Gleason Grade Progression Is Uncommon
ABSTRACT Gleason grade is universally used for pathologic scoring of the differentiation of prostate cancer. However, it is unknown whether prostate tumors arise well differentiated and then progress to less differentiated forms or if Gleason grade is an early and largely unchanging feature. Prostate-specific antigen (PSA) screening has reduced the proportion of tumors diagnosed at advanced stage, which allows assessment of this question on a population level. If Gleason grade progresses as stage does, one would expect a similar reduction in high-grade tumors. We studied 1,207 Physicians' Health Study and Health Professionals Follow-up Study participants diagnosed with prostate cancer from 1982 to 2004 and treated with prostatectomy. We compared the distribution of grade and clinical stage across the pre-PSA and PSA screening eras. We re-reviewed grade using the ISUP 2005 revised criteria. The proportion of advanced stage tumors dropped more than six-fold, from the earliest period (12/1982-1/1993), 19.9% stage ≥T3, to the latest (5/2000-12/2004), 3% stage T3, none T4. The proportion of Gleason score ≥8 decreased substantially less, from 25.3% to 17.6%. A significant interaction between stage and diagnosis date predicting grade (P = 0.04) suggests that the relationship between grade and stage varies by time period. As the dramatic shift in stage since the introduction of PSA screening was accompanied by a more modest shift in Gleason grade, these findings suggest that grade may be established early in tumor pathogenesis. This has implications for the understanding of tumor progression and prognosis, and may help patients diagnosed with lower grade disease feel more comfortable choosing active surveillance. Cancer Res; 73(16); 5163-8. ©2013 AACR.
SourceAvailable from: Erina Vlashi[Show abstract] [Hide abstract]
ABSTRACT: Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.Seminars in Cancer Biology 07/2014; DOI:10.1016/j.semcancer.2014.07.001 · 9.14 Impact Factor
Cancer Medicine 08/2014; 3(4). DOI:10.1002/cam4.248
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ABSTRACT: Objectives Targeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer. Methods and materials A total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer. Results All cancers on initial biopsy had either Gleason score 3+3 = 6 (n = 63) or 3+4 = 7 (n = 11). At initial biopsy, 23 cancers were within an MRI target, and 51 were found on systematic biopsy. Cancer detection rate on repeat biopsy (29/74, 39%) was independent of Gleason score on initial biopsy (P = not significant) but directly related to initial cancer core length (P<0.02). Repeat sampling of cancerous sites within MRI targets was more likely to show cancer than resampling of tumorous systematic sites (61% vs. 29%, P = 0.005). When initial cancer core length was≥4 mm within an MRI target, more than 80% (5/6) of follow-up tracking biopsies were positive. An increase of Gleason score was uncommon (9/74, 12%). Conclusions Monitoring of specific prostate cancer–containing sites may be achieved in some men using an electronic tracking system. The chances of finding tumor on repeat specific-site sampling was directly related to the length of tumor in the initial biopsy core and presence of tumor within an MRI target; upgrading of Gleason score was uncommon. Further research is required to evaluate the potential utility of site-specific biopsy tracking for patients with prostate cancer on active surveillance.Urologic Oncology 10/2014; 32(7). DOI:10.1016/j.urolonc.2014.04.003 · 3.36 Impact Factor