Wright et al conducted a 12-core biopsy study evaluating the location of unique prostate carcinoma. 35 The most common site of isolated disease was the anterior apex, where 17% of cancers would have been missed if these areas had not been biopsied. Furthermore, as noted previously, our additional cores at the extreme apex identified the highest unique cancer detection rate. These recent findings stress the importance of anterior and apical biopsies for detecting prostate cancer, especially when suspicion persists of cancer following initial negative biopsy.

The final issue regarding the prior biopsy involves the type of ultrasound probe used. We have shown that the end-fire probe can more reliably reach the anterior and apical aspects of the gland that are likely to harbor unrecognized cancer, identifying almost 20% more cancers than the side-fire probe. 36 Thus, if the initial biopsy was performed with the more common, side-fire probes, we will often preferentially use the end-fire probe that allows more direct sampling of the apex and anterior horn.


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Saturation biopsy

Karakiewicz et al demonstrated that as prostate gland size increased, the yield of the sextant biopsy decreased based on significant under sampling. 37 Djavan and colleagues have developed tables to recommend higher numbers of cores for larger glands, but these have met limited clinical application. The reason we believe this is that the complexity of these tables makes them difficult to adopt in daily practice. 38


Thus, the procedure known as saturation biopsy was developed, allowing enough cores that gland size, age, or other parameters did not change the use of a defined, increased number of cores. Borboruglu and Stewart published almost simultaneous initial reports of 20-24 core saturation biopsy under regional or general anesthesia 39,40 and Jones et al established 24 cores as an initial threshold for saturation biopsy based on the pioneering work of those authors.

Today, saturation biopsy is considered as a minimum of 20 cores taken at biopsy, based on findings that the parasagittal cores yield minimal additional information during repeat biopsy. Thus, the focus is on the lateral and apical aspects. Ex-vivo work has validated that there appears to be little justification to obtain more than 20 cores. 41

Although there has been much interest in transperineal saturation biopsy performed via a brachytherapy grid under general anesthesia, to date there are limited published data despite significant unpublished “buzz”. Such biopsy via a brachytherapy grid has shown similar detection rates but higher rates of urinary retention compared with transrectal saturation biopsy. 42,43,44

Studies of transrectal saturation 
biopsy in the repeat biopsy population have yielded an approximately 30% cancer detection rate regardless of the type of previous biopsy scheme. Patel and colleagues reported on their saturation biopsy protocol in 2004, which includes dividing the prostate hemispheres into five sectors. 25


In 116 patients undergoing repeat biopsy, overall cancer detection was 29%. There were no reported unique medially located tumors. Thus, sampling in the medial sectors was reduced to one core in each sector, for a total of 20 cores on repeat saturation biopsy 
(Figure 1). From the same series, Rabets et al noted that patients with only one prior biopsy had a 33% 
cancer detection rate compared with 24% for patients who had more than one 
prior biopsy. 45

Walz et al reported cancer in 41% of patients undergoing repeat saturation biopsy using a mean of 24 cores. 46 In addition, de la Taille and colleagues reported that saturation biopsy detected cancer in 25% of patients undergoing their first repeat biopsy, whereas patients who had more than one previous prostate biopsy had less than a 3% cancer detection rate, supporting our findings noted above that a third repeat biopsy is usually unnecessary if the patient has undergone repeat saturation biopsy. 47

Furthermore, it is likely that small “insignificant” cancers may be detected if excessive biopsies are performed, which we found in up to 30% of patients in our series during multiple biopsies.

The safety and efficacy of saturation biopsy has been well established. In our experience with more than 1,200 saturation biopsies, we have not had increased complications compared with extended biopsy schema. 15 In addition, we have performed essentially all saturation biopsies in an office setting with periprostatic nerve block and have not had to give analgesics, sedatives, or other pain medications to any patient except for fewer than 20 men who required anesthesia for rectal pain abnormalities that precluded placement of the ultrasound probe into the rectum.

Imaging to detect undiagnosed prostate cancer


A number of centers have shown that magnetic resonance imaging (MRI) using a number of adjuncts can detect small prostate cancers, with the main limitation being that few centers are equipped to optimally use this technology. Moreover, the true negative predictive value has not been established, so the reader is cautioned against using MRI to rule out PCa following negative biopsy. Rather, MRI appears to offer the most value in identifying lesions to target with biopsy in some cases.


It is necessary to wait six to eight weeks after prior biopsy because recent biopsy needle sites will create distortion of the image. Nevertheless, the concept is promising, especially based on the work of Kurhanewicz and Vigneron in the United States 48 and Villers et al in Europe, which as noted above identified the surprisingly high frequency of unrecognized anterior tumors. 49 For now, we reserve such imaging for cases with high index of suspicion and following two negative biopsies, or when the patient is highly motivated to avoid repeat biopsy, although many centers use MRI imaging earlier in the evaluation of these challenging patients.