The impact of prostate volume in the decision of prostate biopsy technique and of when to perform a repeat prostate biopsy is still a matter of debate. Given that sextant prostatic systematic biopsies sample only about 90 mm of prostate tissue (6 x 15 mm cores), increased prostatic volume may significantly reduce the chance of detecting cancer.2-4
Owing to the wide variation in gland sizes and shapes, it seems logical that in smaller glands the prostate biopsy leads to a more extensive sampling and less extensive or suboptimal sampling of larger prostates with accompanying significant differences in biopsy yields.5,6 Several groups have proposed new biopsy strategies, often increasing the number of biopsies and the sectors to be sampled or performing biopsies more laterally, but controversial data have also been reported about the real advantage of these new techniques.7-10 Concerned by the fact that the original sextant method may not include adequate sampling of the prostate, Norberg etal. found in a prospective study including 512 patients that the standard method left 15% of cancers undetected as compared with the results of a more extensive procedure using 8-10 biopsies.11
Recently, the influence of the total and transition zone (TZ) prostate volumes on prostate cancer detection was prospectively analyzed in 1018 men using two successive sets of sextant biopsies plus two TZ biopsies.12 As compared to patients diagnosed with prostate cancer after the first set of biopsies, patients diagnosed after the second set had larger total prostate and TZ volumes (43.1 ± 13.0 cm 3 vs. 32.5 ± 10.6cm3, P <0.0001 and 20.5 ± 8.3cm3 vs. 12.8 ± 6.0cm3, P <0.0001). Receiver operator characteristic (ROC) curves showed that total and TZ volumes of 45 cm3 and 22.5 cm3, respectively, provided the best combination of sensitivity and specificity for discriminating between patients diagnosed with prostate cancer after the first from those diagnosed after a second set. In patients with total prostate volume above 45 cm3 and TZ above 22.5 cm3, a single set of sextant biopsies was not sufficient to rule out prostate cancer and a repeat biopsy was to be considered in case of a negative first biopsy.
Evaluating the variation of cancer detection in relation to prostate size, through random systematic sextant biopsies, Uzzo et al. found 23% of the patients had cancer and a large prostate ^50 cm3 compared to 38% in patients with smaller prostates (P < 0.01).13 This group concluded that significant sampling errors may occur in men with large glands, suggesting the need for repeat biopsies.
One of the central difficulties elucidating the relationship of prostate size and biopsy yield is the fact that prostates without cancer are virtually unavailable for pathologic analysis. Chen and colleagues approached this problem by developing a novel computer simulation that allowed comparison of biopsy results for given prostate and cancer volumes. The authors first evaluated 180 whole-mount radical prostatectomy specimens. The prostates were weighed, step-sectioned and digitized for computer modelling. Tumor volumes were calculated and compared with prostate volumes. Overall 607 tumours in 180 prostates were quantified. Computer-simulated biopsy runs were performed on the digitized prostates. Sextant biopsies in glands weighing ^50 g and glands >50 g were positive in 67% and 48% of cases, respectively. Small-volume cancers were more prevalent in larger prostates. The authors concluded that biopsy rates in large glands were lower than in small glands because biopsy of larger glands is often driven by elevations of PSA that may be produced by benign prostate tissue. They argued that, if sampling error were the primary reason for the consistent finding of lower biopsy yields in larger prostates, larger volume cancers would preferentially be found in large prostates. Chen and associates recommended against obtaining extra biopsies solely because of larger prostate size, arguing that this would be likely to detect a disproportionate number of small-volume cancers. The question of optimal biopsy sites and number of cores (independent of prostate volume) is still unanswered. Chen etal., following a stochastic computersimulation model, developed a 10-case biopsy scheme incorporating midline peripheral zone (PZ), inferior portion of the anterior horn of the PZ, significantly improving cancer detection to 96% and thus recommending the sampling of these zones in the repeat biopsy strategy after prior negative biopsies.14 Eskew etal. have recommended the use of a five-region sampling technique to improve the cancer detection rate, since the 11-core technique increased the percentage of prostate cancer detected from 26% to 40% compared to the usual sextant biopsies.8
The importance of the total volume on prostate cancer yielded by sextant biopsies is generally accepted. The importance of the transition zone was less well investigated.15 Many authors have already stressed the importance of the TZ and especially of the TZ density for predicting prostate cancer in men with serum PSA levels below 10ng/ml.16'17
Recently, another group has used two consecutive sets of transrectal ultrasound-guided sextant biopsies for improving prostate cancer detection.18 These two sets were performed during the same session. Prostate cancer was detected in 43%, 27% and 24% of men with prostate volumes <30 cm3, 30-50 cm3, and >50 cm3, respectively. Analyzing the second set of biopsies, performed in the same session, the probability of detecting a prostate cancer was approximately two-fold greater in men with large prostates compared to men with smaller and intermediate-sized prostates. Letran etal. and Djavan etal. suggested that the total and PZ volumes significantly affected the biopsy yield only when both were above the 75th percentile.16,19
Interestingly, the debate over the need of more lateral biopsies is open. When tumor foci from the 40 cases in which sextant biopsies did not reliably detect tumor were mapped, Chen et al. found that the foci were distributed in areas not biopsied by the sextant method, that is the TZ, midline PZ and inferior portion of the anterior horn of the PZ. A 10-core biopsy scheme incorporating these areas as well as the postero-lateral prostate reliably detected cancer in 141 of 147 patients (96%) with total tumor volumes greater than 0.5 cm3.14
A systematic five-region biopsy technique has been proposed where, in addition to random sextant biopsies, two sets of lateral PZ and three midline biopsies were obtained.8 A total of 12-15 cores were taken when the prostate volume was less than 50 cm3 and up to 18 cores if the prostate was larger than 50 cm3. An improvement in diagnostic yield of 35% over the systematic sextant biopsy method alone was noted, with 83% of the additional tumors identified having a Gleason score of six or more.8 Levine and coworkers noted that cancer detection rates could be increased by 30% by performing two consecutive sets of sextant biopsies at a single office visit.18
Creating an accurate model for prostate biopsy requires the ability to determine prostate gland volume and the minimum number of cores required to detect cancers with a high degree of certainty. Clinically, patient's age is the major determinant of life-threatening tumor volume at diagnosis. Subsequently, Vashi etal. and Djavan etal. proposed a nomogram concerning the number of cores for biopsy, required to ensure a 90% certainty of cancer detection as a function of prostate gland size and life-threatening volume.20'21 The Vienna nomogram was based on patient's age and gland volume (Table 9.1). The authors evaluated the minimum number of cores needed to detect cancer accurately. This model was based on the findings of the European Prostate Cancer Detection Study (EPCDS) and a three-dimensional model of virtual biopsies taken from prostatectomy specimens.
• Increasing (>6) biopsy cores are needed.
• Biopsies should be directed more laterally (peripheral zone).
• Repeat biopsies should be performed when the initial biopsy shows no prostate cancer in total prostate volumes greater than 45 cm3 and/or greater transition zone volumes than 25 cm3.
• There is a significant sampling error in greater prostate glands (>50 cm3), therefore, a repeat biopsy is needed, when initial biopsy yield showed no prostate cancer.
Size of prostate gland (cm3)
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