The Influence of Prostate Volume on Prostate Cancer Detection

European Urology Supplements

European Urology Supplements 1 (2002) 35±39

The In¯uence of Prostate Volume on Prostate Cancer Detection Michael K. Brawer* Northwest Prostate Institute, Seattle, USA

Abstract Objectives: The in¯uence of prostate volume on the positive yield of the systematic sector biopsy is logical and has been demonstrated in numerous reports. Methods: Literature on prostate biopsy was reviewed and a selection of articles made. Keywords used for the Medline search included: Prostate cancer, Biopsy, Diagnosis. Results: Sextant biopsies have the highest positive biopsy rate (40 g) in small prostates (<20 g), whereas in large prostate (80±90 cc) it drops to 10% only. Conclusions: The present paper reviews the in¯uence of total and peripheral zone volumes of the prostate on prostate cancer detection rates. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Prostate volume; Prostate cancer; PSA In the last two decades, there have been signi®cant changes in the approaches to the diagnosis of prostatic carcinoma. This has arisen owing to three technological advances: ®rst, the development of the springloaded biopsy device; second, transrectal ultrasound to guide biopsies; third, and most importantly, the widespread utilization of prostate speci®c antigen as an indication for biopsy. Indeed, these three changes have resulted in staggering differences in the presentation of prostate cancer today [1]. Associated with these developments has been a signi®cant modi®cation in the biopsy approach. Initially, an abnormality on digital rectal examination resulted in biopsies speci®cally directed either digitally or manually to the area of palpable abnormality was utilized. The development of transrectal prostate ultrasound resulted in a signi®cant change. Initially it was felt that the most common presentation on most common sonographic appearance of prostate cancer was the hypoechoic peripheral zone legion [2±10]. Later, a number of authors suggested that many cancers occur in sonographically normal peripheral zone [11±16]. For example, we noted that in 2036 consecutive patients biopsied, cancer was detected in 25.5%. The cancer was found only in isoechoic sections in 14.4% of these men [42]. * Tel. ‡1-206-368-6591; Fax: ‡1-206-368-1191. E-mail address: [email protected] (M.K. Brawer).

It is now generally assumed that no sonographic appearance is de®nitive 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 identi®ed 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 ®rst observations in this regard actually stem from our initial inability to replicate the intriguing work suggesting the utility of prostate speci®c antigen density. PSA density refers to the quotient of the serum PSA divided by the volume of the prostate gland [17]. 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 speci®c. A number of investigators carried out early work in this regard [17± 26]. As shown in Table 1, initial investigations demonstrated enhanced speci®city with a minimal reduction in test sensitivity when PSA density was utilized [17,18,20,21,25,26]. Our own investigations were unable to recapitulate these ®ndings [24]. We theorized that a number of possible reasons to explain this apparent discrepancy. These included

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M.K. Brawer / European Urology Supplements 1 (2002) 35±39

Table 1 PSA results Prostate volume (cc)a

PSA densitya

7.0 (1.7)* 6.8 (1.8)

28.9 (14.6)* 40.1 (20.2)

0.30 (0.15)* 0.21 (0.11)

115 311

6.87 (1.70) 6.77 (1.71)

29.2 (14.2)* 42.2(21.8)

0.285 (0.147)* 0.199 (0.108)

Positive Negative

68 159

10.7 (11.4)* 5.2 (5.0)

40.5 (16.6) 42.6 (25.6)

0.29 (0.41) 0.14 (0.14)

Bazinet et al. [20]

Positive Negative

217 317

21.4 (29.6)* 9.1 (8.1)

37.6 (21.4)* 51.6 (27.3)

0.63 (0.86)* 0.21 (0.25)

Rommel et al. [21]

Positive Negative

612 1394

15.5 (21.6)* 4.9

42.7 (27.2)* 47.0 (31.6)

0.47 (0.11)* 0.105 (0.09)

Mettlin et al. [25]

Positive Negative

171 650

12.0 (16.0)* 2.1 (2.3),

38.9 (16.4) 33.5 (14.2)

0.35 (0.5)* 0.08 (0.09)

Ohori et al. [26]

Positive Negative

110 134

28.1 (15.1±228.7)b,* 47.3 (13.3±332.6)b,*

0.21 (0.009±39.3)b,* 0.09 (0.007±1.82)b,*

Author

Biopsy

Number of patients

Benson et al. [18]

Positive Negative

98 191

Seaman et al. [19]

Positive Negative

Brawer et al. [24]

PSA (ng/ml)a

9.3 (0.3±1320)b,* 4.8 (0.2±64.1)b,*

a

Data reported as mean (Standard Deviation). Data reported as median (range) p < 0:05. * <0.05. b

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 [24]. Subsequently, it became apparent that in most of the papers in which PSA density appeared to provide enhancement of PSA speci®city, the glands harboring carcinoma were signi®cantly smaller than in men without malignancy [17±21,26]. In our patients in which either there was no difference in the prostate volume between men without cancer. PSA speci®city afforded no bene®t [24]. 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 glandÐthose with a lower PSA density (Fig. 1). In an effort to make density even more speci®c, 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 speci®city [27,28]. We, too, were unable to reproduce these results [29] and again concluded that this was an artifact of missing cancer in the larger glands. In order to further evaluate this observation, we carried out an investigation studying the effect of prostate volume on the yield of needle biopsy [30].

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 ®rst quartile to the second or third quartile. However, when comparing the smallest quartile to the largest

Fig. 1. A schematic example of sampling error that could occur between larger and smaller prostate glands. Cancer in a larger gland is more likely to be missed by systematic sextant needle biopsy. (Taken from Nixon RG, Brawer MK, Re®nements in serum prostate-speci®c antigen testing for the diagnosis of prostate cancer. Recent Advances in Urology. 7 ed. London: Churchill Livingstone; 1998.)

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Table 2 Patient age, serum PSA, and total gland and peripheral zone volumes according to presence or absence of cancer on transrectal ultrasound guided prostate needle biopsy Mean  S.D. (range)

Age Serum PSA (ng/ml) Gland volume (cm3) Peripheral zone volume (cm3)

p-value

Positive biopsy (326 pts.)

Negative biopsy (731 pts.)

67.6 15.5 40.2 24.2

66.2 6.0 48.2 29.3

   

7.6 (46±92) 34.2 (0.6±386.0) 19.3 (10.5±139.4) 12.5 (1.4±93.2)

   

7.9 (31±73) 6.6 (0.1±20.4) 31.2 (4.5±311.5) 21.4 (1.8±204.6)

0.0079 0.0001 0.0001 0.0001

Taken from [30].

Table 3 Biopsy yield as a function of the total gland and peripheral zone volumes using odds ratio analysis

Cut-off volume (cm3) Yield (%) Odds ratio 95% CI p-value

Quartile 1 (265 pts.)

Quartile 2 (264 pts.)

Quartile 3 (264 pts.)

Quartile 4 (264 pts.)

Gland

Peripheral zone

Gland

Peripheral zone

Gland

Peripheral zone

Gland

Peripheral zone

27.91 or less

15.98 or less

38.42 or less

23.06 or less

55.60 or less

33.61 or less

237.1 or less

204.6 or less

32.95

32.83

34.85 0.946 0.745±1.2 Not significant

32.58 1.012 0.79±1.29 Not significant

33.71 0.978 0.75±1.22 Not significant

34.47 0.956 0.75±1.22 Not significant

21.97 1.5 1.128±1.995 Significant

23.11 1.421 1.08±1.88 Significant

Taken from [30].

quartile of patients, a signi®cantly lower cancer detection rate was noted (odds ratio 1.5). We concluded that the positive yield of the systematic sector biopsy decreases signi®cantly when total gland volume is greater than 55.6 cc (Table 3). These ®ndings were reproduced by the work of Karakiewicz et al. [31] as well as Uzzo et al. [32]. 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. [32] noted similar results. 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 Table 4 Prostate cancer detection rate with corresponding number of biopsy cores References

Number of pts.

Number of cores

% Ca detection

Eskew et al. [37]

119 119

6 11

26.1 40.3

Reitbergen et al. [38]

617

6 7

24.5 25.4

40 40 40

6 12 18

22.0 25.0 31.0

Levine et al. [40]

124 124

6 12

33.0 45.0

Brown et al. [41]

254 254

6 8

33.9 35.0

Nava et al. [39]

Fig. 2. Cancer detection rate as function of total gland volume. (Taken from Letran J, Meyer G, Loberiza F, Brawer M: The effect of prostate volume on the yield of needle biopsy. J Urol 160(5):1718±1721, 1998.)

Taken from [30].

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articles indicating cancer detection in 20±40% of men with an initial negative biopsy [16,33,34]. 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. We are unaware of any study which prospectively used prostate volume as a determinant of the number of cores obtained. This would provide the de®nitive 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 ®ve 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 [35]. Two additional cores obtained from each side in an extreme lateral position to increase sampling of peripheral zone tissue extending into the anterior horn as suggested by Stamey [36]. It would seem prudent to utilize prostate volume as a factor in determining the need for repeat biopsy in a man with an initial negative prostate biopsy.

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