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November 12, 1997, Vol 278, No. 18 >
ARTICLE | November 12, 1997

Early Detection of Prostate Cancer: Title and subTitle BreakSerendipity Strikes Again FREE

Mary McNaughton Collins, MD, MPH; David F. Ransohoff, MD; Michael J. Barry, MD
[+] Author Affiliations

Presented in part at the national meeting of the Society of General Internal Medicine, Washington, DC, May 3, 1996.

Reprints: Michael J. Barry, MD, Medical Practices Evaluation Center, Massachusetts General Hospital, 50 Staniford St, Ninth Floor, Boston, MA 02114 (e-mail: Barry.Michael@mgh.harvard.edu).


JAMA. 1997;278(18):1516-1519. doi:10.1001/jama.1997.03550180066039
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Article
References

An underappreciated characteristic of prostate cancer screening is that it may detect some prostate cancers solely by serendipity or chance. Serendipity, previously described in the detection of colonic neoplasms, could affect prostate cancer detection when a screening test result is abnormal for reasons other than the presence of prostate cancer, but prostate cancer is coincidentally detected during the subsequent evaluation of the abnormal screening result. We reviewed published articles about prostate cancer screening, searching for evidence of serendipity. We defined serendipity in digital rectal examination (DRE) screening as the discovery of a prostate cancer by the random biopsy of an area of the prostate gland other than the palpable suspicious area that prompted the biopsy. We defined serendipity in prostate-specific antigen (PSA) screening as the discovery of a prostate cancer by the random biopsy of a nonpalpable (stage T1c) prostate cancer less than 1.0 cm3 in volume, since tumors less than 1.0 cm3 are generally too small to cause elevated PSA levels. We found that serendipity may be responsible for the detection of more than one quarter of apparently DRE-detected prostate cancers and up to one quarter of apparently PSAdetected cancers. Additionally, serendipity played a larger role in the detection of smaller tumors that are common but of uncertain clinical significance. We conclude that serendipity-detected prostate cancers contribute to an overestimation of the true information value of DRE and PSA screening. Whether serendipity is advantageous in prostate cancer screening depends on the as yet uncertain outcomes for men with smaller prostate cancers. However, given our estimates of the potential magnitude of the impact of serendipity, the currently popular DRE-and PSA-based screening strategy may not be optimal. If smaller prostate cancers are important, then we are not finding enough; if they are unimportant, then we are finding too many that we may feel compelled to treat aggressively.

REFERENCES

1 +
Barry MJ, Fleming C, Coley CM, Wasson JH, Fahs MC, Oesterling JE.  Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? I: framing the debate . Urology . 1995;;46:2-13.
2 +
Woolf SH.  Screening for prostate cancer with prostate-specific antigen: an examination of the evidence . N Engl J Med . 1995;;333:1401-1405.
3 +
Kramer BS, Brown ML,Prorok PC, Potosky AL, Gohagan JK.  Prostate cancer screening . Ann Intern Med . 1993;;119:914-923.
4 +
Krahn MD, Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS.  Screening for prostate cancer . JAMA . 1994;;272:773-780.
5 +
US Preventive Services Task Force.  Screening for prostate cancer . In: Guide to Clinical Preventive Services . 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;:119-134.
6 +
Ransohoff DF, Lang CA.  Small adenomas detected during fecal occult blood test screening for colorectal cancer . JAMA . 1990;;264:76-78.
7 +
Mandel JS, Bond JH, Church TR, et al.  Reducing mortality from colorectal cancer by screening for fecal occult blood . N Engl J Med . 1993;;328:1365-1371.
8 +
Richie JP, Catalona WJ, Ahmann FR, et al.  Effect of patient age on early detection of prostate cancer with serum prostate-specific antigen and digital rectal exam . Urology . 1993;;42:365-374.
9 +
Gann PH, Hennekens CH, Stampfer MF.  A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer . JAMA . 1995;; 273:289-294.
10 +
Barry MJ.  PSA level had moderate sensitivity for prostate cancer presenting within 4 years (commentary) . ACP Journal Club . 1995;;123:19.
11 +
Karakiewicz PI, Aprikian AG, Meshref AW, Bazinet M.  Computer-assisted comparative analysis of four-sector and six-sector biopsies of the prostate . Urology . 1996;;48:747-750.
12 +
Eskew LA, Bare RL, McCullough DL.  Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate . J Urol . 1997;;157:199-203.
13 +
Levine MA, Melamed J, Ittmann M, Lepor H.  Two consecutive sets of transrectal ultrasound (TRUS) guided sextant biopsies of the prostate for the diagnosis of prostate cancer . J Urol . 1997;;157 ( (suppl) ):64. Abstract.
14 +
Harmon T, Keetch DW, Catalona WJ.  Diagnostic value of serial prostate biopsies in men with normal prostate-specific antigen (PSA) levels and suspicious digital rectal examination (DRE) . J Urol . 1997;;157( (suppl) ):365. Abstract.
15 +
Vashi AR, Wojno KJ, Gillespie B, Oesterling JE.  Patient age and prostate gland size determine the appropriate number of cores per prostate biopsy . J Urol . 1997;;157( (suppl) ):365. Abstract.
16 +
Billebaud T, Villers A, Astier L, et al.  Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer . Eur Urol . 1992;;21:6-14.
17 +
Flanigan RC, Catalona WJ, Richie JP, et al.  Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer . J Urol . 1994;;152:1506-1509.
18 +
Brawn PN, Speights VO, Kuhl D, et al.  Protatespecific antigen levels from completely sectioned, clinically benign, whole prostates . Cancer . 1991;;68:1592-1599.
19 +
Stamey TA, Kabalin JN, McNeal JE, et al.  Prostate-specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate, II: radical prostatectomy treated patients . J Urol . 1989;;141:1076-1083.
20 +
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E.  Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate . N Engl J Med . 1987;;317:909-916.
21 +
Oesterling JE, Suman VJ, Zincke H, Bostwick DG.  PSA-detected (clinical stage T1c or B0) prostate cancer . Urol Clin North Am . 1993;;20:687-693.
22 +
Humphrey PA, Keetch DW, Smith DS, Shepherd DL, Catalona WJ.  Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate-specific antigen based screening . J Urol . 1996;;155:816-820.
23 +
Scaletscky R, Koch MO, Eckstein CW, Bicknell SL, Gray GF, Smith JA.  Tumor volume and stage in carcinoma of the prostate detected by elevations in prostate-specific antigen . J Urol . 1994;;152:129-131.
24 +
Epstein JI, Walsh PC, Carmichael M, Brendler CB.  Pathologic and clinical findings to predict tumor extent of nonpalpable (stage Tic) prostate cancer . JAMA . 1994;;271:368-374.
25 +
Ohori M, Wheeler TM, Scardino PT.  The new American Joint Committee on Cancer and International Union Against Cancer TNM Classification of prostate cancer . Cancer . 1994;;74:104-114.
26 +
Mettlin C, Jones G, Averett H, Gusberg SB, Murphy GP.  Defining and updating the American Cancer Society guidelines for the cancer-related checkup . CA Cancer J Clin . 1993;;43:42-47.
27 +
Scardino PT, Weaver R, Hudson MA.  Early detection of prostate cancer . Hum Pathol . 1992;;23:p-222.
28 +
Catalona WJ, Richie JP, Ahmann FR, et al.  Comparison of digital rectal examination and serum prostate-specific antigen in the early detection of prostate cancer . J Urol . 1994;;151:1283-1290.
29 +
Coley CM, Barry MJ, Fleming C, Wasson JH, Fahs MC, Oesterling JE.  Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? II: early detection strategies . Urology . 1995;;42:p-141.
30 +
Dugan JA, Bostwick DG, Myers RP, Qian J, Bergstralh EJ, Oesterling JE.  The definition and preoperative prediction of clinically insignificant prostate cancer . JAMA . 1996;;275:288-294.
31 +
Geary ES, Stamey TA.  Pathological characteristics and prognosis of nonpalpable and palpable prostate cancers with a Hybritech prostate-specific antigen of 4 to 10 ng/ml . J Urol . 1996;;156:1056-1058.
32 +
Gohagan JK, Prorok PC, Kramer BS, Cornett JE.  Prostate cancer screening in the prostate, lung, colorectal, and ovarian screening trial of the National Cancer Institute . J Urol . 1994;;152:1905-1909.
33 +
Prorok P.  The National Cancer Institute multiscreening trial . Can J Oncol . 1994;;4( (suppl) ):98-101.
34 +
Schroder FH.  The European Screening Study for Prostate Cancer . Can J Oncol . 1994;;4( (suppl) ):102-105.

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1 +
Barry MJ, Fleming C, Coley CM, Wasson JH, Fahs MC, Oesterling JE.  Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? I: framing the debate . Urology . 1995;;46:2-13.
2 +
Woolf SH.  Screening for prostate cancer with prostate-specific antigen: an examination of the evidence . N Engl J Med . 1995;;333:1401-1405.
3 +
Kramer BS, Brown ML,Prorok PC, Potosky AL, Gohagan JK.  Prostate cancer screening . Ann Intern Med . 1993;;119:914-923.
4 +
Krahn MD, Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS.  Screening for prostate cancer . JAMA . 1994;;272:773-780.
5 +
US Preventive Services Task Force.  Screening for prostate cancer . In: Guide to Clinical Preventive Services . 2nd ed. Baltimore, Md: Williams & Wilkins; 1996;:119-134.
6 +
Ransohoff DF, Lang CA.  Small adenomas detected during fecal occult blood test screening for colorectal cancer . JAMA . 1990;;264:76-78.
7 +
Mandel JS, Bond JH, Church TR, et al.  Reducing mortality from colorectal cancer by screening for fecal occult blood . N Engl J Med . 1993;;328:1365-1371.
8 +
Richie JP, Catalona WJ, Ahmann FR, et al.  Effect of patient age on early detection of prostate cancer with serum prostate-specific antigen and digital rectal exam . Urology . 1993;;42:365-374.
9 +
Gann PH, Hennekens CH, Stampfer MF.  A prospective evaluation of plasma prostate-specific antigen for detection of prostatic cancer . JAMA . 1995;; 273:289-294.
10 +
Barry MJ.  PSA level had moderate sensitivity for prostate cancer presenting within 4 years (commentary) . ACP Journal Club . 1995;;123:19.
11 +
Karakiewicz PI, Aprikian AG, Meshref AW, Bazinet M.  Computer-assisted comparative analysis of four-sector and six-sector biopsies of the prostate . Urology . 1996;;48:747-750.
12 +
Eskew LA, Bare RL, McCullough DL.  Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate . J Urol . 1997;;157:199-203.
13 +
Levine MA, Melamed J, Ittmann M, Lepor H.  Two consecutive sets of transrectal ultrasound (TRUS) guided sextant biopsies of the prostate for the diagnosis of prostate cancer . J Urol . 1997;;157 ( (suppl) ):64. Abstract.
14 +
Harmon T, Keetch DW, Catalona WJ.  Diagnostic value of serial prostate biopsies in men with normal prostate-specific antigen (PSA) levels and suspicious digital rectal examination (DRE) . J Urol . 1997;;157( (suppl) ):365. Abstract.
15 +
Vashi AR, Wojno KJ, Gillespie B, Oesterling JE.  Patient age and prostate gland size determine the appropriate number of cores per prostate biopsy . J Urol . 1997;;157( (suppl) ):365. Abstract.
16 +
Billebaud T, Villers A, Astier L, et al.  Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer . Eur Urol . 1992;;21:6-14.
17 +
Flanigan RC, Catalona WJ, Richie JP, et al.  Accuracy of digital rectal examination and transrectal ultrasonography in localizing prostate cancer . J Urol . 1994;;152:1506-1509.
18 +
Brawn PN, Speights VO, Kuhl D, et al.  Protatespecific antigen levels from completely sectioned, clinically benign, whole prostates . Cancer . 1991;;68:1592-1599.
19 +
Stamey TA, Kabalin JN, McNeal JE, et al.  Prostate-specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate, II: radical prostatectomy treated patients . J Urol . 1989;;141:1076-1083.
20 +
Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E.  Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate . N Engl J Med . 1987;;317:909-916.
21 +
Oesterling JE, Suman VJ, Zincke H, Bostwick DG.  PSA-detected (clinical stage T1c or B0) prostate cancer . Urol Clin North Am . 1993;;20:687-693.
22 +
Humphrey PA, Keetch DW, Smith DS, Shepherd DL, Catalona WJ.  Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate-specific antigen based screening . J Urol . 1996;;155:816-820.
23 +
Scaletscky R, Koch MO, Eckstein CW, Bicknell SL, Gray GF, Smith JA.  Tumor volume and stage in carcinoma of the prostate detected by elevations in prostate-specific antigen . J Urol . 1994;;152:129-131.
24 +
Epstein JI, Walsh PC, Carmichael M, Brendler CB.  Pathologic and clinical findings to predict tumor extent of nonpalpable (stage Tic) prostate cancer . JAMA . 1994;;271:368-374.
25 +
Ohori M, Wheeler TM, Scardino PT.  The new American Joint Committee on Cancer and International Union Against Cancer TNM Classification of prostate cancer . Cancer . 1994;;74:104-114.
26 +
Mettlin C, Jones G, Averett H, Gusberg SB, Murphy GP.  Defining and updating the American Cancer Society guidelines for the cancer-related checkup . CA Cancer J Clin . 1993;;43:42-47.
27 +
Scardino PT, Weaver R, Hudson MA.  Early detection of prostate cancer . Hum Pathol . 1992;;23:p-222.
28 +
Catalona WJ, Richie JP, Ahmann FR, et al.  Comparison of digital rectal examination and serum prostate-specific antigen in the early detection of prostate cancer . J Urol . 1994;;151:1283-1290.
29 +
Coley CM, Barry MJ, Fleming C, Wasson JH, Fahs MC, Oesterling JE.  Should Medicare provide reimbursement for prostate-specific antigen testing for early detection of prostate cancer? II: early detection strategies . Urology . 1995;;42:p-141.
30 +
Dugan JA, Bostwick DG, Myers RP, Qian J, Bergstralh EJ, Oesterling JE.  The definition and preoperative prediction of clinically insignificant prostate cancer . JAMA . 1996;;275:288-294.
31 +
Geary ES, Stamey TA.  Pathological characteristics and prognosis of nonpalpable and palpable prostate cancers with a Hybritech prostate-specific antigen of 4 to 10 ng/ml . J Urol . 1996;;156:1056-1058.
32 +
Gohagan JK, Prorok PC, Kramer BS, Cornett JE.  Prostate cancer screening in the prostate, lung, colorectal, and ovarian screening trial of the National Cancer Institute . J Urol . 1994;;152:1905-1909.
33 +
Prorok P.  The National Cancer Institute multiscreening trial . Can J Oncol . 1994;;4( (suppl) ):98-101.
34 +
Schroder FH.  The European Screening Study for Prostate Cancer . Can J Oncol . 1994;;4( (suppl) ):102-105.

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