PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer amongst PSA screen-detected men, the most histologically well-differentiated, and 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 within 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, histologic 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. There is near consensus that Gleason 6 meets pathologic definitions of cancer but controversy whether it meets commonly accepted molecular and genetic features of cancer. Multiple clinical series suggest the metastatic potential of contemporary Gleason 6 is negligible but not zero. Population based-studies in the US suggest greater 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 diminish 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 PSA-based screening strategies such as targeting high-risk populations, decreasing the frequency of screening, recommendations on screening cessation, incorporation of remaining life expectancy estimates, shared decision-making, novel biomarkers, and eliminating PSA screening entirely. Large non-randomized and randomized studies have shown active surveillance to be 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.
CONCLUSION: The definition and clinical relevance of Gleason 6 prostate cancer has changed substantially since introduced nearly 50 years ago. A high proportion of screen-detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing diagnosis and treatment of Gleason 6 is likely to have a favorable impact on the net benefit of prostate cancer screening.
Eggener SE, Badani K, Barocas DA, Barrisford GW, Cheng JS, Chin AI, Corcoran A, Epstein JI, George AK, Gupta GN, Hayn MH, Kauffman EC, Lane B, Liss MA, Mirza M, Morgan TM, Moses K, Nepple KG, Preston M, Rais-Bahrami S, Resnick MJ, Siddiqui MM, Silberstein J, Singer EA, Sonn GA, Sprenkle P, Stratton KL, Taylor J, Tomaszewski J, Tollefson M, Vickers A, White WM, Lowrance WT. Are you the author?
Reference: J Urol. 2015 Apr 4. pii: S0022-5347(15)03689-7.