Gleason 6 Prostate Cancer: Translating Biology into Population Health

Abstract

Purpose Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. Materials and Methods Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. Results The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. Conclusions The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over‐treatment

“…For many years, the definition of pathologically insignificant PCa was based on the pathological Epstein criteria, including a TV <0.5 cm 3 , Gleason score 6 and stage pT2 on prostatectomy [7]. More recent epidemiological data have shown that a TV of <0.5 cm 3 is a considerable underestimation of the threshold for pathologically insignificant PCa [8].…”

Prediagnostic prostate‐specific antigen kinetics and the risk of biopsy progression in active surveillance patients

“…4 Furthermore, rebiopsy is associated with complications and mental distress, 5 and is thus a serious problem for both patients and physicians alike. 1 More reliable and less invasive methods are required for favorable outcomes after AS.…”

“…Many of these men do not benefit from immediate treatment and thus could be managed expectantly, a strategy currently known as AS. 1 Identification of such patients is usually based on the biopsy findings and values of PSA and its derivatives, such as PSAD. 2 The rate of PSA change over time, known as PSA dynamics or kinetics, was conceptually introduced by Carter in 1992.…”

Optimizing Patient Population for MP-MRI and Fusion Biopsy for Prostate Cancer Detection

“…Active surveillance (AS) is a treatment option for men with low-risk prostate cancer, which addresses the overtreatment of indolent cancers [47]. Many different AS protocols exist, which are based on multiple clinical parameters as well as the pathology results from standard sextant biopsy sessions.…”