Department of Urology, Mount Sinai Medical Center, New York, New York 10022, USA.
J Urol. 2012 Nov;188(5):1667-75. doi: 10.1016/j.juro.2012.07.055. Epub 2012 Sep 19.
The Gleason scoring system has been the traditional basis for studies on the assessment and treatment of prostate cancer. Recent reports of long-term prostate cancer outcomes stratified by Gleason score based on the 2005 ISUP (International Society of Urological Pathology) update suggest that important aspects of the biology of prostate cancer correlate with commonly available histopathological information. In this review we present a conceptual framework for the possible existence of distinct but interrelated developmental pathways in the context of the Gleason score in considering various biological and clinical aspects of prostate cancer. This may be useful in characterizing prostate cancer as an indolent condition in some and an aggressive disease in others, in decision making for treatment, and in the interpretation of the biological course and treatment outcomes.
A comprehensive review of clinical, pathological and investigational biological literature on this topic was conducted. In addition, the biological behavior of prostate cancer as interpreted from this survey was compared to that of other solid neoplasms in developing a schema for characterizing the pathogenesis of various forms of the disease.
The Gleason scoring system has been found to have fundamental value in predicting the behavior of prostate cancer and assessing outcomes of its treatment. Increasingly, the proportion of Gleason pattern 4 in a prostatectomy specimen is being recognized as a critical factor in predicting the rates of biochemical recurrence and prostate cancer specific mortality. Under the current Gleason classification, a Gleason 3 + 3 = 6 cancer carries a minimal long-term risk of progression or mortality. Risk of biochemical recurrence and prostate cancer specific mortality increases with increasing proportions of the Gleason 4 component in the prostatectomy specimen, from 3 + 3 = 6 with tertiary 4 (ie less than 5% of a 4 component) to 3 + 4 = 7, 4 + 3 = 7 and 4 + 4 = 8. Assuming that the Gleason 4 component increases in volume more rapidly with time than well differentiated components, it can be inferred that a smaller proportion of Gleason 4 could mean that the cancer has been identified at an earlier phase in the natural history of the disease. This could explain the improved prognosis on the basis of length and lead time biases, and conceivably on the basis of a decreased likelihood of cancer cells having metastasized. Correspondingly, increasing amounts of Gleason 4 cancer in a prostate specimen might be explained in 2 ways, as the preferential growth of a single clone of Gleason 4 cells, possibly with intraprostatic spread, or the evolution of Gleason 3 cancer cells to become Gleason 4. These hypotheses have been examined by genetic analysis of metastatic deposits and by comparisons of multiple foci of cancer within individual prostates. The clinical significance of these concepts in regard to disease status at diagnosis, treatment selection, outcomes of treatment, and implications for future research on the basis of clinical and molecular observations are the basis of the developmental schemata we propose.
Given the relatively benign nature of homogeneous, low volume Gleason 3 tumors, and the progressive risk of biochemical recurrence and prostate cancer specific mortality with increasing quantities of Gleason 4 components, we propose that Gleason 4 (and 5) cancers constitute cancer diatheses distinct from that of Gleason 3 cancer. This distinction may contribute to the understanding of the prognosis intrinsic to these biological behavioral patterns, and help guide the translation of findings at molecular and histological levels to a more precise selection of treatments.
格里森评分系统一直是评估和治疗前列腺癌的传统基础。最近有报道称，基于 2005 年国际泌尿病理学会（ISUP）更新的格里森评分对前列腺癌进行长期预后分层的研究表明，前列腺癌生物学的重要方面与常用的组织病理学信息相关。在这篇综述中，我们提出了一个概念框架，即在考虑前列腺癌的各种生物学和临床方面时，假设格里森评分中存在不同但相互关联的发育途径，这可能有助于将前列腺癌描述为某些情况下的惰性疾病，而在其他情况下则为侵袭性疾病，从而有助于治疗决策，并有助于解释生物学过程和治疗结果。
对该主题的临床、病理和研究生物文献进行了全面审查。此外，从这项调查中推断出前列腺癌的生物学行为，并将其与其他实体瘤进行比较，以制定一种方案来描述各种形式疾病的发病机制。
格里森评分系统在预测前列腺癌的行为和评估其治疗结果方面具有重要价值。越来越多的证据表明，前列腺切除术标本中格里森模式 4 的比例是预测生化复发和前列腺癌特异性死亡率的关键因素。根据目前的格里森分类，格里森 3+3=6 癌症的长期进展或死亡风险极小。随着前列腺切除术标本中格里森 4 成分比例的增加（从三级 4（即 4 成分小于 5%）到 3+4=7、4+3=7 和 4+4=8），生化复发和前列腺癌特异性死亡率的风险增加。假设格里森 4 成分比分化良好的成分随时间更快地增加体积，可以推断出较小比例的格里森 4 可能意味着癌症在疾病自然史的早期阶段就被识别出来。这可以解释基于长度和领先时间偏倚的改善预后，并且可以想象基于癌症细胞转移的可能性降低。相应地，前列腺标本中越来越多的格里森 4 癌症可以通过两种方式来解释，一种是格里森 4 细胞的单一克隆优先生长，可能伴有前列腺内扩散，另一种是格里森 3 癌细胞演变成格里森 4 癌细胞。这些假设已经通过对转移灶的遗传分析以及对单个前列腺内多个癌灶的比较进行了检查。这些概念在疾病诊断时的状态、治疗选择、治疗结果以及基于临床和分子观察的未来研究的意义是我们提出的发育图式的基础。
鉴于同质、低体积格里森 3 肿瘤的相对良性性质，以及随着格里森 4 成分数量的增加而发生生化复发和前列腺癌特异性死亡率的风险增加，我们提出格里森 4（和 5）癌症与格里森 3 癌症的癌症易感性不同。这种区别可能有助于理解这些生物学行为模式固有的预后，并有助于指导从分子和组织学水平到更精确选择治疗方法的发现。
