STATEMENT OF NEED

Prostate cancer is the most commonly diagnosed solid malignancy in men, found in 1 of 6 men sometime through their lifetime. The prevalence of prostate cancer has increased over the past decade due to increased screening, but much controversy remains regarding systemic treatment. Specifically, questions remain regarding the use of androgen deprivation therapy (ADT) in early disease, the timing of chemotherapy in advanced disease, and the role of more novel targeted systemic therapies.

Part one of this activity will focus on clinical and pathological characteristics of prostate cancer. According to the American Urological Association (AUA), widespread prostate-specific antigen (PSA) screening has led to a shift toward identification of earlier-stage disease and better short-term outcomes after diagnosis, but there is an absence of randomized trials documenting that early detection and aggressive treatment can reduce mortality [2]. Several screening trials are currently underway to fill this evidence gap [3,4]. A recent analysis of the European Randomized Study of Screening for Prostate Cancer (ERSPC) evaluated the effects of screening on advancing the time of diagnosis (ie, lead time) and detecting cancers that would not have been diagnosed in the absence of screening (ie, overdetection) [5]. The ERSPC showed that overdetection of incidental prostate cancer is an important consequence of screening. To date, most of the screening data appear to tilt away from demonstrating a benefit of widespread screening. In the era of PSA screening, clinicians have observed migration of clinical stage of newly diagnosed disease, from a decrease in the prevalence of advanced (cT34) disease to a marked increase in the detection of early-stage (cT1c) disease from 1987 to 2003 [6]. At the Duke Prostate Center (DPC), there has been a shift toward low volume disease among men undergoing radical prostatectomy [7]. Radical prostatectomy therefore may be performed on many men who have incidental prostate cancer. At the DPC, 19.2% of prostatectomy patients treated from 2002 to 2006 had unilateral cancer upon pathologic assessment [8]. Analysis of the DPC has also shown significant discrepancies between diagnostic and pathologic Gleason sums [9]. Overall, patients who underwent radical prostatectomy appear to have excellent long term survival. Whether focal therapy can improve on these outcomes is unknown. An association between obesity-related hemodilution and PSA concentration among men with prostate cancer has been identified [10], and additional studies on the effects of obesity on the natural history of prostate cancer suggest that obese patients have worse clinical outcomes. Data have shown that higher body mass index is associated with high-grade disease, positive surgical margins, and biochemical progression. Given the clearly detrimental effect of obesity on current prostate cancer outcomes, additional research focusing on the optimal diagnosis and treatment of prostate cancer in obese men is needed. Many novel targeted therapies for prostate cancer are under investigation, comprising a multitude of different approaches, including vaccines, small molecule tyrosine kinase inhibitors, and specific inhibitors of cell survival or resistance pathways. Part two of this activity will focus on approaches to modulate apoptosis and metabolism in prostate cancer therapy, highlighting ongoing translational studies at the Cancer Institute of New Jersey (CINJ).

TARGET AUDIENCE

This publication is intended for urologists and other medical professionals involved in screening for, diagnosing and treating prostate cancer.

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