solved. First, we must have a proven method to differentiate between aggressive cancers and clinically indolent cancers. Secondly, we must have outcome studies that definitively show benefit from treatments such as radical prostatectomy. As both of these issues remain unsettled, it is premature to endorse PSA as a screening test. Michael E. Stuart, MD Matthew R Handley, MD Michael R. Conger, MD Group Health Cooperative of Puget Sound Seattle, Wash 1.
Oesterling JE. Prostate-specific antigen: improving the ability to diagnose early
prostate
cancer.
JAMA. 1992;267:2236-2238.
2. Hinman F Jr. Screening for prostatic carcinoma. J Urol. 1991;145:126. 3. Nomura AM, Koloveil N. Prostate cancer: a current perspective. Am J Epidemiol.
The other corroborative studies cited by Johansson et al also suffer from the same patient selection bias, yet all show substantial prostate cancer progression rates. The inescap¬ able conclusion from these studies is that, given time, pros¬ tate cancer progresses—slowly in low-grade tumors and rap¬ idly in high-grade tumors. The results of the study by Johansson et al cannot be "generalized to patients with early-stage disease in other populations" without first formally testing their hypothesis. It does not seem prudent to withhold potentially curative therapy from younger patients and those with higher grade tumors until equivalent results of expectant management have been demonstrated in a representative patient population.
Catalona, MD Washington University William J.
1991;13:205.
H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 5. Optenberg S, Thompson IM. Economics of screening for carcinoma of the pros-
St Louis, Mo
4. Johansson J-E, Adami
tate. Urol Clin North Am.
1990;17:719-737.
To the Editor.\p=m-\Thestudy by Johansson et al1 is of limited relevance because their selection criteria resulted in a study group that is not representative of the patient population with early prostate cancer. Their study group included an inordinately high proportion of men over the age of 75 years, most of whom had low-grade tumors too small to be detected on rectal examination. Nearly half of the tumors were discovered at the time of an operation for presumed benign hyperplasia. Because such tumors progress slowly and most patients were elderly to begin with, it is not surprising that most patients died of other causes. The patient selection process was a self-fulfilling prophesy. During the first 2 years of their study, only patients with grade 1 tumors were accepted for the untreated group, which enriched the group with low-grade tumors. During the last 5 years, some patients under the age of 75 years with grade 2 or 3 tumors were excluded from the untreated group, which selectively eliminated some of the high-risk patients. All men over 75 years of age were assigned to the untreated group, which enriched the group with elderly men more likely to die of other causes. The selection process resulted in a patient group that differed dramatically from my personal series of radical prostatectomy patients as illustrated below. In the study by Johansson et al, 48% (106/223) of the men had stage TO prostate cancer, which by definition cannot be detected on rectal examination. By comparison, in my per¬ sonal radical prostatectomy series, only 18% (128/700) had this stage of disease. In the study by Johansson et al, 66% (148/223) had grade 1 tumors as compared with 23% (158/700) in my radical prostatectomy series. In the study by Johansson et al, 62% (138/223) of men were over the age of 70 years and 17% (38/223) were over 80 years. The mean age at diagnosis was 72 years. By comparison, in my series, only 27% (189/700) were over the age of 70 years, 3% (20/700) were over 75 years, and their mean age was 64 years. In the study by Johansson et al, only 8.5% of patients died of prostate cancer within 10 years. In contrast, in a recent study2 in which patients with the same stages of cancer were treated with radiation therapy, the cancer death rate was 15% with a mean follow-up of only 7.3 years (actuarial pro¬ jection, 20% ±7% at 10 years). The conclusion by Johansson et al that 91.5% of patients with early prostate cancer need not worry about dying from the disease is not generally valid. In this regard, 348 (53%) of the 654 new cancer patients diagnosed during the study by Johansson et al had advanced cancer at the time of diagnosis. Certainly, each of these men once had an early cancer that did progress, and what are their future prospects?
H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 2. Lerner SP, Seale-Hawkins C, Carlton CE Jr, Scardino PT. The risk of dying of prostate cancer in patients with clinically localized disease. J Urol. 1991;146:1040\x=req-\ 1045. 1. Johansson J-E, Adami
To the Editor.\p=m-\Weread with interest the article by Johanset al1 and the Editorial by Oesterling2 regarding screening and treatment for prostate cancer. We agree with Johansson et al "that without evidence of benefit from controlled clinical trials, the radical treatment of early-stage prostate cancer remains in its experimental phase." We disagree with the editorial statement by Oesterling that recommends "a serum . PSA concentration and . DRE. If both are normal, the patient should be followed with annual evaluations [his italics]. This statement is not convincingly supported by the medical literature or the majority of expert panel recommendations.3,4 Such an editorial position is of particular concern because an ongoing national prostate cancer screening program, organized and sponsored by a pharmaceutical corporation, also pressures physicians to adopt screening strategies of unproven benefit. The Schering Corporation, manufacturer of flutamide, has sponsored National Prostate Cancer Awareness Week (PCAW) for the past 3 years. Signs posted in our hospital primary care areas said, "Take a minute to have a free pros¬ tate examination. It could be worth your life." The posters announced that medical centers nationwide were offering rectal examinations for early detection and successful treat¬ ment of prostate cancer and recommended that "men aged 40 and over should have a simple exam each year." Patients with abnormal examinations had a PSA determination. A letter from the corporation states that the "success of PCAW speaks for itself. In 1989, approximately 15 000 men were screened at 91 locations. In 1990, 150000 men were tested at 750 locations. (In 1991) the growth of the program continued when 1500 locations provided free screenings for 400 000 men" (Keith Patterson, May 4, 1992, written communication). In 1992, PCAW will expand to 2 weeks and will include a public relations campaign designed by a professional firm. As the results of Johansson et al demonstrate, the fact that an increasing number of men have been screened for prostate cancer does not confirm the medical success of the program or prove its desirability. Success should be measured in im¬ provement of health outcomes rather than the number of patients screened. There has never been a randomized con¬ trolled trial of screening and treatment for prostate cancer, which could address biases such as lead time and length of time inherent in other study designs. This explains why initial enthusiasm for prostate cancer screening has given way to concern regarding unproven benefits and unwarranted costs. The first-year cost in the United States to screen and treat son
.
."
.
.
Downloaded From: http://jama.jamanetwork.com/ by a University of Pennsylvania User on 06/15/2015
.
.
.
between 50 and 70 years of age for prostate cancer is estimated to range from $3.8 billion to $23.6 billion. This represents greater than 0.06% to 5% of the health care bud¬ get.5 We are concerned that so much effort is spent encour¬ aging mass screening for prostate cancer with its attendant increasing technology, complexity, and cost, rather than to develop controlled clinical trials to scientifically evaluate screening practices. The PCAW and the JAMA Editorial put unwarranted pressure on physicians to adopt unproven screen¬ men
ing strategies.
Timothy J. Wilt, MD, MPH Anne M. Joseph, MD, MPH Kristine E. Enstud, MD, MPH University of Minnesota Minneapolis 1. Johansson J-E, Adami H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 2. Oesterling JE. Prostate-specific antigen: improving its ability to diagnose early
prostate cancer. JAMA. 1992;267:2236-2237. 3. Hayward RSS, Steinberg EP, Ford DE, Roizen MF, Roach KW. Preventive care guidelines: 1991. Ann Intern Med. 1991;114:758-783. 4. Canadian Task Force on the Periodic Health Examination. Periodic health examination, 1991 update: secondary prevention of prostate cancer. Can Med Assoc J.
1991;145:413-428. Optenberg SA, Thompson IM. Economics of screening for carcinoma of the pros1990;17:719-737.
5.
tate. Urol Clin Noth Am.
Reply.\p=m-\Theabove Letters to the Editor touch on many important issues that I will address in the following comIn
ments.
The tate
prevalence of incidental, clinically insignificant prosis undoubtedly quite high; the overall estimated
cancer
value for men 50 years of age or older is 30% to 40%.1 These are microscopic lesions that most physicians would argue are not of clinical importance, and thus, do not need to be identified or treated. However, neither PSA testing, DRE, nor transrectal ultrasonography (TRUS) possess the sensitivity to detect such small, clinically insignificant lesions. Depending on the series, 38% to 45% of patients with organ-confined prostate cancer\p=m-\theideal candidates for definitive treatment and the most likely ones to be cured\p=m-\havea serum PSA value within the reference range.2 Thus, with such low sensitivity, it is unlikely that the routine use of PSA testing will increase our detection rate of these microscopic cancers that are of no biological significance to the patient. It is also true that the medical community has not estab¬ lished, in a definitive manner, that screening for prostate cancer will result in a decreased mortality rate for this dis¬ ease. Although the National Cancer Institute has recently initiated a 16-year, multicenter, randomized, controlled study to address this specific issue, the results are still many years away. While we are waiting, many productive men of our society with potentially curable prostate cancer will die of this disease unless we use PSA testing, DRE, and TRUS in a prudent fashion. Several prostate cancer screening studies, involving thousands of patients, have now demonstrated that the routine use of PSA testing can increase significantly the detection rate of prostate cancer.3·4 These studies also have clearly indicated that PSA testing can identify malignancies not detectable by DRE or TRUS. Prostate-specific antigen, however, is not perfect; some cancers detectable by DRE are not identifiable by PSA. Thus, based on all data available to date, the most complete evaluation of the prostate gland is achieved through the combined use of DRE and PSA testing. While DRE may be subjective and varies significantly from one examiner to the next, PSA testing is simple, readily accepted by the patient, and represents a reproducible, ob¬ jective evaluation. Who then should be subjected to this combined approach of DRE and PSA testing for evaluating the prostate gland?
For all physicians engaged in the care of men at risk for developing prostate cancer and interested in diagnosing pros¬ tate cancer at an early, potentially curable stage, I would suggest the guidelines proposed by the American Urological Association.5 It is the opinion of this national organization that all
men
50 years of age
or
older be evaluated
by
a
physician for the early detection of prostate cancer using both a serum PSA determination and DRE. This approach would be most applicable to those men with a life expectancy of 10 years or more. For patients with a family history of prostate
cancer, this evaluation should be started at the age of 40 years. Transrectal ultrasonography should be used to further assess the prostate gland only in those individuals with an abnormal DRE or an elevated serum PSA level. Since there are no curative treatments for advanced prostate cancer, it is only through a committed effort for early diagnosis, such as this, that we will be able to truly decrease the mortality rate from prostate cancer.
Joseph E. Oesterling, Mayo Clinic
MD
Rochester, Minn
1. Scardino PT. Early detection of prostate cancer. Urol Clin North Am. 1989;16: 635-655. 2. Oesterling JE. Prostate-specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907-923. 3. Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991;324:1156\x=req-\ 1161. 4. Brawer MK, Chetner MP, Beatie J, Buchner DM, Vesselia AL, Lange PH. Screening for prostatic carcinoma with prostate-specific antigen. J Urol. 1992;147:
841-845. 5. American Urological Association Policy Statement. Early detection of prostate cancer and use of transrectal ultrasound. In: American Urological Association 1992 Policy Statement Book. Baltimore, Md: American Urological Association; 1992:4.20.
In Reply.\p=m-\Weare well aware that our results challenge the value of a surgical procedure that many think is the treatment of choice, and that they are thus controversial. Dr Catalona is eager to explain away the fact that we traced every incident case of the disease in a strictly defined area and subjected them to complete, extensive, and standardized long-term follow-up, which included measurements of serum acid phosphatase. He also fails to recognize that experimental methods need proper scientific assessment in clinical trials before they are implemented in general practice. The present article and a previous one1 show unequivocally that age at diagnosis is not an important determinant in our population of disease progression and death in prostate cancer. The age mix of the patients is therefore not an issue; individuals are followed until they die from intercurrent diseases and cannot further influence estimates of progression, relative survival, corrected survival, or hazard rates. Catalona is also preoccupied with subgroups other than those defined by age. To accommodate him, we analyzed and presented our data in such detail that inferences can be drawn, according to age, stage, and grade. Catalona's claims about nonrepresentativeness due to inclusion of TO cases are con¬ tradicted by the similar hazard rates in TO, Tl, and T2 tumors after adjustment for grade. They are further contradicted by the similar death rates from prostatic cancer in the entire study cohort and in the subcohort who met current suggested indications for radical prostatectomy. Catalona's extensive comparison of figures from our study with a personal series of his own tells us nothing about the natural course of prostate cancer or possible therapeutic ben¬ efit of operation among his patients. His demand for "formal testing" of the external validity of the results obtained in our population-based study is therefore somewhat surprising. Finally, the claim that patients with more advanced disease are selected for surgery at some centers has no relevance to
Downloaded From: http://jama.jamanetwork.com/ by a University of Pennsylvania User on 06/15/2015
Oesterling JE. Prostate-specific antigen: improving the ability to diagnose early
prostate
cancer.
JAMA. 1992;267:2236-2238.
2. Hinman F Jr. Screening for prostatic carcinoma. J Urol. 1991;145:126. 3. Nomura AM, Koloveil N. Prostate cancer: a current perspective. Am J Epidemiol.
The other corroborative studies cited by Johansson et al also suffer from the same patient selection bias, yet all show substantial prostate cancer progression rates. The inescap¬ able conclusion from these studies is that, given time, pros¬ tate cancer progresses—slowly in low-grade tumors and rap¬ idly in high-grade tumors. The results of the study by Johansson et al cannot be "generalized to patients with early-stage disease in other populations" without first formally testing their hypothesis. It does not seem prudent to withhold potentially curative therapy from younger patients and those with higher grade tumors until equivalent results of expectant management have been demonstrated in a representative patient population.
Catalona, MD Washington University William J.
1991;13:205.
H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 5. Optenberg S, Thompson IM. Economics of screening for carcinoma of the pros-
St Louis, Mo
4. Johansson J-E, Adami
tate. Urol Clin North Am.
1990;17:719-737.
To the Editor.\p=m-\Thestudy by Johansson et al1 is of limited relevance because their selection criteria resulted in a study group that is not representative of the patient population with early prostate cancer. Their study group included an inordinately high proportion of men over the age of 75 years, most of whom had low-grade tumors too small to be detected on rectal examination. Nearly half of the tumors were discovered at the time of an operation for presumed benign hyperplasia. Because such tumors progress slowly and most patients were elderly to begin with, it is not surprising that most patients died of other causes. The patient selection process was a self-fulfilling prophesy. During the first 2 years of their study, only patients with grade 1 tumors were accepted for the untreated group, which enriched the group with low-grade tumors. During the last 5 years, some patients under the age of 75 years with grade 2 or 3 tumors were excluded from the untreated group, which selectively eliminated some of the high-risk patients. All men over 75 years of age were assigned to the untreated group, which enriched the group with elderly men more likely to die of other causes. The selection process resulted in a patient group that differed dramatically from my personal series of radical prostatectomy patients as illustrated below. In the study by Johansson et al, 48% (106/223) of the men had stage TO prostate cancer, which by definition cannot be detected on rectal examination. By comparison, in my per¬ sonal radical prostatectomy series, only 18% (128/700) had this stage of disease. In the study by Johansson et al, 66% (148/223) had grade 1 tumors as compared with 23% (158/700) in my radical prostatectomy series. In the study by Johansson et al, 62% (138/223) of men were over the age of 70 years and 17% (38/223) were over 80 years. The mean age at diagnosis was 72 years. By comparison, in my series, only 27% (189/700) were over the age of 70 years, 3% (20/700) were over 75 years, and their mean age was 64 years. In the study by Johansson et al, only 8.5% of patients died of prostate cancer within 10 years. In contrast, in a recent study2 in which patients with the same stages of cancer were treated with radiation therapy, the cancer death rate was 15% with a mean follow-up of only 7.3 years (actuarial pro¬ jection, 20% ±7% at 10 years). The conclusion by Johansson et al that 91.5% of patients with early prostate cancer need not worry about dying from the disease is not generally valid. In this regard, 348 (53%) of the 654 new cancer patients diagnosed during the study by Johansson et al had advanced cancer at the time of diagnosis. Certainly, each of these men once had an early cancer that did progress, and what are their future prospects?
H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 2. Lerner SP, Seale-Hawkins C, Carlton CE Jr, Scardino PT. The risk of dying of prostate cancer in patients with clinically localized disease. J Urol. 1991;146:1040\x=req-\ 1045. 1. Johansson J-E, Adami
To the Editor.\p=m-\Weread with interest the article by Johanset al1 and the Editorial by Oesterling2 regarding screening and treatment for prostate cancer. We agree with Johansson et al "that without evidence of benefit from controlled clinical trials, the radical treatment of early-stage prostate cancer remains in its experimental phase." We disagree with the editorial statement by Oesterling that recommends "a serum . PSA concentration and . DRE. If both are normal, the patient should be followed with annual evaluations [his italics]. This statement is not convincingly supported by the medical literature or the majority of expert panel recommendations.3,4 Such an editorial position is of particular concern because an ongoing national prostate cancer screening program, organized and sponsored by a pharmaceutical corporation, also pressures physicians to adopt screening strategies of unproven benefit. The Schering Corporation, manufacturer of flutamide, has sponsored National Prostate Cancer Awareness Week (PCAW) for the past 3 years. Signs posted in our hospital primary care areas said, "Take a minute to have a free pros¬ tate examination. It could be worth your life." The posters announced that medical centers nationwide were offering rectal examinations for early detection and successful treat¬ ment of prostate cancer and recommended that "men aged 40 and over should have a simple exam each year." Patients with abnormal examinations had a PSA determination. A letter from the corporation states that the "success of PCAW speaks for itself. In 1989, approximately 15 000 men were screened at 91 locations. In 1990, 150000 men were tested at 750 locations. (In 1991) the growth of the program continued when 1500 locations provided free screenings for 400 000 men" (Keith Patterson, May 4, 1992, written communication). In 1992, PCAW will expand to 2 weeks and will include a public relations campaign designed by a professional firm. As the results of Johansson et al demonstrate, the fact that an increasing number of men have been screened for prostate cancer does not confirm the medical success of the program or prove its desirability. Success should be measured in im¬ provement of health outcomes rather than the number of patients screened. There has never been a randomized con¬ trolled trial of screening and treatment for prostate cancer, which could address biases such as lead time and length of time inherent in other study designs. This explains why initial enthusiasm for prostate cancer screening has given way to concern regarding unproven benefits and unwarranted costs. The first-year cost in the United States to screen and treat son
.
."
.
.
Downloaded From: http://jama.jamanetwork.com/ by a University of Pennsylvania User on 06/15/2015
.
.
.
between 50 and 70 years of age for prostate cancer is estimated to range from $3.8 billion to $23.6 billion. This represents greater than 0.06% to 5% of the health care bud¬ get.5 We are concerned that so much effort is spent encour¬ aging mass screening for prostate cancer with its attendant increasing technology, complexity, and cost, rather than to develop controlled clinical trials to scientifically evaluate screening practices. The PCAW and the JAMA Editorial put unwarranted pressure on physicians to adopt unproven screen¬ men
ing strategies.
Timothy J. Wilt, MD, MPH Anne M. Joseph, MD, MPH Kristine E. Enstud, MD, MPH University of Minnesota Minneapolis 1. Johansson J-E, Adami H-O, Andersson S-E, Bergstr\l=o"\mR, Holmberg L, Krusemo UB. High 10-year survival rate in patients with early, untreated prostatic cancer. JAMA. 1992;267:2191-2196. 2. Oesterling JE. Prostate-specific antigen: improving its ability to diagnose early
prostate cancer. JAMA. 1992;267:2236-2237. 3. Hayward RSS, Steinberg EP, Ford DE, Roizen MF, Roach KW. Preventive care guidelines: 1991. Ann Intern Med. 1991;114:758-783. 4. Canadian Task Force on the Periodic Health Examination. Periodic health examination, 1991 update: secondary prevention of prostate cancer. Can Med Assoc J.
1991;145:413-428. Optenberg SA, Thompson IM. Economics of screening for carcinoma of the pros1990;17:719-737.
5.
tate. Urol Clin Noth Am.
Reply.\p=m-\Theabove Letters to the Editor touch on many important issues that I will address in the following comIn
ments.
The tate
prevalence of incidental, clinically insignificant prosis undoubtedly quite high; the overall estimated
cancer
value for men 50 years of age or older is 30% to 40%.1 These are microscopic lesions that most physicians would argue are not of clinical importance, and thus, do not need to be identified or treated. However, neither PSA testing, DRE, nor transrectal ultrasonography (TRUS) possess the sensitivity to detect such small, clinically insignificant lesions. Depending on the series, 38% to 45% of patients with organ-confined prostate cancer\p=m-\theideal candidates for definitive treatment and the most likely ones to be cured\p=m-\havea serum PSA value within the reference range.2 Thus, with such low sensitivity, it is unlikely that the routine use of PSA testing will increase our detection rate of these microscopic cancers that are of no biological significance to the patient. It is also true that the medical community has not estab¬ lished, in a definitive manner, that screening for prostate cancer will result in a decreased mortality rate for this dis¬ ease. Although the National Cancer Institute has recently initiated a 16-year, multicenter, randomized, controlled study to address this specific issue, the results are still many years away. While we are waiting, many productive men of our society with potentially curable prostate cancer will die of this disease unless we use PSA testing, DRE, and TRUS in a prudent fashion. Several prostate cancer screening studies, involving thousands of patients, have now demonstrated that the routine use of PSA testing can increase significantly the detection rate of prostate cancer.3·4 These studies also have clearly indicated that PSA testing can identify malignancies not detectable by DRE or TRUS. Prostate-specific antigen, however, is not perfect; some cancers detectable by DRE are not identifiable by PSA. Thus, based on all data available to date, the most complete evaluation of the prostate gland is achieved through the combined use of DRE and PSA testing. While DRE may be subjective and varies significantly from one examiner to the next, PSA testing is simple, readily accepted by the patient, and represents a reproducible, ob¬ jective evaluation. Who then should be subjected to this combined approach of DRE and PSA testing for evaluating the prostate gland?
For all physicians engaged in the care of men at risk for developing prostate cancer and interested in diagnosing pros¬ tate cancer at an early, potentially curable stage, I would suggest the guidelines proposed by the American Urological Association.5 It is the opinion of this national organization that all
men
50 years of age
or
older be evaluated
by
a
physician for the early detection of prostate cancer using both a serum PSA determination and DRE. This approach would be most applicable to those men with a life expectancy of 10 years or more. For patients with a family history of prostate
cancer, this evaluation should be started at the age of 40 years. Transrectal ultrasonography should be used to further assess the prostate gland only in those individuals with an abnormal DRE or an elevated serum PSA level. Since there are no curative treatments for advanced prostate cancer, it is only through a committed effort for early diagnosis, such as this, that we will be able to truly decrease the mortality rate from prostate cancer.
Joseph E. Oesterling, Mayo Clinic
MD
Rochester, Minn
1. Scardino PT. Early detection of prostate cancer. Urol Clin North Am. 1989;16: 635-655. 2. Oesterling JE. Prostate-specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145:907-923. 3. Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med. 1991;324:1156\x=req-\ 1161. 4. Brawer MK, Chetner MP, Beatie J, Buchner DM, Vesselia AL, Lange PH. Screening for prostatic carcinoma with prostate-specific antigen. J Urol. 1992;147:
841-845. 5. American Urological Association Policy Statement. Early detection of prostate cancer and use of transrectal ultrasound. In: American Urological Association 1992 Policy Statement Book. Baltimore, Md: American Urological Association; 1992:4.20.
In Reply.\p=m-\Weare well aware that our results challenge the value of a surgical procedure that many think is the treatment of choice, and that they are thus controversial. Dr Catalona is eager to explain away the fact that we traced every incident case of the disease in a strictly defined area and subjected them to complete, extensive, and standardized long-term follow-up, which included measurements of serum acid phosphatase. He also fails to recognize that experimental methods need proper scientific assessment in clinical trials before they are implemented in general practice. The present article and a previous one1 show unequivocally that age at diagnosis is not an important determinant in our population of disease progression and death in prostate cancer. The age mix of the patients is therefore not an issue; individuals are followed until they die from intercurrent diseases and cannot further influence estimates of progression, relative survival, corrected survival, or hazard rates. Catalona is also preoccupied with subgroups other than those defined by age. To accommodate him, we analyzed and presented our data in such detail that inferences can be drawn, according to age, stage, and grade. Catalona's claims about nonrepresentativeness due to inclusion of TO cases are con¬ tradicted by the similar hazard rates in TO, Tl, and T2 tumors after adjustment for grade. They are further contradicted by the similar death rates from prostatic cancer in the entire study cohort and in the subcohort who met current suggested indications for radical prostatectomy. Catalona's extensive comparison of figures from our study with a personal series of his own tells us nothing about the natural course of prostate cancer or possible therapeutic ben¬ efit of operation among his patients. His demand for "formal testing" of the external validity of the results obtained in our population-based study is therefore somewhat surprising. Finally, the claim that patients with more advanced disease are selected for surgery at some centers has no relevance to
Downloaded From: http://jama.jamanetwork.com/ by a University of Pennsylvania User on 06/15/2015
