Role of transition zone sampling by TURP in patients with raised PSA and multiple negative transrectal ultrasound-guided prostatic biopsies.

The purpose of the study was to determine the role of transurethral resection of the prostate (TURP) to detect prostate cancer in patients with consistently negative transrectal ultrasound-guided biopsies of the prostate. We retrospectively identified and analysed the patients who also had at least two sets of transrectal ultrasound guided sextant prostate biopsies before their TURP during the period between 1998 and 2002. A total of 14 such patients were identified and the outcome of TURP was analysed. Three patients were found to have cancer in the resected specimen (3/14 = 21%). All three cancers were significant (Gleason scores between 6 and 8) and required further treatment. In patients who have rising levels of prostate-specific antigen and who have had multiple negative peripheral zone biopsies, the presence of biologically important transition zone cancers needs to be considered. This can be detected by transurethral resection of the prostate that samples the transition zone of the prostate.

Percutaneous embolization of varicoceles: outcomes and correlation of semen improvement with pregnancy.

OBJECTIVES: To assess the technical feasibility and compare the semen quality in men with or without pregnancy after percutaneous embolization of varicoceles in the management of infertility. METHODS: The records of 102 patients who underwent retrograde varicocele embolization between January 1997 and January 2002 were reviewed through the Hospital Information Support System. Infertility was the indication for embolization in 71 cases. The present study consisted of this group of patients. The size of the varicoceles, the size of the testis, the pre-embolization semen analysis parameters, the technical details of embolization procedure, any anomalous vessels seen on venography, and, if unsuccessful, the reason for failure of the procedure were noted. A record of postembolization semen parameters (at least two) was made. Patients were divided into four groups depending on the pre-embolization semen density, and a correlation of this was assessed with improvements in morphology and motility. Follow-up was performed using a questionnaire to evaluate the success rate of the procedure, complications, and any treatment for infertility by the patient or his partner after the procedure. Patients who had a successful pregnancy were compared with those who did not to determine the correlation between the changes in semen quality and pregnancy rate. RESULTS: Between January 1997 and January 2002, 71 patients underwent retrograde varicocele embolization, using an embolizing coil, for infertility. In 68 (95.7%), it was technically successful. Nineteen patients (26.7%) had various anomalous vessels on venography. A statistically significant improvement (P = 0.002) was noted in the motility parameters in patients with a pre-embolization semen density between 10 and 30 million/mL. All patients were followed up by questionnaire. Follow-up was possible in 51 patients (75%). One patient had varicocele recurrence and underwent open inguinal surgical ligation. Of 45 patients, the partners of 18 (40%) had a successful pregnancy. A comparison of the postembolization semen quality between those with and without a successful pregnancy found no correlation between the changes in the semen parameters and the pregnancy rate. CONCLUSIONS: Varicocele embolization is a technically feasible, minimally invasive, outpatient procedure that improves semen quality significantly in patients with a pre-embolization semen density of 10 to 30 million/mL. However, no correlation was found between the improvements in semen quality and the pregnancy rate.

How important is urinary cytology in the diagnosis of urological malignancies?

OBJECTIVE: To audit clinical usefulness of urine cytology examination in a subspecialised urological unit setting. PATIENTS AND METHODS: Data from the hospital information support system on urinary cytology examinations carried out at one centre was audited over a period of 15 months. Source of urine cytology specimens, clinical profile of patients and the findings of urinary cytology were analysed and collated. RESULTS: A total of 1400 urinary cytology specimen on 900 patients were requested during 15 months study period. Urologists requested 1092 (78%) and non-urologists (general practitioners, physician or general surgeons) requested 318 (22%) specimens. The majority of specimens, 1115 (80%) did not show any cytological evidence of malignancy. 83 specimens (6%) showed cytological evidence of malignant cells consistent with origin from a urothelial malignancy. Among this group 87% (72) were more than 50 years of age and 60 (72%) had history of gross heamaturia. 159 (11.35) cases were reported as being suspicious of malignancy or showing atypical cells requiring further evidence. A total of 43 (3.04%) specimens were poorly preserved or insufficient for diagnosis. The positivity rate amongst urologist and non-urologists request was 56% and 6% respectively (p=0.00001 value). The source in 37 (86%) specimens reported, as poorly preserved or insufficient for diagnosis was non-urologists compared to 6 (14%) from urologists with significant p value (0.00001). CONCLUSIONS: Urinary cytology for malignant cells is a contributory investigation in the diagnosis of urological malignancy. It should be only ordered in the proper clinical situation.

Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol.

OBJECTIVE: To investigate whether taking two transition zone (TZ) and four lateral peripheral zone (PZ) biopsies in addition to routine parasaggital sextant biopsies would improve detection rates in men with suspected prostate cancer. PATIENTS AND METHODS: The study included 493 consecutive men (mean age 68.7 years, sd 8.2) with elevated serum prostate-specific antigen (PSA) levels and/or abnormal findings on a digital rectal examination who underwent transrectal ultrasonography-guided prostate biopsy. In addition to sextant biopsies, six further biopsies were obtained, two from the TZ (mid-gland) and four from the lateral PZ (base and mid-gland). Pathological findings for the additional biopsies were compared with those of the sextant regions. RESULTS: Prostatic adenocarcinoma was diagnosed in 164 of the 493 (33%) men biopsied. Men with cancer were older, had smaller prostates and higher median PSA levels than men with negative biopsies. Sextant biopsies were positive for cancer in 133 of 164 (81%) men. All three sets of biopsies were positive in 53 (32%) cases. In 50 (30%) men both the sextant and lateral PZ biopsies were positive, while in six (4%) men, both sextant and TZ biopsies were positive. Thirty-one (19%) tumours were not detected by sextant biopsies, 10 (6%) where the lateral PZ biopsies alone were positive, 17 (10%) where the TZ biopsies alone were positive and four (3%) where both the TZ and lateral PZ together were positive. There were no differences in median PSA concentration, total prostate volume or TZ volume between men with an isolated TZ cancer and men with cancer elsewhere in the prostate. However, 77% of men with TZ cancer had a PSA of > 10 ng/mL, compared with 60% of men with cancer at other sites within the prostate (P = 0.015). CONCLUSION: An extended-core biopsy protocol significantly improves the detection rate for prostate cancer when compared with the standard sextant biopsy protocol alone. Routine TZ biopsies should be considered for men with serum PSA levels of >10 ng/mL.

Seminoma metastatic to the prostate resulting in a rectovesical fistula.

We report an unusual presentation of metastatic seminoma within the prostate gland. Histological diagnosis was obtained using trans-rectal ultrasound guided prostatic biopsy. The patient developed a rectovesical fistula after ten weeks of chemotherapy, which healed following a complete radiological response to treatment

Diagnostic dilemmas in detection of prostate cancer in patients undergoing transrectal ultrasound-guided needle biopsy of the prostate.

Transrectal ultrasound (TRUS)-guided needle biopsy of the prostate is a widely practised method for obtaining high quality tissue cores for histological diagnosis in men with suspected prostate cancer. Technological advances such as high-resolution hand held probes with biplanar imaging capabilities and spring-loaded needles that easily permit multiple biopsies to be obtained have ensured that this technique has rightly taken its place at the forefront of prostate cancer diagnosis. However, the capacity for TRUS to identify prostate cancer remains limited because of poor specificity and variability in the ultrasonic appearance of tumours. Widespread prostate-specific antigen (PSA) testing has increasingly resulted in greater numbers of tumours being diagnosed at an early stage, when they are clinically impalpable and ultrasonically indistinguishable from surrounding normal prostate tissue. In this setting, the principal role for TRUS is to facilitate systematic sampling of all relevant zones of the prostate. Despite advances in technology and in our understanding of this disease, a number of diagnostic dilemmas arise. Should we perform lesion-directed or random biopsies? How many tissue cores should be obtained for optimal diagnostic yield, to reduce the incidence of false-negative biopsies? What areas of the prostate should be biopsied to give the best diagnostic results? If the initial biopsies fail to detect cancer, who should undergo repeat biopsy? Some have also voiced concern that TRUS risks identifying clinically insignificant disease. Here, we review the studies that have addressed these issues and have lead to the evolution of TRUS-guided prostate biopsy into an essential tool in the detection of carcinoma of the prostate. Prostate Cancer and Prostatic Diseases (2000) 3, 13-20

Elevated serum prostate specific antigen levels in conjunction with an initial prostatic biopsy negative for carcinoma: who should undergo a repeat biopsy?

OBJECTIVE: To determine the outcome of repeated prostatic biopsies in men attending with suspected prostate cancer but an initial negative biopsy. PATIENTS AND METHODS: Patients who had undergone two or more transrectal ultrasonography (TRUS)-guided prostate biopsies were identified from the Hospital Information Support System database. Indications for TRUS were a raised prostate-specific antigen (PSA) level (>4.0 ng/mL), with or without an abnormal digital rectal examination (DRE). Sextant prostate biopsies plus biopsies of any suspicious hypoechoic area or area of DRE abnormality were obtained for histology. Forty-eight patients underwent repeat TRUS-guided prostatic biopsies (mean age 67.5, sd 7. 25, range 53-82 years). RESULTS: The mean (sd, median, range) PSA level was 16.9 (13.5, 11.6, 5.2-61.8) ng/mL. Fifteen patients (31%) had carcinoma on repeat biopsy, 11 after the second and four after a third biopsy. The positive repeat biopsy rate was 24% where the PSA level was 4.0-9.9 ng/mL, 33% if the level was 10.0-19.9 ng/mL and 39% if it was >/=20.0 ng/mL. There was no significant difference in age or initial PSA concentration between those men with positive and those with negative repeat biopsies. However, patients with cancer had significantly higher PSA levels before repeat biopsy than at first biopsy (P=0.0043) and had greater PSA velocities than had patients with no diagnosis of cancer (P=0.0067). CONCLUSION: Where sufficient clinical suspicion exists, despite an initial negative biopsy, repeat TRUS-guided prostate biopsies should be carried out to exclude carcinoma of the prostate.

Free/total serum prostate-specific antigen ratio: how helpful is it in detecting prostate cancer?

OBJECTIVE: To determine whether the use of free/total (f/t) serum prostate specific antigen (PSA) ratio would help reduce the number of prostate biopsies performed without compromising the detection of prostate cancer. in the setting of a transrectal ultrasonography (TRUS) clinic. PATIENTS AND METHODS: The study included 93 consecutive patients referred to the clinic for TRUS and biopsy. Serum samples were assessed for total PSA and free PSA, and the f/t PSA ratio calculated: 70 biopsies were taken. Patients over the age of 70 years with TRUS findings consistent with benign prostatic hyperplasia and with PSA levels < 10 ng/mL were not biopsied. RESULTS: Tumour was detected in 23 patients; receiver operating characteristic curves showed no advantage for the f/t PSA ratio when compared with total PSA in detecting prostate cancer. If a f/t PSA ratio of < 0.15 had been used to determine the necessity for biopsy in the group with a total PSA of 4-10 ng/mL, then two-thirds of all tumours would have been undetected. CONCLUSION: The f/t PSA ratio had no advantage over total PSA in improving specificity at a given sensitivity for detecting prostate cancer. Therefore, it cannot be recommended as a means of decreasing unnecessary biopsies in patients with a raised PSA level and/or an abnormal digital rectal examination. This applied particularly to the group of patients with a total PSA of 4-10 ng/mL.

Anatomy of the prostate and distribution of early prostate cancer.

Many of the difficulties in understanding diseases of the prostate have arisen through poor understanding of the anatomy of the prostate. The recent description of histologically separate zones in the prostate has been an important advance, allowing evaluation of separate cancers arising in the transition and peripheral zones of the prostate. While the majority of cancers sampled at transurethral resection of the prostate (TURP) are of transition zone origin, most of these prostates contain separate cancers in the peripheral zone. The peripheral zone cancers have a higher grade-to-volume ratio and are more frequently associated with histological features of progression (extracapsular extension, seminal vesicle invasion) than transition zone cancers. Furthermore, peripheral zone cancers are frequently associated with prostatic intraepithelial neoplasia, in contrast to transition zone cancers. These findings suggest a greater biological activity for cancers arising in the peripheral zone. The majority of cancers detected by digital rectal examination are of peripheral zone origin. While associated transition zone cancers are less frequently present than in TURP sampled prostates, a similarly high association of peripheral zone cancers with histological indicators of biological activity is seen. DNA ploidy analysis of separate foci in radical prostatectomy specimens confirms a significantly higher rate of non-diploidy in cancers of peripheral zone origin, some of very small volume, which further suggests a greater biological activity compared to transition zone cancers.

DNA ploidy and clonal selection in ras + myc-induced mouse prostate cancer.

An important goal in prostate cancer research is to define specific molecular and cellular alterations that are associated with malignant progression. The mouse prostate reconstitution model is a relevant and useful system as it allows the study of early events in cancer progression under conditions where oncogene-initiated cells are surrounded by normal tissue. Using this model, activated ras and myc oncogenes are introduced into urogenital sinus cells via the recombinant retrovirus Zipras/myc 9. After 4 weeks' growth as subcapsular renal grafts, poorly differentiated carcinomas are produced in C57BL/6 mice. In this study we examined the temporal relationships between morphological alterations, growth, DNA ploidy status and clonal selection as determined by Southern blotting in ras + myc-initiated carcinomas. Nuclear image analysis demonstrated that the emergence of a cycling DNA tetraploid cell population strongly correlated with growth and histologic progression. These tightly linked events culminated in the outgrowth of mono- or oligoclonal cancer.

Some small prostate cancers are nondiploid by nuclear image analysis: correlation of deoxyribonucleic acid ploidy status and pathological features.

The biological behavior of a prostate cancer can be predicted to some degree by the volume and extent (stage) of the tumor, and its histological grade. The deoxyribonucleic acid (DNA) ploidy status has been reported by some to be another independent prognostic factor for localized prostate cancer. We determined the DNA ploidy value of each individual focus of cancer in radical prostatectomy specimens using nuclear image analysis (CAS 200 system). Ploidy results were correlated with the volume, Gleason grade and zone of origin (transition zone or peripheral zone) of each tumor, and with the presence of extracapsular extension or seminal vesicle invasion. There were 141 separate cancers in 68 patients (mean 2.1 per prostate): 9 clinical stage A1, 22 stage A2, 23 stage B1 and 14 stage B2. DNA ploidy correlated significantly (p < 0.0001) with volume, grade, extraprostatic spread and zone of origin. Remarkably, some small cancers (1 cc or less) were nondiploid (3 as small as 0.03 cc). Overall, 15% of cancers 0.01 to 0.1 cc and 31% of those 0.11 to 1.0 cc in volume were nondiploid. Of 101 cancers confined to the prostate 76% were diploid, compared to only 13% of those with extraprostatic spread. Most cancers of transition zone origin (86%) were diploid, compared to only 49% of peripheral zone cancers, and ploidy and volume relationships were significantly different for peripheral zone cancers compared to transition zone cancers. All small nondiploid cancers arose in the peripheral zone, while in the transition zone the smallest nondiploid cancer was 1.17 cc. We conclude that prostate cancers that are nondiploid are highly likely to have adverse pathological features. Some small prostate cancers contain a nondiploid cell population and these cancers arise predominantly within the peripheral zone of the prostate. Ploidy and volume relationships provide further support for the hypothesis that there is a difference in malignant potential between cancers of peripheral zone and transition zone origin.

Clinical relevance of the individual prostate cancer focus.

The course of stage A prostate cancer is difficult to predict because some of the tumors sampled at TURP are histologically "latent" (resembling cancer discovered incidentally at autopsy) and others have the ability to progress clinically. TURP selectively samples cancer in the transition zone, but, as we noted, the pattern of cancer in the TURP was a limited predictor of residual cancer. Furthermore, peripheral zone cancer appeared histologically to have a higher grade, volume for volume, than transition zone cancer and, in our study, was more frequently associated with extraprostatic spread of cancer. Peripheral zone cancer, while sampled in a minority of TURPs (less than 20%), is associated with histological predictors of poor prognosis. In the ploidy study, peripheral zone cancer was sampled in 5 patients, 4 of whom had nondiploid residual cancer in the radical prostatectomy specimen. Three of these 5 had extracapsular extension and 2 had seminal vesicle invasion. The frequent pattern in stage A1 is, therefore, a low-volume, diploid, transition zone cancer in the TURP specimen. In most cases this was associated with one or more small diploid transition zone or peripheral zone cancers in the radical prostatectomy specimen. However, in some cases, a residual nondiploid cancer was present that could eventually cause progression. The pattern of cancer in stage A2 differs from that in stage A1 in that most large transition zone cancers are selected into this stage and some of these are nondiploid. Stage A2, therefore, includes the minority of transition zone cancers that are nondiploid as well as a considerable number of peripheral zone cancers that are nondiploid. In both stages A1 and A2 nondiploid peripheral zone cancers outnumbered nondiploid transition zone cancers. The relationship of tumor volume with ploidy is clearly different for peripheral zone and transition zone cancers. Eight peripheral zone cancers less than 2.0 cc were nondiploid but only 1 transition zone cancer less than 2.0 cc was nondiploid. Furthermore, all peripheral zone cancers greater than 2.0 cc were nondiploid whereas only 50% of transition zone cancers greater than 2.0 cc were nondiploid. There was a significant difference between tumor volume of diploid and nondiploid cancers. Presumably, nondiploid cell lines have a growth advantage and are more poorly differentiated than diploid cancers. Whether DNA ploidy changes occur as a consequence of tumor growth and tumor cell heterogeneity is unclear because of range in volume of tumors studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of the pathologic features and DNA ploidy value of prostate cancers detectable by sonography and by palpation.

Ultrasonography of the prostate detects some cancers that are not palpable, but the pathologic features of such cancers have not been well described. Since screening trials consistently find sonography more sensitive (though less specific) than digital rectal examination, nonpalpable cancers that are visible as hypoechoic lesions on ultrasound have been postulated to be early cancers of limited malignant potential and may not require aggressive treatment. To test this hypothesis, we determined the pathologic features and DNA ploidy value of prostate cancers in 63 radical prostatectomy specimens taken from patients with clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%), the cancer appeared hypoechoic on ultrasound. The median volume of these cancers was 4.19 cm3 (range 0.45-19.22); 80% exhibited extra-capsular extension (ECE); 30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35 patients, the tumor was palpable, and the pathologic features and DNA ploidy values (94% nondiploid) of these cancers were similar to those of the tumors that were visible on ultrasound. In seven patients, the cancer was visible by ultrasound but not palpable by digital rectal examination. Median tumor volume was 1.72 cm3 (range 0.45-18.98); four patients (57%) had ECE; one (14%) had SVI, and six (86%) had nondiploid cancers. We conclude that most cancers that appear hypoechoic on ultrasound are clinically important and exhibit aggressive pathologic features. Palpable cancers and sonographically visible cancers are similar and should be staged and treated similarly.

Detection of residual prostate cancer after radiotherapy by sonographically guided needle biopsy.

Detection of persistent or recurrent prostate cancer by digital rectal examination (DRE) after definitive radiotherapy is difficult. With the availability of transrectal ultrasonography (TRUS), the detection of prostate cancer has improved substantially. Since 1987 we have used TRUS to evaluate the prostate after definitive radiotherapy. A hypoechoic lesion suggestive of cancer was identified in 45 of 56 patients (80%) studied. Sonographically directed transrectal needle biopsies were performed in 27 of these (60%), and 16 (59%) were positive for cancer. The presence of a palpable nodule suggestive of cancer (present in 7 patients) was not predictive of a positive biopsy specimen. In 14 patients ultrasound-guided and digitally-guided biopsies were performed at the same time; 8 (57%) of the ultrasound-guided biopsy specimens were positive compared with only 4 (29%) of the digitally-guided biopsy specimens. In all 7 patients with an elevated serum level of prostate-specific antigen (PSA) an ultrasound-guided biopsy result was positive. Random biopsies of sonographically normal (isoechoic) areas of the prostate were performed in 8 patients, but only 2 specimens (25%) were positive for cancer. Ultrasound-guided transrectal biopsy of hypoechoic lesions was a safe and effective technique for identifying residual cancer in the irradiated prostate, regardless of the palpable findings. In the presence of an elevated PSA level, such biopsies invariably identified residual cancer. The use of TRUS, ultrasound-guided biopsy, and the measurement of PSA, in addition to DRE, may aid in the detection of residual cancer after definitive radiotherapy.

Unusual hyperechoic appearance of prostate cancer on transrectal ultrasonography.

A series of 157 patients with prostate cancer underwent transrectal ultrasonography prior to radical prostatectomy. In 112 patients (71.3%) the tumours appeared hypoechoic relative to the echo pattern of the normal peripheral zone; in 43 (27.4%) they appeared isoechoic, and in only 2 (1.3%) did they appear purely or predominantly hyperechoic. These 2 hyperechoic tumours were unusual ductal adenocarcinomas with central necrosis and dystrophic calcification within solid tumour nests, a pattern similar to that of comedo-carcinoma of the breast. Calcification within prostate cancer was found in 4 of the 157 radical prostatectomy specimens, including 2 other hypoechoic cancers which contained intraluminal or psammomatous calcification. Although the most common sonographic appearance of localised prostate cancer is hypoechoic, a predominantly hyperechoic pattern is seen occasionally and suggests the presence of a high grade ductal adenocarcinoma.

Relationship between clinical stage and histological zone of origin in early prostate cancer: morphometric analysis.

A detailed morphometric analysis of 96 radical prostatectomy specimens (13 clinical stage A1, 29 A2, 34 B1 and 20 B2) was undertaken to examine the relationship of zone of origin to volume, grade and extraprostatic extension of cancer. In patients with stage A disease, transition zone (TZ) cancer (present in 81%) was significantly larger but of lower grade than peripheral zone (PZ) cancer (present in 90%). The total volume of cancer in stage A1 patients averaged 1.55 ml with 72% of TZ origin. In patients with stage A2 disease, tumour volume averaged 5.83 ml with only 57% of TZ origin. Specimens taken during transurethral resection of the prostate (TURP) revealed TZ cancer in 82% and PZ cancer either alone or with TZ cancer in 22%. The 9 patients with PZ cancer in the TURP specimen included 5 of the 11 with extracapsular extension and all 5 of those with seminal vesicle invasion. Every patient with stage B disease had PZ cancer which, in all except 3 cases, was of significantly larger volume and higher grade than any TZ cancer (present in 43%) in the same gland. In patients with stage B cancer, total tumour volume was 5.13 ml with 91% of PZ origin. TZ cancer tended to be well differentiated in all patients, even at large volumes, whereas PZ cancer was often moderately or poorly differentiated even at low volumes. In patients with stage B disease, TZ cancer appeared to be incidental and of no clinical importance, while in stage A patients PZ cancers were sometimes large, poorly differentiated and extended outside the prostate. Progression of a stage A cancer seems more likely to result from PZ cancer than TZ cancer, and the finding of PZ cancer in a TURP specimen should probably preclude its classification as stage A1.

A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate.

To determine the characteristics of transition zone and peripheral zone prostate cancer, we examined a series of 42 stage A and 54 stage B radical prostatectomy specimens with particular attention to the number of separate foci of cancer, zone of origin, volume and grade of each focus, and presence of severe intraductal dysplasia (high grade prostatic intraepithelial neoplasia), extra-capsular extension and seminal vesicle invasion associated with cancer in each zone. We found that there were fundamental differences between transition zone and peripheral zone cancers, and that the features that characterize these tumors were apparent in stages A and B disease. Although the total tumor burden was similar in stages A (3.98 cc) and B (4.56 cc) disease, stage A cancer tended to be multifocal (3.1 tumors per prostate) and more diffuse. While 81% of stage A prostate specimens contained a tumor of transition zone origin and 93% had cancer of peripheral zone origin, transurethral resection of the prostate sampled a transition zone cancer in 77% and a peripheral zone cancer in 31% (8% had both types). Stage B cancer tended to be more focal (2.3 cancers per prostate). All stage B prostate specimens contained a peripheral zone cancer and 43% had a transition zone cancer as well. In only 1 stage B cancer patient was the transition zone tumor the palpable or index cancer. In stages A and B disease, peripheral zone tumors were less well differentiated (median Gleason sum 6 and 7) than transition zone tumors (5 and 5, respectively) and more likely to extend through the capsule (44% versus 11%). Seminal vesicle invasion arose from 19% of the peripheral zone but none of the transition zone cancers. Peripheral zone tumors were almost always (93%) associated with high grade prostatic intraepithelial neoplasia, while none of the transition zone cancers was so associated. For peripheral zone disease there was a moderate correlation between volume and grade (tau = 0.46, p less than 0.001) so that the larger the tumor the higher the Gleason sum but within transition zone disease this correlation was poor (tau = 0.23) and not statistically significant (p greater than 0.05). Extracapsular extension occurred at a smaller volume with peripheral zone cancer (mean 3.86, minimum 0.06 cc) than transition zone cancer (mean 4.98, minimum 0.39 cc). Cancer that arises in the transition zone appears to have a different histogenesis, is associated with more favorable pathological features and may have less malignant potential than tumors that arise in the peripheral zone.

DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report.

The malignant potential of an individual focus of prostate cancer is difficult to determine. The established pathological features associated with malignant behavior include tumor volume, grade, and invasiveness (local extension or metastasis). We used nuclear image analysis to determine the DNA ploidy value of each cancer in a series of 30 radical prostatectomy specimens from patients with early stage prostate cancer in order to further explore the malignant potential of each separate focus of cancer. The volume, grade, invasiveness (extracapsular extension or seminal vesicle invasion), and zone of origin of each of the 63 separate cancers were determined. The DNA ploidy histogram of 200 cancer cells was compared with 50 normal epithelial nuclei on the same Feulgen-stained tissue sections. Sixty % of the cancers were diploid, and 40% were nondiploid. Ploidy correlated with volume and grade. All cancers less than 0.02 cm3 were diploid; 26% of foci 0.02 to 2.0 cm3 and 82% of foci greater than 2.0 cm3 were nondiploid. There were 16 cancers of transition zone origin ranging in size from 0.02 to 12.1 cm3 and only one (7.3 cm3) was nondiploid. There were 47 cancers of peripheral zone origin (range, 0.01 to 18.98) and 24 (51%) were nondiploid. Eight of the 24 nondiploid cancers were small (less than 1.0 cm3), and two were only 0.03 cm3. We conclude that some very small prostate cancers are nondiploid and that progression of prostate cancer is not a function of volume alone, whereby tumors only acquire full malignant potential at large volumes. Cancers of peripheral zone origin acquire a nondiploid cell population at a smaller volume than do cancers of transition zone origin, further supporting a fundamental difference between cancers arising in these zones.

Transrectal ultrasonography in stage A prostate cancer: detection of residual tumor after transurethral resection of prostate.

To evaluate the ability of transrectal ultrasonography to detect residual cancer in the prostate gland after transurethral resection in patients with stage A cancer, we studied 38 patients with stage A disease (11 stage A1 and 27 stage A2) in whom transrectal ultrasonography was done at least 3 weeks after resection. Each patient underwent radical prostatectomy, and residual cancer was present in 97% of the specimens (peripheral zone cancer in 95% and transition zone cancer in 61%). At sonography we identified hypoechoic areas suggestive of cancer in 10 patients (26%). In the pathological specimen residual cancer was present at the hypoechoic area in 8 of these cases (positive predictive value 80%). In a retrospective review of the sonograms we identified 25 hypoechoic lesions greater than 5 mm. in diameter, including 15 that corresponded to cancer in the radical prostatectomy specimens (positive predictive value 60%). Granulomas due to the transurethral resection were found in 92% of the radical prostatectomy specimens but none appeared hypoechoic on ultrasound. A total of 103 separate cancers was identified in the whole mount step sections of the radical prostatectomy specimens (2.7 cancers per patient). Of the 103 separate cancers 54 were less than 0.1 cc in volume and none of these could be identified in the retrospective review of the sonograms, 37 were 0.1 to 1.0 cc and 5 of these (14%) appeared hypoechoic, and 12 were greater than 1.0 cc and 10 of these (83%) appeared hypoechoic. Hypoechoic lesions greater than 5 mm. in diameter in the transition zone proved to be cancer in 47% of the cases, while 88% of similar lesions in the peripheral zone proved to be cancer. We conclude that suspicious-appearing hypoechoic lesions suggestive of cancer, whether in the peripheral zone or the transition zone, should be biopsied before expectant management of stage A prostate cancer is considered. Transrectal ultrasonography is useful for restaging after transurethral resection and for evaluating the extent of residual cancer in stages A1 and A2 prostate cancer.

The distribution of residual cancer in radical prostatectomy specimens in stage A prostate cancer.

To assess the volume and distribution of residual cancer after transurethral resection of the prostate in stage A cancer patients 42 step-sectioned radical prostatectomy specimens were examined, and the volume, location, grade and extracapsular extension of the residual tumor were recorded. A total of 13 patients had stage A1 tumors (5% or less tumor in the transurethral resection specimen and a Gleason sum of 7 or less) and 29 had stage A2 disease. Residual cancer was present in the radical prostatectomy specimen in 41 patients (98%) with a mean volume of 1.28 cc. The location of residual cancer, that is multifocal (76%), peripheral (81%) and distal to the verumontanum (66%), makes complete removal or even identification of residual tumor (restaging) by repeat transurethral resection improbable. Of the stage A1 cancer patients 4 (30%) had more than 1 cc residual tumor volume, extracapsular extension or seminal vesicle invasion. On the other hand, 14 of the stage A2 cancer patients (48%) had less than 1 cc residual tumor completely confined to the gland. Foci of residual cancer were found in the transition zone in 67% and in the peripheral zone in 90% of the patients. The grade of the residual peripheral zone cancer was significantly higher than that of the transition zone cancer in the same gland (p = 0.0004). Eight of 13 instances of extracapsular extension and all 5 of seminal vesicle invasion were directly attributable to peripheral zone cancer. These observations imply that the greatest threat to patients with stage A prostate cancer may be a separate, associated cancer in the peripheral zone rather than the primary transition zone cancer incidentally removed at transurethral resection.