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In the last two decades, there have been significant changes in the approaches to the diagnosis of prostatic carcinoma. This has arisen owing to three technological advances: first, the development of the spring-loaded biopsy device; second, transrectal ultrasound to guide biopsies; third, and most importantly, the widespread utilization of prostate specific antigen as an indication for biopsy. Indeed, these three changes have resulted in staggering differences in the presentation of prostate cancer today [
Associated with these developments has been a significant modification in the biopsy approach. Initially, an abnormality on digital rectal examination resulted in biopsies specifically directed either digitally or manually to the area of palpable abnormality was utilized.
The development of transrectal prostate ultrasound resulted in a significant change. Initially it was felt that the most common presentation on most common sonographic appearance of prostate cancer was the hypoechoic peripheral zone legion [
It is now generally assumed that no sonographic appearance is definitive for cancer, and thus biopsy approaches have adopted random nature. Other than concentrating on the peripheral zone where the majority of cancers arise, there is no other sonographically identified target to aim for.
This realization made the prostate volume an essential component in our diagnostic strategy. This stems from the fact that if we have nothing to aim for, we are more likely to identify cancer in a smaller gland with an equivalent number of biopsies than in a larger gland. The first observations in this regard actually stem from our initial inability to replicate the intriguing work suggesting the utility of prostate specific antigen density.
PSA density refers to the quotient of the serum PSA divided by the volume of the prostate gland [
]. Because of the fact that the largest component of prostate volume is benign prostatic hyperplasia, it makes intrinsic sense that normalization of total PSA by the gland volume may make PSA more specific. A number of investigators carried out early work in this regard [
We theorized that a number of possible reasons to explain this apparent discrepancy. These included differences in the accuracy in prostate ultrasound measurement, the size of the prostate in the study population, variability of the histologic makeup in the cohort of men being tested, as well as biopsy sampling error and PSA variability [
]. Subsequently, it became apparent that in most of the papers in which PSA density appeared to provide enhancement of PSA specificity, the glands harboring carcinoma were significantly smaller than in men without malignancy [
]. It made us ponder whether it was not the performance of PSA density calculation that made a difference, but rather the fact that given an equal number of biopsy cores obtained, a larger gland would be more likely to give a false negative test result of biopsy, i.e. more cancers would be missed in the larger gland—those with a lower PSA density (Fig. 1).
In an effort to make density even more specific, a number of authors evaluated the transition zone density where the serum PSA divided by the volume of the transition zone. Reports in this regard again were positive and indicated enhancement of test specificity [
]. In this study, we evaluated the cancer detection of six systematic sector biopsies performed because of either an abnormality on digital rectal examination or an elevation on serum PSA in 1057 men (Table 2). 326 were diagnosed with prostate cancer (30.8%). We observed a trend of decreasing cancer yield in men with larger glands (Fig. 2). Statistical tests utilizing an odds ratio analysis by yield was used to determine the cancer detection rate by quartile increase in total gland volume was utilized. No statistical relationship was observed between gland size and cancer yield when comparing the first quartile to the second or third quartile. However, when comparing the smallest quartile to the largest quartile of patients, a significantly lower cancer detection rate was noted (odds ratio 1.5).
Table 2Patient age, serum PSA, and total gland and peripheral zone volumes according to presence or absence of cancer on transrectal ultrasound guided prostate needle biopsy
We concluded that the positive yield of the systematic sector biopsy decreases significantly when total gland volume is greater than 55.6 cc (Table 3). These findings were reproduced by the work of Karakiewicz et al. [
]. In the Karakiewicz investigation, 1974 men who had systematic sextant biopsies had decreasing yield of biopsy with increasing gland volume (p<0.001). The highest positive biopsy rate (39.6%) was recorded among prostates that were smaller than 20 cc. The lowest biopsy rate in his study (10.1%) was noted in those glands between 80 and 90 cc. Uzzo et al. [
It has been widely reported that the absence of detection of cancer on the initial systematic six biopsy sector approach does not eliminate the possibility of missed cancer. Indeed, the literature is replete with articles indicating cancer detection in 20–40% of men with an initial negative biopsy [
]. This has resulted in a variety of strategies to enhance the yield of cancer by both increasing the number and the trajectory utilized and obtained in the biopsy. A number of authors have carried out investigations where they used a variety of number of needle biopsies and compared cancer yield detection. As shown in Table 4, all of these studies demonstrate increased cancer detection with increased number of cores obtained.
Table 4Prostate cancer detection rate with corresponding number of biopsy cores
We are unaware of any study which prospectively used prostate volume as a determinant of the number of cores obtained. This would provide the definitive answer to the question whether the increased yield with more cores is a function of better sampling but this seems obvious. Our current biopsy methodology is to utilize ten cores with five obtained from each side. We performed systematic sector biopsy as originally described by Hodge in the parasaggital plane between the lateral and middle third of each half of the prostate [