Damian Greene

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.

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.

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.

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.

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.

Oncologic Outcomes of Penile Cancer Treatment at a UK Supraregional Center

OBJECTIVE To report contemporary treatment outcomes of penile squamous cell carcinoma at a UK supraregional center, including patterns of therapy, oncologic results, and long-term survival. PATIENTS AND METHODS Patients with squamous cell carcinoma treated during the period January 2000 to January 2011 were included. Records were reviewed to identify the mode of therapy (penile preserving or amputative surgery), pathology reports (reclassified according to the 2009 tumor-nodes-metastasis classification), recurrence patterns, and cancer-specific survival (CSS). Kaplan-Meier plots were used for survival analyses. RESULTS Two hundred three patients were identified with a median follow-up of 61 months. At presentation, 165 patients (82%) were node negative, 31 (15%) were node positive, and 7 (3%) had metastatic disease. Management was penile preserving surgery (n = 99, 49%), partial penectomy (n = 49, 24%), radical penectomy (n = 48, 24%), and chemotherapy or radiotherapy for metastatic disease (n = 7, 3%). After organ-preserving surgery, the local recurrence rate was 18% (compared with 4% for amputative surgery), with 94% of recurrences occurring within 3 years. Histopathologic staging was as follows, with pTis (20%), pT1 (27%), pT2 (27%), pT3 (7%), and pT4 (1%). Kaplan-Meier analysis showed a 5-year CSS of 85% and a 10-year CSS of 81%. Five-year CSS was noted to decrease with advancing stage with pN0 tumors (92%), N1 (73%), N2 (61%), N3 (33%), and M1 (0%; P <.0001). CONCLUSION Supraregional penile cancer management has led to considerable clinical experience in our center over the past decade. Close follow-up is vital to pick up local recurrence after penile-preserving surgery. Overall oncologic outcomes are good with a 5-year CSS of 85%.

The prognostic value of transrectal ultrasound guided biopsy in patients over 70 years old with a prostate specific Antigen (PSA) level ≤15 ng/ml and normal digital rectal examination: A 10-year prospective follow-up study of 427 consecutive patients

INTRODUCTION As a urologist, it is common to review a patient above the age of 70 being referred to a prostate assessments clinic with an elevated PSA. We evaluate the prognosis of these patients clinically as there is no international consensus on the exact PSA cutoff level or a single international guideline as to when these patients should be offered a prostate biopsy. PATIENTS AND METHODS On receiving ethic committee approval, we recruited 427 consecutive patients aged 70 years and above referred with a PSA of ≥ 4 ng/ml, from January 1996 to December 2000, into our study. All patients were assessed, examined with a digital rectal examination (DRE) of the prostate, and a subsequent prostate biopsy. We followed up on their histologic diagnosis for up to 10 years and analyzed their outcome. The main outcome measures were disease-free survival and overall survival, stratified according to the PSA level (≤ 15 vs. >15 ng/ml) and DRE findings (normal vs. sbnormal). RESULTS There was a statistically significant difference in the overall survival (P value < 0.011) and disease specific survival (P value < 0.0001) of cancer patients with a PSA was >15 ng/ml and an abnormal DRE. However, in patients with a PSA ≤ 15 ng/ml and normal DRE, the incidence of cancer was low and they had no disease-specific or overall survival benefit. CONCLUSIONS A policy of deferring prostate biopsy in patients with a PSA ≤ 15 ng/ml and normal DRE (Group A) would significantly decrease the need of unnecessary prostate biopsies. Within this group, patients did not have any survival advantage compared with those without cancer. We conclude that up to 20% of the prostate biopsies performed in this age group could have been avoided.

MP10-14 PREDICTING INGUINAL AND PELVIC LYMPH NODE STATUS IN PENILE CANCER PATIENTS: A COMPARISON OF COMPUTED TOMOGRAPHY AND DISEASE BURDEN OF INGUINAL LYMPH NODES

INTRODUCTION AND OBJECTIVES: We have previously reported an association between obesity and higher risk of invasive penile cancer in a hospital-based retrospective study. In order to validate the association between obesity and penile cancer at a population level, we conducted a matched case-control study linking the Iowa Department of Motor Vehicles Drivers’ License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI). METHODS: All men diagnosed with invasive penile squamous cell carcinoma from 1973 to 2010 were identified by the SHRI. Three hundred-thirty cancer cases and 990 cancer-free male controls, selected from the Iowa DLD, were matched within 5-year age and calendar year strata at a ratio of 3 controls to each case . Body mass index (BMI) was calculated using self-reported height and weight from the DLD. Conditional logistic regression was used to evaluate the association between BMI and the risk of developing invasive penile cancer. RESULTS: Penile cancer cases were significantly more likely to be overweight or obese as compared to controls. Compared to men with a normal weight (BMI < 25), the risk of invasive penile cancer increased with increasing obesity (Table). When BMI was treated as a continuous variable in the analysis, the risk of invasive penile cancer increased by an estimated 55% for every five-unit increase in BMI (Table). CONCLUSIONS: In this population-based matched case-control study, we found that increasing BMI was associated with a higher risk of developing invasive penile cancer. These results are consistent with our previous hospital-based study. Greater emphasis on education of obese men about this risk might encourage weight loss and persuade them to perform periodic genital self-examination.

188 THE SUPERIORITY OF TRANSPERINEAL TEMPLATE MAPPING BIOPSY OF THE PROSTATE GLAND OVER THE TRANSRECTAL SATURATION APPROACH

INTRODUCTION AND OBJECTIVES: Attempts to maximise the effectiveness of repeat biopsy has given rise to the alternate approaches of saturation biopsy and the transperineal approach. Recent interest in focal treatment of prostate cancer has further highlighted the need for accurate detection of prostate cancer and in response, the introduction of transperineal template mapping biopsy (TTMB). In this study we aim to compare transrectal saturation and TTMB in men attending for repeat prostate biopsy. METHODS: The study included 100 consecutive patients who required repeat biopsy based on rising PSA despite previous negative biopsy. The first 50 patients underwent transrectal saturation biopsies (mean age 65, range 52–77) and the second 50 patients underwent TTMB (mean age 62.9, range 37–75), utilizing a 5mm brachytherapy grid template. Median number of cores 18 (range 11–24) for transrectal saturation biopsy, median number of cores 44 (range 24–65) for TTMB. In the TTMB group, 10 patients opted for radical prostatectomy, allowing pathological comparisons of biopsy specimens and stepsectioned radical prostatectomy specimens. RESULTS: Prostate cancer was detected in 46% (23/50) of the 50 TTMB performed, compared with 22% (11/50) for transrectal saturation biopsy. Of the TTMB biopsies positive for cancer, 43% (10/23) were unilateral and therefore suitable for focal hemi-cryotherapy. Of the TTMB biopsies positive for cancer 26% (6/23) had apical cancer alone, a zone at risk of inadequate sampling with the traditional transrectal route. Good correlation was seen between both groups with 1 out of 10 patients (10%) upgraded from unilateral to bilateral adenocarcinoma on radical prostatectomy histology. TTMB had a complication rate of 12% (5 patients with acute retention of urine, 1 hematuria requiring admission) compared with a complication rate of 22% for the transrectal saturation biopsy group (4 patients with UTI, 1 acute retention of urine, 2 hematuria requiring admission). CONCLUSIONS: TTMB has a similar morbidity to transrectal saturation technique. Our study demonstrates that cancer detection rate is higher in patients who undergo TTMB (46% Vs 22%). Detection rate may be higher in TTMB due to better apical and anterior peripheral zone sampling. Despite the requirement for general anaesthesia and a potential increased urinary retention rate, novel transperineal mapping schemes allow for more accurate sampling of the entire gland. The remit of prostate biopsy now lies beyond pure diagnostics and has become an essential tool for determining optimal therapeutic approach.