USE OF IMAGING TESTS FOR STAGING NEWLY DIAGNOSED PROSTATE CANCER: TRENDS FROM THE CAPSURE DATABASE

W22-5347/9sll606-2102$03.oQIo

Vol. 160,2102-2106, December 1998 Printed in U.S.A.

THE JOURNAL. OF UROLOGY

Copyright 8 1998 by AMERICANUROLOGIW ASS~CIATION, INC.

USE OF IMAGING TESTS FOR STAGING NEWLY DIAGNOSED PROSTATE CANCER: TRENDS FROM THE CAPSURE DATABASE AMY V. KINDRICK,* GARY D. GROSSFELD, DAVID M. STIER,* SCOTT C. FLANDERS," JAMES M. HENNING* AND PETER R. CARROLL From the Department of Urology, University of California and Lewin-TAG, Inc., San Francisco, California, and TAP Holdings, Inc., Deerfield, Illinois

ABSTRACT

Purpose: We describe secular trends in the use of imaging tests to stage prostate cancer, evaluate the impact of selected clinical factors on test use and compare physician actual use with recommendations in recently published literature. Materials and Methods: This retrospective nonrandomized analysis of a longitudinal disease registry enrolled 3,557 men diagnosed with prostate cancer between 1989 and 1997 at 29 urology practices throughout the United States. Using logistic regression the odds of performing pelvic computerized tomography (CT), pelvic magnetic resonance imaging (MRI), bone scan and excretory urogram were determined annually from 1989 to 1997. The frequency of test use was compared with recommendations from a recent urology literature synopsis. Results: Use of MRI, CT, bone scan and excretory urogram was unchanged from 1989 to 1997. Compared to recent findings in the clinical literature bone scan, CT and MRI were used too frequently in patients a t low risk for metastatic disease. Conclusions: Urologists may be overusing bone scan, CT and MRI to stage tumors in patients with a low risk of advanced prostate cancer. Further studies are needed to assess the relationship between individual staging strategies and clinical outcomes. KEY WOFUS:

tomography, magnetic resonance imaging, urography, prostatic neoplasms, neoplasm staging

Optimal decision making about prostate cancer treatment depends on accurate tumor staging before treatment. When malignancy is confined to the prostate, cure is oRen possible with definitive local therapy.'.* When tumor extends beyond the prostate, alternate treatment strategies may be more appropriate. To improve pretreatment assessment of cancer extent and judge better the appropriateness of definitive local therapy, physicians have used a variety of radiographic imaging tests, including magnetic resonance imaging (MRI), computerized tomography (CT), radionuclide bone scan and excretory urogram (IVP).As each of these radiographic studies has become more common successive clinical studies have attempted to define their usefulness in staging newly diagnosed prostate cancer. In September 1997 ODowd et a1 developed practice recommendations based on the review of 140 clinical studies.3 They concluded that for patients with newly diagnosed prostate cancer who are candidates for definitive therapy, that is those with prostate specific antigen (PSA), clinical tumor stage and Gleason grade highly predictive of organ confined disease, cross-sectional imaging and bone scan were unlikely to change the initial treatment decision. Specifically, Chybowski et a1 demonstrated that when serum PSA was 20 ng./ml. or less, only 1 of 306 men with newly diagnosed prostate cancer had a positive bone scan (negative predictive value 99.7%L4 Levran et a1 reported that of 861 men with newly diagnosed prostate cancer only 13 (1.5%)had a positive pelvic CT and all had PSA 20 ng./ml. or greater.5 To date no study has observed to our knowledge which tests physicians order in the course of actual clinical practice or how use of staging tests may be changing with time. Furthermore, it is unclear what clinical and demographic factors, if any, have a n impact on the use of imaging tests to

stage newly diagnosed prostate cancer. Thus, our objectives were to describe secular trends in the use of imaging tests to stage prostate cancer during the 199Os, and determine which patient clinical characteristics influence use and whether current use conforms to recent recommendations from the clinical urology literature. MATERIALS AND METHODS

Registry project description. CaPSURE is a longitudinal, observational database of patients with prostate cancer recruited through a network of 29 urology practices throughout the United States. At each practice site patients with biopsy proved adenocarcinoma of the prostate were invited to join the study in consecutive fashion as they presented for outpatient care. At enrollment a urologist completed a n extensive, retrospective prostate cancer history based on the existing patient medical record, including data on demographic and clinical characteristics, digital rectal examination results, PSA at diagnosis, date and type of diagnostic biopsy, Gleason grade of biopsy specimen, initial clinical TNM stage, radiographic and laboratory tests, current medications, surgical and ofice procedures, and symptoms. Additional clinical data were recorded prospectively at each office visit subsequent to the baseline, including new procedures, treatments, diagnostic tests and diagnoses, as well as changes in medications and symptom status. Patients were followed in the database until death or study withdrawal. Additional details of the project methodology have been published elsewhere.6 Subjects. Between June 1, 1995 and May 31, 1997, 4,229 patients were invited to participate in the CaPSURE project and 4,069 agreed (96%). Subjects were excluded from our analysis if they were diagnosed with prostate cancer before Accepted for publication Jul 17,1998. 1989 (286), date of diagnosis was missing (59) or no initial ported by a grant from JAF' Holdings, Inc. 8nancial interest and/or other relationship with TAP Holdings, treatment was recorded (167). The remaining 3,557 patients Inc. comprise our study population. 2102

2103

USE OF IMAGING TESTS TO STAGE PROSTATE CANCER

Data analysis. Clinical factors extracted from CaPSURE included PSA at diagnosis, total Gleason score of the initial malignant biopsy specimen and clinical tumor TNM stage. Initial treatment included radical prostatectomy, radiation therapy (interstitial or external beam), cryosurgery, hormonal therapy (medical or surgical), neoadjuvant therapy (medical hormonal therapy followed within 9 months by radical prostatectomy, radiation therapy or cryosurgery) or watchful waiting. Each staging interval was defined as the time between the date of initial positive biopsy and date of treatment initiation. Only MRI, CT, bone scan and IVP during the staging interval were counted as staging tests. Our data did not allow us to distinguish between body and endorectal coil MRI. To evaluate secular trends in the use of imaging tests to stage prostate cancer between 1989 and 1997 patients were grouped by calendar year according to the date of initial positive biopsy. Logistic regression was done with performance or nonperformance of a test during the staging interval as the outcome variable and year of prostate cancer diagnosis as the covariate. Year of diagnosis was considered to have a significant impact on staging test use for a p coefficient of nonzero at p <0.05 using the chi-square test. Linear trends in test use with time were estimated by plotting the logistic regression odds ratio estimates for each covariate against year of diagnosis on a linear scale. To determine the impact of clinical factors on test use the proportion of subjects receiving each staging test during the staging interval served as the dependent measure. PSA at diagnosis, biopsy specimen Gleason grade and clinical tumor stage were used to construct categorical independent variables. T tests or analysis of variance was used to determine whether staging test use was significantly different between patients in different clinical strata. In a recent literature review ODowd et a1 proposed informal guidelines for staging test use.3 They identified 140 reports in the literature from 1975 to 1997 evaluating the accuracy of clinical compared to pathological staging, and determined the sensitivity, specificity, and positive and negative predictive values for tests, such as serum tumor markers, histological grade and radiographic imaging studies. They judged the appropriateness of each clinical staging method based on these calculations. While not a formal consensus statement this report represents a comprehensive summary of the available literature to date and, as such, provides a standard for comparison with real-world practice patterns. To compare CaPSURE actual practice patterns with the recommendations of ODowd et a1 the proportion of patients receiving I W and bone scan was calculated, and stratified by serum PSA and Gleason score at diagnosis (table 1). Since CT and MRI are not typically used by urologists to determine primary tumor stage but rather the status of the pelvic lymph nodes, the proportion of patients receiving these crosssectional imaging studies was stratified according to the recommendations of ODowd et a1 for pelvic lymph node dissection.3

TABLE1. CaPSURE actual practice data compared with ODowd et dsrecommendations Staging Test

StudyUndergoing in Actual Practice

Reeommendations in Clinical

6.0

Not recommended except in pts. with hematuria Not recommended except when PSA is greater than 10

%

IVP

Bone scan: PSA 10 or less 68.0 84.5 PSA greater than 10 MRI: PSA less than 20 5.5 PSA 20 or greater 7.5 Gleason less than 8 5.9 Gleason 8-10 5.3 Stage T1 or T2 5.7 Not recommended except 8.5 for pts. with PSA Stage T3 or T4 CT greater than 20, Glea PSA less than 20 30.9 son 8-10. or clinical PSA 20 or greater 39.5 stage T3 or T4 Gleason less than 8 32.5 Gleason 8-10 37.9 Stage T1 or T2 32.5 Stage T3 or T4 41.1 * These are inferences based on the exclusion of low risk patients, that is PSA less than 20, Gleason less than 8 and clinical tumor stage T1 or T2, for whom there is strong evidence suggesting that these tests are not helpful. These inferences remain to be tested in a prospective fashion.

TABLE2 . Patient characteristics No. pts. (56) Age at diagnosis: Younger than 60 60-69 70-79 80 or Older PSA at diagnosis: 4 or Less 4.1-10.0 10.1-20.0 Greater than 20 Gleason score at biopsy: 2 4 F A

7 8-10 Missing data ~ ~ i ctumor a l stage: T1 or T2 T3 or T4 Missine data Length o? staging interval: 6 Mos. or less 7-12 Mos. 13-24 Mos. More than 24 mos. Initial treatment: Radical prostatectomy Radiation therapy (external beam or interstitial) Cryotherapy Hormonal therapy alone (medical or surgical) Watchful waiting Neoadjuvant

339 (9.5) 1,101 (31.0) 1,511 (42.5) 606 (17.0) 471 (13.2) 1,498 (42.1) 819 (23.0) 769 (21.6) 596 (18.0) 1,669 (50.5) 640 (19.4) 398 (12.0) 254 3,022 (89.9) 341 (10.1) 194 3,244 (91.2) 147 (4.1) 87 (2.4) 79 (2.2) 1.504 (42.3) 564 (15.9) 159 (4.5) 799 (22.5) 190 (5.3) 341 (9.6)

physicians (97%)practiced in a community setting and had no primary academic affiliation. Furthermore, none pracRESULTS ticed in a staff model health maintenance organization setPatient and physician characteristics. Clinical and demo- ting. Time trends in staging test use. Year of diagnosis had no graphic characteristics of the patients are summarized in table 2. Mean patient age was 71.2 years, median PSA at statistically significant impact on the use of IVP, CT or MRI, diagnosis was 9.2 ng./ml., mean Gleason score at diagnostic although there were trends toward less l"and less MRI since biopsy was 5.8 and most patients (90%)had clinical T1 or T2 1992, and less CT since 1995. While the use of bone scan has tumor. In addition, most patients (91%)had a 6-month or less diminished with time, it did so significantly only in 1994. The interval between diagnosis and initial treatment, and 42% figure provides a linear approximation of time trends in the use ultimately underwent radical prostatectomy as initial treat- of each staging test annually from 1989 through June 1997. ment. Of 100 urologists who treated the patients 25% prac- This plot shows the odds (derived from the logistic regression ticed in the eastern United States, 22%in the Midwest, 12% parameter estimates) that each staging test was used for pain the South and 8%in the western United States. Nearly all tients undergoing staging evaluation in each calendar year

USE OF IMAGING TESTS TO STAGE PROSTATE CANCER

2104 3

2

f

q

PP

k-

1

O J 1990

MEDIAN PSA (12.3)

1991

1902

(14.1)

1993

(10.1)

1904

1695

YEAR

(9.7)

(8.7)

(9.1)

1006

1007

(9.2)

(8.1)

Time trends in staging test use

compared with 1989. Median PSA for each year, noted along the X axis, trended downward during the study, although not dramatically. Impact of selected clinical factors on staging test use. Staging test use rates stratified by PSA at diagnosis, biopsy specimen Gleason grade and clinical tumor stage are summarized in table 3. PSA at diagnosis was an important factor in the use of IVP, MRI, CT and bone scan. A significantly greater proportion of patients with serum PSA 20 ng./ml. or greater a t diagnosis underwent IVP,MRI, CT and bone scan testing than those with PSA less than 20 ng./ml. (table 3). Total Gleason score from the diagnostic biopsy specimen was also a n important factor for bone scan use. Higher Gleason scores were associated with increased frequency of bone scan but not CT, MRI or IVP (table 4). Finally, CT and MRI use was stratified by clinical tumor stage, which had a significant impact on both. In particular, advanced tumor stages T3 and T4 were associated with significantly higher rates of CT and MRI use compared with T1 and T2 (table 5). Urologist practice compared with recommendations from

TABLE4. Impact of Gleason score on staging test use la

Gleason Score Staging Test

PSA Level

Staging Test

IVP (No. pta.): Less than 20 (2.788) 20 or Greater (769)

MRI: Less than 20 20 or Greater

CT: Less than 20

20 or Greater Bone scan: Less than 20 20 or Greater

SD

Frequency

Frequency Relative to Gleason 5 - 6

la

Frequency Relative to Gleason 7

la Frequency

GF:r to

IVP (No. pts.): 2-4 (596) 5-6 (1,669) 7 (640) a i o (398)

-0.3 -0.8

- 1.8

6.0 5.5 6.3 7.8

23.8 22.8 24.2 26.8

0.5

7.6 4.9 6.7 5.3

26.4 21.7 25.1 22.4

2.7

33.0 31.6 33.4 37.9

47.1 46.5 47.2 48.6

1.4

-0.4 -1.8

-4.9 -6.3 -4.5

73.2 73.5 77.1 89.7

44.4 44.2 42.1 30.4

-0.3

-3.9 -3.6

- 16.5*

-2.3 -1.5

MRI: 2-4

5-6 7 8-10 CT (No. pts.): 2-4 (596) 5-6 (1,669) 7 (640) 8-10 (398) Bone scan: 2-4

5-6 7

aio * p <0.05.

TABLE3. Impact of PSA on staging test use

9%

0.9 - 1.6

2.3 -0.4 1.4

16.2* -12.6*

-

% Frequency PSA Less Than 20 vs. 20 or Greater

Frequency

SD

5.4

22.6

8.1

27.4

5.5 7.5

22.9 26.3

-2.0

30.9 39.5

46.2 48.9

-8.6

71.6 88.1

45.1 32.4

~

(p <0.05 for all imaging tests) -2.7

- 16.5 .

_

_

_

~

-

the clinical urology literature. Table 1 compares the use of imaging tests by study urologists to testing recommendations summarized by O’Dowd et al. Consistent with the recommendations, urologists seldom ordered IVP or MRI (6%).Several studies have suggested that the staging use of bone scan is not warranted in patients with serum PSA less than 10 ng./m1.3.4However, when bone scan use among CaPSURE patients was stratified by PSA, we noted that 68% with PSA 10 or less received staging bone scans. Staging CT has been recommended only when serum PSA, biopsy Gleason score and clinical tumor stage are suggestive of systemic disease. Again, we found that nearly a third of patients received this test despite having PSA less than 20, Gleason grade less than 8,. or clinical stage T1 or T2 tlimor.

USE OF IMAGING TESTS TO STAGE PROSTATE CANCER TABLE5. Zmpact

of clinical tumor stage on staging test use

2105

and recommendations to limit cross-sectional imaging, urologists continue to order MRI and CT for patients at low risk. Clinical Tumor Stage Frequency SD -+ We must acknowledge that some CaPSURE patients may Staging Test have received CT or MRI during the staging interval for (p c0.05 for both imaging purposes other than staging prostate cancer. For example, tests) _patients considered for radiation therapy may have underCT (No. Pts.): gone imaging studies as a part of the treatment planning T1 + T2 (3,022) 32.5 46.8 -8.5 process. Further work is needed to clarify whether patients T3 + T4 (3411 41.0 49.3 MRI: are receiving cross-sectional imaging studies appropriately. T1 + T2 5.7 23.2 -2.8 Our findings suggest that enhanced efforts may be reT3 + T4 8.5 27.9 quired to communicate the importance of using measures, such as PSA and Gleason score, to help estimate the risk of metastatic disease before choosing bone scan, CT or MRI studies for staging newly diagnosed prostate cancer. Given DISCUSS I 0 N the cost implications of overuse of bone scan and crossAdenocarcinoma of the prostate is a major health problem sectional imaging, and clinical implications of under-use our in older men, accounting for significant morbidity and mor- data support the need for improving the clinical reliability tality in the aging United States population. After the wide- and cost efficiency of prostate cancer staging, a need that new spread adoption of PSA screening for early detection in men clinical practice guidelines may help meet. older than 50 years the annual incidence of prostate cancer Multivariate analyses are needed to assess the complex increased d r a m a t i ~ a l l y .Furthermore, ~.~ routine use of PSA interactions among patient demographic factors, medical cohas resulted in a stage migration with a high proportion of morbidities and clinical factors that predict risk for metacancers presumed organ confined at diagno~is.~ This rising static disease, and to measure the impact of these factors on number of new prostate cancer cases, particularly early stage staging test use in newly diagnosed prostate cancer. A better cases, has resulted in a corresponding increase in health care understanding of these issues may help clarify whether nonexpenditures associated with staging and treating newly di- clinical barriers to optimal staging for newly diagnosed prosagnosed disease.10 tate cancer exist and, if so, what they are and how they might Accurate pretreatment staging of prostate cancer is crucial be overcome. for selecting the most appropriate treatment strategy for Clinical practice guidelines may help improve the clinical newly diagnosed disease. Under staging may result in inef- reliability and cost efficiency of staging newly diagnosed fective local treatment (surgery or radiation therapy) with prostate cancer. Our survey of the literature revealed only 1 the attendant risks and costs. Over staging may result in such set of guidelines developed in 1995 by the American withholding potentially curative therapy when a tumor College of Radiology (ACRl.13 In actual practice urologists might be amenable to definitive local treatment. We describe used CT and bone scan for patients at low risk more often community urologist practice patterns in the use of imaging than ACR guidelines recommended. Additionally, CT and studies to stage newly diagnosed prostate cancer during the bone scan use was essentially the same before and after these era of widespread PSA screening, how they compare with the guidelines were developed, suggesting that urologists were emerging clinical recommendations and the impact of clinical not familiar or did not agree with them. Clinical practice factors on use. Our findings suggest that there is wide vari- guidelines in the urology literature may have a more signifation in staging by community urologists, and developing and icant impact on staging practice patterns. Additional outimplementing clinical staging guidelines may help optimize comes studies using longitudinal data like those from CaPSURE will be needed to assess the impact of new guidelines care. Our major finding is that physicians seem to overuse bone on usual practice in real-world clinical settings. Advantages of our study. CaPSURE provided a unique scan, CT and MRI when staging newly diagnosed prostate cancer in patients at low risk for pelvic lymph node metas- opportunity to observe how urologists manage prostate cantases and systemic spread of disease. Our data indicate that, cer in the real world apart from heavily structured protocols, consistent with the urology literature, a greater proportion of such as those of clinical trials. We used primary data collecpatients at high risk for systemic metastases undergo bone tion methods to track physician practice during a time of scan or cross-sectional imaging than those at low risk. How- significant changes in standards of care for prostate cancer ever, a substantial number of patients at low risk still receive screening, detection, staging and treatment. Data were colthese tests, despite literature recommendations t o the con- lected with no consideration of any particular research questrary. It has been suggested that bone scan is not necessary tion and, thus, are free of bias that may occur when data are for asymptomatic patients with PSA less than 10 ng./m1.3,4 collected with a specific hypothesis in mind. The 3 previous Nonetheless, a substantial number of patients at low risk studies of staging test use in newly diagnosed prostate cancer underwent bone scan. It has been suggested that CT and were based on physician survey responses,l2.14. l5 whereas MRI should be used only when staging pelvic lymph node our study analyzed data reported from actual clinical pracdissection is considered.3 Approximately 30 and 6% of pa- tice, which documented what clinicians actually do, rather tients at low risk received CT and MRI, respectively, despite than what they say they would do in a hypothetical clinical a body of evidence indicating that these tests provide little scenario. As new practice guidelines emerge our study establishes a baseline for tracking the adoption of new treatment useful information for them. Our time trend analysis yielded similar results regarding standards into community based urology practice, and idenrisk stratification and cross-sectional imaging use in the tifying barriers to adoption. Study limitations. A portion of our data collection was database. CT and MRI use was relatively consistent among urologists during the study, although the clinical literature retrospective, which increases the vulnerability to reporting since 1989 suggests little role for either in staging newly bias. However, we compared the use of staging tests in padiagnosed prostate cancer." Consistent with the report of tients diagnosed before June l, 1995 when prospective data Gee et al," there was no significant decrease with time in CT collection began with use in patients diagnosed after that and MRI use by urologists, although median PSA among date, and found no appreciable difference (data not shown). patients demonstrated a downward trend during that time. Clinical practice sites were not recruited at random and, thus This finding supports the notion that, despite declining dis- may not represent a statistically valid sample of the specease seventy at prostate cancer detection as well as evidence trum of United States urology practice. Nonetheless, to the % Frequency T1 + T2 vb. T3 T4 ~~

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USE OF IMAGING TESTS TO STAGE PROSTATE CANCER

extent that study urologists represent a diverse group of community based practitioners across the country, our results may be generalizable to similar practices in the United states. We cannot be certain that we have accounted for staging tests ordered by physicians other than study urologists. This issue is important in light of recent trends toward greater primary care physician involvement in the management of illnesses previously treated mainly by specialists. Our data collection method would have missed diagnostic tests not documented in the urology office medical record. We suspect that during the study urologists managed most staging evaluations for newly diagnosed prostate cancer and documented the results of most staging tests ordered by others. However, in future studies of test use it may be important that all types of physicians who care for patients with prostate cancer be represented in the study sample. Finally, we have measured urologist practice against recommendations based on literature review. However, the recommendations of neither ACR nor O'Dowd et a1 have yet been tested prospectively to document clinical and economic outcomes for cancer treated in accordance with the respective criteria. Without such outcomes data it is impossible to verify whether urologists order too many bone scans, CT and MRI studies or whether the guidelines recommend too few. CONCLUSIONS

Between 1989 and 1997 use of IVP, CT, MRI and bone scan has remained unchanged for staging newly diagnosed prostate cancer. Accordingto published criteria urologists may be ordering too many bone scans and cross-sectional imaging studies for patients at low risk for lymph node metastases and systemic disease spread. New practice guidelines formulated by urologists and highly publicized in professional arenas may ultimately have a greater impact on practice patterns for staging prostate cancer. Clinical guidelines that are successfully implemented may have a useful role in standardizing the approach to staging newly diagnosed prostate cancer and help achieve better clinical outcomes cost effectively. Further studies are needed to evaluate the penetration of clinical guidelines into usual practice and examine the impact of new guidelines on prostate cancer clinical outcomes. Karen Meng, David Pasta and Lori Potter assisted with statistical analysis, Karen Warolin with data management and Megeen Egan with manuscript preparation. REFERENCES

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2. Pound, C. R., Partin, A. W., Epstein, J. I. and Walsh, P. C.: prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol. Clin. N. Amer., 24: 395, 1997. 3. ODowd, G. J., Veltri, R. W., Orozco, R., Miller, M. C. and Oesterling, J . E.: Update on the appropriate staging evaluation for newly diagnosed prostate cancer. J. Urol., 158 687, 1997. 4. Chybowski, F. M., Keller, J . J., Bergstralh, E. J . and Oesterling, J. E.: Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: prostate specific antigen is superior to all other clinical parameters. J. Urol., 145: 313,1991. 5. L.evran, A,, Gonzalez, J. A., Diokno, A. C., Jafri, S. Z. and Steinert, B. W.: Are pelvic computed tomography, bone scan, and pelvic lymphadenectomynecessary in the staging of prostatic cancer? Brit. J . Urol., 7 5 778,1995. 6. Lubeck, D. P., Litwin, M. S., Henning, J. M., Stier, D. M., Mazonson, P., Fisk, R. and Carroll, P. R.: The CaPSURETM database: a methodology for clinical practice and research in prostate cancer. Urology, 4 8 773,1996. 7. Potosky, A. L., Miller, B. A., Albertsen, P. C. and Kramer, B. S.: The role of increasing detection in the rising incidence of prostate cancer. J.A.M.A., 2 7 3 548, 1995. 8. Jacobsen, S.J., Katusic, S. K., Bergstralh, E. J., Oesterling, J. E., Ohrt, D., Klee, G. G., Chute, C. G. and Lieber, M. N.: Incidence of prostate cancer diagnosis in the eras before and after serum prostate-specific antigen testing. J.A.M.A., 274: 1445,1995. 9. Catalona, W.J., Smith, D. S., Ratliff, T. L. and Basler, J. W.: Detection of organ-confined prostate cancer is increased through prostate-specific antigen-based screening. J.A.M.A., 270: 948,1993. 10. Taplin, S . H.,Barlow, W., Urban, N., Mandelson, M. T., Timlin, D. J., Ichikawa, L. and Nefcy, P.: Stage, age, comorbidity and direct costs of colon, prostate, and breast cancer care. J . Natl. Cancer Inst., 87:417, 1995. 11. Wolf, J . S.,Jr., Cher, M., Dall'era, M., Presti, J . C., Jr., Hricak, H. and Carroll, P. R.: The use and accuracy of cross-sectional imaging and fine needle aspiration cytology for detection of pelvic lymph node metastases before radical prostatectomy. J. Urol., 153: 993, 1995. 12. Gee, W. F., Holtgrewe, H. L., Albertsen, P. C., Litwin, M. S., Manyak, M. J., OLeary, M. P. and Painter, M. R.: Practice trends in the diagnosis and management of prostate cancer in the United States. J . Urol., 154 207,1995. 13. American College of Radiology, Expert Panel of Urologic Imaging: Pretreatment staging of clinically localized prostate cancer: appropriateness criteria. American College of Radiology, September 1995. 14. Barry, M. J., Fowler, F. J., Jr., Bin, L. and Oesterling, J. E.: A nationwide survey of practicing urologists: current management of benign prostatic hyperplasia and clinically localized prostate cancer. J. Urol., 158 488, 1997. 15. Plawker, M. W.,Fleisher, J. M., Vapnek, E. M. and Macchia, R. J.: Current trends in prostate cancer diagnosis and staging among United States urologists. J. Urol., 1 5 8 1853,1997.