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Glinsky Genetic signatures of lethal disease in early stage prostate cancer

patients into subgroups with markedly distinct therapy malignant field effect in human prostates harboring
outcomes after the initial treatment defined by different tumors of different degrees of aggressiveness. It will
indicators of clinical progression such as biochemical be of interest to investigate the molecular and genetic
recurrence, disease relapse, and appearance of mechanisms of this phenomenon. Prospectively
recurrent tumors [Table 4]. validated GES of lethal prostate cancer in biopsy
specimens of Gleason 6 and 7 tumors will help
DISCUSSION practicing physicians to identify at the time of diagnosis
individual patients who should be considered for
Decision making process in clinical management of exclusion from the active surveillance programs and
low-risk localized prostate cancer is likely to affect who would most likely benefit from the immediate
life and death of thousands of patients. The problem curative interventions.
is confounded by the fact that statistically significant
survival benefits of curative therapy are evident only One of the distinguishing features of this unique 281
10 years after diagnosis of the early-stage prostate patients’ cohort that will never be replicated for ethical
cancer. Therefore, any genetic or molecular tests and humanitarian reasons, is that prostate cancer
designed to aid physicians and patients in this process patients were never treated and just subjected to the
would require the regulatory approval following the long-term follow-up observations. In this context, the
successful prospective clinical trial. Classification outcome data on the prostate cancer-specific death of
performance of the reported in this study 98 genes these patients reveal what would happen to prostate
GES of lethal prostate cancer appears highly suitable cancer patients who will not be treated (i.e. subjected
to meet design and feasibility requirements of the to “watchful waiting”). Importantly, it demonstrates
prospective 4 to 6 years clinical trial. One of the that a majority of prostate cancer patients diagnosed
most remarkable features of the 98-gene signature with Gleason 6 and 7 tumors will die from prostate
is that it appears to perform successfully in patients’ cancer when left untreated. A distinguishing feature
stratification with as little as 2% of cancer cells in of the patients’ cohort analyzed in this study is that it
a specimen, indicating that this GES captures a represents patients diagnosed with symptomatic early

Figure 6: ROC area under the curve analysis of the patients’ classification based on the 98-genes signature score in training (n = 141) and
test (n = 140) groups (A) and different clinically-relevant sub-groups (B-D) of patients. ROC: receiver operating characteristic
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ September 21, 2017 187