Older Age Predicts Decreased Metastasis and Prostate Cancer-Specific Death for Men Treated With Radiation Therapy: Meta-Analysis of Radiation Therapy Oncology Group Trials

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.

Serum Sex Steroids Depict a Nonlinear U-Shaped Association with High-Risk Prostate Cancer at Radical Prostatectomy

“…Interestingly, Pierorazio and colleagues (9) recently showed that higher levels of serum free T are associated with an increased risk of aggressive prostate cancer among older men. In contrast, some data support even less aggressive prostate cancer in older men (37). Our analysis found that preoperative BMI did not achieve independent predictor status for high-risk prostate cancer, although restricted cubic spline functions depicted a sort of U-shaped correlation (Fig.…”

High-Throughput Transcriptomic Analysis Nominates Proteasomal Genes As Age Specific Biomarkers and Therapeutic Targets in Prostate Cancer

“…4,5 However, clinical findings to support this notion have to date been mixed. [6][7][8][9][10][11][12][13][14] Independent of the prognosis of early versus late-life onset PCa, it is possible that the biological pathways that drive this disease differ by age. However, to date, there have been no studies examining the similarities and differences in the prognostic drivers of PCa in different age groups.…”

Nuclear Stiffening Inhibits Migration of Invasive Melanoma Cells

“…(22) Decreased metastasis can be statistically associated with old age,(47) but the impact of age in cancer progression is still a subject of high controversy and may depend on type of cancer. (47) Previous reviews have reported that expression of the Δ50LA variant in nature is a cryptic error and serves no function, and lamin A appears to be expendable to some degree. (48) However, we suggest that the nuclear stiffening that is associated with aging may serve some purpose.…”