VOLUME
䡠
33
NUMBER
9
䡠
MARCH
20
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Mortality in Older Men With Low-Risk Prostate Cancer and High Comorbidity TO THE EDITOR: In their recent article in Journal of Clinical Oncology, Prasad et al1 conclude that there is a need to “ameliorate the decreased survival following a prostate cancer diagnosis in the depressed male patient,” based on the claim that their study shows that “preexisting diagnosis of depressive disorder is independently associated with treatment choice and outcomes of localized prostate can-
A
B P 1.3 (0.6 to 2.4)
Low Risk
1.4 (0.1 to 6.7)
Age < 65 years CCI 0 CCI 1 CCI 2+
P 8.2 (6.3 to 10.3) 29.5 (17.4 to 42.7) < .001 36.8 (24.5 to 49.2)
Age 65-75 years CCI 0 CCI 1 CCI 2+
19.0 (17.0 to 21.1) 36.5 (30.1 to 42.9) < .001 46.9 (38.8 to 54.5)
4.3 (3.3 to 5.4) 6.2 (3.4 to 10.1) .321 4.3 (1.9 to 8.4)
Age > 75 years CCI 0 CCI 1 CCI 2+
6.6 (4.9 to 8.6) 9.8 (5.8 to 15.0) .255 6.8 (3.5 to 11.8)
Age > 75 years CCI 0 CCI 1 CCI 2+
49.6 (45.8 to 53.4) 62.4 (53.9 to 69.8) < .001 77.1 (69.3 to 83.2)
Age < 65 years CCI 0 CCI 1 CCI 2+
8.3 (5.1 to 12.6) 7.3 (1.3 to 20.8) .956 8.7 (1.5 to 24.0)
Age < 65 years CCI 0 CCI 1 CCI 2+
9.2 (5.9 to 13.2) 45.9 (26.4 to 63.4) < .001 62.2 (40.1 to 78.1)
Age 65-75 years CCI 0 CCI 1 CCI 2+
27.3 (25.0 to 29.6) 43.5 (37.0 to 49.7) < .001 52.6 (44.7 to 59.8)
Age > 75 years CCI 0 CCI 1 CCI 2+
50.8 (48.0 to 53.4) 64.7 (59.1 to 69.7) < .001 74.5 (69.1 to 79.1)
Age < 65 years CCI 0 CCI 1 CCI 2+
13.9 (9.7 to 18.7) 21.2 (7.7 to 39.1) < .001 49.3 (28.0 to 67.5)
Age 65-75 years CCI 0 CCI 1 CCI 2+
28.2 (26.2 to 30.3) 44.7 (39.2 to 50.0) < .001 57.1 (50.4 to 63.3)
Age > 75 years CCI 0 CCI 1 CCI 2+
48.0 (46.2 to 49.8) 60.6 (56.9 to 64.1) < .001 69.6 (66.0 to 73.0)
Age 65-75 years CCI 0 CCI 1 CCI 2+
12.1 (10.4 to 13.8) 10.8 (7.2 to 15.2) .866 9.9 (5.9 to 15.1)
Age > 75 years CCI 0 CCI 1 CCI 2+
15.6 (13.7 to 17.6) 14.5 (10.8 to 18.7) .811 11.7 (8.3 to 15.8)
Age < 65 years CCI 0 CCI 1 CCI 2+
32.7 (26.9 to 38.7) 21.8 (7.9 to 40.0) .342 27.6 (9.7 to 49.2)
Age 65-75 years CCI 0 CCI 1 CCI 2+
29.4 (27.3 to 31.5) 23.0 (18.6 to 27.7) .102 21.8 (16.7 to 27.3)
Age > 75 years CCI 0 CCI 1 CCI 2+
31.2 (29.6 to 32.9) 27.4 (24.2 to 30.7) .178 23.1 (20.0 to 26.4) 0
20
40
60
80
100
Cumulative Probability of Death From Prostate Cancer (%)
Intermediate Risk
Age 65-75 years CCI 0 CCI 1 CCI 2+
High Risk
Intermediate Risk
Low Risk
Age < 65 years CCI 0 CCI 1 CCI 2+
High Risk
cer.” Few physicians would object to this conclusion; however, there are absolutely no results in the report by Prasad et al in support of this claim, because no data on death resulting from prostate cancer are presented. In their study, Prasad et al1 make use of SEER data, and they investigate all-cause mortality in men age ⬎ 67 years diagnosed with prostate cancer from 2004 to 2007 and observed until end of 2009 (ie, maximum of 5-year follow-up). Many men with depression were age ⬎ 75 years (48%), and 24% had a Charlson comorbidity index ⱖ 2. In terms of National Comprehensive Cancer Network risk category, there were 10,860 men (28%) with low-risk cancer, 17,105
0
20
40
60
80
100
Cumulative Probability of Death From Other Causes (%)
Fig 1. Cumulative 10-year mortality resulting from prostate cancer and other causes (95% CIs) by risk category, age, and Charlson comorbidity index (CCI). Estimates are based on men in National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009.3 Capture of NPCR is 98% of all incident cases of prostate cancer in Swedish Cancer Register, in which registration is mandatory and regulated by law.4 1086
© 2015 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 9 (March 20), 2015: pp 1086-1087
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Correspondence
(44%) with intermediate-risk cancer, and 11,416 (28%) with high-risk cancer, and the median serum level of prostate-specific antigen was 7 ng/mL, confirming that this was a group with localized prostate cancer. Expectant management was slightly more frequent in men with depression (32%) than in men without (24%). The highest risk of death in depressed men, compared with men without depression, was observed for those with low-risk cancer (relative risk [RR], 1.86), followed by those with intermediate-risk cancer (RR, 1.25) and high-risk cancer (RR, 1.16). The difference in mortality was observed after just 2 years in men with low-risk cancer, but not in men with high-risk cancer. On the basis of previous knowledge on outcomes in localized prostate cancer, how likely is it that prostate cancer was the cause of death among these depressed men, particularly those with low-risk cancer? Because the 5-year relative survival in men with low-risk prostate cancer is virtually 100%,2 it is extremely unlikely that few if any of these men died as a result of prostate cancer; even among men with intermediate-risk cancer, it is unlikely that death was caused by prostate cancer, because follow-up was merely ⱕ 5 years. The fact that the difference in mortality was highest for low-risk cancer further supports the probability that non–prostate cancer death was the most common cause. What is known about causes of death among older men with prostate cancer? In a study from the National Prostate Cancer Register of Sweden based on a total of 117,328 men diagnosed from 1991 to 2009, of whom 26,410 had low-risk prostate cancer, the cumulative probability of death resulting from prostate cancer and other causes was investigated using competing-risk analysis.3 In men age ⱖ 75 years with low-risk cancer and Charlson comorbidity index ⱖ 2 treated expectantly, 10-year prostate cancer mortality was 7% (95% CI, 4% to 12%), and other-cause mortality was 77% (95% CI, 69% to 83%; Fig 1). In light of these data,2,3 it is suggested that a more appropriate interpretation of the results is that the increased risk of death was the result of causes other than prostate cancer. Consequently, the increased risk of death among the depressed men should not be taken as an indication for more aggressive cancer treatment but rather that less aggressive treatment would be indicated. In these elderly men with prostate cancer, of whom a large proportion were age ⬎ 75 years, and
many of whom had several comorbidities, expectant management should have been the treatment of choice for the majority of low- and intermediate-risk cancers; however, only 5,100 (19%) of 27,000 men in these risk categories received expectant management. From a general perspective, these depressed men should have received more intense medical attention from their family physician. In conclusion, in their article, Prasad et al1 point out that “clinical needs, preferences and appropriateness of intervention” should guide treatment selection, and although perhaps for the wrong reasons, a slightly higher proportion of depressed men than nondepressed men in fact received expectant management, the most appropriate treatment option for low- and intermediate-risk cancers in older men with high comorbidity. A higher use of conservative management strategies (ie, expectant management in older men and active surveillance in younger men) is warranted for low-risk prostate cancer.5
Pär Stattin Umea˚ University, Umea˚, Sweden
ACKNOWLEDGMENT
Supported by Swedish Research Council Grant No. 2010-5950. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the author are available with this article at www.jco.org. REFERENCES 1. Prasad SM, Eggener SE, Lipsitz SR, et al: Effect of depression on diagnosis, treatment, and mortality of men with clinically localized prostate cancer. J Clin Oncol 32:2471-2478, 2014 2. National Cancer Institute: SEER Stat Fact Sheets: Prostate Cancer. http:// seer.cancer.gov/statfacts/html/prost.html 3. Rider JR, Sandin F, Andrén O, et al: Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol 63:88-96, 2013 4. Tomic K, Berglund A, Robinson D, et al: Capture rate and representativity of the National Prostate Cancer Register of Sweden. Acta Oncol 18:1-6, 2014 5. Hayes JH, Ollendorf DA, Pearson SD, et al: Observation versus initial treatment for men with localized, low-risk prostate cancer: A cost-effectiveness analysis. Ann Intern Med 158:853-860, 2013
DOI: 10.1200/JCO.2014.58.2536; published online ahead of print at www.jco.org on February 2, 2015
■ ■ ■
www.jco.org
© 2015 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1087
Correspondence
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Mortality in Older Men With Low-Risk Prostate Cancer and High Comorbidity The following represents disclosure information provided by author of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Pär Stattin Consulting or Advisory Role: Ferring
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
䡠
33
NUMBER
9
䡠
MARCH
20
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Mortality in Older Men With Low-Risk Prostate Cancer and High Comorbidity TO THE EDITOR: In their recent article in Journal of Clinical Oncology, Prasad et al1 conclude that there is a need to “ameliorate the decreased survival following a prostate cancer diagnosis in the depressed male patient,” based on the claim that their study shows that “preexisting diagnosis of depressive disorder is independently associated with treatment choice and outcomes of localized prostate can-
A
B P 1.3 (0.6 to 2.4)
Low Risk
1.4 (0.1 to 6.7)
Age < 65 years CCI 0 CCI 1 CCI 2+
P 8.2 (6.3 to 10.3) 29.5 (17.4 to 42.7) < .001 36.8 (24.5 to 49.2)
Age 65-75 years CCI 0 CCI 1 CCI 2+
19.0 (17.0 to 21.1) 36.5 (30.1 to 42.9) < .001 46.9 (38.8 to 54.5)
4.3 (3.3 to 5.4) 6.2 (3.4 to 10.1) .321 4.3 (1.9 to 8.4)
Age > 75 years CCI 0 CCI 1 CCI 2+
6.6 (4.9 to 8.6) 9.8 (5.8 to 15.0) .255 6.8 (3.5 to 11.8)
Age > 75 years CCI 0 CCI 1 CCI 2+
49.6 (45.8 to 53.4) 62.4 (53.9 to 69.8) < .001 77.1 (69.3 to 83.2)
Age < 65 years CCI 0 CCI 1 CCI 2+
8.3 (5.1 to 12.6) 7.3 (1.3 to 20.8) .956 8.7 (1.5 to 24.0)
Age < 65 years CCI 0 CCI 1 CCI 2+
9.2 (5.9 to 13.2) 45.9 (26.4 to 63.4) < .001 62.2 (40.1 to 78.1)
Age 65-75 years CCI 0 CCI 1 CCI 2+
27.3 (25.0 to 29.6) 43.5 (37.0 to 49.7) < .001 52.6 (44.7 to 59.8)
Age > 75 years CCI 0 CCI 1 CCI 2+
50.8 (48.0 to 53.4) 64.7 (59.1 to 69.7) < .001 74.5 (69.1 to 79.1)
Age < 65 years CCI 0 CCI 1 CCI 2+
13.9 (9.7 to 18.7) 21.2 (7.7 to 39.1) < .001 49.3 (28.0 to 67.5)
Age 65-75 years CCI 0 CCI 1 CCI 2+
28.2 (26.2 to 30.3) 44.7 (39.2 to 50.0) < .001 57.1 (50.4 to 63.3)
Age > 75 years CCI 0 CCI 1 CCI 2+
48.0 (46.2 to 49.8) 60.6 (56.9 to 64.1) < .001 69.6 (66.0 to 73.0)
Age 65-75 years CCI 0 CCI 1 CCI 2+
12.1 (10.4 to 13.8) 10.8 (7.2 to 15.2) .866 9.9 (5.9 to 15.1)
Age > 75 years CCI 0 CCI 1 CCI 2+
15.6 (13.7 to 17.6) 14.5 (10.8 to 18.7) .811 11.7 (8.3 to 15.8)
Age < 65 years CCI 0 CCI 1 CCI 2+
32.7 (26.9 to 38.7) 21.8 (7.9 to 40.0) .342 27.6 (9.7 to 49.2)
Age 65-75 years CCI 0 CCI 1 CCI 2+
29.4 (27.3 to 31.5) 23.0 (18.6 to 27.7) .102 21.8 (16.7 to 27.3)
Age > 75 years CCI 0 CCI 1 CCI 2+
31.2 (29.6 to 32.9) 27.4 (24.2 to 30.7) .178 23.1 (20.0 to 26.4) 0
20
40
60
80
100
Cumulative Probability of Death From Prostate Cancer (%)
Intermediate Risk
Age 65-75 years CCI 0 CCI 1 CCI 2+
High Risk
Intermediate Risk
Low Risk
Age < 65 years CCI 0 CCI 1 CCI 2+
High Risk
cer.” Few physicians would object to this conclusion; however, there are absolutely no results in the report by Prasad et al in support of this claim, because no data on death resulting from prostate cancer are presented. In their study, Prasad et al1 make use of SEER data, and they investigate all-cause mortality in men age ⬎ 67 years diagnosed with prostate cancer from 2004 to 2007 and observed until end of 2009 (ie, maximum of 5-year follow-up). Many men with depression were age ⬎ 75 years (48%), and 24% had a Charlson comorbidity index ⱖ 2. In terms of National Comprehensive Cancer Network risk category, there were 10,860 men (28%) with low-risk cancer, 17,105
0
20
40
60
80
100
Cumulative Probability of Death From Other Causes (%)
Fig 1. Cumulative 10-year mortality resulting from prostate cancer and other causes (95% CIs) by risk category, age, and Charlson comorbidity index (CCI). Estimates are based on men in National Prostate Cancer Register (NPCR) of Sweden diagnosed from 1991 through 2009.3 Capture of NPCR is 98% of all incident cases of prostate cancer in Swedish Cancer Register, in which registration is mandatory and regulated by law.4 1086
© 2015 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 9 (March 20), 2015: pp 1086-1087
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Correspondence
(44%) with intermediate-risk cancer, and 11,416 (28%) with high-risk cancer, and the median serum level of prostate-specific antigen was 7 ng/mL, confirming that this was a group with localized prostate cancer. Expectant management was slightly more frequent in men with depression (32%) than in men without (24%). The highest risk of death in depressed men, compared with men without depression, was observed for those with low-risk cancer (relative risk [RR], 1.86), followed by those with intermediate-risk cancer (RR, 1.25) and high-risk cancer (RR, 1.16). The difference in mortality was observed after just 2 years in men with low-risk cancer, but not in men with high-risk cancer. On the basis of previous knowledge on outcomes in localized prostate cancer, how likely is it that prostate cancer was the cause of death among these depressed men, particularly those with low-risk cancer? Because the 5-year relative survival in men with low-risk prostate cancer is virtually 100%,2 it is extremely unlikely that few if any of these men died as a result of prostate cancer; even among men with intermediate-risk cancer, it is unlikely that death was caused by prostate cancer, because follow-up was merely ⱕ 5 years. The fact that the difference in mortality was highest for low-risk cancer further supports the probability that non–prostate cancer death was the most common cause. What is known about causes of death among older men with prostate cancer? In a study from the National Prostate Cancer Register of Sweden based on a total of 117,328 men diagnosed from 1991 to 2009, of whom 26,410 had low-risk prostate cancer, the cumulative probability of death resulting from prostate cancer and other causes was investigated using competing-risk analysis.3 In men age ⱖ 75 years with low-risk cancer and Charlson comorbidity index ⱖ 2 treated expectantly, 10-year prostate cancer mortality was 7% (95% CI, 4% to 12%), and other-cause mortality was 77% (95% CI, 69% to 83%; Fig 1). In light of these data,2,3 it is suggested that a more appropriate interpretation of the results is that the increased risk of death was the result of causes other than prostate cancer. Consequently, the increased risk of death among the depressed men should not be taken as an indication for more aggressive cancer treatment but rather that less aggressive treatment would be indicated. In these elderly men with prostate cancer, of whom a large proportion were age ⬎ 75 years, and
many of whom had several comorbidities, expectant management should have been the treatment of choice for the majority of low- and intermediate-risk cancers; however, only 5,100 (19%) of 27,000 men in these risk categories received expectant management. From a general perspective, these depressed men should have received more intense medical attention from their family physician. In conclusion, in their article, Prasad et al1 point out that “clinical needs, preferences and appropriateness of intervention” should guide treatment selection, and although perhaps for the wrong reasons, a slightly higher proportion of depressed men than nondepressed men in fact received expectant management, the most appropriate treatment option for low- and intermediate-risk cancers in older men with high comorbidity. A higher use of conservative management strategies (ie, expectant management in older men and active surveillance in younger men) is warranted for low-risk prostate cancer.5
Pär Stattin Umea˚ University, Umea˚, Sweden
ACKNOWLEDGMENT
Supported by Swedish Research Council Grant No. 2010-5950. AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the author are available with this article at www.jco.org. REFERENCES 1. Prasad SM, Eggener SE, Lipsitz SR, et al: Effect of depression on diagnosis, treatment, and mortality of men with clinically localized prostate cancer. J Clin Oncol 32:2471-2478, 2014 2. National Cancer Institute: SEER Stat Fact Sheets: Prostate Cancer. http:// seer.cancer.gov/statfacts/html/prost.html 3. Rider JR, Sandin F, Andrén O, et al: Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol 63:88-96, 2013 4. Tomic K, Berglund A, Robinson D, et al: Capture rate and representativity of the National Prostate Cancer Register of Sweden. Acta Oncol 18:1-6, 2014 5. Hayes JH, Ollendorf DA, Pearson SD, et al: Observation versus initial treatment for men with localized, low-risk prostate cancer: A cost-effectiveness analysis. Ann Intern Med 158:853-860, 2013
DOI: 10.1200/JCO.2014.58.2536; published online ahead of print at www.jco.org on February 2, 2015
■ ■ ■
www.jco.org
© 2015 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
1087
Correspondence
AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Mortality in Older Men With Low-Risk Prostate Cancer and High Comorbidity The following represents disclosure information provided by author of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Pär Stattin Consulting or Advisory Role: Ferring
© 2015 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Rutgers University on August 8, 2015 from 128.6.218.72 Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
