Feasibility of integrating canine olfaction with chemical and microbial profiling of urine to detect lethal prostate cancer

Abstract

Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70–76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.

Drift compensation on electronic nose data for non-invasive diagnosis of prostate cancer by urine analysis

“…No exclusion criteria regarding medical history, hormonal status, diet, clinical treatments, or tobacco consumption were considered for the selection of participants. Although some of these could be hypothesized as confounding factors for the olfactory discrimination, previous researches ( Biehl et al., 2019 ; Guest et al., 2021 ; Kokocińska-Kusiak et al., 2021 ; Mazzola et al., 2020 ) demonstrated that, if well-standardized protocols are involved for recruitment, conservation of urine samples and analysis, they do not affect the classification performance.…”

Assessing volatile organic compounds exposure and prostate-specific antigen: National Health and Nutrition Examination Survey, 2001–2010

“…More and more evidence revealed that VOCs might be the dangerous factors influencing public health. Although some studies reveal that urinary volatiles and chemical characteristics may help detect prostate changes in a non-invasive way (60)(61)(62), the association between environmental VOCs exposure and PSA concentrations has not been reported previously.…”

Hope for Ostomates: A Carbon and Zeolite Impregnated Polyester Fabric Inhibits Urine Odor in Cancer Patients: A Randomized Experimental Study

“…Weetjens et al, (2009) reported that African giant-pouched rats (Crietomys gambianus) were successfully trained to identify Mycobacterium tuberculosis in sputa of patients suspected of having tuberculosis, with a sensitivity of 89.1% and specificity of 80.1%. The use of sniffer dogs has a long history and a wider variety of applications, including the detection of explosives or land mines, the detection of drugs or the search of missing peoples, health-threatening microbial contaminations in hospitals and apartments (Fischer-Tenhagen et al, 2013;Fischer-Tenhagen et al, 2017;Else, 2020;Grandjean et al, 2020;Mazzola et al, 2020;Guest et al, 2021). Dogs are thought to poses an extremely keen sense of smell that is reported to be 10000 to 100000 times more accurate than in humans (Rygg et al, 2017;Else, 2020).…”

“…Some studies have reported thresholds ranging from parts-per-million to part-for-trillion (Leitch et al, 2013). It has also been reported that highly trained dogs can accurately detect distinctive odors, also named volatile organic compounds (VOCs) that are present in urine of men with prostate cancer as products of cell metabolism (Willis et al, 2004;Gordon et al, 2008;Cornu et al, 2011;Jobu et al, 2012;Leitch et al, 2013;Taverna et al, 2015;Taverna et al, 2016;Guest et al, 2021). As dogs can reliably detect these compounds, it follows that they could also be used to test scent control products, such as a fabric stoma pouch cover.…”

“…As dogs can reliably detect these compounds, it follows that they could also be used to test scent control products, such as a fabric stoma pouch cover. The literature also reports the reliability of dogs to detect distinctive VOC urine odors (Taverna et al, 2015;Taverna et al, 2016;Guest et al, 2021). In this study, we aimed to evaluate the efficacy of a fabric to reduce or inhibit urine odor.…”