Photodynamic diagnosis of shed prostate cancer cells in voided urine treated with 5-aminolevulinic acid.

Yasushi Nakai,Akihide Hirayama,Yoshitomo Chihara,Masaomi Kuwada,Nobumichi Tanaka,Kiyohide Fujimoto,Katsunori Yoshida,Satoshi Anai,Yoshihiko Hirao,Makito Miyake

doi:10.1186/1471-2490-14-59

Abstract

BackgroundPast attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. To improve the sensitivities, we evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples.MethodsOne hundred thirty-eight patients with an abnormal digital rectal exam (DRE) and/or abnormal prostate-specific antigen (PSA) levels were recruited between April 2009 and December 2010. Voided urine specimens were collected before prostate biopsy. Urine specimens were treated with 5-ALA and imaged by fluorescence microscopy and reported as protoporphyrin IX (PPIX) positive (presence of cells demonstrating simultaneous PPIX fluorescence) or PPIX negative (lack of cells demonstrating fluorescence).ResultsOf the 138 patients, PCa was detected on needle biopsy in 81 patients (58.7%); of these 81 patients with PCa, 60 were PPIX-positive (sensitivity: 74.1%). Although 57 patients did not harbor PCa by conventional diagnostic procedures, 17 of these at-risk patients were found to be PPIX-positive (specificity: 70.2%). PPIX–PDD was more sensitive compared with DRE and transrectal ultrasound and more specific compared with PSA and PSA density. The incidence of PPIX–PDD positivity did not increase with increasing total PSA levels, tumor stage or Gleason score.ConclusionsTo our knowledge, this is the first successful demonstration of PPIX in urine sediments treated with 5-ALA used to detect PCa in a noninvasive yet highly sensitive manner. However, further studies are warranted to determine the role of PPIX–PPD for PCa detection.

Highlights

Past attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities
Unlike bladder cancer, wherein voided urinary cytology has proven useful in cancer detection and surveillance, past attempts at detecting PCa cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities [3,4,5]
protoporphyrin IX (PPIX)–photodynamic diagnosis (PDD) was more sensitive compared with digital rectal examination (DRE) and transrectal ultrasonography (TRUS) and more specific compared with

Summary

Introduction

Past attempts at detecting prostate cancer (PCa) cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities. We evaluate the feasibility and clinical utility of photodynamic diagnosis (PDD) of prostate cancer by using 5-aminolevulinic acid (5-ALA) to examine shed prostate cancer cells in voided urine samples. Unlike bladder cancer, wherein voided urinary cytology has proven useful in cancer detection and surveillance, past attempts at detecting PCa cells in voided urine by traditional cytology have been impeded by undesirably low sensitivities but high specificities [3,4,5]. In bladder cancer, several investigators have used photodynamic agents such as 5-aminolevulinic acid (5-ALA) to induce protoporphyrin IX (PPIX) accumulation in malignant tissue, which enables it to be differentiated from benign tissue [6,7,8,9]. Selective PPIX accumulation in malignant tissue provides an intense color contrast between the red fluorescence of malignant lesions and the nonfluorescence of normal tissue

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