How do we diagnose prostate cancer?

As Mark Emberton said, for many men, prostate cancer develops silently, and by the time any symptoms appear, it’s often very advanced. This is because there’s no single, definitive test for prostate cancer. To date, one test we have relied upon heavily looks for a protein biomarker called PSA - prostate specific antigen. It does have its uses, but some dub it a poison chalice owing to its potential to mislead. So how reliable is the result for diagnostic purposes? Chris Smith went for a wander across the Essex countryside with Vincent Gnanapragasam, a professor of urology at the University of Cambridge…

Vincent - The PSA is a protein produced by the prostate gland, primarily to keep sperm healthy. It stands for prostate-specific antigen. The link between that and prostate cancer was found in the 1980s and was really observational—levels were high in men presenting with prostate cancer. It took off in a major way and has become the de facto test for prostate cancer. But it’s not really specific for cancer—it’s more specific to the prostate itself.

Chris - So does that mean lots of things could make it high, not just cancer?

Vincent - Perhaps not lots, but certainly infections, inflammation of the prostate, and prostate enlargement will all cause PSA to rise—and of course, prostate cancer.

Chris - How do you disentangle them then? If you’ve got someone in front of you and the only thing that's been measured is this blood test—and it’s high—how do you decide what that means?

Vincent - Well, that’s the conundrum and why screening and testing for prostate cancer is so controversial. Generally, a high PSA is associated with prostate cancer—but “high” is variable. No doubt if you're in the tens, hundreds, or thousands, it’s almost certainly prostate cancer.
But there’s more nuance. People have tried to define what “high” means, leading to the concept of the age-referenced PSA—which, frankly, lacks scientific validity. The age-referenced levels have changed and continue to do so. In the UK, up until recently—and possibly still, depending on location—you might have different PSA thresholds. So the concept of “high” is based on cut-offs derived from epidemiological studies, but it’s open to interpretation.

Chris - How should someone proceed then? Say someone like me—just over 50—not sure about risk factors. What advice would someone like you give?

Vincent - Putting aside the complexities, let’s talk practically. If you’re over 50 and you have a PSA test, and the level is high based on your area’s reference range, you'd be referred to hospital, which would trigger further investigation. Things have changed dramatically in the last 10 years. At one time, a raised PSA would lead straight to a prostate biopsy. Now, you’d get an MRI scan first. This has been very helpful in reducing unnecessary biopsies where the prostate may not harbour anything.

Chris - Is that any good? Does scanning help?

Vincent - Absolutely. If an MRI comes back with nothing to see, and you go ahead with a biopsy anyway, chances are you won’t find cancer. It’s more nuanced, though—a negative MRI doesn’t guarantee no cancer. But if the radiologist sees an area of concern, that’s a strong trigger for further investigation.

Chris - So someone has a high PSA, has a scan, and it shows a lesion—something in the prostate that looks like cancer. What next?
Vincent - That’s where the prostate biopsy comes in. It’s a procedure under local anaesthetic where we use a needle to take samples from the prostate. The diagnosis of prostate cancer is histological—it comes from analysing those tissue samples, not just from the scan.

Chris - Once you’ve got those samples, how do you decide how severe or aggressive the cancer is?

Vincent - First, if there’s prostate cancer in the biopsy samples, our histopathology colleagues will grade it—from 1 to 5. One is least aggressive, five is most. But that’s just part of the assessment. We also look at the PSA level and the MRI findings—not just whether there’s a lesion, but whether the cancer appears confined to the prostate or has breached the lining. Putting all that together, we can assign a Cambridge Prognostic Group score—which is the UK standard for classifying non-metastatic prostate cancer. So, two distinct but complementary methods: the biopsy tells us the grade, and the combined data give us one of five prognostic groups. Each tells us the likelihood of harm—that is, mortality—from the diagnosis.