Applying recommended definition of aggressive prostate cancer: a validation study using high-quality data from the Cancer Registry of Norway

The Prostate Cancer Cohort Consortium (PC3) Working Group proposed a definition for aggressive prostate cancer (PC) for aetiologic epidemiologic research. We aimed to validate this definition as well as a second approach utilising only information on stage at diagnosis.
First primary PCs diagnosed 2004 − 2009 in the population-based Janus Serum Bank (JSB) cohort were identified by linkage to the population-based Cancer Registry of Norway (CRN) (n = 3568). The CRN and Norwegian Prostate Cancer Registry provided clinicopathological data for these cases. Approach 1 classified PC as aggressive if it was clinically T4, or N1, or M1, or had a Gleason score ≥8 at diagnosis (as proposed). Approach 2 classified PC as aggressive if CRN stage at diagnosis was ‘regional spread’ or ‘distant metastases’. Both approaches were validated by calculating the sensitivity and positive predictive value (PPV) against PC-death within 10 years of diagnosis.
Overall, 555 died from PC within 10 years. Approach 1 classified 24.7% of cases as aggressive and 13.6% were unclassified due to missing information. Approach 2 classified 19.6% as aggressive and 29% were unclassified. Sensitivity was highest for Approach 1 (0.76, 95% CI: 0.72 − 0.80 vs 0.69, 95% CI: 0.64 − 0.73), while PPVs were similar for both approaches (0.43, 95% CI: 0.40 − 0.46 and 0.40, 95% CI: 0.36 − 0.44). We observed similarly high sensitivity and higher PPVs than those reported by the PC3 Working Group.
The proposed definition of aggressive PC was applicable and valid in the JSB cohort. Stage at diagnosis can be useful if data on cTNM or Gleason score is unavailable.

前列腺癌队列联盟（Prostate Cancer Cohort Consortium, PC3）工作组提出了适用于病因流行病学研究的侵袭性前列腺癌（prostate cancer, PC）定义。本研究旨在验证该定义，同时验证第二种仅利用诊断时分期信息的分类方法。
通过与以人群为基础的挪威癌症登记处（Cancer Registry of Norway, CRN）联动，在人群队列简纳斯血清库（Janus Serum Bank, JSB）中识别出2004年至2009年确诊的首发性前列腺癌病例共3568例。挪威癌症登记处与挪威前列腺癌登记处为这些病例提供了临床病理数据。方法1按照工作组提议，将满足以下任一条件的前列腺癌归类为侵袭性：临床分期T4、N1、M1，或确诊时格里森评分（Gleason score）≥8。方法2则将确诊时挪威癌症登记处分期为“区域扩散”或“远处转移”的前列腺癌归类为侵袭性。通过计算确诊后10年内前列腺癌死亡病例的灵敏度与阳性预测值（positive predictive value, PPV），对两种分类方法进行验证。
总计555例患者在确诊后10年内死于前列腺癌。方法1将24.7%的病例归类为侵袭性，另有13.6%的病例因信息缺失无法分类；方法2将19.6%的病例归类为侵袭性，29%的病例因信息缺失无法分类。方法1的灵敏度更高（0.76，95%置信区间：0.72~0.80 vs 方法2的0.69，95%置信区间：0.64~0.73），而两种方法的阳性预测值相近（分别为0.43，95%置信区间：0.40~0.46；与0.40，95%置信区间：0.36~0.44）。本研究观察到的灵敏度较高，且阳性预测值高于PC3工作组此前的报道结果。
本研究验证了所提出的侵袭性前列腺癌定义在JSB队列中的适用性与有效性。若无法获得临床TNM分期或格里森评分数据，诊断时分期可作为有效的替代分类依据。