PDF(Pubmed)
Abstract：
OBJECTIVE: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential.
RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed \'unfavourable histology\'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology.
CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.
RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed \'unfavourable histology\'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology.
CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.
摘要：
目的：前列腺癌的组织学分级是一个强有力的预后工具，但是当前的等级分配标准尚未完全优化。我们的目标是开发和测试一个简化的组织学分级模型，主要基于大型筛状/导管内癌，具有预测转移潜力的优化灵敏度。
结果：确定了两个独立的非重叠队列：419例前列腺癌根治术后患者的长期临床随访队列和209例前列腺癌根治术后患者的队列，其中所有患者都有病理证实的转移性疾病。对所有前列腺切除术的高风险组织学模式进行了重新审查，称为“不良组织学”。不利的组织学定义为任何经典的格里森模式5组件，任何大的筛状形态（>0.25mm）或导管内癌，复杂的管腔内乳头状结构，3级基质源性癌和复杂吻合的脐带样生长。对于结果队列，Kaplan-Meier分析比较生化复发，组织学有利和不利的受试者之间的转移和死亡，按病理分期和分级组分层。多变量Cox比例风险模型评估了在纪念斯隆·凯特琳癌症中心（MSKCC）前列腺切除术后的列线图中添加不利组织学并按不利组织学百分比进行分层。在15年不利的组织学预测生化复发，灵敏度为93%，特异性为88%，转移性疾病为100％和48％，死亡率为100％和46％。具有不利组织学的2级前列腺癌与转移相关，而与病理分期无关。而那些没有风险的人。仅基于大的筛状/导管内癌或筛状大小的直径增加来预测转移的组织学模型提高了特异性，但灵敏度较低。多变量Cox比例风险模型表明，不利的组织学显着提高了MSKCC前列腺切除术后生化失败的列线图的辨别能力（似然比检验P<0.001）。在对所有患者均已确诊转移性疾病的单独RP队列的回顾性研究中，没有明确有利的组织学。
结论：前列腺癌根治术的不良组织学与转移风险相关，预测不良结局优于目前的分级和分期系统，并改善了MSKCC前列腺切除术后的列线图。最重要的是,不利的组织学分层2级前列腺癌进入那些有和没有转移潜力，独立于舞台。虽然不利的组织学主要由大型筛状/导管内癌驱动，识别和包含其他特定的结构模式增加了预测转移性疾病的敏感性.此外，简化的二分法模型可以改善沟通，并可以增加实施。
结果：确定了两个独立的非重叠队列：419例前列腺癌根治术后患者的长期临床随访队列和209例前列腺癌根治术后患者的队列，其中所有患者都有病理证实的转移性疾病。对所有前列腺切除术的高风险组织学模式进行了重新审查，称为“不良组织学”。不利的组织学定义为任何经典的格里森模式5组件，任何大的筛状形态（>0.25mm）或导管内癌，复杂的管腔内乳头状结构，3级基质源性癌和复杂吻合的脐带样生长。对于结果队列，Kaplan-Meier分析比较生化复发，组织学有利和不利的受试者之间的转移和死亡，按病理分期和分级组分层。多变量Cox比例风险模型评估了在纪念斯隆·凯特琳癌症中心（MSKCC）前列腺切除术后的列线图中添加不利组织学并按不利组织学百分比进行分层。在15年不利的组织学预测生化复发，灵敏度为93%，特异性为88%，转移性疾病为100％和48％，死亡率为100％和46％。具有不利组织学的2级前列腺癌与转移相关，而与病理分期无关。而那些没有风险的人。仅基于大的筛状/导管内癌或筛状大小的直径增加来预测转移的组织学模型提高了特异性，但灵敏度较低。多变量Cox比例风险模型表明，不利的组织学显着提高了MSKCC前列腺切除术后生化失败的列线图的辨别能力（似然比检验P<0.001）。在对所有患者均已确诊转移性疾病的单独RP队列的回顾性研究中，没有明确有利的组织学。
结论：前列腺癌根治术的不良组织学与转移风险相关，预测不良结局优于目前的分级和分期系统，并改善了MSKCC前列腺切除术后的列线图。最重要的是,不利的组织学分层2级前列腺癌进入那些有和没有转移潜力，独立于舞台。虽然不利的组织学主要由大型筛状/导管内癌驱动，识别和包含其他特定的结构模式增加了预测转移性疾病的敏感性.此外，简化的二分法模型可以改善沟通，并可以增加实施。
