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Glinsky Genetic signatures of lethal disease in early stage prostate cancer

cancer appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial, which is essential
for regulatory approval of diagnostic and prognostic tests in clinical setting. Prospectively validated GES of lethal PC in biopsy
specimens of G6 and G7 tumors will help physicians to identify, at the time of diagnosis, patients who should be considered for
exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.

INTRODUCTION radical prostatectomy for treatment of early prostate
cancer have contributed to a significant extent to the
In the United States, widespread implementation of the reported 98-100% 5-year survival rates since 1998 in
prostate-specific antigen (PSA) screening programs the United States (SEER 13 areas statistics).
enabled diagnosis of more than 200,000 cases of
prostate cancer each year. Clinically localized However, there is a lack of consensus regarding the
[1]
prostate cancer represents the vast majority of new benefits of a population-scale PSA screening and a
cases. Therefore, one of the most significant benefits controversy about the potential for overdiagnosis
[2]
of the widespread use of PSA screening is that the and overtreatment of clinically insignificant disease
prevalence of the late stage, advanced and high grade that would not likely to become life-threatening in a
prostate cancer at diagnosis has declined dramatically man’s lifetime. Further socio-economic arguments in
[9]
and the vast majority of newly diagnosed prostate support of significant overdiagnosis and overtreatment
cancers are early stage and low grade tumors. have been presented in studies indicating that
prevention of one prostate cancer death would require
The natural history of early stage clinically localized active treatment of 48 men for 9 years or 12 men for
prostate cancer is considered favorable and other 14 years. [10,11] Outcome studies from contemporary
[3]
types of cancer such as lung cancer are considered population-based cohorts reported cumulative 10-
hundreds times as deadly. Despite this seemingly year prostate cancer-specific mortality in patients with
“indolent” nature, prostate cancer is the second low-risk disease 2.4% and 0.7% in the surveillance
leading cause of cancer-related deaths and accounts group and curative intent groups, respectively,
[12]
for 3.5% of all male deaths. Development of clear, which indicates that the surveillance may be a
[4]
consensus guidelines for physicians’ decision-making suitable treatment option for majority of patients with
process in clinical management of early stage localized low-risk prostate cancer. Clinical evidence that active
prostate cancer is one of the most significant public surveillance may be a safe, perhaps preferred option
healthcare problems. Inevitable and fast approaching for older men diagnosed with a very low-grade or
demographic changes in the Western world underscore small-volume form of prostate cancer were published
the critical economic and logistical needs for a rational, recently by Tosoian et al. Therefore, active
[13]
evidence-based approach to the clinical management surveillance with curative intent for low-risk prostate
of the early stage localized prostate cancer. A path to cancer is under active consideration as a potentially
solutions to this problem is complicated by a multitude safe alternative to immediate curative intervention
of competing positions attempting to emphasize the with the expectations that it may reduce overtreatment
perceived shortcomings and benefits of different and therapy-associated adverse events. It certainly
approaches and need to balance multiple variables would reduce the escalating economic burden of cost
such as public health care costs, individual patients’ of prostate cancer treatment. The major limitation of
benefits, interests, socio-economic status, ethical and these studies is a short follow-up time [for example,
[13]
professional responsibilities of the medical personnel, in the John Hopkins study, the total cohort has a
and humanitarian considerations. median follow-up of 2.7 years (range 0.01 to 15)]
which requires the use of biochemical recurrence or
Conclusive statistical evidence of the life-saving other “proxy” end-points for disease-specific mortality.
therapeutic benefits of radical prostatectomy versus This limitation is particularly relevant for early prostate
watchful waiting in early prostate cancer have been cancer because the overall survival benefits of
documented in a randomized multicenter clinical radical prostatectomy versus watchful waiting are
trial: radical prostatectomy reduces disease-specific not statistically apparent until 10 years follow-up [5-7]
mortality, overall mortality, and the risks of metastasis due to the fact that a majority of death events in the
and local progression. [5-7] Immediate curative watchful waiting cohorts of early prostate cancer
interventions are the predominant therapy choice occurs at or after 10 years follow-up (this study). [5-7]
and 168,000 prostatectomies are performed each Furthermore, significantly longer follow-up data are
year to treat prostate cancer. It seems reasonable required because most patients currently diagnosed
[8]
to conclude, that early detection of prostate cancer with localized prostate cancer are aged 60-70 years
facilitated by PSA screening and aggressive use of and have a life expectancy of more than 15 years.
[12]
178 Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ September 21, 2017