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German researchers say that highly trained dogs are able to reliably sniff out lung cancer in human breath.
In its early stages, lung cancer has few symptoms, making it difficult for doctors to catch it early, when it's still treatable.
"This is the holy grail," says Suresh S. Ramalingam, MD, associate professor and director of the lung program at Emory University's Winship Cancer Institute in Atlanta.
"The whole field is focused on using something that's readily available that does not involve an expensive surgery or scan that would allow us to find early cancers," says Ramalingam, who is developing technology that aims to replicate the ability of dogs to smell trace amount of chemicals produced by cancerous tumors. He was not involved in the research.
Recently a large, government-funded study found that longtime smokers at high risk for lung cancer who received annual rapid computed tomography (CT) scans of their lungs cut their risk of dying of the disease by 20%.
But that test has caused controversy because it falsely detects cancer in about one out of four people, leading to further invasive procedures.
Checking for Lung Cancer
The new study, which is published in the European Respiratory Journal, found that four trained dogs -- two German shepherds, an Australian shepherd, and a Labrador retriever -- correctly identified cancer in 71 of 100 samples from lung cancer patients.
They also ruled out cancer in 372 out of 400 samples that were known not to have cancer, giving them a very low rate of false positives, about 7%.
"The surprising result of our study is the very high specificity of our dogs to identify lung cancer," says study researcher Thorsten Walles, MD, a lung surgeon at Schillerhoehe Hospital in Gerlingen, Germany.
"It even surpasses the combination of chest computed tomography (CT) scan and bronchoscopy, which is an invasive procedure that needs some form of anesthesia," Walles tells WebMD in an email.
Doctors have previously reported cases in which dogs have alerted their owners to undiagnosed skin, breast, and lung cancers by repeatedly pawing or nosing an affected body part. Some dogs have even been trained to smell low blood sugar levels in people who have diabetes.
But dogs have had more mixed success in carefully controlled studies, where samples from healthy people and sick people have been mixed.
A study published in BMJ in 2004 found that dogs correctly identified bladder cancer an average of about 40% of the time, a rate that was better than the 14% accuracy that could be expected by chance, but was lower than available tests.
But in June, researchers in Japan reported that dogs could detect the presence of colon cancer in human breath and stool samples with nearly 90% accuracy, a success rate only slightly lower than colonoscopy.
The length of time the dogs are trained may be an important difference between the studies, Walles says. In his study, the four dogs were trained for nine months. Other studies have used dogs trained for as little as three weeks.
The kind of sample the dogs are asked to smell -- urine, breath, blood, or stool -- may also influence the results, he says.
In his study, 220 volunteers -- 110 who were healthy, 60 who had lung cancer, and 50 with chronic obstructive pulmonary disease (COPD) -- were asked to exhale into a glass tube filled with fleece.
The tubes were mixed up so neither the dogs' handlers nor two observers who placed the samples on the floor in front of the dogs knew the status of the person they were from, to avoid inadvertently giving the dogs clues about what they should find.
The dogs were presented with five tubes at a time. Only one contained a sample from a person with cancer.
The dogs were trained to lie down and put their nose to the tube if they detected lung cancer.
The dogs appeared to be able to accurately identify the samples from cancer patients, even when they were in very early stages of the disease. And they were able to pick up the scent despite competing odors of cigarette smoke or food on a person's breath.
How Dogs Detect Cancer
Researchers think dogs and other animals are able to smell disease by picking up on minute changes in compounds called volatile organic compounds (VOCs) that comprise chemical signatures in the body.
As many as 4,000 different VOCs, for example, have been identified in human breath.
A dog's sense of smell has been estimated to be 100 to 1,000 times more powerful than a human's, says Gary K. Beauchamp, PhD, director of the Monell Chemical Senses Center in Philadelphia.
"It's not just how sensitive their nose is. It's how they process this into a recognition pattern," Beauchamp says. "The reason dogs can do this is that they're recognizing a complex picture, and that's the big trick, to find out how to mimic that in some sort of device that could be useful for diagnostic purposes in human disease."
Other researchers agree.
Ramalingam says because success rates vary between dogs and between samples, the real value of knowing dogs can detect cancer will likely be in building technology that can reliably repeat what they can do.
"The dogs show that it can be done. We need to find out what the dogs are sniffing so we can do it in a more scientific manner."
An investigational urine test stratifies prostate cancer risk in men with elevated levels of prostate specific antigen (PSA), according to newly reported results from more than 1000 men.
Previous research has indicated that the urine test is 100% accurate in detecting a gene fusion directly linked to prostate cancer, say the authors.
However, the urine test, which detects the fusion of 2 genes (TMPRSS2 and ERG), has a weakness: this tell-tale gene fusion occurs in only about 50% of prostate cancers.
For this reason, in the new prospective study, the urine test was combined with another marker, prostate cancer antigen 3 (PCA3).
The study was published online August 3 in Science Translational Medicine.
All of the men in this study had elevated PSA levels and had undergone either biopsy or prostatectomy, report the researchers, headed by Scott Tomlins, MD, PhD, from the University of Michigan Health System in Ann Arbor.
The men in the study were also evaluated for TMPRSS2:ERG and PCA3, but some were tested with the initial version of the gene fusion test and others with the second-generation test. Hence, the researchers chose not to directly compare individual men; instead, they stratified patients into risk groups by score (low, intermediate, and high).
Of 1065 men who received biopsies, 363 (34%), 346 (32%), and 356 (33%) were in the lowest, intermediate, and highest TMPRSS2:ERG + PCA3 score groups, respectively.
These scores were then compared to biopsy results.
Biopsies indicated cancer in 21% of men in the low-score group, 43% in the intermediate-score group, and 69% in the high-score group. The difference between the low- and high-score groups was significant (P < .001).
"Testing for TMPRSS2:ERG and PCA3 significantly improves the ability to predict whether a man has prostate cancer," said Dr. Tomlins in a press statement. "We think this is going to be a tool to help men with elevated PSA decide if they need a biopsy, or if they can delay having a biopsy and follow their PSA and urine TMPRSS2:ERG and PCA3."
In effect, the test, if it reaches the clinic, would help improve the murky decision-making that plagues many men with elevated PSA levels as they consider a biopsy.
"Many more men have elevated PSA than actually have cancer, but it can be difficult to determine this without biopsy. This test will help in this regard. The hope is that this test will be an intermediate step before getting a biopsy," said senior study author Arul Chinnaiyan, MD, PhD, from the Michigan Center for Translational Pathology and University of Michigan Medical School in Ann Arbor.
In 2009 at the Genitourinary Cancers Symposium, when the first-ever clinical results of the urine test were presented, an expert not involved with the research praised the rapid development of the test.
"This is an amazingly short interval between the discovery [of the gene fusion] and [the emergence of a] possible clinical application in diagnosis," said Howard Sandler, MD, from the Samuel Oschin Comprehensive Cancer Institute, Cedars–Sinai Medical Center, in Los Angeles, California. The gene fusions quantified in the test were first reported in 2005, he said.
Scores Correlate with Aggressiveness
The men in the study were patients at 3 academic medical centers and 7 community-based hospitals, and had specimens collected from 2006 to 2009.
In addition to helping predict the likelihood of prostate cancer, the urine test scores correlated with aggressiveness, as indicated by Gleason score. Only 7% of men in the low-score group had an aggressive tumor (Gleason score above 6), compared with 20% in the intermediate-score group and 40% in the high-score group. The difference between the low- and high-score groups was significant (P < .001).
The researchers also found that, of the 966 men with enough information to determine the Epstein criteria for significance of cancer on biopsy, 15%, 33%, and 61% of men in the 3 groups, respectively, had Epstein-criteria-defined significant cancer.
The researchers also compared the TMPRSS2:ERG + PCA3 score with Prostate Cancer Prevention Trial (PCPT) risk calculator, a commonly used online tool.
"Calculated PCPT risks of cancer (or Gleason score >6 cancer) differed markedly from the actual risks observed in the lowest and highest TMPRSS2:ERG + PCA3 score groups of men," they write.
For instance, almost all of the men (90%) of PCPT-evaluable men in the highestTMPRSS2:ERG + PCA3 score group had PCPT risk scores less than their actual risk of cancer on biopsy, they say.
The combined TMPRSS2:ERG and PCA3 test is not yet available as a prostate cancer screening tool. The Michigan Center for Translational Pathology is working with Gen-Probe Inc., which has licensed the technology, to develop the testing strategy. The University of Michigan hopes to offer it to patients within the year, according to the press statement.
The study was funded by Gen-Probe Inc., the Early Detection Research Network, National Institutes of Health, Prostate Cancer Foundation, Burroughs Wellcome Fund, Doris Duke Foundation, and the Howard Hughes Medical Institute. Dr. Chinnaiyan reports serving as a consultant to Gen-Probe. Coauthor Yves Fradet, MD, from University of Laval Cancer Research Centre, in Québec City, Quebec, is cofounder of Diagnocure, which licensed diagnostic rights to the PCA3 gene to Gen-Probe.
