Benign and Malignant Neoplasms of the Prostate

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T H E JOURNALOF UROLOGY Copyright 8 1991 by AMERICANUROI.OCICALASSOCIATION,INC.

Vol. 145,210-233, January 1991 Printed in U.S.A.

ABSTRACTS BENIGN AND MALIGNANT NEOPLASMS OF THE PROSTATE Benign Prostatic Hyperplasia and Growth Factors R. K. LAWSON,Department of Urology, Medical College of Wisconsin, Milwaukee, Wisconsin Urologe - (A), 29: 5-7, 1990 Permission to Publish Abstract Not Granted

Editorial Comment: A brief, current, informative and critical review is provided of the role of growth factors in the pathogenesis of benign prostatic hyperplasia by one of the leaders in the field. Although no definite link between growth factors and benign prostatic hyperplasia has been established, there is still much to be learned in this burgeoning area of basic science regarding the role of growth factors in benign and malignant diseases of the prostate. Patrick 6. Walsh, M.D.

Comparison of Ethanol Absorption During Continuous and Intermittent Flow Irrigation in Transurethral Resection R. G. HAHN,LA. ALGOTSSON AND K. TORNEBRANDT, Departments of Anaesthesiology, Lunds University Hospital, Lund, and Huddinge University Hospital, Huddinge, Sweden Scand. J. TJrol. Nephrol., 24: 27-30, 1990 Transurethral resection of the prostate was performed using intermitt,ent-flowbladder irrigation (n = 50), or by continuousflow irrigation, using a suprapubic trocar (n = 50). The irrigant 1% ethanol and fluid absolution contained 1.5% glycine sorption was measured from the ethanol content of the expired breath. Fluid absorption was significantly lower in patients receiving continuous-flow irrigation (p < 0.007) although major absorption occurred in one of these patients. The immediate detection of absorption with the ethanol method allowed us to stop one of the operations performed with intermittent bladder irrigation, at which 2 1 of fluid had been absorbed in 20 min. With correction for the amount of removed prostatic tissue, there were no differences in operation time or blood loss between the two types of irrigation.

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Editorial Comment: A clever technique for estimating systemic absorption of irrigating fluid. The authors demonstrate less absorption using continuous flow irrigation with a suprapubic trocar. Patrick 6. Walsh, M.D.

Foundation, Cleveland, and University of Michigan, Ann Arbor, Departments of Radiology, Surgery and Pathology, Johns Hopkins Medical Institutions, Baltimore, and Department of Health Care Policy, Harvard Medical School, Boston New E n d . J. Med., 323: 621-626, 1990 Background. In 1987, a cooperative study group consisting of five institutions was formed to determine the relative benefits of magnetic resonance imaging (MRI) and endorectal (transrectal) ultrasonography in evaluating patients with clinically localized prostate cancer (stage T a or Tb). Methods. Over a period of 15 months, 230 patients were entered into the study and evaluated with identical imaging techniques. We compared imaging results with information obtained at the time of surgery and on pathological analysis. Results. MRI correctly staged 77 percent of cases of advanced disease and 57 percent of cases of localized disease; the corresponding figures for ultrasonography were 66 and 46 percent ( P not significant). These figures did not vary significantly between readers; moreover, simultaneous interpretation of MRI and ultrasound scans did not improve accuracy. In terms of detecting and localizing lesions, MRI identified only 60 percent of all malignant tumors measuring more than 5 mm on pathological analysis and ultrasonography identified only 59 percent. Conclusions. The MRI and ultrasonography equipment that is currently available is not highly accurate in staging early prostate cancer, mainly because neither technique has the ability to identify microscopic spread of disease. Further evaluation with improved equipment may improve the accuracy of these techniques.

Editorial Comment: For selecting men who will benefit most from definitive treatment for localized prostatic cancer, improved imaging techniques a r e necessary. Unfortunately using currently available equipment, MRI and ultrasonography a r e not accurate enough to identify the ideal patient who will benefit most. It is hoped that new techniques, such as MRI with the use of intrarectal surface coils, will provide improved accuracy. Our early experience with this technique is encouraging. Patrick C. Walsh, M.D.

Capsular Penetration in Prostate Cancer: Significance for Natural History and Treatment

J. E. MCNEAL,A. A. VILLERS,E. A. REDWINE, F. S. FREIHA T . A. STAMEY, Division of Urology, Stanford University School of Medicine, Stanford, California

AND

Amer. J. Surg. Path., 14: 240-247, 1990

We established the location and extent of complete capsule penetration by prostate cancer in 176 radical prostatectomy Comparison of Magnetic Resonance Imaging and Ultraspecimens and related these findings to cancer volume, location sonography in Staging Early Prostate Cancer: Results of positive surgical margins, and presence of nodal metastases of a Multi-Institutional Cooperative Trial or seminal vesicle (SV) invasion. Extent of capsule penetration, M. D. RIFKIN,E. A. ZERHOUNI, C. A. GATSONIS,L. E. QUINT, cancer volume, and positive nodes/SV were strongly intercorD. M. PAUSHTER, J. I. EPSTEIN,U. HAMPER,P. C. WALSH related. It could not be shown that capsule penetration was related to prognosis independently of its correlation with cancer AND B. J. MCNEIL,Departments of Radiology, Thomas Jefferson University Hospital, Philadelphia, Cleveland Clinic volume. Twelve cubic centimeters was a critical cancer volume;

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above that, combinations of extensive capsule penetration, positive surgical margins, and positive nodes/SV were almost universal. In cancers under 12 cc, positive surgical margins were only moderately correlated with cancer volume; they often represented surgical resection into the capsule rather than a complication of capsule penetration by tumor and were most common at the apex, where dissection is most difficult. In nontransition zone cancers (148 cases), capsule penetration was most common posterolaterally, where nerves penetrate the capsule. In transition zone cancers (28 cases), capsule penetration was much less common and was located more anteriorly. Apical positive margins were also relatively common in transition zone cancers, but seminal vesicle invasion was never seen.

extending just to the inked margin, and only one (12.5%) had tumor in the neurovascular bundle. All 20 cases with negative assigned margins had complete removal of tumor from this area with none of the neurovascular bundles containing tumor. This study demonstrated that negative capsular margins in radical prostatectomy specimens often contain only a scant amount of soft tissue. Of the 33 cases with true negative margins, the amount of soft tissue between the inked margin and tumor was only >I mm in two cases and 51 m in 20 cases (<0.5 mm in 13 cases with <0.25 mm in eight of these cases). Furthermore, 11 cases with tumor extending to the inked margin of resection showed no residual tumor in additional tissue removed from these regions.

Editorial Comment: Another important study from McNeal and coworkers o n the detailed pathological evaluation o f specimens removed at radical prostatectomy. T h i s study demonstrates that large tumor volume (greater than 12 cc) was the dominant factor i n predicting capsular penetration. In these large tumors extensive capsular penetration, positive surgical margins and positive lymph nodes or seminal vesicles were almost universal. Below that c u t o f f point the presence o f positive surgical margins was often caused b y dissecting into tumor that was located inside the prostate and had not extended beyond the capsule, especially at the apex. This emphasizes t h e importance o f dividing the striated urethral sphincter under direct vision at the apex, thus enabling the surgeon t o identify the correct dissection plane outside all layers o f Denonvilliers' fascia posteriorly. T h e authors also point out that i n stage A (transition zone) cancers capsular penetration was most commonly located anteriorly. Patrick C. Walsh, M.D.

Editorial Comment: Before 1983 there was little mention o f surgical margins i n radical prostatectomy specimens. Since then there have been numerous articles dealing w i t h this pathological condition. However, because there is little soft tissue covering the prostate, there is no consensus regarding the definition o f a positive surgical margin. Some have considered any patient with penetration through the prostatic capsule t o have a positive surgical margin and others have used t h e t e r m positive surgical margin t o refer only to those cases when the tumor involved the bladder neck or urethra. Furthermore, there has been little feedback to pathologists on the validity o f what they were calling positive or close margins o f resection. In this study the author tests the definition o f positive surgical margins w i t h criteria that have been used at T h e Johns Hopkins Hospital for a long time. I f the surgical margin was definitely positive, i n 40% o f t h e cases there was no tumor in the adjacent tissue. In patients w i t h "equivocal margins" only 12% had tumor in the adjacent tissue and i n all cases that were designated negative there was no residual tumor i n adjacent tissue. This is an important study that objectively evaluates the definition o f a positive surgical margin. Even with the conservative approach to capsular margins used i n this study, 40% o f the cases with positive margins did not have residual tumor. Therefore, this study calls into question the routine use o f postoperative radiotherapy for radical prostatectomy with positive margins. However, long-term clinical followup o f patients will be necessary t o confirm these findings. Patrick @. Walsh, M.D.

Evaluation o f Radical Prostatectomy Capsular Margins o f Resection: T h e Significance o f Margins Designated as Negative, Closely Approaching, and Positive

J. I. EPSTEIN,Departments of Pathology and Urology, The Johns Hopkins Hospital, Baltimore, Maryland Amer. J . Surg. Path., 14: 626-632, 1990 Capsular margins of resection in radical prostatectomy specimens performed for carcinoma of the prostate are difficult to assess because of the scant soft tissue removed with the prostate. There is little objective information as to the validity of what are designated as positive or negative capsular margins of resection. From January 1, 1984 through June 30, 1989 there were 40 radical prostatectomies performed in which the prostate was initially removed leaving the neruovascular bundle within the patient in order to preserve potency. However, based on the surgeons' gross examination of the prostate a t the time of radical prostatectomy, the neurovascular bundle was then subsequently removed during the same operation and submitted to pathology as a separate specimen. In these 40 cases the capsular margin in the region of the neurovascular bundle was assessed blindly without knowledge of tumor presence or absence in the subsequently resected neurovascular bundle, and then compared to whether the neurovascular bundle contained tumor. Of the 10 cases called positive based on review of the radical prostatectomy, only six neurovascular bundles (60%) contained tumor. Eight cases had equivocal margins with tumor

Radical Prostatectomy 1972-198'9 Single Institutional Experience: Comparison o f Standard Radical Prostateetomy and Nerve-Sparing Technique J . R. DRAGO,R. A. BADALAMENT AND J. A. NESBITT,Department of Surgery, Division of Urology, College of Medicine, Ohio State University, Columbus, Ohio Urology, 35: 377-380, 1990 During the period of time from 1972 to 1987 a total of 104 radical prostatectomies were performed at the Ohio State University. From 1972 to 1985, standard radical retropubic prostatxtomy was done in 60 patients and from'1986 to June 30, 1987, radical retropubic nerve-sparing prostatectomy was carried out in 44 patients. Transrectal ultrasound evaluation was available only for three quarters of the patients in the latter

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group. In the early part of the series, standard prostatectomy revealed 51 percent of the patients to have organ-confined disease and in the latter series 75 percent had organ-confined disease. In the earlier study only a retrospective analysis of the pathology reports was available, and in the latter study prospective evaluation was available with regard to pre- and postoperative staging, erectile function, blood loss and replacement, PSA data, and clinical and pathologic staging. It appears the radical nerve-sparing prostatectomy has several advantages including decreased blood loss, increased reservation of erectile function in 70 percent of the patients who were potent preoperatively, and a more accurate assessment of clinical stage prior to surgery through the use of transrectal ultrasonography.

Incidence o f Surgical Margin Involvement i n Various Forms o f Radical Prostatectorny S. WAHLE, M. REZNICEK, B. FALLON, C. PLATZ AND R. WILLIAMS,Departments of Urology and Pathology, T h e University of Iowa Hospitals and Clinics, Iowa City, Iowa Urology, 36: 23-26,1990 The pathologic specimens of 64 patients who underwent radical prostatectomy for clinical Stage A or B carcinoma of the prostate were reviewed retrospectively for surgical margin involvement with cancer. Fourteen of the operations were performed by the radical transperineal method, 30 by the standard radical retropubic approach, and 20 by the nerve-sparing radical retropubic technique. Seventy-eight percent of the radical transperineal group had resection margin involvement, as opposed to 30 percent of the standard radical retropubic cases, and 45 percent of the nerve-sparing radical retropubic cases. The average tumor burden of the transperineal group was larger than that of the other two groups. Resection margin involvement in all groups was associated with a higher Gleason histologic score. No significant difference was noted between the two retropubic groups in terms of resection margin involvement (P = 0.28), suggesting that nerve-sparing radical retropubic prostatectomy does not compromise the surgical goal of radical prostatectomy for carcinoma over that of the standard radical retropubic prostatectomy.

Editorial Connment: These 2 articles evaluate the use o f an anatomical approach t o radical prostatectomy. Drago et al noted decreased blood loss and preservation o f sexual function ina 70% o f the patients w h o were potent preoperatively. Wisely, they widely excised the neurovascular bundle on t h e involved side i n a11 patients w i t h stage B2 disease. Wahle et al found that the frequency o f positive surgical margins w i t h this technique was no different f r o m that w i t h standard radical retropubic prostatectomy and that both retropubic techniques were superior t o the perineal approach. Patrick C. Wa1sh, M.D.

For this study, 136 patients treated at Stanford University Hospital for prostatic cancer between 1971 and 1980 were selected for review. The patients had received no prior therapy, and had no evidence of bone metastases a t time of radiation treatment based on radiographic studies and bone scan. Of this group, 71 patients received extended-field irradiation (paraaortic and pelvic fields), and 65 patients received pelvic irradiation. The pelvic field was treated to 50 Gy and the paraaortic field received 45 Gy to 60 Gy. All patients subsequently underwent routine follow-up examinations and studies at Stanford University Hospital: 1,513 follow-up X rays, bone scans, and CTscans were analyzed for site-specific recurrence. The follow-up ranged from 14 months to 16 yrs from the time of initial treatment, with a mean follow-up of 7 yrs. Lower extremities and ribs were found to be the most common sites of bone metastases. Irradiation of the lumbar spine to a dose of 35 to 60 Gy, coincidental to irradiation of the paraaortic lymph nodes prevented or delayed the development of lumbar spine metastases. The potential niechanism and clinical implications are discussed.

Editorial Comment: This study demonstrates that w h e n bones have been radiated t h e subsequent development o f bone metastases is delayed. Optimistically, the authors suggest that this may be secondary t o the control o f rnicrometastases and indicate that early radiation t o the spine t o a moderate but as yet undetermined radiation dose could significantly delay metastases. Although this is possible, I have always ascribed this e f f e c t t o the "soil99theory, which they also discuss. It is well k n o w n that radiation therapy has a profound impact o n bone marrow reserve. Biopsies o f radiated bone marrow inn these patients o f t e n demonstrate severe depletion. For prostate cancer t o metastasize t o bone marrow there must be a significant blood supply. 1 have always believed that the absence o f metastases i n the radiated pelvic girdle and Bumbar spine represented depletion o f bone marrow, absence o f adequate blood supply and inadequate "soil" for tumor t o grow. I f this is correct, early radiation t o bone marrow would only be harmful. Patrick C- Walsh, M.D.

IMAGING Suspected Testicaalas Torsion and Ischemia: Evaluation W i t h Color Doppler Sonography

ID. D. BUHKS,R. J. MARKEY, T. K. BURKNARD, Z. N. BALSARA, R/1. M. HALUSZKA AND D. A. CANNING, 1)epartments of Radiology, Urology and Clinical Inu~stigation,Department of the Navy, Naval Hospital, S a n Diego, California Radiology, 875: 815-821, 1990

Color Doppler sonography was performed in 32 patients with a painful scrotum in whom testicular ischemia from torsion or Reduction o f Spinal Metastases After Preemptive Irrapostherniorrhaphy was clinically suspected. Surgical correladiation i n Prostatic Cancer tion was available in 15 patients, and scintigraphic correlation I. D. KAPLAN,R. VALDAGNI, R. S. COXAND M. A. RAGSHAW, was available in 17 patients. Seven of the 32 patients were Departments of Radiation Oncology, Stanford University diagnosed as having testicular ischemia from torsion. Color School of Medicin.e, Stanford, Californ,ia, and Centro S. Pio Doppler flow imaging demonstrated a lack of intratesticular X , Milano, Italy flow in six of the seven testes with torsion and relatively normal intratesticular flow in one of the patients with acute torsion. Int. J. Rad. Oncol. Biol. Physiol., 18: 1019-1025, 1990