The history and future of melanoma staging

The evolution and progressive refinement of an internationally accepted melanoma staging system over the last 50 years has resulted in much greater accuracy and increased utility, but the staging process has become more complex and less intuitive. This raises the question of whether melanoma staging should continue to develop with ever-increasing levels of complexity, or whether attempts should be made to produce an alternative system that is simpler and more intuitive. The current, TNM-based American Joint Committee on Cancer (AJCC) staging system for melanoma incorporates only some of the prognostic factors of proven significance. However, the information that is now available about these and other, well-documented prognostic factors allows accurate prediction of an individual melanoma patient's prognosis using a computer-generated estimate. Thus an alternative staging strategy that could be considered in the future would be to use such an estimate to obtain a numerical score for each patient, based on all available information agreed to be of prognostic relevance. A stage grouping could then be assigned on the basis of that score, according to previously determined score ranges for each stage and substage. The advantages of such a system would be that it would allow more reliable comparison of treatment results within and between institutions, and would provide more equivalent stratification groups for patients entering clinical trials of new therapies and those entering adjuvant therapy trials. A further advantage would be that because there would be a direct link between staging and prognostic estimate, such a system would be more readily able to be understood in an intuitive fashion.     

Rhabdomyosarcoma: the Stanford experience using a TNM staging system

Seventy-four patients with rhabdomyosarcoma were initially staged according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping classification and then retrospectively using a TNM staging system based on the initial clinical extent of disease. The TNM system includes T1, tumor confined to site or organ of origin; T2, regional extension beyond the site of origin; N0, normal lymph nodes; N1, lymph nodes containing tumor; M0, no evidence of metastases; and M1, distant metastases. All patients received combination chemotherapy, and more than 90% received radiation therapy as part of their initial treatment program with curative intent. Fifty-three of 74 patients (72%) were group III according to the IRS system, indicating unresectable or gross residual tumor. A more uniform distribution was achieved using the TNM system. Freedom from relapse (FFR) was 43% and the actuarial survival rate was 47% for the entire study group at 10 years. All but one relapse occurred within 3 years of initial diagnosis, and only three of 38 relapsed patients were salvaged. All TNM stage I patients are surviving disease free. Among patients having stages II, III, and IV disease by the TNM system, FFR was 53%, 26%, and 11%, and the survival rates were 47%, 36%, and 33%, respectively. Thirty-two of 74 patients (43%) had evidence of lymph node involvement at presentation, and 28 (88%) of these had primary lesions that extended beyond the site of origin (T2 primary). Histologic subtype and primary site had little impact on outcome in a multivariate analysis, and T stage was identified as the single most significant covariate correlated with survival; a model composed of both T stage and M stage was the best one for predicting relapse. The presented data support a study using a prospectively assigned TNM staging system based on the initial clinical extent of disease for use in future therapeutic trials.     

New TNM staging criteria for head and neck tumors

Cancers of the head and neck have always represented a unique perspective in cancer staging. Not only are these lesions numerous in terms of anatomic sites of origin, but, unlike most other major cancers, they frequently and readily lend themselves to adequate clinical assessment by visual inspection and palpation, which greatly facilitates documentation by the trained clinician. In addition, their location often involves treatment programs that focus on nonsurgical organ-preservation strategies, and thus anatomic and histological data for comprehensive pathologic staging are often not available. Nevertheless, the processes involved in surgical decision-making and radiotherapy treatment planning require meticulous assessment and documentation of the extent of locoregional disease. For all these reasons it is especially important to perform reliable and accurate pretreatment clinical staging of head and neck cancers. Also, many patients who succumb to head and neck cancer do so as a result of locoregional disease. Therefore, the staging system must take into account detailed local anatomic features that dictate management, since the degree of involvement of these structures by tumor may be as important as distant metastasis in threatening survival. For this reason the most recent cancer staging classification (6th edition) of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) includes new criteria for the more advanced cases (e.g., T4 categories and stage IV disease). These criteria reflect the fact that in heterogeneous populations there is a realistic opportunity for cure in some patients but not in others. This review summarizes the criteria used in the new TNM for head and neck tumors, and outlines the rationale behind the current changes. It also provides some guidance regarding optimal source data to facilitate classification in the registry setting. In addition, the need for additional changes in the future is recognized.     

Clinical relevance of TNM staging system according to breast cancer subtypes

BackgroundThere has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM (tumor–node–metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes.Patients and methodsWe conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed.ResultsThousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC.ConclusionsThe current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.     

TNM staging system for renal-cell carcinoma: current status and future perspectives

The Tumour, Nodes, and Metastasis (TNM) staging system is a method of stratifying patients with cancer and is based on data obtained from large multicentre studies that involved large numbers of patients, and have a good level of evidence. However, despite continual revisions to the methodology to incorporate evidence from new clinical studies, the optimum stratification of patients with renal-cell carcinoma (RCC) using the TNM staging system remains controversial and further revisions, in our opinion, are needed. Revision of the TNM staging system for renal-cell cancer could also result in the simultaneous update of the integrated prognostic systems that are currently used along side this traditional method of staging. These integrated systems could become key instruments for guiding patient counselling, for appropriate follow up strategies, for patient selection for clinical trials, and for appropriate assessment of results if the perception that they are complex is overcome. This perception is driven by the presence of more than one system, the heterogeneity of clinical and pathological variables included in the methodology, and the need for robust comparative studies between the various systems. Therefore, in everyday clinical practice, the TNM system is regarded as a more reliable method of staging. In this Essay, we aim to highlight the problems associated with the current version of the TNM staging system and highlight areas in which this grading instrument can be improved in future to become a more refined and standardised method of communication between all clinicians involved in clinical management of RCC.     

Malignant melanoma prognostic factors 5: clinical staging

Regional lymph node enlargement, as determined by palpation, is a useful prognostic factor--even if these nodes are histologically free of metastases. This is true not only for malignant melanoma but also for mycosis fungoides and carcinoma of the vulva.     

Pathologic staging of renal cell carcinoma: significance of tumor classification with the 1997 TNM staging system

BACKGROUND: The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS: Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS: Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS: The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.     

肺癌临床TNM分期与手术病理TNM分期的比较分析

背景与目的　肺癌临床TNM分期准确与否直接关系到患者的处理决策是否恰当。本研究旨 在探讨肺癌临床与手术病理TNM分期的一致性并分析其原因。方法　随机抽取我院2000年以来接受手术 治疗的肺癌患者150例,根据1997年新修订的国际肺癌分期标准分别进行临床和手术病理TNM分期,对两 种分期结果采用Kappa统计量进行一致性分析,同时比较T分期各亚组临床与手术病理分期的符合率。结 果　临床与手术病理T分期的一致性较为满意(Kappa值=0.729),但将病例分层分析后发现,临床T3、临床 T4组与手术病理结果的符合率明显低于临床T1和临床T2组(P<0.01)。临床与手术病理N分期的一致性 不够理想(Kappa值=0.108),两种TNM分期的一致程度也随之降低(Kappa值=0.287)。结论　目前基于 CT的肺癌临床T分期能较为真实地反映肿瘤的部位、大小,但是当原发灶靠近胸壁或者纵隔时,其边界不易 确定,部分临床T4病例仍可获得完全性切除。临床与手术病理N分期的一致程度不够理想,寻找更可靠的 术前诊断淋巴结转移的技术是提高肺癌临床TNM分期准确性的关键。     

Comparison of TNM staging systems for nasopharyngeal carcinoma,and proposal of a new staging system

Background:

There are few systematic evaluations regarding the sixth and seventh editions of the UICC/AJCC TNM Staging System (TNM6th, TNM7th) and Chinese 2008 Staging System (TNMc2008) for nasopharyngeal carcinoma (NPC).

Methods:

We classified 2333 patients into intensity-modulated radiotherapy (IMRT) cohort (n=941) and conventional radiotherapy (CRT) cohort (n=1392). Tumour staging defined by TNM6th, TNM7th and TNMc2008 was compared based on Akaike information criterion (AIC) and Harrell''s concordance index (c-index).

Results:

For T-classification, TNM6th (AIC=2585.367; c-index=0.6390385) had superior prognostic value to TNM7th (AIC=2593.242; c-index=0.6226889) and TNMc2008 (AIC=2593.998; c-index=0.6237146) in the IMRT cohort, whereas TNMc2008 was superior (AIC=5999.054; c-index=0.623547) in the CRT cohort. For N-classification, TNMc2008 had the highest prognostic value in both cohorts (AIC=2577.726, c-index=0.6297874; AIC=5956.339, c-index=0.6533576). Similar results were obtained when patients were stratified by chemotherapy types, age and gender. Using staging models in the IMRT cohort, we failed to identify better stage migrations than TNM6th T-classification and TNMc2008 N-classification. We therefore proposed to combine these categories; resultantly, stage groups of the proposed staging system showed superior prognostic value over TNM6th, TNM7th and TNMc2008.

Conclusion:

TNM6th T-classification and TNMc2008 N-classification have superior prognostic value in the IMRT era. By combining them with slight modifications, TNM criteria can be unified and its prognostic value be improved.     

鼻腔癌临床TNM新分期的研究

目的根据对目前几种主要鼻腔癌临床分期的分析,提出新的临床分期标准。方法运用122例鼻腔癌患者的临床资料,对目前主要的鼻腔癌临床分期进行分析。并结合临床资料,通过计算机优化和筛选,提出新的临床分期。生存分析采用Kaplan-Meier法,多因素分析采用Cox回归模型。结果根据新的临床分期标准,本组122例中,T1期16例,12期32例,13期42例,T4期32例,其5年生存率分别为78．8％,64．6％,49．9％和30．0％;Ⅰ期患者16例,Ⅱ期患者26例,Ⅲ期患者45例,Ⅳ期患者35例,其5年生存率分别为78．8％,68．4％,51．3％和29．0％。全组总的5年生存率为61．6％。新的临床分期标准结合了现代影像学技术,与现有各分期比较,更符合TNM分期的一般原则,各期例数分布均匀,生存曲线有显著差异。结论新的临床分期标准在各项参数上均优于现存的鼻腔癌各临床分期法,值得临床应用和推广。