0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S. Population–Based Cohort of Men With Prostate Cancer

Timothy J. Daskivich, MD; Kang-Hsien Fan, MS; Tatsuki Koyama, PhD; Peter C. Albertsen, MD; Michael Goodman, MD, MPH; Ann S. Hamilton, PhD; Richard M. Hoffman, MD, MPH; Janet L. Stanford, PhD, MPH; Antoinette M. Stroup, PhD; Mark S. Litwin, MD, MPH; and David F. Penson, MD, MPH
[+] Article and Author Information

From University of California, Los Angeles, and University of Southern California, Los Angeles, California; Vanderbilt University and Veterans Affairs Tennessee Valley Geriatric Research, Education, and Clinical Center, Nashville, Tennessee; University of Connecticut, Farmington, Connecticut; Emory University, Atlanta, Georgia; University of New Mexico and New Mexico Veterans Affairs Health Care System, Albuquerque, New Mexico; Fred Hutchinson Cancer Center, Seattle, Washington; and University of Utah, Salt Lake City, Utah.

Acknowledgment: The authors thank the men who participated in PCOS who, by their participation, have contributed to a better understanding of the effects of prostate cancer on men's lives; the physicians in the 6 SEER areas who assisted in the collection of data from their patients and from medical records; all of the study managers and chart abstractors for their outstanding efforts in data collection; and all of the staff in the 6 cancer registries for their help with the study.

Grant Support: By grant R01CA114524 from the National Cancer Institute of the National Institutes of Health. Dr. Daskivich is supported by grants from the Robert Wood Johnson Clinical Scholars Foundation, American Cancer Society, and American Urological Association.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-1703.

Reproducible Research Statement: Study protocol: Detailed in the Methods section and available at the discretion of Dr. Penson. Statistical code: Available at the discretion of Dr. Penson. Data set: Restricted to members of the PCOS team and their designates.

Requests for Single Reprints: David F. Penson, MD, MPH, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, TN 37203-1738.

Current Author Addresses: Dr. Daskivich: Robert Wood Johnson Clinical Scholars, University of California, Los Angeles, 7th Floor, Suite 710, 10940 Wilshire Boulevard, Los Angeles, CA 90024.

Mr. Fan and Dr. Koyama: Vanderbilt University, 571 Preston Research Building, Nashville, TN 37232-6848.

Dr. Albertsen: Division of Urology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3955.

Dr. Goodman: Department of Epidemiology, Emory University Rollins School of Public Health, 1518 Clifton Road NE, Atlanta, GA 30322.

Dr. Hamilton: University of Southern California, Health Services Campus, SSB 318E, M/C 9239, Los Angeles, CA 90089-9239.

Dr. Hoffman: Department of Internal Medicine, New Mexico VA Health Care System, General Internal Medicine 111GIM, 1501 San Pedro Drive, SE, Albuquerque, NM 87108.

Dr. Stanford: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Box 358080 M4-B874, 1100 Fairview Avenue North, Building M, PO Box 19024, Mailstop M4-B874, Seattle, WA 98195-1024.

Dr. Stroup: Department of Clinical Epidemiology, University of Utah, Utah Cancer Registry, 650 Komas Drive, Suite 106B, Salt Lake City, UT 84108.

Dr. Litwin: Department of Urology, University of California, Los Angeles, Box 957383, 924 Westwood Boulevard, Suite 1000, Los Angeles, CA 90095-7383.

Dr. Penson: Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, TN 37203-1738.

Author Contributions: Conception and design: T.J. Daskivich, P.C. Albertsen, R.M. Hoffman, J.L. Stanford, A.M. Stroup, M.S. Litwin, D.F. Penson.

Analysis and interpretation of the data: T.J. Daskivich, K.H. Fan, T. Koyama, P.C. Albertsen, J.L. Stanford, A.M. Stroup, M.S. Litwin, D.F. Penson.

Drafting of the article: T.J. Daskivich, T. Koyama, A.M. Stroup, D.F. Penson.

Critical revision of the article for important intellectual content: T.J. Daskivich, T. Koyama, P.C. Albertsen, M. Goodman, A.S. Hamilton, R.M. Hoffman, J.L. Stanford, M.S. Litwin, D.F. Penson.

Final approval of the article: T.J. Daskivich, P.C. Albertsen, M. Goodman, A.S. Hamilton, R.M. Hoffman, J.L. Stanford, A.M. Stroup, M.S. Litwin, D.F. Penson.

Provision of study materials or patients: A.S. Hamilton, J.L. Stanford, A.M. Stroup.

Statistical expertise: K.H. Fan, T. Koyama, M.S. Litwin.

Obtaining of funding: P.C. Albertsen, J.L. Stanford, M.S. Litwin, D.F. Penson.

Administrative, technical, or logistic support: M. Goodman, J.L. Stanford, A.M. Stroup, M.S. Litwin, D.F. Penson.

Collection and assembly of data: P.C. Albertsen, M. Goodman, A.S. Hamilton, R.M. Hoffman, J.L. Stanford, A.M. Stroup, D.F. Penson.


Ann Intern Med. 2013;158(10):709-717. doi:10.7326/0003-4819-158-10-201305210-00005
Text Size: A A A

Chinese translation

Background: Accurate estimation of life expectancy is essential to offering appropriate care to men with early-stage prostate cancer, but mortality risks associated with comorbidity are poorly defined.

Objective: To determine the effect of age, comorbidity, and tumor risk on other-cause and prostate cancer–specific mortality in men with early-stage disease.

Design: Prospective cohort study.

Setting: A nationally representative, population-based cohort.

Patients: 3183 men with nonmetastatic prostate cancer at diagnosis.

Measurements: Baseline self-reported comorbidity (scored as a count of 12 major comorbid conditions), tumor characteristics, initial treatment, and overall and disease-specific mortality through 14 years of follow-up. Survival analyses that accounted for competing risks were performed.

Results: Fourteen-year cumulative other-cause mortality rates were 24%, 33%, 46%, and 57% for men with 0, 1, 2, and 3 or more comorbid conditions, respectively. For men diagnosed at age 65 years, subhazard ratios for other-cause mortality among those with 1, 2, or 3 or more comorbid conditions (vs. none) were 1.2 (95% CI, 1.0 to 1.4), 1.7 (CI, 1.4 to 2.0), and 2.4 (CI, 2.0 to 2.8), respectively. Among men with 3 or more comorbid conditions, 10-year other-cause mortality rates were 26%, 40%, and 71% for those aged 60 years or younger, 61 to 74 years, and 75 years or older at diagnosis, respectively. Prostate cancer–specific mortality was minimal in patients with low-risk (3%) and intermediate-risk (7%) disease but appreciable in those with high-risk disease (18%) and did not vary by number of comorbid conditions (10% to 11% in all groups).

Limitation: Comorbid conditions were self-reported.

Conclusion: Older men with multiple major comorbid conditions are at high risk for other-cause mortality within 10 years of diagnosis and should consider this information when deciding between conservative management and aggressive treatment for low- or intermediate-risk prostate cancer.

Primary Funding Source: National Cancer Institute.

Figures

Grahic Jump Location
Appendix Figure.

Study flow diagram.

PCOS = Prostate Cancer Outcomes Study.

Grahic Jump Location
Grahic Jump Location
Figure 1.

Cumulative incidence curves for other-cause and prostate cancer–specific mortality, by number of comorbid conditions.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Competing-risks model depicting cumulative incidence of other-cause and prostate cancer–specific mortality, by number of comorbid conditions, for men aged <60 y (AandB), 60 to 70 y (CandD), and >70 y (EandF).

Grahic Jump Location
Grahic Jump Location
Figure 3.

Competing-risks model depicting cumulative incidence of other-cause and prostate cancer–specific mortality, by D'Amico risk criteria, for men aged <60 y (AandB), 60 to 70 y (CandD), and >70 y (EandF).

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Comorbidity and competing mortality
Posted on June 4, 2013
Michael Froehner, MD, Rainer Koch, PhD, Manfred P. Wirth, MD
Dresden University of Technology
Conflict of Interest: None Declared

A population-based cohort [1] does not necessarily represent the best mimic of relevant clinical scenarios in men with early prostate cancer awaiting a treatment decision. Population-based cohorts contain sick patients with an over-proportional impact on medium-term survival rates who would immediately be eliminated by selection during clinical decision making. Incorporating comorbidity considerations in counseling patients with early prostate cancer requires knowing the prognostic impact of comorbid conditions in the treatment subgroups the individual patient could qualify for. Compared with this population-based cohort [1], in our radical prostatectomy series (n=2205, treated 1992-2005, mean follow-up 10 years), patients aged 70 years or older had considerably lower 10-year competing mortality rates particularly in the healthier subgroups (conventional Charlson score [2] versus modified Charlson score [1]; class 0: 11 % (95 % confidence interval 6-16 %) versus 35 % [1]; class 1: 21 % (95 % confidence interval 11-31 %) versus 40 % [1]; class 2: 22 % (95 % confidence interval 7-38 %) versus 42 % [1]; class 3 or higher: 42 % (95 % confidence interval 19-65 %) versus 57 % [1]). Particularly at advanced ages, counseling patients who could be candidates for curative treatment of early prostate cancer should be based on the actual competing mortality risk and not on that of an unselected population with a clearly shorter life expectancy.

 


References:

 

1 Daskivich TJ, Fan KH, Koyama T, Albertsen PC, Goodman M, Hamilton AS, et al. Effect of age, tumor risk, and comorbidity on competing risks for survival in a U.S. population–based cohort of men with prostate cancer. Ann Intern Med. 2013;158:709-717.

 

2 Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis. 1987;40:373-383.


Indication for biopsy in aging societies
Posted on June 18, 2013
Masayoshi Nagata, Tetsuya Tanimoto, Masahiro Kami
National Center for Global Health and Medicine, Navitas Clinic, University of Tokyo
Conflict of Interest: None Declared

Daskivich et al.

1 shows an accurate estimation of life expectancy of men with early-stage prostate cancer in their study. However, in men with low- or intermediate-risk prostate cancer, we should consider additional issues when deciding treatment strategy, that is, whether conservative management and aggressive treatment. Particularly for older patients with multiple major comorbid conditions, urologists are required to perform more careful judgment in choosing aggressive therapy, such as prostatectomy or radiation. In a previous report, there were no significant relative differences in disease-specific functional outcomes among men undergoing prostatectomy or radiotherapy at 15 years. Nonetheless, men with aggressive treatment commonly had declines in all functional domains during 15 years of follow-up compared to conservative management.

2 Considering quality of life after diagnosis with prostate cancer as well as overall survival, indication for aggressive treatment should be given careful consideration. The American Urological Association (AUA) recently published clinical guidance that recommends against performing “all” routine prostate-specific antigen (PSA)-based screening for prostate cancer, as well as all screening in men older than 70, men younger than 40 and average-risk men ages 40-54.

3 This current study has possibility to support the AUA recommendation. Older men with multiple major comorbidities include many prostate cancer patients who don’t have the necessity of confirming cancer diagnosis or even PSA screening. The life expectancy is getting longer in most developed countries. In recent years Japan has an unprecedented scale of super aging society with the average lifespan of 79. 4 years for Japanese men.

4 Many local governments in Japan provide a free PSA checkup with no age limit, which is a controversial policy. The Japanese Urological Association (JUA) has comparatively positive trend for PSA screening. We would be grateful if the authors could provide the detailed information before diagnosis for prostate cancer in the enrolled patients of this study, such as first chief complaints, medical PSA checkup, or time period to biopsy. It is necessary to comprehend the whole history of early-stage prostate cancer from diagnostic process to outcome. It is preferable to consider indication for prostate biopsy at first, before choosing approach to treatment for prostate cancer, in particular, for older men with multiple major comorbidities. The number of men who are diagnosed as prostate cancer unrelated their prognosis and are incited anxiety could be reduced by avoiding inessential prostate biopsy.

Indication for biopsy in aging societies
Posted on June 26, 2013
Masayoshi Nagata 1, Tetsuya Tanimoto 2, Masahiro Kami 3
1 Department of Urology, National Center for Global Health and Medicine, 2 Navitas Clinic, 3 Division of Social Communication System for Advanced Clinical Research, Institute of Medical Science, Unive
Conflict of Interest: None Declared

Daskivich et al.[1] shows an accurate estimation of life expectancy of men with early-stage prostate cancer in their study. However, in men with low- or intermediate-risk prostate cancer, we should consider additional issues when deciding treatment strategy, that is, whether conservative management and aggressive treatment. Particularly for older patients with multiple major comorbid conditions, urologists are required to perform more careful judgment in choosing aggressive therapy, such as prostatectomy or radiation. In a previous report, there were no significant relative differences in disease-specific functional outcomes among men undergoing prostatectomy or radiotherapy at 15 years. Nonetheless, men with aggressive treatment commonly had declines in all functional domains during 15 years of follow-up compared to conservative management.[2] Considering quality of life after diagnosis with prostate cancer as well as overall survival, indication for aggressive treatment should be given careful consideration. The American Urological Association (AUA) recently published clinical guidance that recommends against performing “all” routine prostate-specific antigen (PSA)-based screening for prostate cancer, as well as all screening in men older than 70, men younger than 40 and average-risk men ages 40-54.[3] This current study has possibility to support the AUA recommendation. Older men with multiple major comorbidities include many prostate cancer patients who don’t have the necessity of confirming cancer diagnosis or even PSA screening. The life expectancy is getting longer in most developed countries. In recent years Japan has an unprecedented scale of super aging society with the average lifespan of 79.4 years for Japanese men.[4] Many local governments in Japan provide a free PSA checkup with no age limit, which is a controversial policy. The Japanese Urological Association (JUA) has comparatively positive trend for PSA screening. We would be grateful if the authors could provide the detailed information before diagnosis for prostate cancer in the enrolled patients of this study, such as first chief complaints, medical PSA checkup, or time period to biopsy. It is necessary to comprehend the whole history of early-stage prostate cancer from diagnostic process to outcome. It is preferable to consider indication for prostate biopsy at first, before choosing approach to treatment for prostate cancer, in particular, for older men with multiple major comorbidities. The number of men who are diagnosed as prostate cancer unrelated their prognosis and are incited anxiety could be reduced by avoiding inessential prostate biopsy.

References

[1]. Daskivich TJ, Fan KH, Koyama T, et al. Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S. Population–Based Cohort of Men With Prostate Cancer. Ann Intern Med. 2013;158(10):709-717. [2]. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013 ;368(5):436-45

[3]. Carter HB, Albertsen PC, Barry MJ, et al. EARLY DETECTION OF PROSTATE CANCER: AUA GUIDELINE, AUA 2013

[4]. The population survey report in 2012, annual health, labour and welfare report 2012. Tokyo: Ministry of Health, Labour and Welfare, 2012.

Author's Response
Posted on June 28, 2013
Timothy J. Daskivich, MD, Mark S. LItwin, MD MPH, David F. Penson, MD, MPH
UCSF
Conflict of Interest: None Declared

Determining long-term mortality outcomes using a surgical population that is pre-selected to be the healthiest- which is what Froehner and colleagues are suggesting- incurs selection bias that drastically overestimates survival for the average person. This phenomenon has been shown previously in the Urology literature (1). While we agree that a few older men with multiple comorbidities may be unusually fit and that these men may have sufficient longevity to benefit from treatment, it is disingenuous to generalize these outliers to a broader population considering treatment. We feel that our population-based estimates of ten-year mortality by age and comorbidity—which are consistent with other population-based estimates by comorbidity outside of the U.S. (2)—present the most relevant information to the average man deciding between aggressive and non-aggressive treatment. The survival estimates presented in our report will help the majority of older, sicker men avoid unnecessary aggressive treatment that can result in significant morbidity. Timothy J. Daskivich, MD, Mark S. Litwin MD, MPH and David F. Penson, MD, MPH

1. Tewari A, Johnson CC, Divine G, Crawford ED, Gamito EJ, Demers R, Menon M. Long-term survival probability in men with clinically localized prostate cancer: a case-control, propensity modeling study stratified by race, age, treatment and comorbidities. J Urol 2004; 171:1513-9.

2. Berglund A, Garmo H, Tishelman C, Holmberg L, Stattin P, Lambe M. Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden. J Urol 2011; 18:833-9.

Submit a Comment

Summary for Patients

Effect of Age, Tumor Risk, and Comorbidity on Prostate Cancer Survival

The full report is titled “Effect of Age, Tumor Risk, and Comorbidity on Competing Risks for Survival in a U.S. Population–Based Cohort of Men With Prostate Cancer.” It is in the 21 May 2013 issue of Annals of Internal Medicine (volume 158, pages 709-717). The authors are T.J. Daskivich, K.H. Fan, T. Koyama, P.C. Albertsen, M. Goodman, A.S. Hamilton, R.M. Hoffman, J.L. Stanford, A.M. Stroup, M.S. Litwin, and D.F. Penson.

Read More...

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)