Kidney cancer. Principles and practice. Second edition. Primo N. Lara, Jr. Eric Jonasch (Editors). Springer International Publishing (2015)
Proper selection of patients who may benefit from adjuvant therapy is dependent upon an accurate and reproducible assessment of risk. Risk assessment is important for identifying patients with significant enough chance of recurrence to warrant additional treatment while sparing patients at lower risk from the potential toxic effects of adjuvant therapy. The most fundamental yet powerful assessment of risk is determination of tumor stage.
Historic staging systems for RCC include those proposed by Flocks and Kadesky , Petkovic , and Robson [6, 7]. The Robson criteria were in common use until the development of the tumor, node, metastasis (TNM) system by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC) (Table 14.1) [8–11]. While the Robson system focused particular attention on differentiating among tumors with spread beyond the kidney, the TNM system has placed more emphasis on discriminating between intrarenal tumors and is therefore particularly appropriate for use in adjuvant therapy decisions in patients having undergone nephrectomy with curative intent. From its inception in 1978, the TNM renal carcinoma staging system has evolved in an attempt to more accurately distinguish T1 and T2 tumors. The most recent 7th Edition of the TNM system has incorporated further changes to finetune risk assessment of tumors confined to the kidney . For example, T2 tumors, previously defined as >7 cm and limited to the kidney, have been subclassified into T2a (>7 cm but =10 cm) and T2b (>10 cm) based on retrospective data suggesting worse survival for larger tumors within this stage . Tumor size has been found to have a significant correlation with outcome when modeled as a continuous variable, suggesting that any arbitrary size cut-point may be associated with a survival difference if the sample size is large enough . A working knowledge of the changing nomenclature of the TNM system is helpful in interpreting historic adjuvant trials in RCC, which have applied various versions of the staging systems over the years.
Table 14.1. TNM staging systems for RCC since 1987 edition
Observed 5-year survival rates from the National Cancer Data Base (2001–2002) using the current AJCC staging system are 80.9% for stage I (T1N0M0), 73.7% for stage II (T2N0M0), 53.3% for stage III (N1 and/or T3), and 8.2% for stage IV (T4 or M1) . It is yet unknown what the impact of multiple new systemic treatments available since 2005 will have on these observed survival rates.
Additional clinical variables have been shown to have prognostic value in RCC beyond TNM stage and include histologic subtype, performance status, Fuhrman nuclear grade, and tumor necrosis [14, 15]. Further refinement of risk has been addressed by the development of several multivariate prognostic systems (Table 14.2). These models differ in their clinical and pathologic covariates, clinical end points, and the constructs of the tool (prognostic category vs. nomogram). The two systems most studied have been the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score and the University of California Los Angeles Integrated Staging System (UISS) [16, 17]. The SSIGN system is based on data from 1,801 patients with clear cell RCC and incorporates TNM stage, tumor size, nuclear grade, and histological tumor necrosis to predict cancer-specific survival . The UISS includes three variables as predictors of overall survival for RCC (inclusive of clear cell and non-clear cell): TNM stage, Fuhrman’s grade, and ECOG PS [17, 18]. Both systems have been externally validated [19–21]. Two postoperative nomograms have been published by researchers at the Memorial Sloan Kettering: a four-variable system based on data from 601 patients predictive of a 5-year recurrence-free survival and a five-variable system specific for clear cell carcinoma from 701 patients and predictive of a 5-year freedom from recurrence [22, 23]. While these nomograms are useful in predicting risk of recurrence for an individual patient, the SSIGN and UISS systems provide stratification into risk groups which are well suited to adjuvant trial design.
Table 14.2. Comparison of RCC prognostic systems
An additional scoring system from the Mayo Clinic was developed to predict progression to metastatic disease as opposed to survival end points . The Leibovich Score incorporates the same variables as the SSIGN system and proposes classification of patients into three risk groups based on score.
[contact-form-7 id=»5168″ title=»Контактная форма 1″]