says small local recurrences can be missed there. Teams reduce this with water, emptying the bladder, and sometimes a water tablet or later pictures.[5]
• Hormone treatment. Starting hormone treatment can lower the PSMA signal, so the guideline advises scanning before it is started where possible.[5]
• The tracer used. F-18 PSMA-1007 leaves the body mainly through the liver, so there is little tracer in the bladder, but bone findings are harder to judge with it. Ga-68 PSMA-11 and F-18 DCFPyL leave in the urine.[5]
• Cancer that shows little PSMA. About 5% of prostate cancers, especially a less common, faster-growing kind called neuroendocrine prostate cancer, do not show much PSMA.[5] Published figures are higher in advanced disease.

That last point is often confused with a negative scan. A negative scan usually means too little cancer to see. PSMA-negative disease means a tumour that shows little PSMA even when there is plenty of it, which is uncommon. Do all prostate cancers express PSMA? →

Reading these scans is also a skill. In the prospective study above, experienced readers agreed with each other most of the time, but not always.[2]

What usually happens next

A negative scan does not close the door on treatment. The American guideline says salvage radiotherapy to the prostate bed should not be withheld when the PET-CT is negative.[3] Its panel notes that waiting can miss the window when a small amount of disease is easiest to treat.[3]

The European guideline says: ‘Do not wait for a PSA threshold before starting treatment.’ It offers early salvage radiotherapy to men with two rising PSA values.[4]

Your team may also add a pelvic MRI, which the American guideline says may be used with a PET-CT to look for local recurrence.[3] What happens for you depends on your surgery or radiotherapy, your PSA and how fast it is rising.

Repeating the scan later

The same scan often works better once the PSA is higher, because there is more to see. In a registry study of men whose first PSMA PET was negative, a later scan found something in about 56 in 100.[6]

It was positive more often when the PSA had risen above 0.5, and when the PSA was doubling in under a year.[6] There is no guideline rule for when to repeat the scan, so the timing is a decision for your treating team. Waiting for a repeat scan is not a reason to postpone salvage radiotherapy your team has already advised.

When a second reading helps

Be clear about what a second reading can do. It cannot make an invisible deposit appear. If the cancer is below the size a PET can show, reading the same images again will not find it.

It can help when there is something to judge. Examples: a report that calls a finding unclear, the prostate bed next to a full bladder, a single spot in a rib, or earlier scans that were never compared.

In a study of PET-CT scans done at other centres, a specialist re-reading changed the opinion about cancer in 13 of every 100 scans. Where the answer could later be checked, the re-reading was right in 25 of 28 cases.[7] That study was of FDG PET-CT, not PSMA PET-CT.

When a Second Read can’t help

• It cannot find what the scan could not see. A blank scan read again is usually still blank.
• It needs the actual images (a DICOM link), not only the PDF report.
• It does not recommend a treatment. Whether and when to have salvage radiotherapy is decided by your urologist and radiation oncologist.
• It should not delay treatment. If your team has advised salvage radiotherapy, a second reading is not a reason to postpone it.
• It is not for emergencies. New severe pain, breathlessness, weakness or bleeding needs your doctor or a hospital now.

If your PSA is rising and the CT and bone scan were clear, this page may also help: PSA is rising after surgery, but the scans are clear.