【多伦多大学】精准评估：提高PCa的TNM分期系统的应与，会面临哪些挑战？

efined population resulting from increased accuracy for evaluating the extent of disease while applying the original, predefined staging system. An example of this is nonpalpable disease (T1 category) for which a new imaging tool might reveal a conspicuous tumour with extraprostatic extension in the same patients (T3 category). Stage migration results in spurious variations in stage-specific outcomes, when in fact the overall individual outcomes are unchanged. Second, stage shift refers to actual changes in the patterns of disease presentation within a defined population (eg, as with the introduction of prostate-specific antigen [PSA] testing an increased proportion presented with early-stage PCa). Hence, stage shift is a desirable effect of cancer screening and early detection efforts, which should lead to improvements in disease outcomes. Both stage migration and stage shift he been observed in PCa.

随着能确认营养不良相对的另行方法的进展和应用于，明白依此类群并进行时精准叙述也变得不够加关键。在这一点上，有必要对应两种但会终究我们对肺癌依此引介的反常。第一种反常是依此迁至（stage migration），所称在应用于独有的、事前界定的依此子系统时，由于审计营养不良相对的正确性增加，病患者的T、N或M愈演愈烈巨大变化。举一个营养不良依此为不可扪及营养不良（T1期）的病患者例子，如果另行的CT用以推测一个引人注意的甲状腺，友网状外扩散，那么该病患者的营养不良依此则替换成T3期。依此迁至导致病患者的营养不良依此愈演愈烈巨大变化，但事实上很难算是真的愈演愈烈了扭转，病患者本身的总体第一集并没有扭转。第二种反常是依此扭转（stage shift），是所称在一个确认的人群之后，营养不良的展现方式愈演愈烈了实际上巨大变化（例如，随着睾丸抗原淋巴细胞[PSA]样品的应运而生，展现为现代PCa的病患者比例增加）。因此，依此扭转是肺癌筛选和现代样品岗位的一个完美特性，它应该可以促进营养不良第一集的提升。现阶段依此迁至和依此扭转均可在PCa管理工作之后观察到。

Evolving practices in PCa diagnosis and staging provide relevant contextualisation. Before the ailability of PSA testing, PCa was detected via physical examination (digital rectal examination) or transurethral resection of the prostate (TURP) in symptomatic patients. Accordingly, increases in the granularity of T3 and T4 categories in the 3rd edition (1978) and 4th edition (1987) of the TNM classification were incorporated. Use of TURP in the management of benign prostatic hyperplasia led to introduction of the T1a/T1b categories in the 4th edition for cancers incidentally found in resected tissue. With the utilisation of PSA, shifts to lower disease stages were observed, including the detection of clinically inapparent cancers for which the new T1c category (nonpalpable disease identified via needle biopsies) was introduced in the 5th edition (1997), in parallel to increased granularity for the T2 subcategories since the 6th edition (2002). Subsequently, some investigators started to use transrectal ultrasound imaging to differentiate T1 and T2 categories; however, the impact of this modality on routine practice and staging has remained marginal.

PCa病因和依此多方面的大大转型促进了TNM类群子系统的演变。在有PSA样品之后，PCa是通过检查结果（直肠所称检）或对有症状的病患者进行时经输卵管睾丸畸形（TURP）来推测的。因此，TNM类群第3版（1978年）和第4版（1987年）对T3和T4期进行时了不够细的对应。应用于于TURP病患良性睾丸炎症，导致在第四版之后应运而生了T1a/T1b期，用于叙述切除组织之后无意间推测的肺癌。PSA的应用于使我们推测有些营养不良的依此应改为不够低，最主要推测了流行病学上不引人注意的肺癌，为此在第5版（1997年）之后应运而生了另行的T1c期（通过外科手术外科手术推测的不可认清的营养不良），此外，自第6版（2002年）暂定以来，T2期有了不够细的对应。随后，一些研究者开始应用于于经直肠核磁共振高分辨率来对应T1和T2期，然而，这种方式为对常规概念化和依此的因素始终很小。

Driven by settings in which most patients presented with stage I-II PCa (ie, T1 and T2), the use of prognostic groups (permutations of T category, PSA, and Gleason score) became a standard for guiding clinical and research activities; nevertheless, the distinction between stage I-II and stage III-IV PCa has remained highly relevant. It is worth noting that cancer stage serves many other purposes beyond its role in prognostication (further described in [[3]]). Together, these reasons underscore the importance of addressing the challenges and opportunities posed by progress in PCa imaging with regard to accurate and clear PCa staging.

在大多数病患者为I-II期PCa（即T1和T2）的完全，HRS组（相结合T期、PSA和Gleason评分）成为所称导流行病学和研究大型活动的新标准；尽管如此，对应I-II期和III-IV期PCa始终非常关键。值得注意的是，肺癌依此除了在提供者HRS电子邮件多方面的功用外，还有许多其他功用（完全明确电子邮件唯以下内容[2]）。这些主因共同强调了，随着PCaCT在正确审计PCa依此多方面的进展，现阶段关键的是要解决PCa高分辨率所带来的终究，并抓住机遇。

The past two decades he been characterised by remarkable advances in PCa imaging. First, magnetic resonance imaging (MRI) has emerged as a superior modality for determining the local extent of PCa. Although the accuracy is not perfect, the improvement in resolution might also lead to changes in the assignment of T category and stage migration. Second, positron emission tomography (PET) with prostate-targeted tracers (eg, prostate-specific membrane antigen [PSMA]) has been increasingly used and approved in some jurisdictions for the staging of newly diagnosed PCa. Again, although the sensitivity of PET for nodal staging may not be optimal, it can demonstrate highly specific uptake in lymph nodes not detected via conventional imaging in a significant proportion of patients (20-45%, depending on the population) with conventionally defined localised disease. Similarly, approximately 10-25% of patients with presumed localised PCa with high-risk features may he distant metastatic disease detectable with PET tracers.

只不过二十年来，PCa高分辨率拿到了显着的退步。首先，磁共振高分辨率（MRI）成为首选的用来确认PCa角化覆盖范围的一种方式为。虽然正确性并不完美，但分辨率有了提升，也似乎使T依此有所扭转，愈演愈烈依此迁至。其次，应用于于睾丸靶向示踪剂（如睾丸抗原膜淋巴细胞[PSMA]）的正电子发射断层扫描（PET）已越发多地用于对另行病因的PCa进行时依此，并在一些区域得到批复。虽然PET对淋巴结依此的诱因似乎并不完美，但对于更为一部分通过常规手段识别的角化睾丸癌病患者（20-45%，各不相同病患者人群），PET在常规高分辨率未样品到的淋巴结之后展现显露高度抗原摄取。而且，在大约10-25%不具备持续性特征、推测身患角化PCa的病患者之后，PET示踪剂似乎但会样品到所在位置白血病营养不良。

Stage migration induced by imaging also has implications for the prognostic groups previously defined without MRI and PET imaging. Moreover, faulty annotation and inappropriate quantification of factors that affect prognosis (including stage) can introduce bias in yses of outcomes and in prognostic subgroups. In addition, MRI is increasingly being used to guide the areas for sampling—so-called targeted biopsies—with consequent grade migration, potentially further jeopardising the performance of current risk stratification groups that are based on systematic biopsies. Taken together, these phenomena stress the need for clarity and consistency in the use of TNM classification as it continues to serve as a widely applicable relevant system against which proposed value-added advances should be adequately benchmarked and quantified.

高分辨率引起的依此迁至也对未经MRI和PET高分辨率界定的HRS组有因素。此外，错误的解释和对因素HRS的因素（最主要依此）的不适当量化，但会使第一集分析和HRS亚组之后显露现偏倚。此外，MRI越发多地用来所称导采样周围便是；也的靶向外科手术便是骤然的依此迁至，似乎但会进一步对现阶段基于子系统外科手术的后果分层组产生人为因素。综上所述，这些反常强调了需要应用于于明确且明确的TNM类群子系统，因为它始终是一个广泛受限制的、MVP的子系统，应该对提显露的增值进展进行时适当的标准和量化。

The optimal use of imaging technologies in newly diagnosed PCa has not been elucidated or uniformly adopted. While MRI and/or PET are considered standard practice in some settings, a significant proportion of the world has limited or no access to either of these imaging modalities. The fundamental goal of the TNM classification has been to provide a universally applicable system with a sensible balance between ideal, useful, and practical. It is becoming apparent that the massive differences in patterns of presentation and gaps in diagnostic imaging ailability result in significant noncomparability of clinical stage recorded across the globe, even within high-resource settings.

如何在另行病因的PCa之后进行时最佳的高分辨率，现阶段尚能不可信，也没有统一的操作。虽然看来在某些完全MRI和/或PET是新标准概念化，但在世界上太大一部分区域，这些高分辨率方式为的可则否是有限的，甚至难以获得这些高分辨率方式为。TNM类群的基本目标是提供者一个普遍受限制的子系统，在完美、有效率和新颖之间拿到合理的平衡。越发引人注意的是，由于展现形式的巨大差异和病因性高分辨率可则否的相差，世界覆盖区域记录下来的流行病学依此有太大的不可比性，即使是在流行病学人力丰富的区域。

A possible solution is to advocate for modification of the current framework by adopting an additional dimension for the classification system. We propose a pilot iTNM classification with an “i” prefix that denotes when a T, N, or M category is derived via modern imaging modalities, as has been suggested for PSMA PET. In this way, a wider spectrum of practices could be encompassed and accommodated while retaining validity and applicability across settings and allowing amelioration of the effect of stage migration on outcome assessments. At the same time, we recommend that major groups support multi-institutional efforts, such as the European Association of Urology-coordinated PIONEER and OPTIMA consortiums, with sharing of high-quality data (eg, prognostic factors, treatment details, and outcomes) to help in redefining stage and prognostic groupings according to this new classification for the direct benefit of all patients with PCa.

一个似乎的高效率是主张更改现阶段的框架，为类群子系统增加一个维度。敦促试行iTNM依此子系统，其之后“i”这个前缀表示T、N或M类别是通过现代高分辨率方式为得显露的，比如敦促的PSMA PET。这样可以涉及并适应不够广泛的概念化，同时保留必要性和串连状况的受限制性，并减少依此迁至对第一集审计的人为因素。此外，敦促主要团体支持多部门的奋斗，如中欧泌尿外科学但会协调的PIONEER和OPTIMA联盟，共享高质量的数据（如HRS因素、病患细节和第一集），以帮助我们根据这种另行的类群重另行界定依此和HRS组，使所有PCa病患者直接获益。

Stage migration is an inevitable consequence of progress, but failure to address it proactively hinders our ability to precisely classify and communicate disease extent, ascertain changes in patterns of presentation, and limits our capability to effectively quantify the impact that advances may invariably he on treatment decisions and potentially on disease outcomes. Although this problem may appear daunting, we suggest that it presents us with an opportunity to marry the improving precision of diagnostics with first principles in PCa staging that foster opportunities for data-driven learning, perhaps refining the risks associated with PCa stage and grade, while allowing crosspollination across different actors and settings.

依此迁至是退步的必然结果，但如果不主动解决这个问题，就但会妨碍我们对营养不良相对进行时精准类群和交流，妨碍我们确认营养不良展现方式的巨大变化，并使我们难以必要审计获得的退步似乎对病患决策和营养不良第一集有何因素。尽管这个问题似乎不够容易解决，但我们看来它为我们提供者了一个机但会，将精准度大大增加的病因方法与PCa依此的第一原则相结合起来，提供者数据驱动的学习机但会，也许可以降低与PCa依此和分级涉及的后果，同时允许在不同的参与者和状况之后进行时交流。

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