Olfactory System of Highly Trained Dogs Detects Prostate Cancer in Urine Samples

No AccessJournal of UrologyInvestigative Urology1 Apr 2015Olfactory System of Highly Trained Dogs Detects Prostate Cancer in Urine Samples Gianluigi Taverna, Lorenzo Tidu, Fabio Grizzi, Valter Torri, Alberto Mandressi, Paolo Sardella, Giuseppe La Torre, Giampiero Cocciolone, Mauro Seveso, Guido Giusti, Rodolfo Hurle, Armando Santoro, and Pierpaolo Graziotti Gianluigi TavernaGianluigi Taverna Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Lorenzo TiduLorenzo Tidu Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy , Fabio GrizziFabio Grizzi Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Valter TorriValter Torri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy , Alberto MandressiAlberto Mandressi Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Paolo SardellaPaolo Sardella Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy , Giuseppe La TorreGiuseppe La Torre Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy , Giampiero CoccioloneGiampiero Cocciolone Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy , Mauro SevesoMauro Seveso Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Guido GiustiGuido Giusti Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Rodolfo HurleRodolfo Hurle Humanitas Clinical and Research Center, Rozzano, Milan, Italy , Armando SantoroArmando Santoro Humanitas Clinical and Research Center, Rozzano, Milan, Italy , and Pierpaolo GraziottiPierpaolo Graziotti Humanitas Clinical and Research Center, Rozzano, Milan, Italy View All Author Informationhttps://doi.org/10.1016/j.juro.2014.09.099AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We established diagnostic accuracy in terms of the sensitivity and specificity with which a rigorously trained canine olfactory system could recognize specific volatile organic compounds of prostate cancer in urine samples. Materials and Methods: Two 3-year-old female German Shepherd Explosion Detection Dogs were trained to identify prostate cancer specific volatile organic compounds in urine samples. They were tested on 362 patients with prostate cancer (range low risk to metastatic) and on 540 healthy controls with no nonneoplastic disease or nonprostatic tumor. This cross-sectional design for diagnostic accuracy was performed at a single Italian teaching hospital and at the Italian Ministry of Defense Military Veterinary Center. Results: For dog 1 sensitivity was 100% (95% CI 99.0–100.0) and specificity was 98.7% (95% CI 97.3–99.5). For dog 2 sensitivity was 98.6% (95% CI 96.8–99.6) and specificity was 97.6% (95% CI 95.9–98.7). When considering only men older than 45 years in the control group, dog 1 achieved 100% sensitivity and 98% specificity (95% CI 96–99.2), and dog 2 achieved 98.6% sensitivity (95% CI 96.8–99.6) and 96.4% specificity (95% CI 93.9–98.1). Analysis of false-positive cases revealed no consistent pattern in participant demographics or tumor characteristics. Conclusions: A trained canine olfactory system can detect prostate cancer specific volatile organic compounds in urine samples with high estimated sensitivity and specificity. Further studies are needed to investigate the potential predictive value of this procedure to identify prostate cancer. References 1 : Cancer statistics, 2012. CA Cancer J Clin2012; 62: 10. Google Scholar 2 : Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med2004; 350: 2239. Google Scholar 3 : Screening and prostate-cancer mortality in a randomized European study. N Engl J Med2009; 360: 1320. Google Scholar 4 : Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements. JAMA1997; 277: 1452. Google Scholar 5 : Prostate cancer detection at low prostate specific antigen. J Urol2000; 163: 806. Link, Google Scholar 6 : Complications of prostate biopsy. Expert Rev Anticancer Ther2013; 13: 829. Google Scholar 7 : Does the yield of prostate cancer biopsy and repeat biopsy justify the frequency of their use?. Nat Clin Pract Urol2008; 5: 246. Google Scholar 8 : Genetics of canine olfaction and receptor diversity. Mamm Genome2012; 23: 132. Google Scholar 9 : Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc Natl Acad Sci U S A1971; 68: 2374. Google Scholar 10 : Canine olfactory detection of cancer versus laboratory testing: myth or opportunity?. Clin Chem Lab Med2012; 50: 435. Google Scholar 11 : Sniffer dogs in the melanoma clinic?. Lancet1989; 1: 734. Google Scholar 12 : Another sniffer dog for the clinic?. Lancet2001; 358: 930. Google Scholar 13 : Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ2004; 329: 712. Google Scholar 14 : Olfactory detection of human bladder cancer by dogs: cause or association?. BMJ2004; 329: 1286. Google Scholar 15 : Olfactory detection of human bladder cancer by dogs: another cancer detected by “pet scan”. BMJ2004; 329: 1286. Google Scholar 16 : Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integr Cancer Ther2006; 5: 30. Google Scholar 17 : Canine olfactory detection of malignant melanoma. BMJ Case RepOctober 14, 2013; . Google Scholar 18 : Human ovarian carcinomas detected by specific odor. Integr Cancer Ther2008; 7: 76. Google Scholar 19 : Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward. BMC Cancer2013; 13: 396. Google Scholar 20 : Using a dog's superior olfactory sensitivity to identify Clostridium difficile in stools and patients: proof of principle study. BMJ2012; 345: e7396. Google Scholar 21 : The use of canines in the detection of human cancers. J Altern Complement Med2008; 14: 61. Google Scholar 22 : Olfactory detection of prostate cancer by dogs sniffing urine: a step forward in early diagnosis. Eur Urol2011; 59: 197. Google Scholar 23 : A single injection of lidocaine as local anesthesia for ultrasound guided needle biopsy of the prostate. J Urol2002; 167: 222. Link, Google Scholar 24 : Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4: when should we stop?. J Urol2001; 166: 1679. Link, Google Scholar 25 : Risk of repeat biopsy and prostate cancer detection after an initial extended negative biopsy: longitudinal follow-up from a prospective trial. BJU Int2013; 111: 988. Google Scholar 26 : Acceptability and complications of prostate biopsy in population-based PSA screening versus routine clinical practice: a prospective, controlled study. Urology2002; 60: 846. Google Scholar 27 : Rectourethral fistula after repeat transrectal prostate biopsy. Urology2013; 82: e18. Google Scholar 28 : Systematic review of complications of prostate biopsy. Eur Urol2013; 64: 876. Google Scholar 29 : Detection of prostate cancer by an electronic nose: a proof of principle study. J Urol2014; 192: 230. Link, Google Scholar 30 : Prostate cancer diagnosis through electronic nose in the urine headspace setting: a pilot study. Prostate Cancer Prostatic Dis2014; 17: 206. Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4April 2015Page: 1382-1387Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordsdiagnosisprostatic neoplasmsdogsolfactory perceptionvolatile organic compoundsAcknowledgmentsProf. Alberto Mantovani, Humanitas Clinical and Research Center provided assistance. Prof. Loraine Willis provided linguistic revision. Profs. Hywel Williams, Nicola Portinaro, Giuseppe Lippi and Aldo Maggioni, and Drs. Lidia Rota-Vender, Luca Balzarini, Salvatore Badalamenti, Fabio Baticci, Michele La Gioia, Michele Tedeschi and Alberto Trinchieri provided comments. Gens. di Corpo d'Armata Claudio Graziano, Piervalerio Manfroni and Gen. Federico Marmo, Ten. Cols. Mario Marchisio and Paolo Di Bona, Col. Luca Virgilio and Gen. Gianfranco Giardella provided technical support.MetricsAuthor Information Gianluigi Taverna Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Lorenzo Tidu Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy More articles by this author Fabio Grizzi Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Valter Torri Istituto di Ricovero e Cura a Carattere Scientifico, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy More articles by this author Alberto Mandressi Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Paolo Sardella Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy More articles by this author Giuseppe La Torre Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy More articles by this author Giampiero Cocciolone Italian Ministry of Defense Military Veterinary Center, Grosseto, Milan, Italy More articles by this author Mauro Seveso Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Guido Giusti Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Rodolfo Hurle Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Armando Santoro Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Pierpaolo Graziotti Humanitas Clinical and Research Center, Rozzano, Milan, Italy More articles by this author Expand All Advertisement PDF downloadLoading ...