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Urologic Oncology: Prostate Cancer
0022-5347/03/1701-0312/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 170, 312–346, July 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000069500.65586.e5
ABSTRACTS UROLOGIC ONCOLOGY: PROSTATE CANCER Calcium Intake and Prostate Cancer Risk in a Long-Term Aging Study: The Baltimore Longitudinal Study of Aging S. I. BERNDT, H. B. CARTER, P. K. LANDIS, K. L. TUCKER, L. J. HSIEH, E. J. METTER AND E. A. PLATZ, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions and National Institute on Aging, Laboratory of Clinical Investigation, Baltimore, Maryland, and Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts Urology, 60: 1118 –1123, 2002 Objectives. To investigate the association between prostate cancer and calcium and other nutrients thought to influence the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D]. Methods. We included in the analysis 454 male participants in the Baltimore Longitudinal Study of Aging who were 46 to 92 years old at the time of completion of a food frequency questionnaire. Among them, 69 men were diagnosed with prostate cancer during their lifetime. In 68% of the cases, the food frequency questionnaire was completed after the diagnosis of cancer. Multiple logistic regression analysis was used to calculate the odds ratio and 95% confidence interval of prostate cancer. Results. The median calcium intake was 788 mg/day. The adjusted odds ratio of prostate cancer for the highest tertile compared with the lowest tertile of calcium intake was 0.92 (95% confidence interval 0.48 to 1.77; Ptrend ⫽ 0.89). Likewise, no significant trends were found for phosphorus, vitamin D, fructose, or animal protein intake. Dairy products, including milk, were not associated with an increased risk of prostate cancer. The adjusted odds ratio of prostate cancer was 1.26 (95% confidence interval 0.57 to 2.79; Ptrend ⫽ 0.73) for men with high dairy intakes compared with those with low dairy intakes. Conclusions. The results of this study suggest that calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. Editorial Comment: This study is reassuring. It suggests that calcium intake within moderate limits is not associated with an increased risk of prostate cancer. Other studies, which evaluated higher intakes of calcium (greater than 2 gm per day), have shown an association with an increased risk of advanced and metastatic prostate cancer. It is presumed that this effect may be mediated by a reduction in the synthesis of the active form of vitamin D, 1,25dihydroxyvitamin D. The rationale behind this association is that prostate cancer cells express vitamin D receptors and in vitro experiments have demonstrated that 1,25-dihydroxyvitamin D can bind to these receptors, reduce cellular proliferation and enhance cellular differentiation. I have always found this association to be worrisome when advising patients about their dietary intake of calcium. I think now I can relax. Patients with moderate calcium intake (700 to 800 mg per day) are at no increased risk. Patrick C. Walsh, M.D.
Screening for Prostate Cancer: An Update of the Evidence for the U.S. Preventive Services Task Force R. HARRIS AND K. N. LOHR, Cecil G. Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina Ann Intern Med, 137: 917–929, 2002 Background: In U.S. men, prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer death. Screening for prostate cancer is controversial. Purpose: To examine for the U.S. Preventive Services Task Force the evidence of benefits and harms of screening and earlier treatment. Data Sources: MEDLINE and the Cochrane Library, experts, and bibliographies of reviews. Study Selection: Researchers developed eight questions representing a logical chain between screening and reduced mortality, along with eligibility criteria for admissible evidence for each question. Admissible evidence was obtained by searching the data sources. Data Extraction: Two reviewers abstracted relevant information using standardized abstraction forms and graded article quality according to Task Force criteria. Data Synthesis: No conclusive direct evidence shows that screening reduces prostate cancer mortality. Some screening tests can detect prostate cancer at an earlier stage than clinical detection. One study 312
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provides good evidence that radical prostatectomy reduces disease-specific mortality for men with localized prostate cancer detected clinically. No study has examined the additional benefit of earlier treatment after detection by screening. Men with a life expectancy of fewer than 10 years are unlikely to benefit from screening even under favorable assumptions. Each treatment is associated with several well-documented potential harms. Conclusions: Although potential harms of screening for prostate cancer can be established, the presence or magnitude of potential benefits cannot. Therefore, the net benefit of screening cannot be determined.
Screening for Prostate Cancer: Recommendation and Rationale U.S. PREVENTIVE SERVICES TASK FORCE Ann Intern Med, 137: 915–916, 2002 No Abstract Editorial Comment: The recommendations of the United States Preventive Services Task Force are always looked to as the highest standard for evidence based medicine. In the past they have recommended against prostate specific antigen screening. In this latest analysis they conclude that they “found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes.” Until the results of 2 major screening studies, the one in the United States and the one in Europe, are concluded this recommendation will probably not change. Patrick C. Walsh, M.D.
Overdiagnosis Due to Prostate-Specific Antigen Screening: Lessons From U.S. Prostate Cancer Incidence Trends R. ETZIONI, D. F. PENSON, J. M. LEGLER, D. DI TOMMASO, R. BOER, P. H. GANN AND E. J. FEUER, Fred Hutchinson Cancer Research Center and Veterans Affairs Medical Center, Seattle, Washington, Applied Research Branch, Cancer Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, RAND Corporation, Santa Monica, California, and Northwestern University Medical School, Chicago, Illinois J Natl Cancer Inst, 94: 981–990, 2002 Background: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient’s lifetime. Methods: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60 – 84 years old in 1988. Given values for the expected lead time—that is, the time by which the test advanced diagnosis—and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. Results: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. Conclusions: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing. Editorial Comment: We are constantly being told that PSA screening over diagnoses prostate cancer. This article is reassuring. The authors conclude “that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.” The next time someone tries to tell you otherwise, quote this important study. It also showed something
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interesting: the lead time for diagnosis in white men (5 years) is shorter than in black men (7 years). Patrick C. Walsh, M.D.
Mass Screening for Prostate Cancer: A Comparative Study in Natori, Japan and Changchun, China M. KUWAHARA, T. TOCHIGI, S. KAWAMURA, Y. OGATA, N. XU, H. WANG, H. ZHANG, S. LI, X. LI AND X. ZHAO, Division of Urology, Miyagi Cancer Center, Natori, Japan, and Department of Urology, 1st Jilin University Hospital, Department of Urology, 3rd Jilin University Hospital and Department of Pathophysiology, Jilin University College of Basic Medicine, Changchun, China Urology, 61: 137–141, 2003 Objectives. To study the natural background of prostate cancer in Japan and China, mass checks with prostate-specific antigen (PSA)-based screenings were performed using identical procedures in Natori, Japan and Changchun, China. Methods. For 7 years (1995 to 2001) in Natori, Japan, and for 3 years (1998 to 2000) in Changchun, China, 2212 Japanese and 3566 Chinese men older than 55 years were mass checked by PSA-based screening (serum PSA cutoff value 4.1 ng/mL). Results. The PSA-positive rates (PSA 4.1 ng/mL or greater) and cancer detection rates in the screened persons of Natori and Changchun were 8.5% and 5.2% (P ⬍0.0005) and 2.1% and 0.8% (P ⬍0.0001), respectively. When the number of cancer cases detected was adjusted to a 100% biopsy rate for men who were PSA positive in both cities, the cancer detection rate was estimated at 2.3% and 1.3% in Natori and Changchun, respectively. This difference was also significant (P ⬍0.01). Conclusions. The results indicate that the percentage of PSA-positive men 55 years or older in Changchun was lower than that in Natori. The analysis of the results suggests that the prostate cancer incidence and prevalence in Changchun, China are lower than those in Natori, Japan. Editorial Comment: We know that the incidence of prostate cancer is much lower in Asian countries than in Western countries. But what about the incidence within Asia? This study suggests that prostate cancer is more common in Japan than in China. Patrick C. Walsh, M.D.
Complication Rates and Risk Factors of 5802 Transrectal Ultrasound-Guided Sextant Biopsies of the Prostate Within a Population-Based Screening Program ¨ , Department of Urology, R. RAAIJMAKERS, W. J. KIRKELS, M. J. ROOBOL, M. F. WILDHAGEN AND F. H. SCHRODER Academic Hospital Dijkzigt, Rotterdam, The Netherlands Urology, 60: 826 – 830, 2002 Objectives. To evaluate the complication rates and possible risk factors of biopsy of the prostate, with the aim of improving patient counseling and the safety of the procedure. Biopsy of the prostate has to be a relatively safe procedure and the participants have to be well informed about the possible complications. Methods. Within the biopsy protocol of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, we evaluated 5802 transrectal ultrasound-guided systematic sextant biopsies. All participants received prophylactic antibiotic therapy. Results. We performed 5802 biopsies. Hematuria lasting longer than 3 days and hematospermia were present after 22.6% and 50.4% of the procedures, respectively. More severe complications were far less frequent. Two hundred participants (3.5%) developed fever after biopsy. Urinary retention was seen 20 times (0.4%), and hospitalization was needed in 27 cases (0.5%). Twenty-five of these men were admitted because of signs of prostatitis and/or urosepsis. Risk factor analyses revealed that an earlier episode of prostatitis was significantly associated with hospital admission and pain after biopsy. Characteristics of prostatic hyperplasia, such as prostate volume, transition zone volume/total prostate volume ratio, and a higher International Prostate Symptom Score, were all predictors of urinary retention. Conclusions. Minor complications are frequently seen but major complications are rare after prostate biopsy. Assessment of the risk factors before biopsy can help to improve the adequacy of counseling, and precautionary measures can be taken to minimize the risk of complications after the procedure. Transrectal ultrasound-guided sextant biopsy remains a safe procedure for the diagnosis of prostate cancer within the general population.
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Acceptability and Complications of Prostate Biopsy in Population-Based PSA Screening Versus Routine Clinical Practice: A Prospective, Controlled Study T. MÄKINEN, A. AUVINEN, M. HAKAMA, U.-H. STENMAN AND T. L. J. TAMMELA, Department of Urology, Seina joki Central Hospital, Seina joki, Tampere School of Public Health and Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere and Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland Urology, 60: 846 – 850, 2002 Objectives. To compare both the acceptability and the complications of prostate biopsy between men attending screening and hospital-referred symptomatic patients. A screening program cannot be successful unless the screening and diagnostic examinations are well tolerated and the willingness to participate is high. Methods. A total of 200 men, comprising 100 participants in the Finnish prostate cancer screening trial and 100 hospital-referred patients with signs or symptoms suggestive of prostate cancer, were consecutively recruited and underwent transrectal ultrasound-guided prostate biopsies. Immediate complications were recorded at the time of examination. Acceptance and possible late complications of biopsy were requested through a self-administered questionnaire, which was returned by 97% of those screened and 84% of the hospital-referred controls. Results. No major complications were seen immediately after biopsy, but one half of the men had minor rectal hemorrhage and, in a few cases, bleeding from the urethra. Most screened (58%) and hospital-referred (65%) subjects felt no distress before biopsy. The procedure was considered unpleasant by 69% of those screened and 61% of the controls. Correspondingly, 52% and 63% of men reported moderate pain at biopsy, but only 3 of those screened (3%) and 4 controls (5%) experienced severe pain. Nevertheless, a great majority of men in both the screening (82%) and the control (86%) groups would be willing to undergo a repeated biopsy if needed. Persistent rectal bleeding and hematuria were common (13% to 35%, respectively), but less than one fourth considered this disturbing. No significant differences were seen either in complications or acceptability between the groups. Conclusions. The results of our study demonstrated that minor complications are equally frequent among men undergoing prostate biopsy for screening and other men. Despite the complications, prostate biopsy was regarded as acceptable. Nevertheless, such complications may impair the acceptability, and eventually, the effectiveness of screening. Editorial Comment: Most urologists believe that the complication rates from transrectal needle biopsy of the prostate are low and these articles confirm this observation. Interestingly, in the large study from Europe a history of bacterial prostatitis increased the risk of hospitalization and pain after a biopsy. In this study trimethoprim-sulfamethoxazole was used for prophylaxis. The results might have been different if the patients with prostatitis had been given ciprofloxacin. Patrick C. Walsh, M.D.
Predictors of Cancer in Repeat Extended Multisite Prostate Biopsy in Men With Previous Negative Extended Multisite Biopsy B. M. MIAN, Y. NAYA, K. OKIHARA, F. VAKAR-LOPEZ, P. TRONCOSO AND R. J. BABAIAN, Division of Urology, Albany Medical College, Albany, New York, and Departments of Urology and Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas Urology, 60: 836 – 840, 2002 Objectives. To evaluate the factors influencing the cancer detection rate in men whose initial and repeat biopsies were both performed using an extended multisite biopsy scheme. Sextant biopsy of the prostate is associated with a significant false-negative rate, as evident from the high cancer detection rate after repeat prostate biopsy. Extended multisite biopsy schemes have therefore been recommended to maximize cancer detection. Methods. Between June 1997 and August 2001, 939 men underwent prostate biopsy for early detection of prostate cancer using the extended multisite scheme (10 or 11 cores incorporating the anterior horn of the peripheral zone with or without midline peripheral zone and/or the transition zone). Of these 939 men, 89 (9.5%) underwent a repeat extended multisite prostate biopsy. The median prostate-specific antigen level was 6.9 ng/mL (range 0.7–36.1). Twenty-four men (27%) had an abnormal digital rectal examination at presentation. Most men (86%) in the group undergoing repeat biopsy had two or more risk factors for a positive biopsy. The median interval between biopsies was 4 months. Results. Of the 89 men, 15 (17%) had prostate cancer in the repeat biopsy specimen. Seven cancers (47%) were found only in the alternate biopsy sites, 5 (33%) cancers were found only in the sextant sites, and 3 in both sextant and alternate sites. Cancer was present in only one biopsy core in 11 (73%) of the 15 men, and the median Gleason score was 6 (range 6 – 8). On multivariate analysis, the presence of atypical glands
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suspicious for carcinoma (AGSC) was the only independent predictor of cancer in repeat biopsy (P ⬍0.004). Of the 79 men without AGSC in the initial biopsy, 8 (10%) had a positive repeat biopsy. The total and percent free prostate-specific antigen level, digital rectal examination, ultrasound findings, and presence of high-grade prostatic intraepithelial neoplasia were not predictive of cancer detection. Conclusions. The probability of a positive result for a repeat prostate biopsy is lower after an initial extended multisite biopsy compared with an initial sextant biopsy. The presence of AGSC was the only significant predictor of cancer in the repeat biopsy. Because nearly 50% of cancers detected in the repeat biopsy were in alternate sites only, using a sextant biopsy scheme for repeat biopsy would have missed these cancers.
Prostate Cancer Diagnosed After Initial Biopsy With Atypical Small Acinar Proliferation Suspicious for Malignancy is Similar to Cancer Found on Initial Biopsy K. A. ICZKOWSKI, H. M. CHEN, X. J. YANG AND R. A. BEACH, Department of Pathology, Immunology and Laboratory Medicine, University of Florida, and Departments of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Gainesville, Florida, University of Chicago, Chicago, Illinois, and Emory University, Atlanta, Georgia Urology, 60: 851– 854, 2002 Objectives. To compare matched clinical and prostatectomy data between (a) men with an initial biopsy diagnosis of atypical small acinar proliferation (ASAP) suspicious for malignancy whose cancer was diagnosed subsequently, and (b) men with a cancer diagnosis not preceded by an ASAP diagnosis. ASAP diagnoses apply to 1.5%–9.0% of prostatic biopsies and predict definite cancer in about 45% of repeat biopsies. Methods. At our hospitals, during overlapping intervals from 1990 to 2001, 7081 men underwent prostate biopsy, and 227 (3.2%) had an overall diagnosis (based on all cores sampled) of ASAP. We concurred with the ASAP diagnosis in 184 cases (81%). Repeat biopsy was performed in 129 (57%), with 22 again having ASAP and 51 (40%) adenocarcinoma. Nineteen men underwent prostatectomy at our hospitals. The controls comprised men who underwent prostatectomy before and after each man with an initial ASAP diagnosis (2:1 match with cases). Findings included grade, pathologic stage, measured maximum dimension of tumor, resection margin status, patient age, and latest preoperative serum prostate-specific antigen. Results. Men in the initial-ASAP group did not differ significantly from controls with respect to age (63 vs. 61, P ⫽ 0.08). Initial-ASAP and control groups had serum prostate-specific antigen levels of 5.9 and 7.4 ng/mL (P ⫽ 0.08). Initial-ASAP and control groups had serum prostate-specific antigen levels of 5.9 and 7.4 ng/mL (P ⫽ 0.32), respectively; mean Gleason scores were 6.2 and 6.6 (P ⫽ 0.11); mean stages were pT2b and pT2b; and tumor size averaged 0.9 and 1.2 cm (P ⫽ 0.36). Fewer men with initial-ASAP diagnosis on biopsy had positive margins (5%) than did those in the control group (30%, P ⬍0.05). Conclusions. An ASAP diagnosis represents undersampled cancer in at least 40% of cases and places men at risk of prostate cancer with similar clinicopathologic findings as in other men with cancer. Editorial Comment: These 2 studies arrive at the same conclusion. The major factor that increases the probability of cancer on a repeat biopsy is the presence of atypical glands for carcinoma on the original biopsy. Indeed, Iczkowski et al conclude that the presence of atypical glands merely represents under sampling of cancer. That has been my observation as well. Patrick C. Walsh, M.D.
Influence of Prostate Volume in the Detection of Prostate Cancer J. B. BASILLOTE, N. A. ARMENAKAS, D. A. HOCHBERG AND J. A. FRACCHIA, Division of Urology, Lenox Hill Hospital, New York, New York, and Tampa, Florida Urology, 61: 167–171, 2003 Objectives. To assess the influence of prostate volume on prostate cancer (CaP) detection in men who underwent repeated sextant transrectal ultrasound biopsy of the prostate. Methods. Between September 1991 and September 2000, 4376 men underwent sextant transrectal ultrasound-guided biopsy of the prostate. Of the 4376 men, 556 underwent repeat biopsy because of persistent prostate-specific antigen elevation (greater than 4 ng/mL) and/or an abnormal digital rectal examination or suspicious pathologic findings. The percentage of CaP missed on the initial biopsy and detected on the repeat biopsy between arbitrary prostate volumes of less than 50 and 50 cm3 or greater and
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between less than 37.5 and 37.5 cm3 or greater, the median prostate volumes of men with CaP, were compared. Patient age, prostate-specific antigen level, digital rectal examination findings, and Gleason score in each volumetric cutoff group were also compared. Results. CaP was detected in 22% of men who underwent a repeat biopsy. The percentage of CaP missed on the initial biopsy but subsequently detected on the repeat biopsy consistently increased as the volume increased. A statistically significant difference in the percentage of CaP not detected on the initial biopsy was found between prostate volumes of less than 50 and 50 cm3 or greater and between less than 37.5 and 37.5 cm3 or greater (P ⬍0.05). No statistically significant difference in prostate-specific antigen, age, digital rectal examination, or Gleason score was found between each volumetric cutoff group. Conclusions. A significant percentage of men are diagnosed with CaP after a repeat biopsy. We have demonstrated that the percentage of CaP missed on the initial biopsy and detected on the repeat biopsy increases as the prostate volume increases. The results of our study suggest that in men with large prostates, traditional sextant biopsies may not be adequate to detect CaP. Editorial Comment: Another factor which influences the likelihood that a repeat biopsy will show cancer is the volume of the prostate. This study shows that if the volume was greater than 50 ml, it is likely that sextant biopsies under sampled the prostate. Patients with large prostates need more than sextant biopsies initially and if cancer is not found this factor should be considered when advising patients about the need for a repeat biopsy. Patrick C. Walsh, M.D.
Substratification of Stage T1c Prostate Cancer Based on the Probability of Biochemical Recurrence M. B. GRETZER, J. I. EPSTEIN, C. R. POUND, P. C. WALSH AND A. W. PARTIN, James Buchanan Brady Urological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland Urology, 60: 1034 –1039, 2002 Objectives. To evaluate the influence of preoperative prostate-specific antigen (PSA), biopsy Gleason sum, and prostate biopsy quantitative histologic findings on the probability of biochemical failure in an attempt to identify criteria to substratify Stage T1c prostate cancer more accurately. Methods. We reviewed the records of 1149 patients who underwent prostatectomy for T1c disease between 1988 and 2000. Biochemical recurrence (PSA 0.2 ng/mL or greater) defined the endpoint in this study. Recursive partitioning analysis was used to establish cutpoints for preoperative PSA level, biopsy Gleason sum, number of positive biopsy cores, and maximal percentage of any single biopsy core involved with cancer. These cutoff values were then evaluated using Kaplan-Meier estimations to determine the probability of remaining biochemically recurrence free. Results. Using a PSA cutpoint of 10 ng/mL or a biopsy Gleason sum of 7, two groups of patients were identified (T1cI and T1cII). The rate of freedom from PSA recurrence at 3, 5, and 10 years after surgery for T1cI was 98%, 96%, and 96%, respectively, and for T1cII was 86%, 83%, and 73%, respectively (P ⬍0.001). For T1cII patients, the greatest percentage of cancer in a single biopsy core was found to be a predictor of biochemical failure on multivariate analysis and, using a cutoff value of 50%, further stratified the PSA recurrence-free rates for the men in group T1cII (90% and 85% versus 75% and 56% at 5 and 10 years after surgery, respectively, P ⫽ 0.03). Conclusions. The results of this study demonstrate that within Stage T1c there are two populations of patients with significantly different recurrence probabilities: T1cI (Gleason sum less than 7 and PSA 10 ng/mL or less) and T1cII (Gleason sum 7 or greater or PSA greater than 10 ng/mL). Furthermore, using a cutpoint of 50% of cancer in a single core of biopsy tissue, additional risk stratification is afforded to men with higher risk “T1cII” cancer. Editorial Comment: Stage T1c adenocarcinoma of the prostate represents a broad spectrum of patients ranging from men with tiny tumors that may need no treatment to other patients with advanced disease. This study looks at substratifying stage T1c disease into risk categories. We found that the major factor that could be used to substratify patients was PSA greater than 10 ng/ml or a biopsy Gleason sum of 7 or more. In patients without either of these risk factors (T1cI) the probability of having an undetectable PSA at 10 years was 96%. For patients who had either of these 2 risk factors (T1cII) at 10 years only 73% had an undetectable PSA. Testing of these simple criteria in larger populations of patients should be carried out with the hope that this might improve preoperative staging. In this study approximately one-third of the patients had high risk T1cII disease. Patrick C. Walsh, M.D.
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Laparoscopic Radical Prostatectomy: Initial 70 Cases at a U.S. University Medical Center D. M. DAHL, J. O. L’ESPERANCE, A. F. TRAINER, Z. JIANG, K. GALLAGHER, D. E. M. LITWIN AND R. D. BLUTE, JR., Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston and Division of Urology, and Departments of Surgery and Pathology, University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester, Massachusetts Urology, 60: 859 – 863, 2002 Objectives. To report our experience with the first 70 cases of laparoscopic radical prostatectomy. Radical retropubic prostatectomy is an accepted therapy for the management of locally confined prostate cancer. Recently, laparoscopic prostatectomy has been introduced as a minimally invasive alternative to open radical prostatectomy. Several published series from Europe have demonstrated that laparoscopic radical prostatectomy is a safe and feasible approach to the management of localized prostate cancer. Methods. From May 2000 to May 2001, transperitoneal laparoscopic radical prostatectomy was performed on 70 men, aged 40 to 76 years, who were appropriate candidates for radical retropubic prostatectomy. Patient characteristics, surgical statistics, and pathologic results were prospectively collected. Results. The mean preoperative prostate-specific antigen level was 6.6 ng/mL (range 1.5 to 20.7). The preoperative Gleason sum was 6 in 53 patients (75.7%), 7 in 16 (22.9%), and 8 in 1 patient (1.4%). The mean operating time was 274 minutes (range 165 to 495). The estimated blood loss averaged 449 mL (range 50 to 2750), and 4 patients (5.7%) required blood transfusions. In 1 case, we converted to a standard retropubic approach. Two intraoperative (2.9%) and 14 (20%) overall postoperative complications occurred. Positive surgical margins were reported in 8 specimens (11.4%). At a minimum of 3 months’ follow-up, 85% reported use of 0 or 1 pad per day. The operative times, amount of blood loss, and complication rate decreased dramatically with experience. Conclusions. Laparoscopic radical prostatectomy is a technically demanding procedure that is a feasible option for the surgical treatment of localized prostate cancer. The morbidity of this operation is significantly less than that of radical retropubic prostatectomy. The laparoscopic approach shows significant promise for reducing surgical morbidity and improving the anatomic radical prostatectomy.
Prospective Comparison of Radical Retropubic Prostatectomy and Robot-Assisted Anatomic Prostatectomy: The Vattikuti Urology Institute Experience M. MENON, A. TEWARI, B. BAIZE, B. GUILLONNEAU AND G. VALLANCIEN, Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan, Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio, and Department of Urology, L’Institut Mutualiste Montsouris, University Pierre and Marie Curie, Paris, France Urology, 60: 864 – 868, 2002 Objectives. Robotic assistance may enhance the precision of anatomic dissection and increase the feasibility of performing laparoscopic radical prostatectomy for most surgeons. We performed a prospective comparison of 30 consecutive patients undergoing conventional radical retropubic prostatectomy (RRP) and 30 initial patients undergoing robot-assisted anatomic prostatectomy (RAP) at our institution. Methods. The study design was a prospective nonrandomized comparison of anatomic RRP performed using the technique of Walsh and RAP performed with the da Vinci surgical system. We evaluated the baseline patient and tumor characteristics (age, body mass index, serum prostate-specific antigen, Gleason score, and clinical stage), intraoperative parameters (operative time, blood loss, and need for transfusion), postoperative parameters (pain score, hospitalization duration, catheter duration), histopathologic parameters, and complications in the two groups. Results. The preoperative parameters were comparable for both groups of patients. The mean setup time for RAP was 0.95 hours. The mean operating time was 2.3 hours for RRP and 4.8 hours for RAP (P ⬍0.001). One patient required conversion from RAP to RRP because of a lack of progress. The mean blood loss was 970 mL for RRP and 329 mL for RAP (P ⬍0.001). The drop in hemoglobin was greater in the RRP group (4.4 versus 1.2 g in RAP; P ⬍0.05). The mean pain score on postoperative day 1 was 7 in the RRP group and 4 in RAP group (P ⫽ 0.05). The mean hospital stay was 56 hours in the RRP group and 36 hours in the RAP group (P value not significant). Sixty-three percent of the RAP and 0% of the RRP groups were discharged within 23 hours (P ⬍0.001). The mean duration of postoperative catheterization was 14 days for the RRP and 11 days for the RAP groups (difference not significant). The pathologic stage, margin status, and prostate-specific antigen values were not different between the two groups. The setup time, operative time, blood loss amount, and catheterization duration were significantly reduced after the first 20 patients. Conclusions. Currently, RAP is a longer procedure than RRP. However, the blood loss is minimal and patients feel less pain and are discharged earlier from the hospital. In our hands, the margin status and complication rates were comparable for both techniques. Editorial Comment: Where do we stand with laparoscopic radical prostatectomy? There is general agreement that the learning curve is steep and that blood loss is less. There are several
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questions that remain to be answered: is postoperative recovery enhanced, are surgical margins comparable, and what about long-term complications such as incontinence and erectile dysfunction? The study by Dahl et al concludes, “The morbidity of this operation is significantly less than that of radical retropubic prostatectomy” without ever studying it. In the more thorough article by Menon et al, in which robot assisted laparoscopic prostatectomy was compared to the open technique, there were a few differences that were statistically significant but I would question whether or not the magnitude was great enough to be considered clinically significant. Operative time in the open procedure was 2.3 hours versus 4.8 hours in the robot assisted procedure; however, this 4.8-hour time did not include an additional 55 minutes of setup time. This was the operative time for the first 30 cases. With more experience Menon now states that it takes 2 hours including setup time. In the robot assisted patients blood loss was less (330 cc versus 970 cc), postoperative pain score on day 1 was lower (4 versus 7) and the percentage of patients discharged home within 24 hours was greater. The real question is how do these patients feel a week or two after surgery, and a year after surgery what are their continence and potency? In the long run, as reimbursement for everything goes down, we will have to decide whether or not this procedure is cost-effective. Patrick C. Walsh, M.D.
Major Postoperative Complications Secondary to Use of the Bookwalter Self-Retaining Retractor J. NOLDUS, M. GRAEFEN AND H. HULAND, Department of Urology, University Hospital, University of Hamburg, Hamburg, Germany Urology, 60: 964 –967, 2002 Objectives. To report on five serious intraoperative damages to nonprocedure-related organs during 10 years of experience with the Bookwalter device. Self-retaining retractors are helpful devices, particularly during major transperitoneal and retroperitoneal operations. Various retractors are available and allow the use of all combinations of blades to maintain exposure during each step of an operation. Furthermore, by using these devices, most operations can be performed by two surgeons only. Methods. With the help of the operation protocols, more than 4000 applications of the Bookwalter device between January 1992 and December 2001 were retrospectively reviewed. Four cases with damage to the large bowel and one of femoral neuropathy were documented. Results. In one transperitoneal and three retroperitoneal approaches, serious damage to the large bowel occurred. None was recognized before postoperative days 2 and 7. One femoral neuropathy was noted. Conclusions. The Bookwalter self-retaining retractor is a helpful and safe device in exposing the intraoperative situs. However, care must be taken in patients with risk factors, such as immunosuppression and diverticulitis, and particularly in retroperitoneal operations when tightening the blades. When the intraabdominal cavity is not exposed, damage to other organs may not be directly noted, which could explain the delay of several days to the onset of symptoms. Editorial Comment: I selected this article because I have been asked to consult on a number of malpractice cases in which patients sustained an injury following use of the Bookwalter retractor. In this article there was 1 patient with a history of diverticulitis who sustained a perforation to his sigmoid colon. I have always been concerned about the use of a retractor that was fixed to the table because sustained pressure on viscera or nerves (femoral nerve) can occur. When performing radical prostatectomies I have always used a Balfour retractor and have found that it provides excellent exposure with little risk of damage to adjacent organs. The only injuries I have seen occurred when the deep Balfour was used in a relatively thin patient. In this circumstance the lateral wings of the retractor can press on the psoas muscle, damaging the femoral nerve, which is situated 1 or 2 cm deep in the body of this muscle. Patrick C. Walsh, M.D.
Impact of Radical Prostatectomy and TURP on the Hypothalamic-Pituitary-Gonadal Hormone Axis S. MADERSBACHER, G. SCHATZL, C. BIEGLMAYER, W. J. REITER, C. GASSNER, P. BERGER, T. ZIDEK AND M. MARBERGER, Departments of Urology and Laboratory Medicine, and Division of Epidemiology, Institute of Cancer Research, University of Vienna, Vienna and Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria Urology, 60: 869 – 874, 2002 Objectives. To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy
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(RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. Methods. Patients with PCa before RP (n ⫽ 49), those who underwent TURP for BPH (n ⫽ 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n ⫽ 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. Results. No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P ⫽ 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P ⫽ 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P ⫽ 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P ⬍0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. Conclusions. Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH. Editorial Comment: This study confirms an observation that we made several years ago.1 Following radical prostatectomy plasma testosterone levels rise. Because this increase in plasma testosterone is associated with an increase in serum luteinizing hormone levels, it is possible that prostate cancers make a substance that has a negative feedback influence on the hypothalamic-pituitary axis. We speculated that this substance might be inhibin. This article extends upon those observations and suggests that this effect is limited to cancer because it did not occur following transurethral resection of the prostate and because the effect was most pronounced in patients with high grade tumors. Patrick C. Walsh, M.D. 1. Miller, L. R., Partin, A. W., Chan, D. W., Bruzek, D. J., Dobs, A. S., Epstein, J. I. et al: Influence of radical prostatectomy on serum hormone levels. J Urol, 160: 449, 1998
Does Prophylactic Breast Irradiation Prevent Antiandrogen-Induced Gynecomastia? Evaluation of 253 Patients in the Randomized Scandinavian Trial SPCG-7/SFUO-3 A. WIDMARK, S. D. FOSSÅ, P. LUNDMO, J.-E. DAMBER, S. VAAGE, L. DAMBER, F. WIKLUND AND O. KLEPP, Department of Oncology, Umeå University, Umeå and Department of Oncology, Radium Hospital, Oslo, and Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden, Departments of Urology and Oncology, Regional Hospital Trondheim and Department of Urology, Regional Hospital, Stavanger, Norway Urology, 61: 145–151, 2003 Objectives. To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. Methods. In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). Results. Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P ⬍0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P ⬍0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P ⬍0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked “very much” on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors’ and patients’ detection of breast problems was observed. Conclusions. The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness. Editorial Comment: In patients receiving bicalutamide as monotherapy gynecomastia is a major side effect. This study suggests that prophylactic radiotherapy with a single fraction (12 to 15 Gy) significantly reduced the probability of symptomatic gynecomastia at 1 year. Patrick C. Walsh, M.D.
Vol. 170, 312–346, July 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000069500.65586.e5
ABSTRACTS UROLOGIC ONCOLOGY: PROSTATE CANCER Calcium Intake and Prostate Cancer Risk in a Long-Term Aging Study: The Baltimore Longitudinal Study of Aging S. I. BERNDT, H. B. CARTER, P. K. LANDIS, K. L. TUCKER, L. J. HSIEH, E. J. METTER AND E. A. PLATZ, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions and National Institute on Aging, Laboratory of Clinical Investigation, Baltimore, Maryland, and Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts Urology, 60: 1118 –1123, 2002 Objectives. To investigate the association between prostate cancer and calcium and other nutrients thought to influence the synthesis of 1,25-dihydroxyvitamin D [1,25(OH)2D]. Methods. We included in the analysis 454 male participants in the Baltimore Longitudinal Study of Aging who were 46 to 92 years old at the time of completion of a food frequency questionnaire. Among them, 69 men were diagnosed with prostate cancer during their lifetime. In 68% of the cases, the food frequency questionnaire was completed after the diagnosis of cancer. Multiple logistic regression analysis was used to calculate the odds ratio and 95% confidence interval of prostate cancer. Results. The median calcium intake was 788 mg/day. The adjusted odds ratio of prostate cancer for the highest tertile compared with the lowest tertile of calcium intake was 0.92 (95% confidence interval 0.48 to 1.77; Ptrend ⫽ 0.89). Likewise, no significant trends were found for phosphorus, vitamin D, fructose, or animal protein intake. Dairy products, including milk, were not associated with an increased risk of prostate cancer. The adjusted odds ratio of prostate cancer was 1.26 (95% confidence interval 0.57 to 2.79; Ptrend ⫽ 0.73) for men with high dairy intakes compared with those with low dairy intakes. Conclusions. The results of this study suggest that calcium intake within moderate limits is not associated with a notably increased risk of prostate cancer. Editorial Comment: This study is reassuring. It suggests that calcium intake within moderate limits is not associated with an increased risk of prostate cancer. Other studies, which evaluated higher intakes of calcium (greater than 2 gm per day), have shown an association with an increased risk of advanced and metastatic prostate cancer. It is presumed that this effect may be mediated by a reduction in the synthesis of the active form of vitamin D, 1,25dihydroxyvitamin D. The rationale behind this association is that prostate cancer cells express vitamin D receptors and in vitro experiments have demonstrated that 1,25-dihydroxyvitamin D can bind to these receptors, reduce cellular proliferation and enhance cellular differentiation. I have always found this association to be worrisome when advising patients about their dietary intake of calcium. I think now I can relax. Patients with moderate calcium intake (700 to 800 mg per day) are at no increased risk. Patrick C. Walsh, M.D.
Screening for Prostate Cancer: An Update of the Evidence for the U.S. Preventive Services Task Force R. HARRIS AND K. N. LOHR, Cecil G. Sheps Center for Health Services Research, University of North Carolina School of Medicine, Chapel Hill, North Carolina Ann Intern Med, 137: 917–929, 2002 Background: In U.S. men, prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer death. Screening for prostate cancer is controversial. Purpose: To examine for the U.S. Preventive Services Task Force the evidence of benefits and harms of screening and earlier treatment. Data Sources: MEDLINE and the Cochrane Library, experts, and bibliographies of reviews. Study Selection: Researchers developed eight questions representing a logical chain between screening and reduced mortality, along with eligibility criteria for admissible evidence for each question. Admissible evidence was obtained by searching the data sources. Data Extraction: Two reviewers abstracted relevant information using standardized abstraction forms and graded article quality according to Task Force criteria. Data Synthesis: No conclusive direct evidence shows that screening reduces prostate cancer mortality. Some screening tests can detect prostate cancer at an earlier stage than clinical detection. One study 312
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provides good evidence that radical prostatectomy reduces disease-specific mortality for men with localized prostate cancer detected clinically. No study has examined the additional benefit of earlier treatment after detection by screening. Men with a life expectancy of fewer than 10 years are unlikely to benefit from screening even under favorable assumptions. Each treatment is associated with several well-documented potential harms. Conclusions: Although potential harms of screening for prostate cancer can be established, the presence or magnitude of potential benefits cannot. Therefore, the net benefit of screening cannot be determined.
Screening for Prostate Cancer: Recommendation and Rationale U.S. PREVENTIVE SERVICES TASK FORCE Ann Intern Med, 137: 915–916, 2002 No Abstract Editorial Comment: The recommendations of the United States Preventive Services Task Force are always looked to as the highest standard for evidence based medicine. In the past they have recommended against prostate specific antigen screening. In this latest analysis they conclude that they “found good evidence that PSA screening can detect early-stage prostate cancer but mixed and inconclusive evidence that early detection improves health outcomes.” Until the results of 2 major screening studies, the one in the United States and the one in Europe, are concluded this recommendation will probably not change. Patrick C. Walsh, M.D.
Overdiagnosis Due to Prostate-Specific Antigen Screening: Lessons From U.S. Prostate Cancer Incidence Trends R. ETZIONI, D. F. PENSON, J. M. LEGLER, D. DI TOMMASO, R. BOER, P. H. GANN AND E. J. FEUER, Fred Hutchinson Cancer Research Center and Veterans Affairs Medical Center, Seattle, Washington, Applied Research Branch, Cancer Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, RAND Corporation, Santa Monica, California, and Northwestern University Medical School, Chicago, Illinois J Natl Cancer Inst, 94: 981–990, 2002 Background: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient’s lifetime. Methods: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60 – 84 years old in 1988. Given values for the expected lead time—that is, the time by which the test advanced diagnosis—and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. Results: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. Conclusions: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing. Editorial Comment: We are constantly being told that PSA screening over diagnoses prostate cancer. This article is reassuring. The authors conclude “that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.” The next time someone tries to tell you otherwise, quote this important study. It also showed something
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interesting: the lead time for diagnosis in white men (5 years) is shorter than in black men (7 years). Patrick C. Walsh, M.D.
Mass Screening for Prostate Cancer: A Comparative Study in Natori, Japan and Changchun, China M. KUWAHARA, T. TOCHIGI, S. KAWAMURA, Y. OGATA, N. XU, H. WANG, H. ZHANG, S. LI, X. LI AND X. ZHAO, Division of Urology, Miyagi Cancer Center, Natori, Japan, and Department of Urology, 1st Jilin University Hospital, Department of Urology, 3rd Jilin University Hospital and Department of Pathophysiology, Jilin University College of Basic Medicine, Changchun, China Urology, 61: 137–141, 2003 Objectives. To study the natural background of prostate cancer in Japan and China, mass checks with prostate-specific antigen (PSA)-based screenings were performed using identical procedures in Natori, Japan and Changchun, China. Methods. For 7 years (1995 to 2001) in Natori, Japan, and for 3 years (1998 to 2000) in Changchun, China, 2212 Japanese and 3566 Chinese men older than 55 years were mass checked by PSA-based screening (serum PSA cutoff value 4.1 ng/mL). Results. The PSA-positive rates (PSA 4.1 ng/mL or greater) and cancer detection rates in the screened persons of Natori and Changchun were 8.5% and 5.2% (P ⬍0.0005) and 2.1% and 0.8% (P ⬍0.0001), respectively. When the number of cancer cases detected was adjusted to a 100% biopsy rate for men who were PSA positive in both cities, the cancer detection rate was estimated at 2.3% and 1.3% in Natori and Changchun, respectively. This difference was also significant (P ⬍0.01). Conclusions. The results indicate that the percentage of PSA-positive men 55 years or older in Changchun was lower than that in Natori. The analysis of the results suggests that the prostate cancer incidence and prevalence in Changchun, China are lower than those in Natori, Japan. Editorial Comment: We know that the incidence of prostate cancer is much lower in Asian countries than in Western countries. But what about the incidence within Asia? This study suggests that prostate cancer is more common in Japan than in China. Patrick C. Walsh, M.D.
Complication Rates and Risk Factors of 5802 Transrectal Ultrasound-Guided Sextant Biopsies of the Prostate Within a Population-Based Screening Program ¨ , Department of Urology, R. RAAIJMAKERS, W. J. KIRKELS, M. J. ROOBOL, M. F. WILDHAGEN AND F. H. SCHRODER Academic Hospital Dijkzigt, Rotterdam, The Netherlands Urology, 60: 826 – 830, 2002 Objectives. To evaluate the complication rates and possible risk factors of biopsy of the prostate, with the aim of improving patient counseling and the safety of the procedure. Biopsy of the prostate has to be a relatively safe procedure and the participants have to be well informed about the possible complications. Methods. Within the biopsy protocol of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer, we evaluated 5802 transrectal ultrasound-guided systematic sextant biopsies. All participants received prophylactic antibiotic therapy. Results. We performed 5802 biopsies. Hematuria lasting longer than 3 days and hematospermia were present after 22.6% and 50.4% of the procedures, respectively. More severe complications were far less frequent. Two hundred participants (3.5%) developed fever after biopsy. Urinary retention was seen 20 times (0.4%), and hospitalization was needed in 27 cases (0.5%). Twenty-five of these men were admitted because of signs of prostatitis and/or urosepsis. Risk factor analyses revealed that an earlier episode of prostatitis was significantly associated with hospital admission and pain after biopsy. Characteristics of prostatic hyperplasia, such as prostate volume, transition zone volume/total prostate volume ratio, and a higher International Prostate Symptom Score, were all predictors of urinary retention. Conclusions. Minor complications are frequently seen but major complications are rare after prostate biopsy. Assessment of the risk factors before biopsy can help to improve the adequacy of counseling, and precautionary measures can be taken to minimize the risk of complications after the procedure. Transrectal ultrasound-guided sextant biopsy remains a safe procedure for the diagnosis of prostate cancer within the general population.
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Acceptability and Complications of Prostate Biopsy in Population-Based PSA Screening Versus Routine Clinical Practice: A Prospective, Controlled Study T. MÄKINEN, A. AUVINEN, M. HAKAMA, U.-H. STENMAN AND T. L. J. TAMMELA, Department of Urology, Seina joki Central Hospital, Seina joki, Tampere School of Public Health and Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere and Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland Urology, 60: 846 – 850, 2002 Objectives. To compare both the acceptability and the complications of prostate biopsy between men attending screening and hospital-referred symptomatic patients. A screening program cannot be successful unless the screening and diagnostic examinations are well tolerated and the willingness to participate is high. Methods. A total of 200 men, comprising 100 participants in the Finnish prostate cancer screening trial and 100 hospital-referred patients with signs or symptoms suggestive of prostate cancer, were consecutively recruited and underwent transrectal ultrasound-guided prostate biopsies. Immediate complications were recorded at the time of examination. Acceptance and possible late complications of biopsy were requested through a self-administered questionnaire, which was returned by 97% of those screened and 84% of the hospital-referred controls. Results. No major complications were seen immediately after biopsy, but one half of the men had minor rectal hemorrhage and, in a few cases, bleeding from the urethra. Most screened (58%) and hospital-referred (65%) subjects felt no distress before biopsy. The procedure was considered unpleasant by 69% of those screened and 61% of the controls. Correspondingly, 52% and 63% of men reported moderate pain at biopsy, but only 3 of those screened (3%) and 4 controls (5%) experienced severe pain. Nevertheless, a great majority of men in both the screening (82%) and the control (86%) groups would be willing to undergo a repeated biopsy if needed. Persistent rectal bleeding and hematuria were common (13% to 35%, respectively), but less than one fourth considered this disturbing. No significant differences were seen either in complications or acceptability between the groups. Conclusions. The results of our study demonstrated that minor complications are equally frequent among men undergoing prostate biopsy for screening and other men. Despite the complications, prostate biopsy was regarded as acceptable. Nevertheless, such complications may impair the acceptability, and eventually, the effectiveness of screening. Editorial Comment: Most urologists believe that the complication rates from transrectal needle biopsy of the prostate are low and these articles confirm this observation. Interestingly, in the large study from Europe a history of bacterial prostatitis increased the risk of hospitalization and pain after a biopsy. In this study trimethoprim-sulfamethoxazole was used for prophylaxis. The results might have been different if the patients with prostatitis had been given ciprofloxacin. Patrick C. Walsh, M.D.
Predictors of Cancer in Repeat Extended Multisite Prostate Biopsy in Men With Previous Negative Extended Multisite Biopsy B. M. MIAN, Y. NAYA, K. OKIHARA, F. VAKAR-LOPEZ, P. TRONCOSO AND R. J. BABAIAN, Division of Urology, Albany Medical College, Albany, New York, and Departments of Urology and Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas Urology, 60: 836 – 840, 2002 Objectives. To evaluate the factors influencing the cancer detection rate in men whose initial and repeat biopsies were both performed using an extended multisite biopsy scheme. Sextant biopsy of the prostate is associated with a significant false-negative rate, as evident from the high cancer detection rate after repeat prostate biopsy. Extended multisite biopsy schemes have therefore been recommended to maximize cancer detection. Methods. Between June 1997 and August 2001, 939 men underwent prostate biopsy for early detection of prostate cancer using the extended multisite scheme (10 or 11 cores incorporating the anterior horn of the peripheral zone with or without midline peripheral zone and/or the transition zone). Of these 939 men, 89 (9.5%) underwent a repeat extended multisite prostate biopsy. The median prostate-specific antigen level was 6.9 ng/mL (range 0.7–36.1). Twenty-four men (27%) had an abnormal digital rectal examination at presentation. Most men (86%) in the group undergoing repeat biopsy had two or more risk factors for a positive biopsy. The median interval between biopsies was 4 months. Results. Of the 89 men, 15 (17%) had prostate cancer in the repeat biopsy specimen. Seven cancers (47%) were found only in the alternate biopsy sites, 5 (33%) cancers were found only in the sextant sites, and 3 in both sextant and alternate sites. Cancer was present in only one biopsy core in 11 (73%) of the 15 men, and the median Gleason score was 6 (range 6 – 8). On multivariate analysis, the presence of atypical glands
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suspicious for carcinoma (AGSC) was the only independent predictor of cancer in repeat biopsy (P ⬍0.004). Of the 79 men without AGSC in the initial biopsy, 8 (10%) had a positive repeat biopsy. The total and percent free prostate-specific antigen level, digital rectal examination, ultrasound findings, and presence of high-grade prostatic intraepithelial neoplasia were not predictive of cancer detection. Conclusions. The probability of a positive result for a repeat prostate biopsy is lower after an initial extended multisite biopsy compared with an initial sextant biopsy. The presence of AGSC was the only significant predictor of cancer in the repeat biopsy. Because nearly 50% of cancers detected in the repeat biopsy were in alternate sites only, using a sextant biopsy scheme for repeat biopsy would have missed these cancers.
Prostate Cancer Diagnosed After Initial Biopsy With Atypical Small Acinar Proliferation Suspicious for Malignancy is Similar to Cancer Found on Initial Biopsy K. A. ICZKOWSKI, H. M. CHEN, X. J. YANG AND R. A. BEACH, Department of Pathology, Immunology and Laboratory Medicine, University of Florida, and Departments of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Gainesville, Florida, University of Chicago, Chicago, Illinois, and Emory University, Atlanta, Georgia Urology, 60: 851– 854, 2002 Objectives. To compare matched clinical and prostatectomy data between (a) men with an initial biopsy diagnosis of atypical small acinar proliferation (ASAP) suspicious for malignancy whose cancer was diagnosed subsequently, and (b) men with a cancer diagnosis not preceded by an ASAP diagnosis. ASAP diagnoses apply to 1.5%–9.0% of prostatic biopsies and predict definite cancer in about 45% of repeat biopsies. Methods. At our hospitals, during overlapping intervals from 1990 to 2001, 7081 men underwent prostate biopsy, and 227 (3.2%) had an overall diagnosis (based on all cores sampled) of ASAP. We concurred with the ASAP diagnosis in 184 cases (81%). Repeat biopsy was performed in 129 (57%), with 22 again having ASAP and 51 (40%) adenocarcinoma. Nineteen men underwent prostatectomy at our hospitals. The controls comprised men who underwent prostatectomy before and after each man with an initial ASAP diagnosis (2:1 match with cases). Findings included grade, pathologic stage, measured maximum dimension of tumor, resection margin status, patient age, and latest preoperative serum prostate-specific antigen. Results. Men in the initial-ASAP group did not differ significantly from controls with respect to age (63 vs. 61, P ⫽ 0.08). Initial-ASAP and control groups had serum prostate-specific antigen levels of 5.9 and 7.4 ng/mL (P ⫽ 0.08). Initial-ASAP and control groups had serum prostate-specific antigen levels of 5.9 and 7.4 ng/mL (P ⫽ 0.32), respectively; mean Gleason scores were 6.2 and 6.6 (P ⫽ 0.11); mean stages were pT2b and pT2b; and tumor size averaged 0.9 and 1.2 cm (P ⫽ 0.36). Fewer men with initial-ASAP diagnosis on biopsy had positive margins (5%) than did those in the control group (30%, P ⬍0.05). Conclusions. An ASAP diagnosis represents undersampled cancer in at least 40% of cases and places men at risk of prostate cancer with similar clinicopathologic findings as in other men with cancer. Editorial Comment: These 2 studies arrive at the same conclusion. The major factor that increases the probability of cancer on a repeat biopsy is the presence of atypical glands for carcinoma on the original biopsy. Indeed, Iczkowski et al conclude that the presence of atypical glands merely represents under sampling of cancer. That has been my observation as well. Patrick C. Walsh, M.D.
Influence of Prostate Volume in the Detection of Prostate Cancer J. B. BASILLOTE, N. A. ARMENAKAS, D. A. HOCHBERG AND J. A. FRACCHIA, Division of Urology, Lenox Hill Hospital, New York, New York, and Tampa, Florida Urology, 61: 167–171, 2003 Objectives. To assess the influence of prostate volume on prostate cancer (CaP) detection in men who underwent repeated sextant transrectal ultrasound biopsy of the prostate. Methods. Between September 1991 and September 2000, 4376 men underwent sextant transrectal ultrasound-guided biopsy of the prostate. Of the 4376 men, 556 underwent repeat biopsy because of persistent prostate-specific antigen elevation (greater than 4 ng/mL) and/or an abnormal digital rectal examination or suspicious pathologic findings. The percentage of CaP missed on the initial biopsy and detected on the repeat biopsy between arbitrary prostate volumes of less than 50 and 50 cm3 or greater and
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between less than 37.5 and 37.5 cm3 or greater, the median prostate volumes of men with CaP, were compared. Patient age, prostate-specific antigen level, digital rectal examination findings, and Gleason score in each volumetric cutoff group were also compared. Results. CaP was detected in 22% of men who underwent a repeat biopsy. The percentage of CaP missed on the initial biopsy but subsequently detected on the repeat biopsy consistently increased as the volume increased. A statistically significant difference in the percentage of CaP not detected on the initial biopsy was found between prostate volumes of less than 50 and 50 cm3 or greater and between less than 37.5 and 37.5 cm3 or greater (P ⬍0.05). No statistically significant difference in prostate-specific antigen, age, digital rectal examination, or Gleason score was found between each volumetric cutoff group. Conclusions. A significant percentage of men are diagnosed with CaP after a repeat biopsy. We have demonstrated that the percentage of CaP missed on the initial biopsy and detected on the repeat biopsy increases as the prostate volume increases. The results of our study suggest that in men with large prostates, traditional sextant biopsies may not be adequate to detect CaP. Editorial Comment: Another factor which influences the likelihood that a repeat biopsy will show cancer is the volume of the prostate. This study shows that if the volume was greater than 50 ml, it is likely that sextant biopsies under sampled the prostate. Patients with large prostates need more than sextant biopsies initially and if cancer is not found this factor should be considered when advising patients about the need for a repeat biopsy. Patrick C. Walsh, M.D.
Substratification of Stage T1c Prostate Cancer Based on the Probability of Biochemical Recurrence M. B. GRETZER, J. I. EPSTEIN, C. R. POUND, P. C. WALSH AND A. W. PARTIN, James Buchanan Brady Urological Institute and Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland Urology, 60: 1034 –1039, 2002 Objectives. To evaluate the influence of preoperative prostate-specific antigen (PSA), biopsy Gleason sum, and prostate biopsy quantitative histologic findings on the probability of biochemical failure in an attempt to identify criteria to substratify Stage T1c prostate cancer more accurately. Methods. We reviewed the records of 1149 patients who underwent prostatectomy for T1c disease between 1988 and 2000. Biochemical recurrence (PSA 0.2 ng/mL or greater) defined the endpoint in this study. Recursive partitioning analysis was used to establish cutpoints for preoperative PSA level, biopsy Gleason sum, number of positive biopsy cores, and maximal percentage of any single biopsy core involved with cancer. These cutoff values were then evaluated using Kaplan-Meier estimations to determine the probability of remaining biochemically recurrence free. Results. Using a PSA cutpoint of 10 ng/mL or a biopsy Gleason sum of 7, two groups of patients were identified (T1cI and T1cII). The rate of freedom from PSA recurrence at 3, 5, and 10 years after surgery for T1cI was 98%, 96%, and 96%, respectively, and for T1cII was 86%, 83%, and 73%, respectively (P ⬍0.001). For T1cII patients, the greatest percentage of cancer in a single biopsy core was found to be a predictor of biochemical failure on multivariate analysis and, using a cutoff value of 50%, further stratified the PSA recurrence-free rates for the men in group T1cII (90% and 85% versus 75% and 56% at 5 and 10 years after surgery, respectively, P ⫽ 0.03). Conclusions. The results of this study demonstrate that within Stage T1c there are two populations of patients with significantly different recurrence probabilities: T1cI (Gleason sum less than 7 and PSA 10 ng/mL or less) and T1cII (Gleason sum 7 or greater or PSA greater than 10 ng/mL). Furthermore, using a cutpoint of 50% of cancer in a single core of biopsy tissue, additional risk stratification is afforded to men with higher risk “T1cII” cancer. Editorial Comment: Stage T1c adenocarcinoma of the prostate represents a broad spectrum of patients ranging from men with tiny tumors that may need no treatment to other patients with advanced disease. This study looks at substratifying stage T1c disease into risk categories. We found that the major factor that could be used to substratify patients was PSA greater than 10 ng/ml or a biopsy Gleason sum of 7 or more. In patients without either of these risk factors (T1cI) the probability of having an undetectable PSA at 10 years was 96%. For patients who had either of these 2 risk factors (T1cII) at 10 years only 73% had an undetectable PSA. Testing of these simple criteria in larger populations of patients should be carried out with the hope that this might improve preoperative staging. In this study approximately one-third of the patients had high risk T1cII disease. Patrick C. Walsh, M.D.
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Laparoscopic Radical Prostatectomy: Initial 70 Cases at a U.S. University Medical Center D. M. DAHL, J. O. L’ESPERANCE, A. F. TRAINER, Z. JIANG, K. GALLAGHER, D. E. M. LITWIN AND R. D. BLUTE, JR., Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston and Division of Urology, and Departments of Surgery and Pathology, University of Massachusetts Medical School and University of Massachusetts Memorial Health Care, Worcester, Massachusetts Urology, 60: 859 – 863, 2002 Objectives. To report our experience with the first 70 cases of laparoscopic radical prostatectomy. Radical retropubic prostatectomy is an accepted therapy for the management of locally confined prostate cancer. Recently, laparoscopic prostatectomy has been introduced as a minimally invasive alternative to open radical prostatectomy. Several published series from Europe have demonstrated that laparoscopic radical prostatectomy is a safe and feasible approach to the management of localized prostate cancer. Methods. From May 2000 to May 2001, transperitoneal laparoscopic radical prostatectomy was performed on 70 men, aged 40 to 76 years, who were appropriate candidates for radical retropubic prostatectomy. Patient characteristics, surgical statistics, and pathologic results were prospectively collected. Results. The mean preoperative prostate-specific antigen level was 6.6 ng/mL (range 1.5 to 20.7). The preoperative Gleason sum was 6 in 53 patients (75.7%), 7 in 16 (22.9%), and 8 in 1 patient (1.4%). The mean operating time was 274 minutes (range 165 to 495). The estimated blood loss averaged 449 mL (range 50 to 2750), and 4 patients (5.7%) required blood transfusions. In 1 case, we converted to a standard retropubic approach. Two intraoperative (2.9%) and 14 (20%) overall postoperative complications occurred. Positive surgical margins were reported in 8 specimens (11.4%). At a minimum of 3 months’ follow-up, 85% reported use of 0 or 1 pad per day. The operative times, amount of blood loss, and complication rate decreased dramatically with experience. Conclusions. Laparoscopic radical prostatectomy is a technically demanding procedure that is a feasible option for the surgical treatment of localized prostate cancer. The morbidity of this operation is significantly less than that of radical retropubic prostatectomy. The laparoscopic approach shows significant promise for reducing surgical morbidity and improving the anatomic radical prostatectomy.
Prospective Comparison of Radical Retropubic Prostatectomy and Robot-Assisted Anatomic Prostatectomy: The Vattikuti Urology Institute Experience M. MENON, A. TEWARI, B. BAIZE, B. GUILLONNEAU AND G. VALLANCIEN, Vattikuti Urology Institute, Henry Ford Health System, Detroit, Michigan, Department of Urology, Case Western Reserve University School of Medicine, Cleveland, Ohio, and Department of Urology, L’Institut Mutualiste Montsouris, University Pierre and Marie Curie, Paris, France Urology, 60: 864 – 868, 2002 Objectives. Robotic assistance may enhance the precision of anatomic dissection and increase the feasibility of performing laparoscopic radical prostatectomy for most surgeons. We performed a prospective comparison of 30 consecutive patients undergoing conventional radical retropubic prostatectomy (RRP) and 30 initial patients undergoing robot-assisted anatomic prostatectomy (RAP) at our institution. Methods. The study design was a prospective nonrandomized comparison of anatomic RRP performed using the technique of Walsh and RAP performed with the da Vinci surgical system. We evaluated the baseline patient and tumor characteristics (age, body mass index, serum prostate-specific antigen, Gleason score, and clinical stage), intraoperative parameters (operative time, blood loss, and need for transfusion), postoperative parameters (pain score, hospitalization duration, catheter duration), histopathologic parameters, and complications in the two groups. Results. The preoperative parameters were comparable for both groups of patients. The mean setup time for RAP was 0.95 hours. The mean operating time was 2.3 hours for RRP and 4.8 hours for RAP (P ⬍0.001). One patient required conversion from RAP to RRP because of a lack of progress. The mean blood loss was 970 mL for RRP and 329 mL for RAP (P ⬍0.001). The drop in hemoglobin was greater in the RRP group (4.4 versus 1.2 g in RAP; P ⬍0.05). The mean pain score on postoperative day 1 was 7 in the RRP group and 4 in RAP group (P ⫽ 0.05). The mean hospital stay was 56 hours in the RRP group and 36 hours in the RAP group (P value not significant). Sixty-three percent of the RAP and 0% of the RRP groups were discharged within 23 hours (P ⬍0.001). The mean duration of postoperative catheterization was 14 days for the RRP and 11 days for the RAP groups (difference not significant). The pathologic stage, margin status, and prostate-specific antigen values were not different between the two groups. The setup time, operative time, blood loss amount, and catheterization duration were significantly reduced after the first 20 patients. Conclusions. Currently, RAP is a longer procedure than RRP. However, the blood loss is minimal and patients feel less pain and are discharged earlier from the hospital. In our hands, the margin status and complication rates were comparable for both techniques. Editorial Comment: Where do we stand with laparoscopic radical prostatectomy? There is general agreement that the learning curve is steep and that blood loss is less. There are several
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questions that remain to be answered: is postoperative recovery enhanced, are surgical margins comparable, and what about long-term complications such as incontinence and erectile dysfunction? The study by Dahl et al concludes, “The morbidity of this operation is significantly less than that of radical retropubic prostatectomy” without ever studying it. In the more thorough article by Menon et al, in which robot assisted laparoscopic prostatectomy was compared to the open technique, there were a few differences that were statistically significant but I would question whether or not the magnitude was great enough to be considered clinically significant. Operative time in the open procedure was 2.3 hours versus 4.8 hours in the robot assisted procedure; however, this 4.8-hour time did not include an additional 55 minutes of setup time. This was the operative time for the first 30 cases. With more experience Menon now states that it takes 2 hours including setup time. In the robot assisted patients blood loss was less (330 cc versus 970 cc), postoperative pain score on day 1 was lower (4 versus 7) and the percentage of patients discharged home within 24 hours was greater. The real question is how do these patients feel a week or two after surgery, and a year after surgery what are their continence and potency? In the long run, as reimbursement for everything goes down, we will have to decide whether or not this procedure is cost-effective. Patrick C. Walsh, M.D.
Major Postoperative Complications Secondary to Use of the Bookwalter Self-Retaining Retractor J. NOLDUS, M. GRAEFEN AND H. HULAND, Department of Urology, University Hospital, University of Hamburg, Hamburg, Germany Urology, 60: 964 –967, 2002 Objectives. To report on five serious intraoperative damages to nonprocedure-related organs during 10 years of experience with the Bookwalter device. Self-retaining retractors are helpful devices, particularly during major transperitoneal and retroperitoneal operations. Various retractors are available and allow the use of all combinations of blades to maintain exposure during each step of an operation. Furthermore, by using these devices, most operations can be performed by two surgeons only. Methods. With the help of the operation protocols, more than 4000 applications of the Bookwalter device between January 1992 and December 2001 were retrospectively reviewed. Four cases with damage to the large bowel and one of femoral neuropathy were documented. Results. In one transperitoneal and three retroperitoneal approaches, serious damage to the large bowel occurred. None was recognized before postoperative days 2 and 7. One femoral neuropathy was noted. Conclusions. The Bookwalter self-retaining retractor is a helpful and safe device in exposing the intraoperative situs. However, care must be taken in patients with risk factors, such as immunosuppression and diverticulitis, and particularly in retroperitoneal operations when tightening the blades. When the intraabdominal cavity is not exposed, damage to other organs may not be directly noted, which could explain the delay of several days to the onset of symptoms. Editorial Comment: I selected this article because I have been asked to consult on a number of malpractice cases in which patients sustained an injury following use of the Bookwalter retractor. In this article there was 1 patient with a history of diverticulitis who sustained a perforation to his sigmoid colon. I have always been concerned about the use of a retractor that was fixed to the table because sustained pressure on viscera or nerves (femoral nerve) can occur. When performing radical prostatectomies I have always used a Balfour retractor and have found that it provides excellent exposure with little risk of damage to adjacent organs. The only injuries I have seen occurred when the deep Balfour was used in a relatively thin patient. In this circumstance the lateral wings of the retractor can press on the psoas muscle, damaging the femoral nerve, which is situated 1 or 2 cm deep in the body of this muscle. Patrick C. Walsh, M.D.
Impact of Radical Prostatectomy and TURP on the Hypothalamic-Pituitary-Gonadal Hormone Axis S. MADERSBACHER, G. SCHATZL, C. BIEGLMAYER, W. J. REITER, C. GASSNER, P. BERGER, T. ZIDEK AND M. MARBERGER, Departments of Urology and Laboratory Medicine, and Division of Epidemiology, Institute of Cancer Research, University of Vienna, Vienna and Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck, Austria Urology, 60: 869 – 874, 2002 Objectives. To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy
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(RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. Methods. Patients with PCa before RP (n ⫽ 49), those who underwent TURP for BPH (n ⫽ 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n ⫽ 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. Results. No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P ⫽ 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P ⫽ 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P ⫽ 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P ⬍0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. Conclusions. Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH. Editorial Comment: This study confirms an observation that we made several years ago.1 Following radical prostatectomy plasma testosterone levels rise. Because this increase in plasma testosterone is associated with an increase in serum luteinizing hormone levels, it is possible that prostate cancers make a substance that has a negative feedback influence on the hypothalamic-pituitary axis. We speculated that this substance might be inhibin. This article extends upon those observations and suggests that this effect is limited to cancer because it did not occur following transurethral resection of the prostate and because the effect was most pronounced in patients with high grade tumors. Patrick C. Walsh, M.D. 1. Miller, L. R., Partin, A. W., Chan, D. W., Bruzek, D. J., Dobs, A. S., Epstein, J. I. et al: Influence of radical prostatectomy on serum hormone levels. J Urol, 160: 449, 1998
Does Prophylactic Breast Irradiation Prevent Antiandrogen-Induced Gynecomastia? Evaluation of 253 Patients in the Randomized Scandinavian Trial SPCG-7/SFUO-3 A. WIDMARK, S. D. FOSSÅ, P. LUNDMO, J.-E. DAMBER, S. VAAGE, L. DAMBER, F. WIKLUND AND O. KLEPP, Department of Oncology, Umeå University, Umeå and Department of Oncology, Radium Hospital, Oslo, and Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden, Departments of Urology and Oncology, Regional Hospital Trondheim and Department of Urology, Regional Hospital, Stavanger, Norway Urology, 61: 145–151, 2003 Objectives. To examine the development of antiandrogen-induced gynecomastia and breast tenderness in the first 253 patients in a randomized Scandinavian trial (SPCG-7/SFUO-3) with a 12-month complete follow-up evaluation performed by both doctors and patients. Methods. In this study, the treating doctor and patient decided whether prophylactic irradiation (RT) of the breast should be given to prevent antiandrogen-induced gynecomastia. At each visit, the doctor evaluated the occurrence of gynecomastia and breast tenderness. Questions about gynecomastia and breast tenderness were also included in the study quality-of-life questionnaire (Prostate Cancer Symptom Scale). Results. Mammary RT with mostly single fraction (12 to 15 Gy) electrons was given to 174 (69%) of the 253 evaluated patients. At the 1-year follow-up visit, the doctor evaluations indicated some form of gynecomastia in 71% and 28% (P ⬍0.001) of the nonirradiated (no-RT) and irradiated (RT) patients, respectively. The patient evaluations at 1 year showed some form of breast enlargement in 78% and 44% (P ⬍0.001) of the no-RT and RT patients, respectively. The doctors reported some form of breast tenderness at 1 year in 75% and 43% (P ⬍0.001) of the no-RT and RT patients, respectively. The patient evaluations of breast tenderness show an expected significant increase in the RT arm at the 3-month follow-up, which was probably due to skin reactions. At 1 year, significantly more patients who marked “very much” on the Prostate Cancer Symptom Scale were seen in the no-RT group. A weak correlation between the doctors’ and patients’ detection of breast problems was observed. Conclusions. The results show that, with high significance, prophylactic RT of the breast decreases the risk of antiandrogen-induced gynecomastia and breast tenderness. Editorial Comment: In patients receiving bicalutamide as monotherapy gynecomastia is a major side effect. This study suggests that prophylactic radiotherapy with a single fraction (12 to 15 Gy) significantly reduced the probability of symptomatic gynecomastia at 1 year. Patrick C. Walsh, M.D.