Staging and Classification Systems of Renal Cell Carcinoma


In both clinical and scientific classification of renal cell carcinoma, it is recommended to use Tumour Node Metastasis (TNM) classification used in almost all cancers today. [1]
Tumour Node Metastasis (TNM) classification is very helpful and important in determining both treatment and prognosis. However, when the diagnosis is made, the classification is not sufficient. During the whole process, the Tumour Node Metastasis (TNM) classification of the tumour should be reviewed and re-performed. [2, 3]
With a publication published in 2012, the final version of the Tumour Node Metastasis (TNM) classification was confirmed by both single and multiple institution studies. [4, 5]

1. Staging

Factors currently used in Tumour Node Metastasis (TNM) classification include tumor size, venous invasion, renal capsular invasion, adrenal gland involvement, lymph node involvement and distant metastases.

The first letters of the Tumour Node Metastasis (TNM) classification indicates the different properties of the primary tumor. The letter T stands for the size of the tumor, the letter N for lymph node involvement and the letter M stands for distant metastasis.

You can find a summary of Tumour Node Metastasis (TNM) classification at the bottom. Click here to directly access the table.

a. T – Primary Tumor

Here, the letters and numbers next to the letter T provide information about the size and invasion of the tumor.

Tx means that the tumor cannot be assessed.

T1/T1a/T1b

T1 indicates that the tumor is 7 cm or smaller in size and limited to the kidney.

If the tumor size is 4 cm or smaller, then T1a expression is used. If the primary tumor is larger than 4 cm but has a size of 7 cm or smaller, then T1b is used.

T2/T2a/T2b

The tumors included in the T2 classification are tumors larger than 7 cm in size and limited to the kidney.

This section is also divided into two in itself. T2a indicates that the tumor is larger than 7 cm but has a size of 10 cm or less. In addition, T2b is used for masses that are limited to the kidney and are larger than 10 cm.

T3/T3a/T3b/T3c

T3 is used when the tumor extends to perirenal tissues or major veins such as the vena cava. However, the masses in this classification have not yet gone beyond the ipsilateral adrenal gland or Gerota fascia.

The T3 classification is divided into three sub-sections.

T3a is used if the tumor is extended to the renal vein or segmental branches of the renal vein, or extended to the perirenal and/or renal sinus adipose tissue (peripelvic fat tissue) but not beyond the Gerota fascia.

If the tumor has grossly extended to the vena cava under the diaphragm, it is expressed by T2b, if it has grossly extended to vena cava over the diaphragm, and if there is involvement in the vessel wall then it is expressed byT3b.

T4

Finally, the T4 classification indicates that the tumor invades the Gerota fascia, including the ipsilateral adrenal gland.

b. N – Regional Lymph Nodes

The letter N and the numbers next to it indicate whether the tumor extends into regional lymph nodes, and if so, what degree of involvement.

If regional lymph nodes cannot be evaluated, they are indicated by Nx.

N0

N0 is used to refer to the absence of tumor involvement in any regional lymph node.

N1

N1 classification is used for kidney tumors that have metastasized to regional lymph nodes.

c. M – Distant Metastasis

It is perhaps one of the most important sub-classifications in the Tumour Node Metastasis (TNM) classification. The letter M indicates whether the tumor is metastasized or not. If the tumor is metastasized, it means a stage 4 tumor regardless of any other values. In this case, the overall clinical course, treatment, and prognosis vary greatly.

M0

If the renal tumor is not metastasized to distant organs, then M0 is used.

M1

However, if the tumor has metastases to distant organs, M1 is used, indicating that the tumor is stage 4.

d. Summary Tables

T: Size and Invasion of Primary Tumor
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
T1 Tumour ≤ 7 cm or less in greatest dimension, limited to the kidney
T1a Tumour ≤ 4 cm or less
T1b Tumour > 4 cm but < 7 cm
T2 Tumour > 7 cm in greatest dimension, limited to the kidney
T2a Tumour > 7 cm but ≤ 10 cm
T2b Tumours > 10 cm, limited to the kidney
T3 Tumour extends into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota fascia
T3a Tumour grossly extends into the renal vein or its segmental (muscle-containing) branches, or tumour invades perirenal and/or renal sinus fat (peripelvic fat), but not beyond Gerota fascia
T3b Tumour grossly extends into the vena cava below diaphragm
T3c Tumour grossly extends into vena cava above the diaphragm or invades the wall of the vena cava
T4 Tumour invades beyond Gerota fascia (including contiguous extension into the ipsilateral adrenal gland)
N: Regional Lymph Node Involvement
NxRegional lymph nodes cannot be assessed
N0No regional lymph node metastasis
N1Metastasis in regional lymph node(s)
M: Distant Metasasis
M0No distant metastasis
M1Distant metastasis

2. Uncertainties in Tumour Node Metastasis (TNM) Classification

Although TNM classification is used frequently nowadays, it still has some uncertainties. The current classification currently includes factors such as tumor size, invasion, metastasis, but the existing uncertainties related to these can be listed as follows;

  • Using a cut-off point of 4 cm might not be useful for the treatment of localized cancer as nephron-sparing surgery, in the subclassification of T1 tumors.
  • The stratification of size values used in the subclassification of T2 tumors is still questioned. [6]
  • All tumors with renal sinus adipose tissue invasion have been classified as pT3a since the 2002 version of Tumour Node Metastasis (TNM) Classification.
  • Renal sinus adipose tissue invasion may lead to a worse prognosis than perirenal adipose tissue invasion in some cases, but both are still classified as T3a. [7, 8, 9]
  • In some cases, subclassifications such as T2b, T3a, T3c, and T4 may be overlap. [5]
  • An accurate pre-operative imaging examination with chest and abdominal computerized tomography (CT) is essential for an adequate M classification. [10, 11]

3. Pathologic Tumour Node Metastasis Classification (pTNM)

Once the tumor is diagnosed, individual values are determined according to each letter in the Tumour Node Metastasis (TNM) classification based on size, surrounding tissue and lymph node invasion and presence of distant metastasis. These values are then grouped together to form the pTNM classification, expressed as pathological Tumour Node Metastasis (TNM) classification.

There are 4 stages in this classification. Each stage was formed according to different combinations of T, N, and M.

You can find a summary of Pathological Tumour Node Metastasis (TNM) classification at the bottom. Click here to directly access the table.

a. Stage I

All of the tumors involved in Stage I is in the T1 subgroup of Tumour Node Metastasis (TNM) classification. Also, none of these tumors had lymph node involvement or distant metastasis. Therefore, tumors in this group are T1, N0, and M1.

b. Stage II

Tumors in Stage II are similar to Stage I. None of the tumors in this group had lymph node involvement or distant metastasis. However, unlike Stage I, the tumors in this group have T2 values in the T subgroup in Tumour Node Metastasis (TNM) classification.

c. Stage III

There are multiple combinations in TNM classification on Stage III.

If the value of the tumor in the T subgroup according to TNM classification is T3 and there is no lymph node invasion or distant organ metastasis which means N0 and M0, it is grouped into Stage III.

However, if the lymph node invasion present which meaning N1, tumors that classified as T1 and T2 are also included in this group.

d. Stage IV

The tumors in this group are those in T4 in the T subgroup according to Tumour Node Metastasis (TNM) classification and do not have any lymph node invasion or distant metastasis.

The other tumors in Stage IV are those with distant metastases, as mentioned earlier. Therefore, the values of the T or N classifications of these tumors are not significant. They have the value of M1, in the Tumour Node Metastasis (TNM) classification

e. Table

Pathological Tumour Node Metastasis (pTNM) Classification
Stage I T1, N0, M0
Stage II T2, N0, M0
Stage III T3, N0, M0
T1/T2/T3, N1, M0
Stage IV T4, any N, M0
Any T, any N, M1

For more information and specific questions about the Staging and Classifications of Renal Cell Carcinoma, a help desk is available in the link below:
Help Desk for TNM Classification of Renal Cell Carcinoma


4. Anatomical Classifications

There are also many objective anatomical classifications within the staging and classification systems of renal tumors. Some of those can be listed as; [12, 13, 14]

  • Preoperative Aspects and Dimensions Used for an Anatomical (PADUA)
  • R.E.N.A.L. Nephrometry Score
  • C-index, an Arterial Based Complexity (ABC) Scoring System
  • Zonal NePhRO Scoring System

Factors considered within these systems include tumor size, exophytic or endophytic properties, proximity to the collecting system and renal sinus, anterior / posterior or lower / upper pole location.

The primary purpose of using such a system is to objectively estimate the morbidity of treatment options such as nephron-sparing surgery or tumor ablation. At the same time, these classification systems can be used in the planning of treatment, patient consultations or to compare the treatment techniques such as surgery and ablation.

However, when trying to choose optimal treatment, it should not be fixed only on the scores of anatomical classification systems. In addition, the characteristics of the patient and the experience of the surgeon are extremely important.


References(Show/Hide)

1. Brierley J.D. et al. TNM classification of malignant tumors. UICC International Union Against Cancer. 7th edn. Brierley J.D., Gospodariwicz M., Wittekind C. (eds). Wiley-Blackwell, 2009.

2. Moch, H., et al. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours. Eur Urol, 2016. 70: 93.

3. Gospodarowicz, M.K., et al. The process for continuous improvement of the TNM classification. Cancer, 2004. 100: 1.

4. Kim, S.P., et al. Independent validation of the 2010 American Joint Committee on Cancer TNM classification for renal cell carcinoma: results from a large, single institution cohort. J Urol, 2011. 185: 2035.

5. Novara, G., et al. Validation of the 2009 TNM version in a large multi-institutional cohort of patients treated for renal cell carcinoma: are further improvements needed? Eur Urol, 2010. 58: 588.

6. Waalkes, S., et al. Is there a need to further subclassify pT2 renal cell cancers as implemented by the revised 7th TNM version? Eur Urol, 2011. 59: 258.

7. Bertini, R., et al. Renal sinus fat invasion in pT3a clear cell renal cell carcinoma affects outcomes of patients without nodal involvement or distant metastases. J Urol, 2009. 181: 2027.

8. Poon, S.A., et al. Invasion of renal sinus fat is not an independent predictor of survival in pT3a renal cell carcinoma. BJU Int, 2009. 103: 1622.

9. Bedke, J., et al. Perinephric and renal sinus fat infiltration in pT3a renal cell carcinoma: possible prognostic differences. BJU Int, 2009. 103: 1349.

10. Heidenreich, A., et al. Preoperative imaging in renal cell cancer. World J Urol, 2004. 22: 307.

11. Sheth, S., et al. Current concepts in the diagnosis and management of renal cell carcinoma: role of multidetector ct and three-dimensional CT. Radiographics, 2001. 21 Spec No: S237.

12. Klatte, T., et al. A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy. Eur Urol, 2015. 68: 980.

13. Spaliviero, M., et al. An Arterial Based Complexity (ABC) Scoring System to Assess the Morbidity Profile of Partial Nephrectomy. Eur Urol, 2016. 69: 72.

14. Hakky, T.S., et al. Zonal NePhRO scoring system: a superior renal tumor complexity classification model. Clin Genitourin Cancer, 2014. 12: e13.

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