PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience - PubMed (original) (raw)

doi: 10.1186/s13046-015-0127-8.

Luigi Tomao 2 3, Anna Antenucci 4, Isabella Sperduti 5, Steno Sentinelli 6, Serena Masi 7, Chiara Mandoj 8, Giulia Orlandi 9, Rocco Papalia 10, Salvatore Guaglianone 11, Manuela Costantini 12, Giuseppe Cusumano 13, Giovanni Cigliana 14, Paolo Ascenzi 15 16, Michele Gallucci 17, Laura Conti 18

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PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience

Roberta Merola et al. J Exp Clin Cancer Res. 2015.

Abstract

Background: Prostate cancer (PCa) is the most common male cancer in Europe and the US. The early diagnosis relies on prostate specific antigen (PSA) serum test, even if it showed clear limits. Among the new tests currently under study, one of the most promising is the prostate cancer gene 3 (PCA3), a non-coding mRNA whose level increases up to 100 times in PCa tissues when compared to normal tissues. With the present study we contribute to the validation of the clinical utility of the PCA3 test and to the evaluation of its prognostic potential.

Methods: 407 Italian men, with two or more PCa risk factors and at least a previous negative biopsy, entering the Urology Unit of Regina Elena National Cancer Institute, were tested for PCA3, total PSA (tPSA) and free PSA (fPSA and f/tPSA) tests. Out of the 407 men enrolled, 195 were positive for PCa and 114 of them received an accurate staging with evaluation of the Gleason score (Gs). Then, the PCA3 score was correlated to biopsy outcome, and the diagnostic and prognostic utility were evaluated.

Results: Out of the 407 biopsies performed after the PCA3 test, 195 (48%) resulted positive for PCa; the PCA3 score was significantly higher in this population (p < 0.0001) differently to tPSA (p = 0.87). Moreover, the PCA3 test outperformed the f/tPSA (p = 0.01). The sensitivity (94.9) and specificity (60.1) of the PCA3 test showed a better balance for a threshold of 35 when compared to 20, even if the best result was achieved considering a cutoff of 51, with sensitivity and specificity of 82.1% and 79.3%, respectively. Finally, comparing values of the PCA3 test between two subgroups with increasing Gs (Gs ≤ 6 versus Gs ≥ 7) a significant association between PCA3 score and Gs was found (p = 0.02).

Conclusions: The PCA3 test showed the best diagnostic performance when compared to tPSA and f/tPSA, facilitating the selection of high-risk patients that may benefit from the execution of a saturation prostatic biopsy. Moreover, the PCA3 test showed a prognostic value, as higher PCA3 score values are associated to a greater tumor aggressiveness.

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Figures

Figure 1

Figure 1

tPSA (A), f/tPSA (B) and PCA3 score (C) values for patients negative and positive for PCa.

Figure 2

Figure 2

Relationship between PCA3 score and the percentage of positive biopsies.

Figure 3

Figure 3

ROC analysis with evaluation of the corresponding AUC for tPSA (0.505), f/tPSA (0.607) and PCA3 score (0.865).

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