And, these treatments in men with only Gleason score 6 tumors are now considered to represent overtreatment ( Loeb et al. 5 Yet, the majority of these men in the recent past have nevertheless been treated with aggressive regimens, which may result in significant side effects. Widespread implementation of serum PSA testing, however, led to many men being detected with low-grade cancers (Gleason score 6 or Grade Group 1 ), and it is now recognized that the cancer cells within pure Gleason 6 tumors have exceedingly low capability of metastasizing ( Ross et al.
This decrease appears to be the result, at least in part, of early detection by serum prostate-specific antigen (PSA) testing followed by aggressive treatment with curative intent of clinically localized disease, usually by either radical prostatectomy, radiation therapy, or combined radiation and hormonal treatment ( Loeb et al. Over the last two decades, the death rate from prostate cancer has decreased by ∼40% ( Klotz 2018). Prostate cancer is the most common noncutaneous cancer in males in Western countries, with 150,000 new cases and ∼25,000 deaths projected to occur in the United States in 2018 ( Siegel et al. Here, we review our current understanding of the morphological and molecular pathological features of prostate cancer precursor lesions. Although the prevalence of such PIC lesions is not fully understood, this and other factors can confound the potential of identifying prostate precursors that can be targeted for disease prevention, interception, or treatment.
Notably, recent evidence has suggested that some fraction of such lesions that are morphologically consistent with HGPIN may actually be invasive carcinomas masquerading as HGPIN-a state that we term “postinvasive intraepithelial carcinoma” (PIC). Although there is significant evidence supporting the notion that such HGPIN lesions can give rise to invasive adenocarcinomas of the prostate, there are also numerous complicating considerations and evidence that cloud the picture in many instances. The best-known candidate for such a precursor lesion has been referred to as high-grade prostatic intraepithelial neoplasia (HGPIN).
A better understanding of the early stages of prostate cancer initiation, potentially arising from precursor lesions, may fuel development of powerful approaches for prostate cancer prevention or interception.
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