16 March 2016

By Dr Wendy Winnall - PCFA Research Team

Sometimes the answer to a medical problem needs to come from "left field". A bit of imagination can lead researchers on an unexpected pathway to success. For decades scientists have sought a more accurate test than PSA for detecting prostate cancer. An exciting "left field" approach has tried to use dogs to detect prostate cancer by smelling it.

Due to their highly sensitive sense of smell, dogs are very successful detectors of drugs and explosives, and trackers of missing people. Researchers have had some success training dogs to detect lung cancer by smelling human breath. Can dogs sniff out prostate cancer too?

Researchers have been attempting to train dogs to detect prostate cancer by smelling urine samples. It’s hoped they can do this by detecting the presence of volatile organic compounds (VOCs). These molecules are released from the body in fluids such as urine and sweat, finding their way into nearby noses. VOCs are the by-products of normal cellular metabolism. If a person harbours cells growing out of control, such as in a prostate tumour, it’s possible that the amount and the type of VOCs that are released into urine will be different, and this difference could be detected by a very sensitive nose.

A number of small scale trials have trained dogs to recognise prostate cancer in human urine, but with mixed success. Italian researchers recently trained two German Shepherds by using hundreds of urine samples from men with and without prostate cancer. The dogs recorded excellent results, with few false positives or false negatives.

A British group also trained 10 dogs using urine samples from 50 prostate cancer patients, compared to 67 samples without cancer. Two of the dogs gained the ability to detect urine from prostate cancer patients after the training. However, when these dogs were tested with new samples they had never smelt before, they could only do as well as expected by chance. It seems that these dogs were able to memorise the individual odours of large numbers of training samples rather than generalise on a common odour.

Although these projects have not yet lead to a canine-based prostate cancer test, it has not been a waste of time. These results have demonstrated that the urine of prostate cancer patients likely contains differing patterns of VOCs than the urine of those without cancer. So even if training dogs can be a bit hit-and-miss, we have technologies that can be adapted to detect these VOCs.

This is exactly what a team of UK researchers have done, using a machine called an Odoreader. The Odoreader uses a process called gas-chromatography, which was combined with mathematical algorithms to identify patterns in the urine samples of prostate cancer patients. Not only could their technique discriminate between prostate cancer and normal urine samples, it could also show differences between prostate cancer and bladder cancer. The technique found that 23 different components of the urine odour could be used, together, to predict which of the people had prostate cancer.

As a diagnostic test, gas chromatography had a 95% sensitivity, which means it has a 95% chance of recognising a positive sample as positive. The specificity of the test was 96%, meaning that the rate of false negative results is low. When applied to the same people, the PSA test did not perform as well as gas chromatography. It's important to note here that these figures are calculated based on a diagnostic test, not a screening test. The experiment asked how well the gas chromatography could detect prostate cancer in those with urinary symptoms of this disease.

A much larger clinical trial needs to be conducted in order to validate these promising results. Urine samples are needed from different geographical regions, taking into account factors that will affect the urine such as ethnicity, age, smoking status and family history. If this technique eventually becomes a diagnostic test for prostate cancer, it certainly won’t be the first time that such an innovation has come from ingenious imagination.