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Renal Cell Carcinoma
Table 1: The Tumour, Nodes and Metastasis Staging System
stratification prognosis for patients with pT3–T4 RCC.
17
In 2006 it was
reported that the relative risk of death from RCC in T3a, T3b, T3c and T4
Stage I T1 N0 M0
disease was 11.11 compared with T1 disease. The relative risk of death
Stage II T2 N0 M0
of N1 and N2 disease was 6.77 compared with N0 and Nx disease.
14,18
Stage III T1 N1 M0
There is also debate over the precise thresholds of tumour size and the
T2 N1 M0
significance of tumour thrombus, peri-renal/sinus fat involvement,
T3 N0 M0
T3 N1 M0
adrenal development and lymphadenopathy used in the system.
14
T3a N0 M0
T3a N1 M0 Other Pathological Factors
T3b N0 M0
There are a number of histological subtypes of RCC that can be related
T3b N1 M0
to differing tumour aggressiveness.
14
The four main subtypes of RCC,
T3c N0 M0
as defined by the Heidelberg classification system, are clear-cell,
T3c N1 M0
papillary, chromophobe and collecting-duct.
5
The clear-cell subtype
Stage IV T4 N0 M0
T4 N1 M0
makes up 70–80% of all RCC cancers. Chromophobe RCC accounts for
Any T N2 M0
5–10% of RCC and has a better prognosis than the other main
Any T Any N M1 subtypes. Papillary RCC is the second most common type of RCC,
Using the TNM staging system, stage I tumour classification relates to small tumours (less
accounting for 10–15% of all cases. Clinical opinion suggests that
than one inch) with no evidence of local invasion, no lymph node involvement and absence
patients who have a curative resection for papillary carcinoma may do
of distant disease. Stage II relates to tumours larger than one inch with no evidence of local
invasion, no lymph node involvement and absence of distant disease. Stage III relates to better than those with clear-cell RCC. However, relapsed papillary
tumours of any size that involve one lymph node (less than one inch), tumours that invade
carcinoma is aggressive and difficult to treat. Collecting-duct carcinoma
the adrenal gland or surrounding renal tissues and tumours that invade the renal vein or the
inferior vena cava. Stage IV relates to a mixed group, including tumours that invade adjacent is one of the rarer forms of RCC, comprising less than 1% of all cases;
structures, any tumour that has evidence of distant spread and any tumour in which more
than one lymph node is involved.
these tumours are generally aggressive, and disease is often found to
be metastatic on diagnosis.
14
Primary Tumour
TX Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tumours displaying sarcomatoid features have been identified collectively
T1 Tumour 7cm or less in greatest dimension, limited to the kidney
T1a Tumour 4cm or less in greatest dimension, limited to the kidney as leading to a poor prognosis, and have been associated with reduced
T1b Tumour more than 4cm but not more than 7cm in greatest
response to immunotherapy treatments. There is some debate as to
dimension, limited to the kidney
T2 Tumour more than 7cm in greatest dimension, limited to the kidney whether these tumours are a further specific subtype of RCC, or whether
T3 Tumour extends into major veins or invades adrenal gland or
perinephric tissues, but not beyond Gerota’s fascia
the features of sarcomatoid tumours are poorly differentiated tumours
T3a Tumour directly invades adrenal gland or peri-renal and/or
that can be associated with any of the histological subtypes.
12,14
renal sinus fat but not beyond Gerota’s fascia
T3b Tumour grossly extends into the renal vein or its segmental (muscle-containing)
branches, or vena cava below the diaphragm
The tumour grading of clear-cell carcinomas has been a well documented
T3c Tumour grossly extends into vena cava above diaphragm or invades the wall of
the vena cava
and well recognised independent prognostic tool. The Fuhrman nuclear
T4 Tumour invades beyond Gerota’s fascia
grading system is based on tumour-cell nuclear characteristics – size,
Regional Lymph Nodes (N) contour and nucleoli.
8
These measurements correlate with tumour stage,
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastases
tumour size, development of distant metastases, lymph node
N1 Metastases in a single regional lymph node involvement, renal vein (RV) involvement and peri-renal fat involvement.
N2 Metastasis in more than one regional lymph node
This grading system has been proved as a prognostic tool for RCC and
Distant Metastasis (M)
has been validated in a study of five-year cancer-specific survival rates for
MX Distant metastasis cannot be assessed
M0 No distant metastasis
clear-cell carcinomas following surgical resection of the tumour.
8
Tumour
M1 Distant metastasis
grading using this system has yet to be fully validated for papillary or
Adapted from AJCC Cancer Staging Manual, Sixth Edition (2002), Springer-Verlag, chromophobe carcinomas.
12,14
New York.
http://www.nccn.org/professionals/physician_gls/PDF/kidney.pdf The presence of histological necrosis has been shown to be an adverse
prognostic feature of clear-cell carcinomas. It has been shown in a recent
revised regularly since it was first used to improve its prognostic accuracy, study to confer a two- to three-fold higher risk of death from RCC than
the last review being in 2002.
16
in patients with no tumour necrosis.
12,14
These clinical factors can be
combined with conventional staging systems such as TNM to increase the
RCCs were first classified using the TNM system in 1974, and a number accuracy of the evaluation and prognosis.
14
of studies have shown the system to be accurate in echoing RCC
prognosis. The assessment of RCC using TNM is based on the clinical Non-pathological Factors
presentation and evaluation of the tumour extent during surgical The system of measuring Eastern Co-operative Oncology Group
resection of the primary tumour, with advanced RCC being classed as (ECOG) Performance Status is an independent prognostic tool for RCC.
stage IV. However, a number of recent studies have debated the The ECOG Performance Status is a scoring system based on the
prognostic accuracy of using the TNM system for RCC staging, in ambulatory status of a patient and represents the impact of the
particular in relation to prognoses of locally advanced renal cell disease on the overall health of the patient (see Table 2). The ECOG
carcinoma (pT3–T4 RCC).
14
The 2002 revision of the TNM system has system is currently used for stratifying patients into clinical trials and
been shown in a number of studies not to provide an appropriate for assessing eligibility for immunotherapy regimes.
8
The system has
44 EUROPEAN GENITO-URINARY DISEASE 2007
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