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 · 9.33 Impact Factor
- Cancer 12/2013; 119(23):4057. DOI:10.1002/cncr.28474 · 4.90 Impact Factor
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ABSTRACT: The Epstein histologic criteria (Gleason score <6, <2 cores positive, <50% of any core), established in 1994, have been widely used to select men for active surveillance. However, with the advent of targeted biopsy, which may be more accurate than conventional biopsy, we re-evaluated the likelihood of re-classification upon confirmatory re-biopsy using multi-parametric MRI-ultrasound fusion (mpMRI-US). We identified 113 subjects enrolled in the UCLA active surveillance meeting Epstein Criteria who subsequently underwent confirmatory, targeted biopsy via mpMRI-US. Median age was 64 years, PSA 4.2 ng/ml and prostate volume 46.8 cc. Targets, or regions of interest on mpMRI, were graded by level of suspicion and were biopsied at 3 mm intervals along their longest axis (median 10.5 mm). Additionally, 12 systematic cores were obtained during confirmatory re-biopsy. Our reporting is consistent with START criteria. Overall, confirmatory fusion biopsy resulted in re-classification for 41 men (36%), 26 (23%) due to Gleason grade >6, and 15 (13%) due to high volume Gleason 6 disease. When stratified by suspicion on mpMRI, the likelihood of reclassification was 24% to 29% for men with target grade 0 to 3, 45% for grade 4, and 100% for grade 5 (p=0.001). Men with grade 4 and 5 versus lower grade targets were >3 times (Odds Ratio 3.2, 95% Confidence Interval 1.4, 7.1, p=0.006) more likely to be reclassified. Upon confirmatory re-biopsy using mpMRI-US, men with high-suspicion mpMRI targets were frequently reclassified (45%-100%). Criteria for active surveillance should be re-evaluated when mpMRI-guided prostate biopsy is employed.The Journal of urology 02/2014; 192(2). DOI:10.1016/j.juro.2014.02.005 · 3.75 Impact Factor