Japanese Journal of Clinical Oncology

Department of Urology and Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

To reduce sampling error as much as possible in the detection of prostate cancer, extensive transition zone sampling, in addition to the standard sextant random systematic biopsies, has been proposed. Improved biopsy techniques should make possible earlier and more effective detection of prostate cancer in a population where the incidence is low. Evaluation of such biopsies for elderly Japanese males is thus required. A total of 344 Japanese patients participated in this study. They underwent two transition zone biopsies in addition to systematic biopsy. Fifty-five of the 344 patients (16.0%) had cancer. Both biopsies were positive in 33 patients (60.0%), the standard systematic sextant biopsy alone demonstrated cancer in a further 20 (36.4%) and the transition zone biopy alone was positive in two others (3.6%). The two patients with cancer only in the transition zone biopsy cores had palpable abnormality and elevated prostate specific antigen. None of those with palpably benign glands or those with prior negative biopsies had cancer in the transition zone. Two additional cores from the transition zone led to no increase in morbidity of biopsy. Transition zone biopsy would not significantly contribute to the detection of prostate cancer in the present Japanese elderly male population. Though possibly of some value for certain patients, this biopsy does not warrant routine use.

Key words: prostate cancer - ultrasound-guided biopsy - transition zone biopsy - systematic sextant biopsy - transition zone cancer

INTRODUCTION

Ultrasound-guided biopsy, particularly systematic sextant biopsy, has come to be quite widely used for detecting prostate cancer (1). This technique involves sampling as much of the peripheral zone as possible (2-4). Error in sampling may consequently occur since the transition zone of the prostate is the site of origin of as many as 30% of all adenocarcinomas (5). Approximately 10-40% of prostate cancers with a tumor volume <6 cm³ may be undetected by systematic sextant biopsy according to a computer simulation model (4). To minimize sampling error as much as possible, extensive transition zone sampling alongside standard systematic sextant biopsy has been proposed. Lui et al. reported additional transition zone sextant biopsy alone to be diagnostic in 26.4% of 72 cancers (6), though this was not confirmed in other studies (7-12).

Prostate cancer has become the ninth most common cause of male cancer death in Japan (13). Better biopsy techniques would lead to earlier and greater detection, thus increasing the chance of cure. The indication for transition zone biopsy in elderly Japanese males, who have a lower incidence of and mortality from prostate cancer than do their counterparts in the West, is not adequately understood (13). The present study, the first of its kind, examines the usefulness of and indication for transition zone biopsy in addition to standard systematic sextant peripheral zone biopsy for Japanese males.

SUBJECTS AND METHODS

Of 629 consecutive patients without previous diagnosis of prostate cancer and who had undergone transrectal ultrasound-guided needle biopsy at this Institution between October 1994 and November 1996, 344 underwent transition zone biopsy as well as systematic biopsy, serum prostate specific antigen (PSA) determination, digital rectal examination and transrectal ultrasound imaging. All patients whose digital rectal examination appeared questionable, or whose serum PSA was >2.0 ng/ml, underwent biopsy. An arbitrarily chosen lower PSA cut-off value of 2.0 ng/ml is used at our Institution as an indication for biopsy, rather than that (0-4.0 ng/ml) recommended by the manufacturer of the assay kit (Dainapack IMx PSA, Dinabot, Tokyo) (14-17). Biopsy was indicated partly on the basis of preprostatectomy evaluation in some patients regardless of clinical findings. Indication of transition zone biopsy was based on on-site assessment of the individual patient's tolerance and feelings toward his condition. The clinical stage of cancer was determined in accordance with the TNM classification (18).

Table 1. Clinical characteristics of patients on whom transition zone biopsy was conducted

Patient group	No. pts	Age (yr)			PSA (ng/ml)			PSAD ng/ml.cm3			TZ volume (cm3)			Gland volume (cm3)
		Mean	Median	Range	Mean	Median	Range	Mean	Median	Range	Mean	Median	Range	Mean	Median	Range
1	60	70.9	71.0	55-89	421.7	7.7	1.0-20 100	16.2	0.28	0.05-893.3	17.7	14.8	2.2-54.8	38.5	33.8	14.4-123.7
2	233	66.8	67.0	32-87	10.4	5.2	1.0-350.0	0.21	0.13	0.02-4.56	21.4	18.1	3.0-77.0	42.6	38.5	12.9-144.7
3	51	68.3	69.0	50-86	9.3	7.5	1.9-31.2	0.25	0.18	0.04-1.23	22.6	18.8	3.9-108.0	47.1	40.2	15.0-164.4
Total	344	67.6	68.0	32-89	88.7	5.5	1.0-20 100	3.53	0.13	0.02-893.3	20.7	17.7	2.2-77.0	41.8	38.2	12.9-144.7

PSA, prostate specific antigen; PSAD, prostate specific antigen density; TZ, transition zone; pts, patients; Group 1, patients with palpable abnormality; Group 2, patients with elevated PSA but palpably benign glands; Group 3, patients with elevated PSA or abnormal rectal findings but with previous negative biopsies.

Patient age ranged from 32 to 89 years (mean 67.6, median 68.0). Serum PSA in 340 patients was 1.0-20, 100 ng/ml (mean 88.7, median 5.5). The PSA density (PSAD) in 338 patients was 0.02-893.30 ng/ml.cm³ (mean 3.53, median 0.13) and transition and glandular volumes 2.2-77.0 cm³ (mean 20.7, median 17.7) and 12.9-144.7 cm³ (mean 41.8, median 38.2) respectively (Table 1).

The patients were divided into three groups based on clinical features.

Group 1 included 60 patients aged between 55 and 89 years (mean 70.9, median 71.0), with palpable abnormality, PSA 1.0-20,100 ng/ml (mean 421.7, median 7.7) and PSAD 0.05-893.3 ng/ml.cm³ (mean 16.2, median 0.28). Four patients had a PSA of <= 2.0 ng/ml. Transition zone and glandular volumes were 2.2-54.8 cm³ (mean 17.7, median 14.8) and 14.4-123.7 cm³ (mean 38.5, median 33.8) respectively.

Group 2 consisted of 233 men whose digital rectal examination results were normal (including normal size or hypertrophic glands), with symptoms of prostatism such as frequency, urgency, weak urinary stream, dysuria, microscopic hematuria and pain on micturition. Patient ages were 32-87 years (mean 66.8, median 67.0), PSA 1.0-350.0 ng/ml (mean 10.4, median 5.2), PSAD 0.02-4.56 ng/ml.cm³ (mean 0.21, median 0.13) and transition zone and prostatic volumes 3.0-77.0 cm³ (mean 21.4, median 18.1) and 12.9-144.7 cm³ (mean 42.6, median 38.5) respectively. Ten patients had a PSA of <= 2.0 ng/ml.

The 51 patients in Group 3 showed features suggestive of prostate cancer, although no cancer had been indicated by prior systematic sextant biopsy (mean 1.4 times, range 1-4). Nine patients had abnormal rectal findings and 42 had palpably benign glands with elevated PSA. Time between biopsies was 1.2-63.0 months (mean 17.3, median 17.3). The ages were 50-86 years (mean 68.3, median 69.0), PSA 1.9-31.2 ng/ml (mean 9.3, median 7.5) and PSAD 0.04-1.23 ng/ml.cm³ (mean 0.25, median 0.18). Two patients with palpable abnormality had a PSA of <= 2.0 ng/ml. Transition zone and glandular volumes were 3.9-108.0 cm³ (mean 22.6, median 18.8) and 15.0-164.4 cm³ (mean 47.1, median 40.2) respectively.

Serum PSA was determined by Eiken polyclonal radioimmunoassay (Eiken, Tokyo) up to March 1993 and by Dainapack IMx PSA (Dinabot, Tokyo) thereafter. For uniformity, Eiken PSA was inter-converted as recommended by Machida et al. (15) as follows: IMx PSA = 1.39 × Eiken PSA - 1.02. The PSA density (PSAD) was obtained by dividing serum PSA by prostatic volume, as shown by transrectal ultrasonography, calculated as prostatic length × width × height × ([pi]/6). Digital rectal examination was conducted by the attending physician, and abnormal findings, including irregularity, asymmetry and nodularity or the presence of nodules, were noted. Prostate scanning was done with a Bruel & Kjaer model 1846 scanner equipped with a 7 MHz multiplanar transducer in transverse and sagittal planes.

Subsequent to standard sextant biopsy of the peripheral zone (1), two additional biopsies were conducted anteriorly in the transition zone. To obtain transition zone tissue, the needle was inserted into the mid-portion of each half of the prostate and manually pushed through the peripheral zone. The needle was fired on reaching the transition zone boundary. All transition zone biopsies contained tissue from the left and right sides of the anterior prostate. In certain cases, additional biopsies of suspicious areas noted on ultrasound images or in digital rectal examination were carried out. Antimicrobial prophylaxis was administered in all cases, along with 500 mg of oral ciprofloxacin, twice a day for 2 days from immediately before the biopsy. No Fleet enema was conducted.

Fisher's exact probability, [chi]² and Kruskal-Wallis tests were carried out for comparison, with p < 0.05 being taken as significant.

RESULTS

Prostate biopsy showed that 55 of the 344 patients (16.0%) had cancer. In 33 of these 55 patients (60.0%), both types of biopsy were positive. The standard systematic sextant peripheral zone biopsy alone demonstrated cancer in a further 20 (36.4%) and the transition zone biopsy alone was positive in two others (3.6%) (Table 2, 3).

Of the 60 Group 1 patients with palpable abnormality, 35 (58.3%) were positive for prostate cancer. Among these 35 patients, both biopsies were positive in 20 (57.1%), the standard systematic sextant biopsy alone indicated cancer in a further 13 (37.1%) and the transition zone biopsy results alone were positive in two others (5.7%) (Table 2). The 35 cancers were classified clinically as stages T2aN0M0 in three, T2bN0M0 in 16, T2bNxM1 in two, T2bNxMx in one, T2cN0M0 in one, T2cN0M1 in three, T3cN0M0 in one, T3cN2M0 in one, T3cNxM0 in one and T3cN0M1 in six patients.

Table 2. Results of biopsy by location and clinical parameters in Groups 1 and 2

Parameter	No. patients	Cancer detection no. (%)	Origin of biopsies positive for cancer
			Transition zone only no. (%)	Peripheral zone only no. (%)	Peripheral and transition zone no. (%)
Rectal findings
Abnormal (Group 1)	60	35 (58.3)	2 (5.7)	13 (37.1)	20 (57.1)
Normal - BPH (Group 2)	233	15 (6.4)	0 (0.0)	7 (46.7)	8 (53.3)
Age (yr)
<= 49	7	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
50-59	33	3 (9.1)	0 (0.0)	0 (0.0)	3 (9.1)
60-69	134	19 (14.2)	1 (5.3)	13 (68.4)	5 (26.3)
70-79	99	21 (21.2)	1 (4.8)	4 (19.0)	16 (76.2)
>= 80	20	7 (35.0)	0 (0.0)	3 (42.9)	4 (57.1)
PSA (ng/ml)
<2.0	14	1 (7.1)	0 (0.0)	1 (100.0)	0 (0.0)
2.1-10.0	211	23 (10.9)	1 (4.3)	12 (52.2)	10 (43.5)
>10.1	64	26 (40.6)	1 (3.8)	7 (26.9)	18 (69.2)
Unknown	4	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
PSAD (ng/ml.cm3)
<= 0.15	154	6 (3.9)	0 (0.0)	5 (83.3)	1 (16.7)
>0.15	134	44 (32.8)	2 (4.5)	15 (34.1)	27 (61.4)
Unknown	5	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
TZ volume (cm3)
<= 30.0	227	44 (19.4)	2 (4.5)	15 (34.1)	27 (61.4)
>30.1	61	6 (9.8)	0 (0.0)	5 (83.3)	1 (16.7)
Unknown	5	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Gland volume (cm3)
<= 50.0	215	39 (18.1)	1 (2.6)	15 (38.4)	23 (59.0)
>50.0	77	11 (14.3)	1 (9.0)	5 (45.5)	5 (45.5)
Unknown	1	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Overall	293	50 (17.1)	2 (4.0)	20 (40.0)	28 (56.0)

BPH, benign prostatic hyperplasia; PSA, prostate specific antigen; PSAD, prostate specific antigen density; TZ, transition zone.

Of the 233 Group 2 patients with palpably benign glands, 15 had prostate cancer (6.4%). For seven of these 15 patients (46.7%), standard systematic sextant biopsy alone demonstrated cancer. No cancer was indicated by transition zone biopsy alone. Both biopsies were positive in eight patients (53.3%). The 15 cancers were classified clinically as stages T1cN0M0 in 12, T1cNxMx in one, T3cN0M0 (nonpalpable but visible) in one and T4aN0M1 (nonpalpable but visible) in one patient. Eleven patients with negative biopsy results underwent transurethral resection of the prostate but none of these cases showed cancer.

Prostatic intraepithelial neoplasia (PIN) (19) was found in 8.3% of patients in Group 1 (5/60, low grade in four, high grade in one) and 4.3% of patients in Group 2 (10/233, low grade in eight, high grade in two). All were found in cores from the peripheral zone. No atypical adenomatous hyperplasia was found.

Of the above 293 patients, for those >= 49 years old, 50-59, 60-69, 70-79 and >= 80 years, positive biopsy results were seen in 0%, 9.1%, 14.2%, 21.2% and 35.0% respectively (Table 2). No statistically significant correlation was found between age and positive results (p = 0.318). Rectal findings were significant for predicting prostate cancer (p < 0.001) and positive results increased with PSA levels: 7.1% for <= 2.0 ng/ml, 10.9% for 2.1-10.0 ng/ml and 40.6% for >= 10.1 ng/ml (p = 0.001). The same was noted for PSAD: 3.9% for patients with PSAD <= 0.15 ng/ml.cm³ versus 32.8% for PSAD >0.15 ng/ml.cm³ (p < 0.001). Neither transition zone volume nor glandular volume gave an indication of prostate cancer (p = 0.133 and 0.513 respectively). Transition zone biopsies disclosed cancer for PSAD >0.15 ng/ml.cm³ and transition zone volume <= 30 cm³ in most of these patients.

One of the two patients whose cancer was indicated only by transition zone biopsy underwent radical prostatectomy for clinical stage T2b disease. The surgical specimen showed anterolaterally located peripheral zone cancer foci with poorly differentiated histology. No transition zone cancer could be detected.

Of the 51 Group 3 patients with prior negative biopsy, five (9.8%) had cancer (Table 3). Both biopsies gave positive results for these patients. Transition zone biopsy alone disclosed no cancer. These five cancers were classified clinically as stages T1cN0M0 in three, T2bN0M0 in one and T3cN0M0 in one patient. No statistically significant correlation could be found between age and positive results (p = 0.899). Positive biopsy results increased with PSA: 0.0% for <= 2.0 ng/ml, 2.6% for 2.1-10.0 ng/ml and 36.4% for >= 10.1 ng/ml (p = 0.015). The PSAD significantly predicted prostate cancer: 0.0% for patients with PSAD <= 0.15 ng/ml.cm³ versus 21.7% for PSAD >0.15 ng/ml.cm³ (p = 0.028). No such prediction could be made from transition zone or glandular volume (p = 0.370 and 0.108 respectively). Both biopsies disclosed cancer for PSAD >0.15 ng/ml.cm³ and transition zone volume <= 30 cm³ in these patients.

Table 3. Results of biopsy by location and clinicopathological findings in patients with previous negative biopsies (Group 3)

Parameter	No. patients	Cancer detection no. (%)	Origin of biopsies positive for cancer
			Transition zone only no. (%)	Peripheral zone only no. (%)	Peripheral and transition zone no. (%)
Rectal findings
Abnormal	9	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Normal - BPH	42	5 (11.9)	0 (0.0)	0 (0.0)	5 (100.0)
Age (yr)
50-59	8	1 (12.5)	0 (0.0)	0 (0.0)	1 (100.0)
60-69	23	3 (13.0)	0 (0.0)	0 (0.0)	3 (100.0)
70-79	15	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
>= 80	5	1 (20.0)	0 (0.0)	0 (0.0)	1 (100.0)
PSA (ng/ml)
<= 2.0	2	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
2.1-10.0	38	1 (2.6)	0 (0.0)	0 (0.0)	1 (100.0)
>= 10.1	11	4 (36.4)	0 (0.0)	0 (0.0)	4 (100.0)
PSAD (ng/ml.cm3)
<= 0.15	27	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
>0.15	23	5 (21.7)	0 (0.0)	0 (0.0)	5 (100.0)
Unknown	1	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
TZ volume (cm3)
<= 30.0	38	5 (13.2)	0 (0.0)	0 (0.0)	5 (100.0)
>30.0	9	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Unknown	4	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Gland volume (cm3)
<= 50.0	31	5 (16.1)	0 (0.0)	0 (0.0)	5 (100.0)
>50.0	19	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Unknown	1	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Previous biopsy findings
Low grade PIN	2	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
High grade PIN	2	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Other than PIN	47	5 (11.6)	0 (0.0)	0 (0.0)	5 (100.0)
Overall	51	5 (9.8)	0 (0.0)	0 (0.0)	5 (100.0)

BPH, benign prostatic hyperplasia; PSA, prostate specific antigen; PSAD, prostate specific antigen density; TZ, transition zone; PIN, prostatic intraepithelial neoplasia.

Table 4. Comparison of studies on transition zone biopsies

Study	Presentation	No. cores in TZ biopsy	No. pts	No. cancer (%)	No. exclusive TZ cancer (%)	PSA (ng/ml)		Median PSAD (ng/ml.cm3)
						Mean	Median
1 Lui et al. (6)	Abnl DRE Elevated PSA Neg. prior biopsy	6	187	72 (38.5)	19 (26.4)	21.3*	15.9*	-
2 Terris et al. (12)	Referral, Consecutive pts	1-3	161	55 (34.2)	1 (1.8)	26.2	17.0	-
3 Keetch and Catalona	Screening Elevated PSA Neg. prior biopsy	4	166	19 (11.4)	2 (10.5)	-	7.2 for ca 6.3 for non-ca	0.17 for ca 0.11 for non-ca
4 Fowler et al. (10)	Elevated PSA Neg. prior biopsy	2-4	20	4 (20.0)	1 (25.0)	range 10-42		range 0.09-1.9
5 Bazinet et al. (8)	Abnl DRE Elevated PSA	2	847	279 (32.9)	8 (2.9)	-	7.9	0.19
6 Morgan et al. (9)	Nl DRE Elevated PSA Neg. prior biopsy	2	67	11 (16.4)	1 (9.1)	-	9.5 for ca 9.5 for non-ca	0.33 for ca 0.21 for non-ca
7 Fleshner and Fair (11)	Elevated PSA Neg. prior biopsy Hypoechoic TZ lesion	2-6	185	58 (31.4)	8 (13.8)	11.9	-	-
8 Present study	Abnl DRE Elevated PSA Neg. prior biopsy	2	344	55 (16.0)	2 (3.6)	88.7	5.5	0.13
Overall		1-6	1977	553 (28.0)	42 (7.6)

PSA, prostate specific antigen; PSAD, prostate specific antigen density; TZ, transition zone; DRE, digital rectal examination; ^*converted to Hybritech monoclonal assay level from the polyclonal value; ca, cancer; abnl, abnormal; nl, normal.

There were eight cases (15.7%) of PIN found in Group 3 patients. Previous biopsies alone contained PIN in three patients (low grade in two and high grade in one), while only repeat biopsy cores contained PIN in four patients (low grade in two, high grade in two). One patient had high grade PIN in both the first and subsequent biopsies. All but two cases had PIN in cores taken from the peripheral zone, these two cases having PIN in cores from the transition zone. None of the four patients with PIN in the first biopsies had cancer in subsequent biopsies (Table 3). There was no atypical adenomatous hyperplasia.

Of the 55 patients with prostate cancer, 25 underwent radical prostatectomy. Directed biopsy from suspicious hypoechoic lesions, in addition to transition zone and sextant biopsies, was conducted in two of these 25 patients. One hypoechoic lesion was positive for cancer. Sextant biopsy cores also contained cancerous tissues though cores from the transition zone did not.

None of the patients in this study experienced febrile complication due to bacteremia. In approximately two-thirds of the patients (67.8%), transient macroscopic hematuria was noted for up to 2 weeks following biopsy (mean 3.4 days, range 0-14). No cystoscopy or clot evacuation was required. Only seven (19.4%) of 36 patients capable of ejaculation within one month following biopsy reported hematospermia.

DISCUSSION

Views differ as to the value of transition zone biopsy (Table 4) (6-12). Lui et al. (6) found additional transition zone biopsy alone to be diagnostic in 10.2% of 187 patients, this being 26.4% of all cancers detected. Following standard sextant biopsy, all patients in their study underwent an additional six biopsies anteriorly in the transition zone. Median PSA for these cases was 15.9 ng/ml [converted to Hybritech monoclonal assay level from the polyclonal value of 26.7 ng/ml (20)]. The same investigators recently re-examined the efficacy of routine transition zone biopsy and noted cancer only in the transition zone in just 0.6% of 161 patients (12). Keetch and Catalona (7) noted that all 166 men subjected to PSA-based screening for prostate cancer had an elevated PSA ( >= 4.1 ng/ml, Hybritech assay). These men had previously undergone one or two sets of negative peripheral zone biopsies. They underwent four additional biopsies anteriorly in the transition zone where just two (10.5%) of 19 cancers were detected only in the transition zone. Fowler et al. (10) evaluated the results of additional diagnostic procedures in men with PSA >10 ng/ml and prior negative peripheral zone biopsy. Cancer was identified in 11, including seven (21.2%) of 33 prostatectomy and four (20.0%) of 20 transition zone biopsy specimens. However, three of the four patients with positive transition zone needle biopsies also had carcinoma in the peripheral zone biopsy. Bazinet et al. (8) evaluated the results of additional transition zone biopsy, for 847 patients with suspicious lesions, by digital rectal examination or elevated PSA. All these patients underwent two additional transition zone biopsies. Eight (2.9%) of 279 cancers could be detected only in the transition zone. Using the same biopsy procedure, Morgan et al. (9) found one (9.1%) of 11 newly diagnosed cancers to be only in the transition zone. The percentage of free PSA was of no use for distinguishing patients with positive transition zone biopsy results. Fleshner and Fair (11) also investigated indications for transition zone biopsy. Eight of 58 cancers were found only in the transition zone. None of the analyzed risk factors was significantly greater in men with isolated transition zone cancer. Cancers detected by transition zone biopsy were thus 7.6% (1.8-26.4%) of all cancers on average; this is too small to justify routine use (Table 4). It may thus be concluded that transition zone biopsy would not contribute significantly to the detection of prostate cancer. The present study, on 344 Japanese patients with abnormal rectal findings, elevated PSA and/or previous negative biopsy, confirms this conclusion. Of 55 patients in whom prostate cancer was found, in only two (3.6%) was the cancer detected by transition zone biopsy alone.

More positive results for transition zone biopsy were obtained in the study of Lui et al(6), possibly due to patient selection, differences in biopsy techniques and/or racial differences. Higher PSA may account to some extent for the difference (Table 4) (6-12). However, the latest report from the same Institution, which showed a much lower positive transition zone biopsy rate, had greater values of this parameter (12). Differences in cancer detection rates could thus not be due only to differences in PSA. Keetch and Catalona evaluated the results of population screening whilst others evaluated patients who had been referred to urology clinics (6-12). Transition zone biopsy may detect tumors more efficiently for certain patients with higher incidence of prostate cancer. Lui et al. conducted more extensive sampling of the transition zone than was carried out in other studies (6). The number of biopsy cores was a significant determinant of the rate of positive findings in a computer-assisted analysis (21). Fewer cores would result in less accurate data for anteriorly located transition zone cancers.

The positive biopsy rate in the present study was lower than in Western studies (Table 4). This may in part reflect the lower incidence of prostate cancer in the Japanese male population, which could be due to racial differences in the prevalence and distribution of cancer foci (13). However, this is unlikely since a previous study failed to demonstrate racially-based differences in morphology or distribution of prostate cancer foci in radical prostatectomy specimens (17).

Various factors may contribute to the inadequacy of transition zone biopsy. Fewer samples are covering a larger area in transition zone than in peripheral zone biopsy. Nodules of benign prostatic hypertrophy may resist needle penetration. Selective sampling of internodular rather than glandular tissue is conducted in transition zone biopsy owing to curvature of the needle track, making cancer detection less likely (22).

The patients who would benefit most from additional use of transition zone biopsy would be those with exclusively transition zone cancers. However, transition zone cancer without cancer foci elsewhere in the gland is infrequent owing to the multifocality of prostate cancer. Tumors of transition zone origin were found in 19.6% of surgical specimens from 107 consecutive radical prostatectomies for resectable prostate cancer (T1a-b, 4; T1c, 31; T2, 52; T3, 20) at this Institution. Of these, only 6.5% (7/107) had cancer exclusively in the transition zone (unpublished data). Greene et al. (23) found peripheral zone cancer in 93% of stage A and all stage B prostate cancer specimens. Peripheral zone cancer averaged 1.94 cm³ in stage A and 3.99 cm³ in stage B disease. Transition zone cancers were present in 81% and 43% of these patients respectively, indicating the infrequency of `pure' transition zone cancers. Quite possibly, fewer than 10% of patients would benefit from this type of biopsy. Even so, this is a maximum estimate since some transition zone cancers can be sampled by systematic sextant peripheral zone biopsy as well. During peripheral zone biopsy, the needle may penetrate the transition zone and needle biopsy of this zone may include tissue from the peripheral zone. It is significant that all seven `pure' transition zone cancers in our radical prostatectomy series were detected by systematic sextant peripheral zone biopsy. This was also evident in one patient from the present study, whose transition zone biopsy was positive although in the radical prostatectomy specimen there were only anterolaterally located multiple peripheral zone cancer foci.

The incidence of PIN in needle biopsy ranges from 7.6 to 31% in various reports, depending on the population (19). The incidence in this study was slightly lower, 5-7%. In contrast to previous findings, PIN was not associated with cancer in subsequent biopsies. These findings may be an indication of racial differences, but the number of patients is too small to draw any definitive conclusions. Two additional cores from the transition zone did not lead to greater morbidity of biopsy. The incidence of complications was essentially that in the previous study (24).

The present data are consistent with previous findings that transition zone biopsy does not contribute significantly to the detection of prostate cancer. Though possibly of value for certain patients, the small number of cases found to have cancer only in the transition zone in this study did not allow us to specify groups. Those with markedly elevated or rapidly increasing PSA and previous negative peripheral zone sextant biopsy results may possibly benefit from this procedure. Transurethral resection or extensive sampling of the transition zone may be indicated for such cases. The positive results of transition zone biopsy are but few and thus would not justify its routine use on Japanese patients. Further investigation should be made of patients who would benefit most from two or more biopsies of the transition zone.

Acknowledgments

This study was supported in part by a Grant from the Ministry of Health and Welfare of Japan (7-42).

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Received June 12, 1997; accepted August 21, 1997
For reprints and all correspondence: Shin Egawa, Department of Urology, Kitasato University School of Medicine, 15-1, Kitasato 1-chome, Sagamihara, Kanagawa 228, Japan
Abbreviations: PSA, prostate specific antigen; PSAD, prostate specific antigen density; PIN, prostatic intraepithelial neoplasia.

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