Prostate Cancer in Men Age 50 Years or Younger:: A Review of the Department of Defense Center for Prostate Disease Research Multicenter Prostate Cancer Database

Smith, Carolyn V.; Bauer, John J.; Connelly, Roger R.; Seay, Thomas M.; Kane, Christopher J.; Foley, John B.; Thrasher, J. Brantley; Kusuda, Leo; Moul, Judd W.

doi:10.1016/s0022-5347(05)66929-7

Cited by 100 publications

(65 citation statements)

References 22 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Jackson

Kothari

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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BACKGROUND: Although prostate cancer (PCa) is hypothesized to differ in nature between younger versus older patients, the underlying molecular distinctions are poorly understood. We hypothesized that high-throughput transcriptomic analysis would elucidate biological differences in PCas arising in younger versus older men, and would nominate potential age-specific biomarkers and therapeutic targets. METHODS: The high-density Affymetrix GeneChip platform, encompassing 41 million genomic loci, was utilized to assess gene expression in 1090 radical prostatectomy samples from patients with long-term follow-up. We identified genes associated with metastatic progression by 10 years post-treatment in younger (ageo65) versus older (age ⩾ 65) patients, and ranked these genes by their prognostic value. We performed Gene Set Enrichment Analysis (GSEA) to nominate biological concepts that demonstrated agespecific effects, and validated a target by treating with a clinically available drug in three PCa cell lines derived from younger men. RESULTS: Over 80% of the top 1000 prognostic genes in younger and older men were specific to that age group. GSEA nominated the proteasome pathway as the most differentially prognostic in younger versus older patients. High expression of proteasomal genes conferred worse prognosis in younger but not older men on univariate and multivariate analysis. Bortezomib, a Food and Drug Administration approved proteasome inhibitor, decreased proliferation in three PCa cell lines derived from younger patients. CONCLUSIONS: Our data show significant global differences in prognostic genes between older versus younger men. We nominate proteasomeal gene expression as an age-specific biomarker and potential therapeutic target specifically in younger men. Limitations of our study include clinical differences between cohorts, and increased comorbidities and lower survival in older patients. These intriguing findings suggest that current models of PCa biology do not adequately represent genetic heterogeneity of PCa related to age, and future clinical trials would benefit from stratification based on age.

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Section: Introductionmentioning

confidence: 99%

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

Zhao

Jackson

Kothari

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…3,4 Therefore, the use of lower PSA cutoffs may detect prostate cancer more frequently in its curable stages. 5 As few as 25% of men with a PSA level of 4-10 ng ml À1 have prostate cancer, and up to 25% of men with a PSA of o4 ng ml À1 will have prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

“…2 Early diagnosis of prostate cancer has been of great value, as younger age is an independent predictor of better prognosis. 3,4 Moreover, the use of lower PSA cutoffs may detect prostate cancer more frequently in its curable stages. 5 Patients aged less than 50 years were studied before for early cancer detection.…”

Section: Introduction and Aim Of The Workmentioning

confidence: 99%

The patients less than 50 years: is there a need to lower the PSA cutoff point?

Hekal

2008

Prostate Cancer Prostatic Dis

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“…In their study of 477 men who underwent RP, Smith et al [18] found that younger patients (less than 50 years old) had a better disease-free survival probability (logrank P = 0.010). On multivariate Cox regression analysis, age remained a significant prognostic factor (P = 0.033).…”

Section: The Influence Of Age On Survival Outcomesmentioning

confidence: 99%

“…On multivariate Cox regression analysis, age remained a significant prognostic factor (P = 0.033). They concluded that patients younger than 50 years old have a more favorable disease-free outcome [18]. Obek et al [19] studied 489 patients with localized prostate cancer.…”

Section: The Influence Of Age On Survival Outcomesmentioning

confidence: 99%

Correlations between age, Charlson score and outcome in clinical unilateral T3a prostate cancer

Hsu¹,

Joniau²,

Oyen³

et al. 2008

Asian J Androl

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According to the European Association of Urology (EAU) guidelines, a life expectancy of > 10 years is considered an important factor in the treatment of prostate cancer. The Charlson score is used to predict mortality based on comorbidities. The purpose of this study was to investigate the relationship between age, Charlson score and outcome in patients with cT3a prostate cancer. Between 1987 and 2004, 200 patients, who were with clinical T3a prostate cancer and who underwent radical prostatectomy (RP), were previously detected by digital rectal examination (DRE). Patients were categorized into two age groups (< 65 and ≥ 65 years old). Patients were also divided into two groups according to Charlson score ( = 0 and ≥ 1). Both age and Charlson score were analyzed regarding their predictive power of patients' outcomes. The mean follow-up period was 70.6 months, and the mean age of patients was 63.3 years. In all, 106 patients were < 65 years old and 94 patients were ≥ 65 years old. Age was a significant predictor of overall survival (OS). A Charlson score of 0 was found in 110 patients, and of ≥ 1 in 90 patients. Charlson score was not a significant predictor of biochemical progression-free survival (BPFS), clinical progression-free survival (CPFS) or OS. Cox multivariate analysis showed that margin status was a significant independent factor in BPFS, and cancer volume was a significant independent factor in CPFS. Charlson score does not influence the outcome in patients with clinical locally advanced prostate cancer. Age may influence OS. RP can be performed in motivated healthy older patients. However, the patients need to be counseled regarding possible surgery-related side effects, such as urinary incontinence and erectile dysfunction, which are age-and comorbidity-dependent.

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Prostate Cancer in Men Age 50 Years or Younger:: A Review of the Department of Defense Center for Prostate Disease Research Multicenter Prostate Cancer Database

Abstract: These data suggest that patients in the PSA era who underwent radical prostatectomy and were age 50 years or younger have a more favorable disease-free outcome compared to older men.

Cited by 100 publications

References 22 publications

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

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

The patients less than 50 years: is there a need to lower the PSA cutoff point?

Correlations between age, Charlson score and outcome in clinical unilateral T3a prostate cancer

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