Acra Oncologica Vol. 30 No. 2 1991
FROM THE UROLOGIC-ONCOLOGY GROUP, UNIVERSITY OF CHICAGO, CHICAGO, ILLINOIS, USA.
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
PROSTATE CANCER: TO SCREEN OR NOT TO SCREEN G. CHODAK
Abstract Screening for early detection of prostate cancer seems both necessary and possible but it remains to be proven that it can lower mortality from the disease. Until properly evaluated, the risks of screening at present do not justify either the cost or the potential benefit that could result. An increased awareness of the problems encountered by screening could lead to greater impetus around the world to design and implement the proper studies. The recent information about the outcome following conservative management means that the value of treatment must also be assessed since it is possible that the only tumors cured by radiation therapy or surgery are those that are not life threatening, whereas the most lethal tumors are not identified sufficiently early by the available screening tests to be cured. The increased incidence and mortality from prostate cancer should lead to increased pressure to answer the important questions as soon as possible. Key words: Prostate cancer, screening.
Throughout the world, both the incidence of, and mortality from, carcinoma of the prostate continues to rise. In some countries such as Sweden and the U.S. it is now the most common cancer in men and the first or second most common cause of death from cancer. Two of the reasons for the high mortality are that many patients have incurable disease at the time of diagnosis and patients with potentially curable tumors are rarely symptomatic. To reduce mortality from this disease, screening has frequently been recommended for asymptomatic men in the high risk age group. In order to understand the role of screening for this disease, the following four questions will be addressed: 1) is screening necessary?, 2 ) is screening possible?, 3) is screening justified?, and 4) should screening programs be instituted?
Is screening necessary?
In the past 30 years there has been little decline in the mortality rate from this disease. This can be interpreted to
mean that the current approach to diagnosis and management has not significantly impacted on this cancer. Also, despite the discovery of hormone therapy over 40 years ago, there is still no curative therapy for advanced disease. Finally, the lack of early symptoms means that educating patients about the disease may be ineffective in detecting more localized tumors. Thus, an improvement in early detection is clearly necessary.
Is screening possible? Until recently, the most sensitive method for diagnosing prostate cancer has been the digital rectal examination (DRE). Several studies have used this test for screening and they found that a higher percentage of localized tumors could be detected ( 1, 2) and the survival rate could be improved (I). Over the past several years, transrectal ultrasonography (TRUS) and serum prostate specific antigen (PSA) have been found to detect non-palpable prostate cancer. Both tests have also been tested as possible screening tests for this disease. In two published reports, the detection rate of prostate cancer using sonography was nearly twice that found with DRE (3,4) (Table 1). Importantly, ultrasonography results in detecting a higher percentage of patients with localized disease (4).Thus, both DRE and TRUS appear potentially useful for screening. A major disadvantage, however, is that both tests have a positive predictive value of approximately 17-35% (5). Recent data with PSA also indicate a potential for screening, but the sensitivity is only 85-92% and
Presented at the Conference on Early Prostatic Cancer. The WHO Collaborating Center for Urological Tumors, Karolinska Hospital, Stockholm, March 21 -23, 1990. Accepted for publication 1 October 1990.
285
286
G. CHODAK
Table 1
Table 3
Detection of prostate cancer by digital rectal examination (DRE) and transrectal ultrasonography (TRUS)
Impact of early detection of lung cancer (6)
Screened Controls Prostate cancer detection rate (YO) Authors (ref.)
DRE
TRUS
Lee et al. ( 4 ) Cooner et al. (3)
1.3% 7.5%
2.6% 12.6%
5-year survival (YO) 35% Localized tumors (YO) 46% Mortality rate/l 000 person-years (YO) 3.2%
15% 32% 3.0%
Should screening programs be established? Table 2 Prostate cancer detection rate in men with abnormal TRUS (3,4)
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
DRE
+ + -
PSA
Number of cancers/total (Yo) 66%
-
15% 32% 6%
+ + -
TRUS = transrectal ultrasonography DRE = digital rectal examination
PSA = serum prostate specific antigen
the positive predictive value is only 52% (3,4). When all three tests are used perhaps only 6% of tumors would be missed if DRE and PSA are used initially and TRUS is performed only if one of the tests is abnormal (3,4) (Table 2). This approach would substantially reduce the cost of early detection without markedly affecting the detection rate. Thus, while DRE and PSA would still miss many cancers and the false positive rate is quite high, both could be used for screening at this time.
Is screening justified?
There are three major requirements that must be satisfied to justify screening: 1) early detection must be improved, 2) the survival rate must be increased and 3) most importantly, mortality from prostate cancer must be reduced. Based on all data published to date, screening can improve early detection and increase the survival rate, but there are no data showing the impact of screening on mortality. Although many people assume that mortality should be reduced when early detection and survival are improved, this conclusion may not be true. This is best illustrated by a large perspective randomized screening study for lung cancer which showed that the screened group had both a higher percentage of localized tumors and a higher 5-year survival rate than the controls, yet there was no significant difference in mortality (6) (Table 3). Based on this study, we must state that screening for prostate cancer may not reduce mortality from this disease. Furthermore, we must conclude that currently there is no scientific proof that screening is justified.
In various parts of the U.S. physicians have already begun promoting screening using the various methods available. However, a recent US. Public Health Task Force concluded that ‘There is insufficient evidence either for or against routine digital rectal examinations as an effective screening test for prostate cancer in asymptomatic men’ (7). Furthermore, the report stated that ‘transrectal sonography and serum tumor markers are not recommended for routine screening’ (7). The absence of any data demonstrating that routine screening is effective means that establishing screening programs is unjustified at this time. The only way to establish the value of screening is by a randomized controlled trial which has recently been funded in the U.S. by the National Institute of Health. This study will attempt to enroll 100000 men in order to assess the impact of screening on mortality. Since this study will require 10-15 years to be completed, many people argue that screening should be performed because in the interim, too many people may suffer if screening is postponed. These advocates ignore the potential harm that could result from screening prematurely. One potential problem is that screening may diagnose some cancers that would never shorten the patient’s life and therefore any treatment administered would be unnecessary. Johansson et al. (8) have found that only 5% of patients with a well differentiated localized tumor will die from prostate cancer within 10 years of diagnosis if treated only by TUR or hormone therapy when they become symptomatic. Another problem is the morbidity and mortality of treatment. The average surgical mortality following radical prostatectomy may be approximately 1% (9). If surgery was the principal therapy offered and screening detected cancer in 3% of men screened in the U.S., then 1500 men could die in the first year as a consequence of screening and treatment. In addition, incontinence, impotence and other complications could affect large numbers of men. Psychological anxiety could also result for many of the 2 million men undergoing biopsy. Finally, the economic and manpower costs could divert resources from other areas which could have a greater impact on the health of the society. For all of the above reasons, screening programs should not be initiated at this time.
SCREENING OF PROSTATE CANCER
Corresponding aulfzor: Dr Gerald Chodak, Institution of Urology, Oncology group, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
REFERENCES 1. Gilbertsen VA. Cancer of the prostate gland. JAMA 1971; 215: 81.
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
2. Chodak GW, Schoenberg HW. Early detection of prostate cancer by routine screening. JAMA 1984; 252: 3261. 3. Cooner WH, Mosley BR, Rutherford CL Jr, et al. Clinical application of transrectal ultrasonography and prostate specific antigen in the search for prostate cancer. J Urol 1988; 139: 758-6 I .
287
4. Lee F, Littrup PJ, Torp-Pedersen ST, et al. Prostate cancer: Comparison of transrectal US and digital rectal examination for screening. Radiology 1988; 168: 389-94. 5. Chodak GW, Schoenberg HW. Progress and problems in screening for carcinoma of the prostate. World J Surg 1989; 13: 60-4. 6. Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: The Mayo Program. J Occup Med 1986; 28: 746-50. 7. U.S. Preventive Services Task Force: Guide to clinical preventives services. Screening for prostate cancer. 1989; 42-4. 8. Johansson JE, Adami HO, Anderson SO, Bergstrom R, Krusemo UB, Kraaz W. Natural history of localized prostatic cancer. Lancet 1989; : 799-803. 9. Chodak GW, Crawford ED. Screening for prostate cancer. The controversy. Urology Grand Rounds 1989; 26: 1-7.
FROM THE UROLOGIC-ONCOLOGY GROUP, UNIVERSITY OF CHICAGO, CHICAGO, ILLINOIS, USA.
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
PROSTATE CANCER: TO SCREEN OR NOT TO SCREEN G. CHODAK
Abstract Screening for early detection of prostate cancer seems both necessary and possible but it remains to be proven that it can lower mortality from the disease. Until properly evaluated, the risks of screening at present do not justify either the cost or the potential benefit that could result. An increased awareness of the problems encountered by screening could lead to greater impetus around the world to design and implement the proper studies. The recent information about the outcome following conservative management means that the value of treatment must also be assessed since it is possible that the only tumors cured by radiation therapy or surgery are those that are not life threatening, whereas the most lethal tumors are not identified sufficiently early by the available screening tests to be cured. The increased incidence and mortality from prostate cancer should lead to increased pressure to answer the important questions as soon as possible. Key words: Prostate cancer, screening.
Throughout the world, both the incidence of, and mortality from, carcinoma of the prostate continues to rise. In some countries such as Sweden and the U.S. it is now the most common cancer in men and the first or second most common cause of death from cancer. Two of the reasons for the high mortality are that many patients have incurable disease at the time of diagnosis and patients with potentially curable tumors are rarely symptomatic. To reduce mortality from this disease, screening has frequently been recommended for asymptomatic men in the high risk age group. In order to understand the role of screening for this disease, the following four questions will be addressed: 1) is screening necessary?, 2 ) is screening possible?, 3) is screening justified?, and 4) should screening programs be instituted?
Is screening necessary?
In the past 30 years there has been little decline in the mortality rate from this disease. This can be interpreted to
mean that the current approach to diagnosis and management has not significantly impacted on this cancer. Also, despite the discovery of hormone therapy over 40 years ago, there is still no curative therapy for advanced disease. Finally, the lack of early symptoms means that educating patients about the disease may be ineffective in detecting more localized tumors. Thus, an improvement in early detection is clearly necessary.
Is screening possible? Until recently, the most sensitive method for diagnosing prostate cancer has been the digital rectal examination (DRE). Several studies have used this test for screening and they found that a higher percentage of localized tumors could be detected ( 1, 2) and the survival rate could be improved (I). Over the past several years, transrectal ultrasonography (TRUS) and serum prostate specific antigen (PSA) have been found to detect non-palpable prostate cancer. Both tests have also been tested as possible screening tests for this disease. In two published reports, the detection rate of prostate cancer using sonography was nearly twice that found with DRE (3,4) (Table 1). Importantly, ultrasonography results in detecting a higher percentage of patients with localized disease (4).Thus, both DRE and TRUS appear potentially useful for screening. A major disadvantage, however, is that both tests have a positive predictive value of approximately 17-35% (5). Recent data with PSA also indicate a potential for screening, but the sensitivity is only 85-92% and
Presented at the Conference on Early Prostatic Cancer. The WHO Collaborating Center for Urological Tumors, Karolinska Hospital, Stockholm, March 21 -23, 1990. Accepted for publication 1 October 1990.
285
286
G. CHODAK
Table 1
Table 3
Detection of prostate cancer by digital rectal examination (DRE) and transrectal ultrasonography (TRUS)
Impact of early detection of lung cancer (6)
Screened Controls Prostate cancer detection rate (YO) Authors (ref.)
DRE
TRUS
Lee et al. ( 4 ) Cooner et al. (3)
1.3% 7.5%
2.6% 12.6%
5-year survival (YO) 35% Localized tumors (YO) 46% Mortality rate/l 000 person-years (YO) 3.2%
15% 32% 3.0%
Should screening programs be established? Table 2 Prostate cancer detection rate in men with abnormal TRUS (3,4)
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
DRE
+ + -
PSA
Number of cancers/total (Yo) 66%
-
15% 32% 6%
+ + -
TRUS = transrectal ultrasonography DRE = digital rectal examination
PSA = serum prostate specific antigen
the positive predictive value is only 52% (3,4). When all three tests are used perhaps only 6% of tumors would be missed if DRE and PSA are used initially and TRUS is performed only if one of the tests is abnormal (3,4) (Table 2). This approach would substantially reduce the cost of early detection without markedly affecting the detection rate. Thus, while DRE and PSA would still miss many cancers and the false positive rate is quite high, both could be used for screening at this time.
Is screening justified?
There are three major requirements that must be satisfied to justify screening: 1) early detection must be improved, 2) the survival rate must be increased and 3) most importantly, mortality from prostate cancer must be reduced. Based on all data published to date, screening can improve early detection and increase the survival rate, but there are no data showing the impact of screening on mortality. Although many people assume that mortality should be reduced when early detection and survival are improved, this conclusion may not be true. This is best illustrated by a large perspective randomized screening study for lung cancer which showed that the screened group had both a higher percentage of localized tumors and a higher 5-year survival rate than the controls, yet there was no significant difference in mortality (6) (Table 3). Based on this study, we must state that screening for prostate cancer may not reduce mortality from this disease. Furthermore, we must conclude that currently there is no scientific proof that screening is justified.
In various parts of the U.S. physicians have already begun promoting screening using the various methods available. However, a recent US. Public Health Task Force concluded that ‘There is insufficient evidence either for or against routine digital rectal examinations as an effective screening test for prostate cancer in asymptomatic men’ (7). Furthermore, the report stated that ‘transrectal sonography and serum tumor markers are not recommended for routine screening’ (7). The absence of any data demonstrating that routine screening is effective means that establishing screening programs is unjustified at this time. The only way to establish the value of screening is by a randomized controlled trial which has recently been funded in the U.S. by the National Institute of Health. This study will attempt to enroll 100000 men in order to assess the impact of screening on mortality. Since this study will require 10-15 years to be completed, many people argue that screening should be performed because in the interim, too many people may suffer if screening is postponed. These advocates ignore the potential harm that could result from screening prematurely. One potential problem is that screening may diagnose some cancers that would never shorten the patient’s life and therefore any treatment administered would be unnecessary. Johansson et al. (8) have found that only 5% of patients with a well differentiated localized tumor will die from prostate cancer within 10 years of diagnosis if treated only by TUR or hormone therapy when they become symptomatic. Another problem is the morbidity and mortality of treatment. The average surgical mortality following radical prostatectomy may be approximately 1% (9). If surgery was the principal therapy offered and screening detected cancer in 3% of men screened in the U.S., then 1500 men could die in the first year as a consequence of screening and treatment. In addition, incontinence, impotence and other complications could affect large numbers of men. Psychological anxiety could also result for many of the 2 million men undergoing biopsy. Finally, the economic and manpower costs could divert resources from other areas which could have a greater impact on the health of the society. For all of the above reasons, screening programs should not be initiated at this time.
SCREENING OF PROSTATE CANCER
Corresponding aulfzor: Dr Gerald Chodak, Institution of Urology, Oncology group, University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637, USA.
REFERENCES 1. Gilbertsen VA. Cancer of the prostate gland. JAMA 1971; 215: 81.
Acta Oncol Downloaded from informahealthcare.com by Michigan University on 10/26/14 For personal use only.
2. Chodak GW, Schoenberg HW. Early detection of prostate cancer by routine screening. JAMA 1984; 252: 3261. 3. Cooner WH, Mosley BR, Rutherford CL Jr, et al. Clinical application of transrectal ultrasonography and prostate specific antigen in the search for prostate cancer. J Urol 1988; 139: 758-6 I .
287
4. Lee F, Littrup PJ, Torp-Pedersen ST, et al. Prostate cancer: Comparison of transrectal US and digital rectal examination for screening. Radiology 1988; 168: 389-94. 5. Chodak GW, Schoenberg HW. Progress and problems in screening for carcinoma of the prostate. World J Surg 1989; 13: 60-4. 6. Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: The Mayo Program. J Occup Med 1986; 28: 746-50. 7. U.S. Preventive Services Task Force: Guide to clinical preventives services. Screening for prostate cancer. 1989; 42-4. 8. Johansson JE, Adami HO, Anderson SO, Bergstrom R, Krusemo UB, Kraaz W. Natural history of localized prostatic cancer. Lancet 1989; : 799-803. 9. Chodak GW, Crawford ED. Screening for prostate cancer. The controversy. Urology Grand Rounds 1989; 26: 1-7.
