Objectives Compared to T1a lesions, the natural history of untreated renal masses is >4cm is poorly understood. We sought to assess the growth kinetics and outcomes of cT1b/T2 cortical renal tumors managed with an initial period of active surveillance (AS), and compared these patients to those who underwent definitive delayed intervention. Methods Our institutional, prospectively maintained, renal tumor database was reviewed to identify enhancing solid & cystic masses managed expectantly. Clinically localized tumors >4.0 cm (≥T1b) that were radiographically followed for >6 months were included for analysis. Tumor size at presentation, annual linear tumor growth rate (LGR), Charlson comorbidity index (CCI), length of follow−up (FU), and clinical outcomes were compared between those who remained on AS or those who underwent delayed surgical intervention. Results 72 tumors >4cm in diameter (in 68 patients) were identified. 45 patients (66%) were managed solely with AS, while 23 (34%) progressed to intervention. For all lesions, the median tumor size at presentation was 4.9 cm, and the mean LGR was 0.44 cm/year. 14.7% of masses demonstrated no growth over time. Comparing patients managed exclusively with AS and those progressing to definitive intervention, no differences were noted in median tumor size at presentation (4.9 vs. 4.6 cm, p=0.79) or median CCI (3 vs. 2, p=0.6), while significant differences were seen with respect to median age at presentation (77 vs. 60 years, p=0.0002) and mean LGR (0.37 vs. 0.73 cm/year, p=0.02). Following adjustment, younger patients (OR 0.91 [CI 0.86-0.97]) and tumors with faster LGR (OR 9.1 [CI 1.7-47.8]) were more likely to undergo delayed surgical intervention. With a median FU of 32 months (mean, 38.9 ± 24.0; range 6−105), 9 patients died (13%) from other cause and no patient progressed to metastatic disease. Conclusions Localized cT1b or larger renal masses show comparable growth rates to small tumors managed expectantly with low rates of progression to metastatic disease at short term follow up. An initial period of AS to determine tumor growth kinetics is a reasonable option in select patients with significant competing risks and limited life expectancy.

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.

Background A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). As tumor cells in culture proliferate directly in response to available folic acid, the goal of our study was to determine if there is a similar relationship between patient folate status, and the proliferative capacity of tumors in men with prostate cancer. Methods Serum folate and/or prostate tissue folate was determined in 87 randomly selected patients undergoing surgery for prostate cancer, and compared to tumor proliferation in a subset. Results Fasting serum folate levels were positively correlated with prostate tumor tissue folate content (n= 15; r= 0.577, p<0.03). Mean serum folate was 62.6 nM [7.5–145.2 nM], 39.5% of patients used supplements containing folic acid (n=86). The top quartile of patients had serum folates above 82 nM, six times the level considered adequate. Of these, 48% reported no supplement use. Among 50 patients with Gleason 7 disease, the mean proliferation index as determined by Ki67 staining was 6.17 ± 3.2% and 0.86 ± 0.92% in the tumors from patients in the highest (117 ± 15 nM) and lowest (18 ± 9 nM) quintiles for serum folate, respectively (p<0.0001). Conclusions Increased cancer cell proliferation in men with higher serum folate concentrations is consistent with an increase in prostate cancer incidence observed with folate supplementation. Unexpectedly, more than 25% of patients had serum folate levels greater than 6-fold adequate. Nearly half of these men reported no supplement use, suggesting either altered folate metabolism and/or sustained consumption of folic acid from fortified foods.

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