In 2012, Halpern and colleagues have demonstrated a significant benefit of CEUS comparing to systematic biopsy (PBx) in individuating aggressive neoplasms (Gleason score > 7) and with large volume (>50 % of the core affected by cancer) [5]. Moreover, Frauscher et al. have reported an important increase of detection rate (DR) of prostate cancer (PCa) with CEUS, with a probability 2.6 times higher than PBx in individuating PCa [6].

Mitterberger and colleagues have reported a higher PCa DR with the help of CEUS used together with Doppler during PBx (26 % vs 20 %). Additionally, the Gleason score was higher in the first group [7] (Fig. 53.3, 53.4, 53.5, and 53.6). This approach has the potential to perform targeted biopsies and to reduce the number of cores that can be taken.

In a meta-analysis about the performance of CEUS in patients affected by PCa, Li et al. have concluded that CEUS represents a promising instrument in the identification of PCa, even if it actually cannot substitute PBx [8].

In a recent review, Walz and colleagues have identified six studies about the use of CEUS as guidance for PBx. The authors have reported a higher DR using CEUS compared with standard PBx. The improvement of cancer DR has ranged from 2 up to 18 % [9].

False positives may be due to benign prostatic hyperplasia (BPH) and prostatitis, both acute and chronic [10–12] (Fig. 53.7). Nevertheless, Zhao and colleagues have reported that the percentage of false positives with CEUS is significantly inferior compared with standard US with gray scale [12]. Currently, there are no precise parameters of reference. The study of the intensity curves of wash-in and washout may potentially improve the DR and reduce the percentage of false positives.

False-negative cases may be due to low neoplastic volume or well-differentiated and not aggressive cancers (low Gleason score) or a localization in the transition zone where the cancer is visible with more difficulty [12].

Initially the neoplastic lesions usually show small dimensions and low malignancy. Consequently, they may show a vascular microdensity that is too small to be detected because they are not able to generate signals for CEUS [13–16]. Moreover, the lesions localized inside the transition zone may have a vascularization similar to normal prostatic tissue [17, 18].

Particularly, SonoVue® is the most used contrast media and is able to define the microvascularization of both the lesion and the adjacent tissue, especially due to the real-time observation of its behavior. The recommended dosage is ≥2.4 ml [23, 24]. There are other contrast media and the list is provided in Table 53.1. The main clinical indications for the use of CE-TRUS are resumed in Table 53.2.

The contrast media for a specific disease are very recent; they are constituted by microbubbles with additional ligands directed to specific sites. The possible target receptors for PCa are molecules upregulated during the angiogenesis, especially the vascular endothelial growth factor (VEGF) receptors [19, 20].

Particularly, the prostate-specific membrane antigen (PMSA) is a type II transmembrane glycoprotein exposed on the membrane of the prostatic cells, with different levels of expression among normal prostatic tissue, BPH, first diagnosis-PCa, hormone-refractory PCa, and metastasis, respectively.

Loading nanoscale microbubbles with PCa-targeted specific ligands or antibodies is critical for specific ultrasound imaging in PCa. It has been shown that targeted nanoscale microbubbles can significantly increase peak intensity and duration of contrast enhancement than blank nanoscale microbubbles in transplanted prostate tumors. Increased peak intensity and prolonged duration of enhanced contrast are the main characteristics of targeted nanoscale microbubbles enhanced imaging.

Actually, it represents the most important target of both imaging and immune-mediated therapies [21, 22].

The BPH localizes in the central zone of the gland, and its pathogenesis is complex. Some trials have demonstrated higher levels of the angiogenetic growth factors in the urine of patients affected by BPH compared with the levels in normal tissue. It suggests that an increased angiogenesis may play a fundamental role in the pathogenesis of the BPH itself [25, 26].

Some trials have shown that an increase in the vascularization proximally to BPH nodules and a reduction of the microvascularization in the peripheral can be easily identified. This effect is due to the compression of the adenoma on the peripheral gland.