The Contemporary Concept of Significant Versus Insignificant Prostate Cancer
ABSTRACT The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment.
To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa.
A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer.
The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score ≤ 6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume<0.5 cm(3). Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression.
The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa.
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ABSTRACT: Recent advances in tumor biology have made remarkable achievements in the development of therapy for metastatic castrate-resistant prostate cancer. These advances reflect a growing appreciation for the role of the tumor microenvironment in promoting prostate cancer progression. Prostate cancer is no longer viewed predominantly as a disease of abnormally proliferating epithelial cells but rather as a disease of complex interactions between prostate cancer epithelial cells (epithelial compartment) and the surrounding tissues (stromal compartment) in which they reside. For example, prostate cancers frequently metastasize to bone, an organ that contains a microenvironment rich in extracellular matrix proteins and stromal cells including hematopoietic cells, osteoblasts, osteoclasts fibroblasts, endothelial cells, adipocytes, immune cells, and mesenchymal stem cells. Multiple signaling pathways provide crosstalk between the epithelial and the stromal compartments to enhance tumor growth, including androgen receptor signaling, tyrosine kinase receptor signaling, and immune surveillance. The rationale to disrupt this "two-compartment" crosstalk has led to the development of drugs that target tumor stromal elements in addition to the cancer epithelial cell.CancerSpectrum Knowledge Environment 09/2011; 103(22):1665-75. DOI:10.1093/jnci/djr362 · 15.16 Impact Factor
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ABSTRACT: This study aimed to survey urologists regarding their knowledge, acceptance and practice of active surveillance (AS) for low-risk prostate cancer. An email-based survey was distributed to 4987 urologists. Respondents were surveyed regarding their knowledge and acceptance of AS. Those who felt AS was a reasonable strategy were asked their opinions on the criteria for AS enrollment and the details of their practice of AS. Respondents who felt AS was not a reasonable alternative were queried as to the reasons why. A total of 425 (9%) urologists successfully completed the survey and 387 (91%) were both familiar with AS and aware that AS differed from watchful waiting. Of this latter group, 370 (96%) respondents felt AS was a reasonable management strategy, 95% of whom manage patients with this approach. A minority of respondents (6%) felt that patients with a PSA>10 ng ml(-1) were eligible for AS. Further, most participants (74%) felt that patients required a Gleason score ≤6. There was little agreement on the timing of follow-up biopsies. Respondents who objected to AS were most commonly concerned with missing an opportunity for curative treatment (76%) and the risk of tumor undergrading (65%). The majority of participants were knowledgeable and accepting of AS. Respondents were in relative agreement regarding the PSA and Gleason score criteria for AS enrollment. In contrast, there was a lack of agreement on the timing of follow-up biopsies. In the future, comparative studies are required to determine the optimal enrollment criteria and follow-up protocol for patients managed with AS.Prostate cancer and prostatic diseases 12/2011; 15(2):177-81. DOI:10.1038/pcan.2011.57 · 2.83 Impact Factor