Innovative Diagnostic Methods for Early Prostate Cancer Detection Through Urine Analysis

Prostate cancer represents the second most common cancer in men globally. Prostate cancer is recognized as a complex and multifactorial dynamical disease. It is also known that prostate cancer is characterized by a high degree of pathological and genetic heterogeneity compared to other human cancers. Serum Prostate-Specific Antigen (PSA) is, actually, the most applied biomarker for the detection, follow-up, and therapeutic monitoring of prostate cancer. Although its use has been associated with a significant reduction in prostate cancer mortality, it has also resulted in the over-diagnosis and overtreatment of indolent prostate cancer. Its low specificity and sensitivity are mainly attributable to the fact that serum PSA may also be increased in benign conditions, including benign prostatic hyperplasia and chronic prostatitis. In the last decade, proteomic and genomic technologies have been applied as powerful strategies to discover biomarkers of detection, prognosis, and prediction and to improve the understanding of prostate cancer biology.

In collaboration with the Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico of Milan, Italy, we provided an overview of innovative methods based on the analysis of urine, thereby comparing them with the traditional diagnostic procedures. Our research evidenced that innovative tools investigated in recent years can be mainly grouped into two categories, according to the method adopted: a) the possibility of analyzing urine odor fingerprint, and b) the chemical characterization of liquid urine or of its gaseous headspace, trying to identify potential prostate cancer biomarkers. All approaches propose the comparative analysis of urine samples from healthy men and prostate cancer patients with the aim of discriminating the two classes. In a research conducted with the Italian Ministry of Defense, we have recently demonstrated that a trained canine olfactory system can detect prostate cancer-specific volatile organic compounds (VOCs) in urine samples with high sensitivity and specificity (nearly, 98%). This approach might have the potential to offer a noninvasive alternative to PSA sampling and prostate biopsy for detecting prostate cancer. In addition, the results suggest that prostate cancer-specific VOCs might depend on a metabolic process of the tumor. Considering the limits related to the adoption of trained dogs in the clinical setting, we started investigating the possibility to transfer those experimental observations to an instrumental method based on the analysis of urine samples through electronic noses.

Given the ambitious purpose, a multidisciplinary collaborative team, that includes clinicians, engineering, biologists, ethologists, physicians, and biochemical scientists, is pivotal to understand the complexity of human beings. This way of thinking may further help to clarify concepts and indicate alternative experiments in order to develop appropriate diagnostic methods

Written by:
Gianluigi Taverna, MD, Chief Department of Urology, Humanitas Mater Domini, Castellanza, Varese, Italy, and Fabio Grizzi, PhD, Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Milan, Italy.

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