Since the diffusion of sextant scheme, several authors had shown limitations in PC detection of six-core biopsy and had reported high rates of false-negative biopsies. Therefore, over the last years, there has been increasing interest in defining more accurate PB schemes in order to increase PC DR, the so-called EPBx. As defined by the National Comprehensive Cancer Network, EPBx is essentially a sextant template with at least four additional cores from the lateral peripheral zone, as well as biopsies directed to lesions found on palpation or imaging. To date, little controversy exists regarding the usefulness of the EPBx scheme compared with the sextant scheme in increasing the PC DR.

Nevertheless, the optimal number and location of biopsies needed to identify all patients with PC at the earliest stage possible for optimal treatment, outcome and survival are still controversial. In a systematic review, Eichler et al. showed that there is no significant benefit in taking more than 12 cores and methods requiring more than 18 cores have a poor side-effect profile [3]; other investigators have advocated for additional biopsies. Particularly, Ploussard et al. found that a 21-biopsy scheme improved the rate by 6.7 % overall (p < 0.001) with the six far lateral cores with the highest efficiency in terms of DR. The authors also identified a cut-off PSAD (0.20 ng/mL per gram) below which an extended 21-core scheme might be systematically proposed to significantly improve the overall DR, without increasing the rate of detected insignificant PC [12].

The search for and targeting hypo-echoic lesion on TRUS remains controversial. Some authors demonstrated that the cores directed to the hypo-echoic areas are not considered necessary because their probabilities of being positive are equal to cores directed to the next adjacent area [13]. Conversely, Toi et al. found that biopsies taken when a prostate lesion is identified by TRUS are almost twice as likely to show cancer than when no lesion is visible. The cancers were found to be of higher volume and grade [13].

Even if the extended random PB scheme remains standard in the initial setting, many patients demand advances beyond the “old-fashioned” random biopsy, which is not considered the “future” (Figs. 28.2 and 28.3).

This is due to the fact that standard greyscale TRUS technology has limited specificity and sensitivity to detect PC. This situation has led to the development of new imaging techniques suitable for TRUS, such as the contrast-enhancement US. Newly developed US contrast agents enable to delineate the neo-vascular anatomy of PC foci by enhancing the signal strength form of neo-vessels. Nevertheless, the technique alone is not sufficient to predict which patient has benign or malignant disease.

Additionally, real-time elastography (RTE) is a relatively new imaging modality of PC detection. The differences in tissue stiffness, produced by compression and relaxation of the tissue, can be visualized under real-time conditions, with a mean sensitivity of about 80 % [14]. The major limitation of this technique consists of dependence on user’s experience and on the pressure applied on the probe. The published trials have shown promising results of RTE in PC imaging and detection, especially in conjunction with TRUS, in order to reduce the cores’ number. Nevertheless further clinical studies are mandatory.

Nowadays, multi-parametric magnetic resonance imaging (mpMRI) has demonstrated to have a high degree of accuracy for the detection of clinically significant PC and can be used to define a target area before PB [14–16] (Fig. 28.4). In the last 5 years, the role of image-guided targeted biopsy has grown. The likelihood of detecting cancer in such a visible lesion is definitely higher than with a random biopsy if the DR per core is considered [16]. mpMRI-targeted biopsies have demonstrated superiority over systematic random biopsies for the detection of clinically significant disease and representation of disease burden, while deploying fewer cores [16]. There is evidence that the Gleason score obtained in a targeted biopsy reflects the true Gleason score better than the Gleason score obtained by a random PB [16]. In a recent review about mpMRI-targeted biopsies, men with a clinical suspicion of PC, a PB that used MRI to inform the sampling was associated with a DR of clinically significant PC of 42 %. This approach might permit a reduction in the number of men who need to undergo biopsy if they are deemed to have a normal MRI [15]. The efficiency of the targeted sampling appeared superior to the standard approach (70 % vs. 40 %). Since the random PB was associated with a diagnosis of insignificant PC in 10 % of men biopsied, this cancer diagnosis might have been avoided if men had undergone targeted biopsy alone. The authors also concluded that adopting mpMRI-targeted biopsies rather than random PB, fewer men are biopsied overall, a greater proportion of men with clinically significant PC are biopsied, and fewer men are attributed a diagnosis of clinically insignificant PC.

Conversely, other authors have shown that in cases of combining targeted and random biopsies during one PB session, a substantial number of cancers were detected in only the random cores [15, 16]. Relying on the targeted biopsy alone would have led to a significant rate of under-detection in these studies. There is no doubt that EPBx might better characterize PC volume and cancer extent than just a targeted biopsy: the positive cores give us information on not only the cancer extent but also the number of negative cores. Targeted biopsies seem to reflect the true Gleason score, yet they might underestimate the extent of the cancer.

Probably the combination of both targeted and extended biopsies will show the most appropriate information about the correct characteristics of cancer.

The concept of increasing the number of cores has led to the idea SPBx. In physics and chemistry, saturation refers to a condition or state in which a substance has reached its plateau concentration. Then, the rate of reaction tends to maximum and does not increase by additional substrate (Figs. 28.5 and 28.6). When applied to the field of PB, saturation should theoretically define a sampling technique that detects all PC. In this context, the curve shows that the rate of reaction tends to maximum and does not increase by additional substrate in which 20 or more cores are taken in a systematic fashion, in order to detect all PC [17].