Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy: Meta-analysis of radiation therapy oncology group trials

Daniel A. Hamstra, Kyounghwa Bae, Miljenko V. Pilepich, Gerald E. Hanks, David Grignon, David G. McGowan, MacK Roach, Colleen Lawton, R. Jeffrey Lee, Howard Sandler

Research output: Contribution to journalArticle

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Abstract

Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

Original languageEnglish
Pages (from-to)1293-1301
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume81
Issue number5
DOIs
StatePublished - Dec 1 2011

Fingerprint

Radiation Oncology
metastasis
death
Meta-Analysis
radiation therapy
Prostatic Neoplasms
Radiotherapy
cancer
Neoplasm Metastasis
hazards
Confidence Intervals
confidence
Survival
intervals
regression analysis
Neoplasm Grading
Survival Analysis
deprivation
Androgens
Neoplasms

Keywords

  • Age
  • Hormonal ablation
  • Metastasis
  • Prostate cancer
  • Radiation therapy

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

Cite this

Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy : Meta-analysis of radiation therapy oncology group trials. / Hamstra, Daniel A.; Bae, Kyounghwa; Pilepich, Miljenko V.; Hanks, Gerald E.; Grignon, David; McGowan, David G.; Roach, MacK; Lawton, Colleen; Lee, R. Jeffrey; Sandler, Howard.

In: International Journal of Radiation Oncology Biology Physics, Vol. 81, No. 5, 01.12.2011, p. 1293-1301.

Research output: Contribution to journalArticle

Hamstra, Daniel A. ; Bae, Kyounghwa ; Pilepich, Miljenko V. ; Hanks, Gerald E. ; Grignon, David ; McGowan, David G. ; Roach, MacK ; Lawton, Colleen ; Lee, R. Jeffrey ; Sandler, Howard. / Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy : Meta-analysis of radiation therapy oncology group trials. In: International Journal of Radiation Oncology Biology Physics. 2011 ; Vol. 81, No. 5. pp. 1293-1301.
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abstract = "Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54{\%}) and Gleason scores (GS) of 7 (45{\%}) and 8 to 10 (27{\%}). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55{\%} vs. 41{\%}, respectively; p < 0.0001) and increased NPCD (10-year rate, 28{\%} vs. 46{\%}, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27{\%} vs. 20{\%}, respectively; p < 0.0001) and PCSD (10-year rate, 18{\%} vs. 14{\%}, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95{\%} confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95{\%} CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95{\%} CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.",
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T1 - Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy

T2 - Meta-analysis of radiation therapy oncology group trials

AU - Hamstra, Daniel A.

AU - Bae, Kyounghwa

AU - Pilepich, Miljenko V.

AU - Hanks, Gerald E.

AU - Grignon, David

AU - McGowan, David G.

AU - Roach, MacK

AU - Lawton, Colleen

AU - Lee, R. Jeffrey

AU - Sandler, Howard

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

AB - Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p < 0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p < 0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p < 0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p < 0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

KW - Age

KW - Hormonal ablation

KW - Metastasis

KW - Prostate cancer

KW - Radiation therapy

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