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Urologic Oncology: Prostate Cancer
0022-5347/03/1704-1448/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 170, 1448 –1480, October 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000083695.40872.04
ABSTRACTS UROLOGICAL ONCOLOGY: PROSTATE CANCER
Overweight, Obesity, and Mortality From Cancer in a Prospectively Studied Cohort of U.S. Adults E. E. CALLE, C. RODRIGUEZ, K. WALKER-THURMOND AND M. J. THUN, Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia N Engl J Med, 348: 1625–1638, 2003 BACKGROUND The influence of excess body weight on the risk of death from cancer has not been fully characterized. METHODS In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. RESULTS The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. CONCLUSIONS Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Editorial Comment: This study documents an association between body mass index (the weight in kilograms divided by the square of the height in meters) and mortality from most forms of cancer. The effect was greatest for women with uterine and kidney cancer and for men with cancer of the liver and pancreas. However, mortality also increased in men with prostate cancer. For example for a 6-foot man weighing between 225 and 260 pounds mortality from prostate cancer increased 20% and for a 6-foot man weighing between 270 and 300 pounds mortality increased 34%. In a much smaller study in young men we recently reported an association between obesity in men younger than 50 years and higher grade disease.1 These observations also agree with anecdotal cases I have seen over the years where markedly obese patients presented with advanced prostate cancer. Prior to PSA testing I believed that this occurred because the physician could not feel the prostate on physical examination. However, because the effect of obesity is seen in many other tumors, a delay in diagnosis cannot be the only cause. The authors point out that potential biological mechanisms include an increase in levels of endogenous hormones that are frequently associated with overweight and obesity: sex steroids, insulin and insulin-like growth factor 1. Patrick C. Walsh, M.D. 1. Rohrmann, S., Roberts, W. W., Walsh, P. C. and Platz, E. A.: Family history of prostate cancer and obesity in relationship to high-grade disease and extraprostatic extension in young men with prostate cancer. Prostate, 55: 140, 2003 1448
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Insulin Resistance and Prostate Cancer Risk A. W. HSING, Y.-T. GAO, S. CHUA, JR., J. DENG AND F. Z. STANCZYK, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, Shanghai Cancer Institute, Shanghai, China, Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, New York, and Departments of Obstetrics and Gynecology, and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California J Natl Cancer Inst, 95: 67–71, 2003 Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] ⫽ 0.35, 95% confidence interval [CI] ⫽ 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR ⫽ 2.78, 95% CI ⫽ 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR ⫽ 8.21, 95% CI ⫽ 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies. Editorial Comment: This study may help explain the relationship between obesity and increased mortality from prostate cancer. In this study of Chinese men the authors demonstrate a relationship between men with the highest level of increased insulin resistance and risk of prostate cancer. They go on to speculate that the observed insulin resistance effect provides a plausible biological explanation for the long-standing observation that “westernization” is associated with an increased risk of prostate cancer. Patrick C. Walsh, M.D.
Bone Mass and the Risk of Prostate Cancer: The Framingham Study Y. ZHANG, D. P. KIEL, R. C. ELLISON, A. SCHATZKIN, J. F. DORGAN, B. E. KREGER, L. A. CUPPLES AND D. T. FELSON, Clinical Epidemiology Research and Training Unit, Section of Preventive Medicine and Epidemiology, Evans Department of Medicine and Section of General Internal Medicine, Boston University School of Medicine, Hebrew Rehabilitation Center for Aged Research and Training Institute, Harvard Medical School Division on Aging, and Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, Massachusetts, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland, and Fox Chase Cancer Center, Philadelphia, Pennsylvania Am J Med, 113: 734 –739, 2002 PURPOSE: To examine the relation of bone mass—a potential biologic marker for cumulative exposure to androgens, insulin-like growth factors, and calcium intake—to subsequent development of prostate cancer. METHODS: We used radiogrammetry to measure the second metacarpal cortical area of 1012 white men with no history of prostate cancer who had undergone posteroanterior hand radiography between 1967 and 1970. Participants were followed until the end of 1999. All incidence cases of prostate cancer were confirmed histologically. We examined bone mass in relation to the risk of prostate cancer using a Cox proportional hazards model. RESULTS: During follow-up, 100 men developed prostate cancer. Incidence rates per 1000 person-years were 3.8 among men in the lowest quartile of bone mass, 4.8 in the second quartile, 7.4 in the third quartile, and 6.5 in the highest quartile. Compared with men in the lowest quartile of bone mass, the multivariateadjusted rate ratio was 1.3 (95% confidence interval [CI]: 0.7 to 2.5) for those in the second quartile, 1.9 (95% CI: 1.0 to 3.4) in the third quartile, and 1.6 (95% CI: 0.9 to 3.0) in the highest quartile (P for trend ⫽ 0.06). CONCLUSION: Men with high bone mass may be at an increased risk of prostate cancer. Although the biological mechanisms underlying this relation are not understood, cumulative exposure to high levels of androgen, insulin-like growth factor 1, or calcium intake may be involved. Editorial Comment: Factors that contribute to increased bone mass include exposure to high levels of androgen and insulin-like growth factor 1, and increased calcium intake. Indeed, increased calcium intake has been shown to be associated with an increased risk for the development of metastatic prostate cancer and death from the disease. This prospective study shows that the degree of bone mass based on hand radiographs taken between 1967 and 1970
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correlated with the long-term development of prostate cancer. This raises the possibility that increased bone mass may be another risk factor for the development of prostate cancer. Patrick C. Walsh, M.D.
Prospective Study of Antioxidant Micronutrients in the Blood and the Risk of Developing Prostate Cancer H.-Y. HUANG, A. J. ALBERG, E. P. NORKUS, S. C. HOFFMAN, G. W. COMSTOCK AND K. J. HELZLSOUER, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and Department of Biomedical Research, Our Lady of Mercy Medical Center, Bronx, New York Am J Epidemiol, 157: 335–344, 2003 Antioxidant micronutrients may have chemopreventive effects. The authors examined the associations between prediagnostic blood levels of micronutrients and prostate cancer risk in two nested case-control studies of 9,804 and 10,456 male residents of Washington County, Maryland, who donated blood in 1974 (CLUE I) and 1989 (CLUE II), respectively. Until 1996, 182 men for whom adequate serum remained for assays in the CLUE I cohort and 142 men in the CLUE II cohort developed prostate cancer. Each case was matched with two controls by age, gender, race, and date of blood donation. In both cohorts, cases and controls had similar concentrations of ␣-carotene, -carotene, total carotene, -cryptoxanthin, lutein, lycopene, retinol, and ascorbic acid; serum ␣-tocopherol was weakly associated with prostate cancer risk. Higher retinyl palmitate concentrations were associated with a lower risk in CLUE I but not CLUE II. In CLUE I, cases had lower concentrations of ␥-tocopherol than did controls ( p ⫽ 0.02), but no dose-response trend was observed. A strong inverse association between ␥-tocopherol and prostate cancer risk was observed in CLUE II. Findings do not replicate previous reports of a protective association between lycopene and prostate cancer, but they suggest potential chemopreventive effects of ␥-tocopherol on prostate cancer. Editorial Comment: Patients frequently ask about the type and dose of micronutrients they should be taking. Is lycopene helpful and how much vitamin E should I take and what type (␣ or ␥)? This study prospectively measured antioxidant micronutrients in the blood during 2 eras (1974 and 1989) and followed patients to look at the risk for prostate cancer developing. They found that baseline levels of ␥-tocopherol levels but not ␣-tocopherol nor lycopene significantly reduced the risk for prostate cancer developing. It also showed something interesting: the lead time for diagnosis in white men (5 years) is shorter than in black men (7 years). Patrick C. Walsh, M.D.
Trends in Prostate Cancer Mortality Among Black Men and White Men in the United States K. C. CHU, R. E. TARONE AND H. P. FREEMAN, Center to Reduce Cancer Health Disparities and Biostatistics Branch, Division of Cancer Etiology and Genetics, National Cancer Institute, Bethesda, Maryland Cancer, 97: 1507–1516, 2003 BACKGROUND. Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States. METHODS. The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969 –1999 U.S. prostate cancer mortality rates and the 1975–1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population. RESULTS. Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age-adjusted prostate cancer mortality rates for men age 50 – 84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50 –79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence-based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease. CONCLUSIONS. Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men.
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Editorial Comment: Here are the latest figures on mortality from prostate cancer in white and black men in the United States. Both continue to fall and for white men 50 to 79 years of age the 1998 and 1999 rates were the lowest since 1950. Patrick C. Walsh, M.D.
Predictors of Biochemical Outcome With Salvage Conformal Radiotherapy After Radical Prostatectomy for Prostate Cancer M. S. KATZ, M. J. ZELEFSKY, E. S. VENKATRAMAN, Z. FUKS, A. HUMMER AND S. A. LEIBEL, Departments of Radiation Oncology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York J Clin Oncol, 21: 483– 489, 2003 Purpose: To identify predictors of biochemical outcome following radiotherapy in patients with a rising prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer. Patients and Methods: One hundred fifteen patients with a rising PSA after radical prostatectomy received salvage three-dimensional conformal radiotherapy (3D-CRT) alone or with neoadjuvant androgen deprivation. Tumor-related and treatment-related factors were evaluated to identify predictors of subsequent PSA failure. Results: The median follow-up time after 3D-CRT was 42 months. The 4-year actuarial PSA relapse-free survival, distant metastasis-free survival, and overall survival rates were 46%, 83%, and 95%, respectively. Multivariate analysis, which was limited to 70 patients receiving radiation without androgen deprivation therapy, showed that negative/close margins (P ⫽ .03), absence of extracapsular extension (P ⬍.01), and presence of seminal vesicle invasion (P ⬍.01) were independent predictors of PSA relapse after radiotherapy. Neoadjuvant androgen deprivation did not improve the 4-year PSA relapse-free survival in patients with positive margins, extracapsular extension, and no seminal vesicle invasion (P ⫽ .24). However, neoadjuvant androgen deprivation did improve PSA relapse-free survival when one or more of these variables were absent (P ⫽ .03). Conclusions: Salvage 3D-CRT can provide biochemical control in selected patients with a rising PSA after radical prostatectomy. Among patients with positive margins and no poor prognostic features, 77% achieved PSA control after salvage 3D-CRT. Salvage neoadjuvant androgen deprivation therapy may improve short-term biochemical control, but it requires further study. Editorial Comment: This article from Memorial Sloan-Kettering presents better results with post-prostatectomy salvage radiation therapy. They found that overall at 4 years 46% of patients were PSA relapse-free. They used a slightly higher dose of radiation (6,660 cGy versus 6,120 cGy in the prior study). In this study the authors found that PSA failure was more common in patients who had seminal vesicle invasion, an observation made by many others. However, they also found that PSA failure was more common in patients who had close or negative surgical margins and who had no extracapsular extension. The results at our institution are exactly the opposite.1 The authors reason that patients with positive margins and extracapsular extension are more likely to have local recurrence. Or possibly, maybe the entire prostate was not removed. Patrick C. Walsh, M.D. 1. Partin, A. W., Pearson, J. D., Landis, P. K., Carter, H. B., Pound, C. R., Clemens, J. Q. et al: Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology, 43: 649, 1994
Advanced Age at Diagnosis is an Independent Predictor of Time to Death From Prostate Carcinoma for Patients Undergoing External Beam Radiation Therapy for Clinically Localized Prostate Carcinoma A. V. D’AMICO, K. COTE, M. LOFFREDO, A. A. RENSHAW AND M.-H. CHEN, Departments of Radiation Oncology and Pathology, Brigham and Women’s Hospital, and Dana Farber Cancer Institute, Boston, Massachusetts, and Department of Biostatistics, University of Connecticut, Storrs, Connecticut Cancer, 97: 56 – 62, 2003 BACKGROUND. Whether age at diagnosis is predictive of time to prostate carcinoma specific death after external beam radiation therapy (RT) for patients who are diagnosed with clinically localized prostate carcinoma during the prostate specific antigen (PSA) era has not been investigated previously. METHODS. A multivariate Cox regression analysis was used to evaluate the ability of pretreatment
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risk group and age at diagnosis to predict time to all causes of death and time to death from prostate carcinoma for 381 patients who underwent RT for clinically localized prostate carcinoma. RESULTS. Age at diagnosis, as a continuous variable (Pcontinuous ⫽ 0.04), and risk group (Pcategorical ⫽ 0.02) were independent predictors of time to death from prostate carcinoma, whereas only age at diagnosis (Pcontinuous ⫽ 0.01) was a predictor of time to all causes of death. When analyzed as a categorical variable, beginning at age 73 years, age at diagnosis was an independent predictor (Pcategorical ⬍0.04) of time to death from prostate carcinoma. Upon further analysis, this finding was limited to high-risk patients. For example, age ⱖ 75 years at diagnosis predicted for a shorter median time to death from prostate carcinoma (6.3 years vs. 9.7 years; P ⫽ 0.002) in high-risk patients. CONCLUSIONS. Patients with clinically localized, high-risk prostate carcinoma who were diagnosed at age ⱖ 73 years and were treated with RT had a worse prognosis compared with patients who were diagnosed age ⬍73 years, raising the possibility that a more aggressive prostate carcinoma biology may develop during andro-pause. Editorial Comment: Many people still believe that old men with prostate cancer have indolent disease. This article adds to the growing body of data which shows just the opposite. Old men with prostate cancer have more aggressive disease, presumably because it has been there longer. This has been shown in a number of surgical series and now in this study of radiation therapy. Once more people understand this concept they will be more willing to accept the fact that aggressive screening for prostate cancer should occur in younger men who are more likely to be diagnosed at a time when the disease is curable. Patrick C. Walsh, M.D.
A Phase II Trial of Green Tea in the Treatment of Patients With Androgen Independent Metastatic Prostate Carcinoma A. JATOI, N. ELLISON, P. A. BURCH, J. A. SLOAN, S. R. DAKHIL, P. NOVOTNY, W. TAN, T. R. FITCH, K. M. ROWLAND, C. Y. F. YOUNG AND P. J. FLYNN, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, Jacksonville, Florida, and Scottsdale, Arizona, Geisinger Clinic and Medical Center Community Clinical Oncology Program, Danville, Pennsylvania, Wichita Community Clinical Oncology Program, Wichita, Kansas, Carle Cancer Center Community Clinical Oncology Program, Urbana, Illinois, and Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota Cancer, 97: 1442–1446, 2003 BACKGROUND. Recent laboratory and epidemiologic studies have suggested that green tea has antitumor effects in patients with prostate carcinoma. This Phase II trial explored green tea’s antineoplastic effects in patients with androgen independent prostate carcinoma. METHODS. This study, which was conducted by the North Central Cancer Treatment Group, evaluated 42 patients who were asymptomatic and had manifested, progressive prostate specific antigen (PSA) elevation with hormone therapy. Continued use of luteinizing hormone-releasing hormone agonist was permitted; however, patients were ineligible if they had received other treatments for their disease in the preceding 4 weeks or if they had received a long-acting antiandrogen therapy in the preceding 6 weeks. Patients were instructed to take 6 grams of green tea per day orally in 6 divided doses. Each dose contained 100 calories and 46 mg of caffeine. Patients were monitored monthly for response and toxicity. RESULTS. Tumor response, defined as a decline ⱖ50% in the baseline PSA value, occurred in a single patient, or 2% of the cohort (95% confidence interval, 1–14%). This one response was not sustained beyond 2 months. At the end of the first month, the median change in the PSA value from baseline for the cohort increased by 43%. Green tea toxicity, usually Grade 1 or 2, occurred in 69% of patients and included nausea, emesis, insomnia, fatigue, diarrhea, abdominal pain, and confusion. However, six episodes of Grade 3 toxicity and one episode of Grade 4 toxicity also occurred, with the latter manifesting as severe confusion. CONCLUSIONS. Green tea carries limited antineoplastic activity, as defined by a decline in PSA levels, among patients with androgen independent prostate carcinoma. Editorial Comment: Patients are always grasping at straws to find “natural remedies” that will control their cancer. This study demonstrates that green tea is of no benefit in patients who have androgen independent metastatic prostate cancer. Patrick C. Walsh, M.D.
IMAGING
Effect of Endothelin-A Receptor Blockade With Atrasentan on Tumor Progression in Men With Hormone-Refractory Prostate Cancer: A Randomized, Phase II, Placebo-Controlled Trial M. A. CARDUCCI, R. J. PADLEY, J. BREUL, N. J. VOGELZANG, B. A. ZONNENBERG, D. D. DALIANI, C. C. SCHULMAN, A. A. NABULSI, R. A. HUMERICKHOUSE, M. A. WEINBERG, J. L. SCHMITT AND J. B. NELSON, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, Abbott Laboratories, Abbott Park and Department of Medicine, Section of Hematology/Oncology and Cancer Research Center, University of Chicago, Chicago, Illinois, Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, Germany, Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, and Department of Urology, University Hospital Erasme, Brussels, Belgium J Clin Oncol, 21: 679 – 689, 2003 Purpose: To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptomatic, hormone-refractory prostatic adenocarcinoma. Patients and Methods: A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eightyeight asymptomatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostatespecific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers. Results: The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n ⫽ 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P ⫽ .13). Median time to progression in evaluable patients (n ⫽ 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P ⫽ .021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P ⫽ .002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan. Conclusion: Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa. Editorial Comment: There is no question that patients with hormone refractory prostate cancer represent one of the greatest challenges we face in treatment. This study looks at the efficacy of an endothelin-A receptor antagonist (atrasentan) in this group of patients. They demonstrated that it delayed PSA progression. This is an oral agent with few side effects. To learn more about endothelin there is an excellent review article in Nature Reviews Cancer.1 Patrick C. Walsh, M.D. 1. Nelson, J., Bagnato, A., Battistini, B. and Nisen, P.: The endothelin axis: emerging role in cancer. Nat Rev Cancer, 3: 110, 2003
IMAGING Calcification in Cystic Renal Masses: Is It Important in Diagnosis? G. M. ISRAEL AND M. A. BOSNIAK, Department of Radiology, New York University Medical Center, New York, New York Radiology, 226: 47–52, 2003 PURPOSE: To determine whether the presence of calcifications in cystic renal masses is important in diagnosis and to suggest an approach to the management of calcified cystic renal masses. MATERIALS AND METHODS: Eighty-one cystic renal masses containing calcification in a wall or septum were evaluated by means of review of computed tomographic (CT) images (n ⫽ 81), follow-up CT images (n ⫽ 28), and results of pathologic examination (n ⫽ 40) by the authors in consensus. Images were evaluated for lesion size, amount and morphology of calcification, and any association of calcification with soft-tissue structures. Lesions were categorized according to the Bosniak cyst classification system; the amount of calcification was determined with a subjective grading system. Progression of calcification was qualitatively determined with available follow-up CT scans. RESULTS: Twenty-one lesions were Bosniak category II (benign) and showed small amounts and thin strands of calcification. Nineteen lesions containing more extensive calcification but no enhancing tissue
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Vol. 170, 1448 –1480, October 2003 Printed in U.S.A.
DOI: 10.1097/01.ju.0000083695.40872.04
ABSTRACTS UROLOGICAL ONCOLOGY: PROSTATE CANCER
Overweight, Obesity, and Mortality From Cancer in a Prospectively Studied Cohort of U.S. Adults E. E. CALLE, C. RODRIGUEZ, K. WALKER-THURMOND AND M. J. THUN, Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia N Engl J Med, 348: 1625–1638, 2003 BACKGROUND The influence of excess body weight on the risk of death from cancer has not been fully characterized. METHODS In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. RESULTS The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin’s lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. CONCLUSIONS Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Editorial Comment: This study documents an association between body mass index (the weight in kilograms divided by the square of the height in meters) and mortality from most forms of cancer. The effect was greatest for women with uterine and kidney cancer and for men with cancer of the liver and pancreas. However, mortality also increased in men with prostate cancer. For example for a 6-foot man weighing between 225 and 260 pounds mortality from prostate cancer increased 20% and for a 6-foot man weighing between 270 and 300 pounds mortality increased 34%. In a much smaller study in young men we recently reported an association between obesity in men younger than 50 years and higher grade disease.1 These observations also agree with anecdotal cases I have seen over the years where markedly obese patients presented with advanced prostate cancer. Prior to PSA testing I believed that this occurred because the physician could not feel the prostate on physical examination. However, because the effect of obesity is seen in many other tumors, a delay in diagnosis cannot be the only cause. The authors point out that potential biological mechanisms include an increase in levels of endogenous hormones that are frequently associated with overweight and obesity: sex steroids, insulin and insulin-like growth factor 1. Patrick C. Walsh, M.D. 1. Rohrmann, S., Roberts, W. W., Walsh, P. C. and Platz, E. A.: Family history of prostate cancer and obesity in relationship to high-grade disease and extraprostatic extension in young men with prostate cancer. Prostate, 55: 140, 2003 1448
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Insulin Resistance and Prostate Cancer Risk A. W. HSING, Y.-T. GAO, S. CHUA, JR., J. DENG AND F. Z. STANCZYK, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, Shanghai Cancer Institute, Shanghai, China, Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, New York, and Departments of Obstetrics and Gynecology, and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California J Natl Cancer Inst, 95: 67–71, 2003 Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] ⫽ 0.35, 95% confidence interval [CI] ⫽ 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR ⫽ 2.78, 95% CI ⫽ 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR ⫽ 8.21, 95% CI ⫽ 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies. Editorial Comment: This study may help explain the relationship between obesity and increased mortality from prostate cancer. In this study of Chinese men the authors demonstrate a relationship between men with the highest level of increased insulin resistance and risk of prostate cancer. They go on to speculate that the observed insulin resistance effect provides a plausible biological explanation for the long-standing observation that “westernization” is associated with an increased risk of prostate cancer. Patrick C. Walsh, M.D.
Bone Mass and the Risk of Prostate Cancer: The Framingham Study Y. ZHANG, D. P. KIEL, R. C. ELLISON, A. SCHATZKIN, J. F. DORGAN, B. E. KREGER, L. A. CUPPLES AND D. T. FELSON, Clinical Epidemiology Research and Training Unit, Section of Preventive Medicine and Epidemiology, Evans Department of Medicine and Section of General Internal Medicine, Boston University School of Medicine, Hebrew Rehabilitation Center for Aged Research and Training Institute, Harvard Medical School Division on Aging, and Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, Massachusetts, Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, Maryland, and Fox Chase Cancer Center, Philadelphia, Pennsylvania Am J Med, 113: 734 –739, 2002 PURPOSE: To examine the relation of bone mass—a potential biologic marker for cumulative exposure to androgens, insulin-like growth factors, and calcium intake—to subsequent development of prostate cancer. METHODS: We used radiogrammetry to measure the second metacarpal cortical area of 1012 white men with no history of prostate cancer who had undergone posteroanterior hand radiography between 1967 and 1970. Participants were followed until the end of 1999. All incidence cases of prostate cancer were confirmed histologically. We examined bone mass in relation to the risk of prostate cancer using a Cox proportional hazards model. RESULTS: During follow-up, 100 men developed prostate cancer. Incidence rates per 1000 person-years were 3.8 among men in the lowest quartile of bone mass, 4.8 in the second quartile, 7.4 in the third quartile, and 6.5 in the highest quartile. Compared with men in the lowest quartile of bone mass, the multivariateadjusted rate ratio was 1.3 (95% confidence interval [CI]: 0.7 to 2.5) for those in the second quartile, 1.9 (95% CI: 1.0 to 3.4) in the third quartile, and 1.6 (95% CI: 0.9 to 3.0) in the highest quartile (P for trend ⫽ 0.06). CONCLUSION: Men with high bone mass may be at an increased risk of prostate cancer. Although the biological mechanisms underlying this relation are not understood, cumulative exposure to high levels of androgen, insulin-like growth factor 1, or calcium intake may be involved. Editorial Comment: Factors that contribute to increased bone mass include exposure to high levels of androgen and insulin-like growth factor 1, and increased calcium intake. Indeed, increased calcium intake has been shown to be associated with an increased risk for the development of metastatic prostate cancer and death from the disease. This prospective study shows that the degree of bone mass based on hand radiographs taken between 1967 and 1970
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correlated with the long-term development of prostate cancer. This raises the possibility that increased bone mass may be another risk factor for the development of prostate cancer. Patrick C. Walsh, M.D.
Prospective Study of Antioxidant Micronutrients in the Blood and the Risk of Developing Prostate Cancer H.-Y. HUANG, A. J. ALBERG, E. P. NORKUS, S. C. HOFFMAN, G. W. COMSTOCK AND K. J. HELZLSOUER, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and Department of Biomedical Research, Our Lady of Mercy Medical Center, Bronx, New York Am J Epidemiol, 157: 335–344, 2003 Antioxidant micronutrients may have chemopreventive effects. The authors examined the associations between prediagnostic blood levels of micronutrients and prostate cancer risk in two nested case-control studies of 9,804 and 10,456 male residents of Washington County, Maryland, who donated blood in 1974 (CLUE I) and 1989 (CLUE II), respectively. Until 1996, 182 men for whom adequate serum remained for assays in the CLUE I cohort and 142 men in the CLUE II cohort developed prostate cancer. Each case was matched with two controls by age, gender, race, and date of blood donation. In both cohorts, cases and controls had similar concentrations of ␣-carotene, -carotene, total carotene, -cryptoxanthin, lutein, lycopene, retinol, and ascorbic acid; serum ␣-tocopherol was weakly associated with prostate cancer risk. Higher retinyl palmitate concentrations were associated with a lower risk in CLUE I but not CLUE II. In CLUE I, cases had lower concentrations of ␥-tocopherol than did controls ( p ⫽ 0.02), but no dose-response trend was observed. A strong inverse association between ␥-tocopherol and prostate cancer risk was observed in CLUE II. Findings do not replicate previous reports of a protective association between lycopene and prostate cancer, but they suggest potential chemopreventive effects of ␥-tocopherol on prostate cancer. Editorial Comment: Patients frequently ask about the type and dose of micronutrients they should be taking. Is lycopene helpful and how much vitamin E should I take and what type (␣ or ␥)? This study prospectively measured antioxidant micronutrients in the blood during 2 eras (1974 and 1989) and followed patients to look at the risk for prostate cancer developing. They found that baseline levels of ␥-tocopherol levels but not ␣-tocopherol nor lycopene significantly reduced the risk for prostate cancer developing. It also showed something interesting: the lead time for diagnosis in white men (5 years) is shorter than in black men (7 years). Patrick C. Walsh, M.D.
Trends in Prostate Cancer Mortality Among Black Men and White Men in the United States K. C. CHU, R. E. TARONE AND H. P. FREEMAN, Center to Reduce Cancer Health Disparities and Biostatistics Branch, Division of Cancer Etiology and Genetics, National Cancer Institute, Bethesda, Maryland Cancer, 97: 1507–1516, 2003 BACKGROUND. Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States. METHODS. The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969 –1999 U.S. prostate cancer mortality rates and the 1975–1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population. RESULTS. Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age-adjusted prostate cancer mortality rates for men age 50 – 84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50 –79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence-based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease. CONCLUSIONS. Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men.
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Editorial Comment: Here are the latest figures on mortality from prostate cancer in white and black men in the United States. Both continue to fall and for white men 50 to 79 years of age the 1998 and 1999 rates were the lowest since 1950. Patrick C. Walsh, M.D.
Predictors of Biochemical Outcome With Salvage Conformal Radiotherapy After Radical Prostatectomy for Prostate Cancer M. S. KATZ, M. J. ZELEFSKY, E. S. VENKATRAMAN, Z. FUKS, A. HUMMER AND S. A. LEIBEL, Departments of Radiation Oncology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York J Clin Oncol, 21: 483– 489, 2003 Purpose: To identify predictors of biochemical outcome following radiotherapy in patients with a rising prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer. Patients and Methods: One hundred fifteen patients with a rising PSA after radical prostatectomy received salvage three-dimensional conformal radiotherapy (3D-CRT) alone or with neoadjuvant androgen deprivation. Tumor-related and treatment-related factors were evaluated to identify predictors of subsequent PSA failure. Results: The median follow-up time after 3D-CRT was 42 months. The 4-year actuarial PSA relapse-free survival, distant metastasis-free survival, and overall survival rates were 46%, 83%, and 95%, respectively. Multivariate analysis, which was limited to 70 patients receiving radiation without androgen deprivation therapy, showed that negative/close margins (P ⫽ .03), absence of extracapsular extension (P ⬍.01), and presence of seminal vesicle invasion (P ⬍.01) were independent predictors of PSA relapse after radiotherapy. Neoadjuvant androgen deprivation did not improve the 4-year PSA relapse-free survival in patients with positive margins, extracapsular extension, and no seminal vesicle invasion (P ⫽ .24). However, neoadjuvant androgen deprivation did improve PSA relapse-free survival when one or more of these variables were absent (P ⫽ .03). Conclusions: Salvage 3D-CRT can provide biochemical control in selected patients with a rising PSA after radical prostatectomy. Among patients with positive margins and no poor prognostic features, 77% achieved PSA control after salvage 3D-CRT. Salvage neoadjuvant androgen deprivation therapy may improve short-term biochemical control, but it requires further study. Editorial Comment: This article from Memorial Sloan-Kettering presents better results with post-prostatectomy salvage radiation therapy. They found that overall at 4 years 46% of patients were PSA relapse-free. They used a slightly higher dose of radiation (6,660 cGy versus 6,120 cGy in the prior study). In this study the authors found that PSA failure was more common in patients who had seminal vesicle invasion, an observation made by many others. However, they also found that PSA failure was more common in patients who had close or negative surgical margins and who had no extracapsular extension. The results at our institution are exactly the opposite.1 The authors reason that patients with positive margins and extracapsular extension are more likely to have local recurrence. Or possibly, maybe the entire prostate was not removed. Patrick C. Walsh, M.D. 1. Partin, A. W., Pearson, J. D., Landis, P. K., Carter, H. B., Pound, C. R., Clemens, J. Q. et al: Evaluation of serum prostate-specific antigen velocity after radical prostatectomy to distinguish local recurrence from distant metastases. Urology, 43: 649, 1994
Advanced Age at Diagnosis is an Independent Predictor of Time to Death From Prostate Carcinoma for Patients Undergoing External Beam Radiation Therapy for Clinically Localized Prostate Carcinoma A. V. D’AMICO, K. COTE, M. LOFFREDO, A. A. RENSHAW AND M.-H. CHEN, Departments of Radiation Oncology and Pathology, Brigham and Women’s Hospital, and Dana Farber Cancer Institute, Boston, Massachusetts, and Department of Biostatistics, University of Connecticut, Storrs, Connecticut Cancer, 97: 56 – 62, 2003 BACKGROUND. Whether age at diagnosis is predictive of time to prostate carcinoma specific death after external beam radiation therapy (RT) for patients who are diagnosed with clinically localized prostate carcinoma during the prostate specific antigen (PSA) era has not been investigated previously. METHODS. A multivariate Cox regression analysis was used to evaluate the ability of pretreatment
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risk group and age at diagnosis to predict time to all causes of death and time to death from prostate carcinoma for 381 patients who underwent RT for clinically localized prostate carcinoma. RESULTS. Age at diagnosis, as a continuous variable (Pcontinuous ⫽ 0.04), and risk group (Pcategorical ⫽ 0.02) were independent predictors of time to death from prostate carcinoma, whereas only age at diagnosis (Pcontinuous ⫽ 0.01) was a predictor of time to all causes of death. When analyzed as a categorical variable, beginning at age 73 years, age at diagnosis was an independent predictor (Pcategorical ⬍0.04) of time to death from prostate carcinoma. Upon further analysis, this finding was limited to high-risk patients. For example, age ⱖ 75 years at diagnosis predicted for a shorter median time to death from prostate carcinoma (6.3 years vs. 9.7 years; P ⫽ 0.002) in high-risk patients. CONCLUSIONS. Patients with clinically localized, high-risk prostate carcinoma who were diagnosed at age ⱖ 73 years and were treated with RT had a worse prognosis compared with patients who were diagnosed age ⬍73 years, raising the possibility that a more aggressive prostate carcinoma biology may develop during andro-pause. Editorial Comment: Many people still believe that old men with prostate cancer have indolent disease. This article adds to the growing body of data which shows just the opposite. Old men with prostate cancer have more aggressive disease, presumably because it has been there longer. This has been shown in a number of surgical series and now in this study of radiation therapy. Once more people understand this concept they will be more willing to accept the fact that aggressive screening for prostate cancer should occur in younger men who are more likely to be diagnosed at a time when the disease is curable. Patrick C. Walsh, M.D.
A Phase II Trial of Green Tea in the Treatment of Patients With Androgen Independent Metastatic Prostate Carcinoma A. JATOI, N. ELLISON, P. A. BURCH, J. A. SLOAN, S. R. DAKHIL, P. NOVOTNY, W. TAN, T. R. FITCH, K. M. ROWLAND, C. Y. F. YOUNG AND P. J. FLYNN, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, Jacksonville, Florida, and Scottsdale, Arizona, Geisinger Clinic and Medical Center Community Clinical Oncology Program, Danville, Pennsylvania, Wichita Community Clinical Oncology Program, Wichita, Kansas, Carle Cancer Center Community Clinical Oncology Program, Urbana, Illinois, and Metro-Minnesota Community Clinical Oncology Program, St. Louis Park, Minnesota Cancer, 97: 1442–1446, 2003 BACKGROUND. Recent laboratory and epidemiologic studies have suggested that green tea has antitumor effects in patients with prostate carcinoma. This Phase II trial explored green tea’s antineoplastic effects in patients with androgen independent prostate carcinoma. METHODS. This study, which was conducted by the North Central Cancer Treatment Group, evaluated 42 patients who were asymptomatic and had manifested, progressive prostate specific antigen (PSA) elevation with hormone therapy. Continued use of luteinizing hormone-releasing hormone agonist was permitted; however, patients were ineligible if they had received other treatments for their disease in the preceding 4 weeks or if they had received a long-acting antiandrogen therapy in the preceding 6 weeks. Patients were instructed to take 6 grams of green tea per day orally in 6 divided doses. Each dose contained 100 calories and 46 mg of caffeine. Patients were monitored monthly for response and toxicity. RESULTS. Tumor response, defined as a decline ⱖ50% in the baseline PSA value, occurred in a single patient, or 2% of the cohort (95% confidence interval, 1–14%). This one response was not sustained beyond 2 months. At the end of the first month, the median change in the PSA value from baseline for the cohort increased by 43%. Green tea toxicity, usually Grade 1 or 2, occurred in 69% of patients and included nausea, emesis, insomnia, fatigue, diarrhea, abdominal pain, and confusion. However, six episodes of Grade 3 toxicity and one episode of Grade 4 toxicity also occurred, with the latter manifesting as severe confusion. CONCLUSIONS. Green tea carries limited antineoplastic activity, as defined by a decline in PSA levels, among patients with androgen independent prostate carcinoma. Editorial Comment: Patients are always grasping at straws to find “natural remedies” that will control their cancer. This study demonstrates that green tea is of no benefit in patients who have androgen independent metastatic prostate cancer. Patrick C. Walsh, M.D.
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Effect of Endothelin-A Receptor Blockade With Atrasentan on Tumor Progression in Men With Hormone-Refractory Prostate Cancer: A Randomized, Phase II, Placebo-Controlled Trial M. A. CARDUCCI, R. J. PADLEY, J. BREUL, N. J. VOGELZANG, B. A. ZONNENBERG, D. D. DALIANI, C. C. SCHULMAN, A. A. NABULSI, R. A. HUMERICKHOUSE, M. A. WEINBERG, J. L. SCHMITT AND J. B. NELSON, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, Abbott Laboratories, Abbott Park and Department of Medicine, Section of Hematology/Oncology and Cancer Research Center, University of Chicago, Chicago, Illinois, Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Munich, Germany, Department of Medical Oncology, University Medical Center, Utrecht, The Netherlands, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, and Department of Urology, University Hospital Erasme, Brussels, Belgium J Clin Oncol, 21: 679 – 689, 2003 Purpose: To evaluate the efficacy and safety of atrasentan (ABT-627), an endothelin-A receptor antagonist, in the treatment of asymptomatic, hormone-refractory prostatic adenocarcinoma. Patients and Methods: A double-blind, randomized, placebo-controlled clinical trial of hormone-refractory prostate cancer (HRPCa) patients was conducted in the United States and Europe. Two hundred eightyeight asymptomatic patients with HRPCa and evidence of metastatic disease were randomly assigned to one of three study groups receiving a once-daily oral dose of placebo, 2.5 mg atrasentan, or 10 mg atrasentan, respectively. Primary end point was time to progression; secondary end points included time to prostatespecific antigen (PSA) progression, bone scan changes, and changes in bone and tumor markers. Results: The three treatment groups were similar in all baseline characteristics. Median time to progression in intent-to-treat (ITT) patients (n ⫽ 288) was longer in the 10-mg atrasentan group compared with the placebo group: 183 v 137 days, respectively; (P ⫽ .13). Median time to progression in evaluable patients (n ⫽ 244) was significantly prolonged, from 129 days (placebo group) to 196 days (10-mg atrasentan group; P ⫽ .021). For both ITT and evaluable populations in the 10-mg atrasentan group, median time to PSA progression was twice that of the placebo group (155 v 71 days; P ⫽ .002). Patients who received placebo continued to have significant increases from baseline in serum (lactate dehydrogenase [LDH]), a marker of disease burden; elevations in LDH were uniformly attenuated by atrasentan in the ITT population. Headache, peripheral edema, and rhinitis were primary side effects, typically of mild to moderate severity. Quality of life was not adversely affected by atrasentan. Conclusion: Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa. Editorial Comment: There is no question that patients with hormone refractory prostate cancer represent one of the greatest challenges we face in treatment. This study looks at the efficacy of an endothelin-A receptor antagonist (atrasentan) in this group of patients. They demonstrated that it delayed PSA progression. This is an oral agent with few side effects. To learn more about endothelin there is an excellent review article in Nature Reviews Cancer.1 Patrick C. Walsh, M.D. 1. Nelson, J., Bagnato, A., Battistini, B. and Nisen, P.: The endothelin axis: emerging role in cancer. Nat Rev Cancer, 3: 110, 2003
IMAGING Calcification in Cystic Renal Masses: Is It Important in Diagnosis? G. M. ISRAEL AND M. A. BOSNIAK, Department of Radiology, New York University Medical Center, New York, New York Radiology, 226: 47–52, 2003 PURPOSE: To determine whether the presence of calcifications in cystic renal masses is important in diagnosis and to suggest an approach to the management of calcified cystic renal masses. MATERIALS AND METHODS: Eighty-one cystic renal masses containing calcification in a wall or septum were evaluated by means of review of computed tomographic (CT) images (n ⫽ 81), follow-up CT images (n ⫽ 28), and results of pathologic examination (n ⫽ 40) by the authors in consensus. Images were evaluated for lesion size, amount and morphology of calcification, and any association of calcification with soft-tissue structures. Lesions were categorized according to the Bosniak cyst classification system; the amount of calcification was determined with a subjective grading system. Progression of calcification was qualitatively determined with available follow-up CT scans. RESULTS: Twenty-one lesions were Bosniak category II (benign) and showed small amounts and thin strands of calcification. Nineteen lesions containing more extensive calcification but no enhancing tissue
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