Clinical-Genomic Characterization Unveils More Aggressive Disease Features in Elderly Prostate Cancer Patients with Low-Grade Disease - Beyond the Abstract
It is important to note that current expert guidelines for the treatment of localized prostate carcinoma recommend potentially curative therapy for patients whose life expectancy is at least 10 years.7,8 Patients with limited life expectancy are more likely to die from health conditions other than prostate cancer. This 10-year rule is widely accepted by most urologists and radiation oncologists.9 Additionally, most studies investigating optimal treatment approaches have focused on patients younger than 75 years,6 despite existing evidence showing a clear therapeutic benefit of radical treatments in healthy elderly men.10
There is a growing body of evidence demonstrating that older men with prostate cancer have worse oncological outcomes compared to their younger counterparts.11 Unfortunately, older healthy men with prostate cancer with a life expectancy of more than 10 years are still most commonly offered conservative management.
In this study, we used the Decipher test (Decipher Biosciences, Vancouver, BC, Canada) and the PAM50 molecular subtypes in a large biopsy and radical prostatectomy cohort of patients. Our aim was to identify high-risk prostate cancer among men of all ages. Decipher is a prognostic 22-gene genomic classifier that captures multiple biological pathways occurring in aggressive prostate cancer.12 PAM50 is a gene expression biomarker that subtypes patients into luminal (A or B) and basal tumors. This molecular subtype method is prognostic and predicts response to androgen deprivation therapy and captures important cancer data.13
Our hypothesis was that these molecular biomarkers could demonstrate the important association that age has with aggressive disease features of prostate cancer.
A total of 25,721 patients were analyzed in the study (9434 in the biopsy cohort, and 16,287 in the radical prostatectomy cohort). Overall 18.5% of the patients in the biopsy cohort were older than 75 years, compared with only 4.5% in the radical prostatectomy cohort. Looking at their basic clinical data, both in the biopsy and radical prostatectomy cohorts, older age was associated with worse clinical parameters, more aggressive biopsy and radical prostatectomy results.
Our analyses demonstrated that in patients with low-grade prostate cancer (ISUP grade group 1–2), older patients were more likely to have a genomically defined high-risk disease, translating to a high Decipher score. Age was also positively associated with a higher genomic risk score in univariable and multivariable analyses. Moreover, supporting our findings with Decipher risk score, elderly patients exhibited a higher prevalence of luminal B subtype (which is associated with worse prognosis). This was more evident in the subgroup with low ISUP grade group (1 and 2) both in the biopsy and in the radical prostatectomy cohort.
As mentioned in the actual paper, the European Association of Urology supports the endorsement by the International Society of Geriatric Oncology that elderly men should be treated according to their health status and biological age, rather than their chronological age.14 Despite this, most fit and healthy elderly men with curable localized prostate cancer are commonly managed conservatively and less likely to undergo definitive treatment, which is substantially underutilized in the elderly population.
Our study has some important limitations that need to be mentioned. These include the possible selection bias due to the retrospective nature of this work. Clearly, the healthier and fitter older patients were referred for a biopsy and even more so for surgery. Additionally, it is reasonable to assume that sicker patients with more aggressive disease were referred for surgery, so it should not surprise us that they had a higher risk of genomically defined disease. Lastly, we lacked data on the long-term follow-up of these patients, limiting our ability to validate the prognostic performance of these biomarkers.
Nevertheless, this study provides clear evidence of the benefit of using clinical-genomic characterization of elderly patients for individual treatment decisions. Our results suggest that older patients with assumed favorable pathology (ISUP grade group 1+2) could potentially be harboring a much more aggressive disease than originally thought, especially when compared to their younger counterparts. This does not contradict the well-known fact that low-grade disease will most likely not decrease the life expectancy of elderly patients (older than 75 years) and will most likely not be the cause of their death. As opposed to chronological age, biological age should be one of the main factors affecting treatment decisions. In fact, older fit healthy patients might need a more aggressive treatment plan, if they are shown to be harboring a more high-risk disease than originally thought.
Written by: Hanan Goldberg, MD, MSc, Urology department, SUNY Upstate Medical University, Syracuse, New York, Twitter: @Goldberghanan
References:
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