Moderators: Dr. John Eble and Dr. Brett Delahunt
Section 2 -
Staging of Renal Cell Carcinoma
Stephen M. Bonsib
Renal cell carcinoma (RCC) has a reputation for unpredictable behavior with unusual sites of
metastases, spontaneous regression of metastases, long term survival with metastases, and long interval
between nephrectomy and subsequent metastases. Despite biologic eccentricities the anatomic extent of
disease remains the single most important prognostic feature in renal cell carcinoma (RCC). Stage is
also important in patients with bilateral tumors where the outcome is determined by the individual stage
of each tumor. Therefore accurate staging of a renal tumor is our most important responsibility.
The first staging system for RCC was formulated by Flocks and Kadesky in 1958. The Robson staging
system followed in the 1960s and remained in vogue throughout the 1970s and 80s. The most widely used
staging system today is the TNM system formulated by the American Joint Commission on Cancer (AJCC) and
the International Union Against Cancer (UICC). All 3 systems have in common a renal-limited category, a
category for local spread and a category for distant spread. The TNM classification differs from its
predecessors by having 2 categories for renal limited disease, pT1 and pT2. Each classification has been
shown in large series to stratify patient outcomes by stage, as shown in the tables below. Regrettably,
a significant number of patients succumb to disease despite presenting with putatively renal limited
disease at diagnosis. A lofty goal would be to define a renal limited category with better patient
survivals. It is possible that the 2002 formulation may fulfill this objective as discussed below.
Table 1: Five-year Survival Rate for Renal Cell Carcinoma by Robson Stage
|1st Author ||Year ||# Patients ||Stage 1 ||Stage 2 ||Stage 3 ||Stage 4|
|Robson ||1969 ||88 ||66% ||51% ||33% ||13%|
|McNichols ||1981 ||499 ||67% ||64% ||42% ||11%|
|Selli ||1983 ||115 ||93% ||63% ||80% ||13%|
|Golimbu ||1986 ||326 ||88% ||67% ||40% ||2%|
|Mederios ||1988 ||121 ||85% ||48% ||42% ||0%|
|Dinney ||1992 ||314 ||73% ||68% ||51% ||20%|
Table 2: Collated Survival Data - AJCC/UICC 1987 version
|Stage ||Diagnosis ||Year 1 ||Year 2 ||Year 3 ||Year 4 ||Year 5|
|I ||100% ||94.5% ||91.4% ||89.5% ||87.2% ||84.7%|
|II ||100% ||94.3% ||87.4% ||87.4% ||85.0% ||82.9%|
|III ||100% ||83.1% ||73.4% ||68.0% ||63.1% ||59.8%|
|IV ||100% ||36.6% ||22.6% ||16.7% ||13% ||11.1%|
The TNM staging system is a dynamic formulation, undergoing periodic revisions. Although its capacity
to evolve with advances in understanding tumor biology is strength, it creates difficulties in evaluating
the literature when attempting to compare studies whose patients have been staged using different TNM
versions. Table 3 illustrates the major T-stage differences between the 1978, 1987, and 1997
Table 3: Comparison of Three TNM Formulation
The final patient stage incorporates nephrectomy pathologic features, with other clinical and
pathologic data related to lymph nodes involvement and metastases as shown below.
|T stage ||1978 TNM ||1987 TNM ||1997 TNM|
|pT1 ||"Small tumor" ||< 2.5 cm ||> 2.5 cm|
|pT2 ||"Large tumor" ||< 7.0 cm ||> 7.0 cm|
|pT3 ||Perinephric spread ||-- ||--|
|pT3a ||-- ||Perinephric/adrenal ext ||Perinephric/adrenal ext|
|pT3b ||-- ||RV involved ||RV /VC below diaph|
|pT3c ||-- ||VC below diaphragm ||VC above diaphragm|
|pT4 ||Adjacent organ or abdominal wall ||-- ||Ext beyond Gerota's fas.|
|pT4a ||-- ||Ext. beyond Gerota's fas. ||--|
|pT4b ||-- ||VC above diaphragm ||--|
Table 4: 2002 TNM Staging
2002 TNM Formulation
| ||pT1 ||pT2 ||pT3 ||pT4 ||N ||M|
|Stage I ||X || || || || |
|Stage II || ||X || || || |
|Stage III || || ||X || || |
| ||Or pT 1-3 || || || ||Any N |
|Stage IV || || || ||X ||N 0-1 |
| ||Or any pT || || || ||N 2 |
| ||Or any pT || || || ||N 0-2 ||X|
The 2002 TNM formulation introduced several revisions of the 1997 version following important clinical
and pathologic studies of the late 1990s and early 2000s.
The rationale for pT1 subdivision was based upon outcome data that indicates different recurrence
rates and patient outcomes for pT1 tumors 4-5 cm, compared to larger tumors (Table 5). In a recent
European multi-institutional validation study of 2217 patients with pT1a, pT1b, and pT2 tumors, excellent
stratification in 5- and 10-year disease-specific survival was demonstrated for clear cell renal cell,
although not for papillary renal cell carcinoma.
- pT1a - tumor 4 cm or less
- pT1b - tumor greater than 4 cm to 7 cm.
Table 5: Breakpoint in Patient Outcome versus Tumor Size
|1st Author ||Year ||# Cases ||Tumor Type ||Breakpoint|
|Ficarrio ||2004 ||813 ||RCCa ||5.5 cm|
|Elmore ||2003 ||351 ||RCCa ||5.0 cm|
|Frank ||2002 ||1801 ||RCCa ||5.0 cm|
|Lau ||2002 ||682 ||Clear Cell ||4.5 - 5.0 cm|
|Zisman ||2001 ||661 ||RCCa ||4.5 cm|
|Igarashi ||2001 ||333 ||RCCa (96%CC) ||4 cm|
|Cheville ||2001 ||277 ||RCCa ||5 cm|
|Hafez ||1999 ||485 ||RCCa ||4 cm|
pT3 a, b, and c were expanded:
pT3a and b were expanded because renal carcinomas, especially clear cell renal cell carcinoma, has
been shown to most often extend beyond the kidney by invading the renal sinus. The incidence of sinus
invasion increases markedly for tumors in the 4-5 cm range (Graph 1). Since most sinus invasive tumors
involve muscle containing veins of the renal sinus, this may explain the outcome studies (Table 4) that
show patient outcomes markedly diminish for tumors larger than 4-5 cm.
- pT3a: includes tumor invasion of renal sinus fat
- pT3b: includes involvement of segmental (muscle-containing) branches
- p3Tc: includes invasion of wall of VC (even if below the diaphragm)
Graph 1. Relationship between renal sinus invasion and tumor size: 120 clear cell
renal cell carcinoma (J Urol 174:1-4, 2005)
Future Staging Considerations
pT2 Tumors, should the definition be changed?
Bonsib has shown (Graph 1) that for tumors 4-5 cm, renal sinus invasion is common, and for tumors that
exceed 7 cm, sinus involvement is invariable (>97%). The pT2 category, therefore, contains few tumors
(<1%) when cases are properly examined for sinus involvement minimizing the utility of the category as
currently defined. pT2 should be redefined, possibly reducing it to 4 cm, and deleting subdivision of
In contrast to the above recommendation, the Mayo Clinic group has argued for subdivision of pT2 into
pT2a (tumors 7-10 cm) and pT2b (tumors >10 cm) based upon study of 544 patients treated between 1970
and 2000. They showed a survival difference for "renal limited" tumors 7-10 cm versus tumors >10 cm.
Bonsib's data suggests, however, that a substantial fraction of clear cell carcinomas > 7cm are in
fact pT3 tumors. Assessment of sinus invasion in archival material is difficult since the cases were not
handled to evaluate that feature raising questions regarding the true stage of their tumors.
Adrenal gland invasion, should it be incorporated into pT4?
Adrenal gland involvement can occur by hematogenous metastasis or by direct extension. Metastases
classified in the TNM as M1, occurs in 5%, and correlates with large tumors (ave. 9.8 cm) and high stage
(>80% pT3a or higher). Adrenal gland involvement is included with perinephric fat invasion in 2002
TNM as pT3a. Recent studies have shown that with direct adrenal invasion is there is no difference in
survival between pT4 tumors and pT3 tumors with direct adrenal invasion, leading to the suggestion that
direct extension should be categorized as pT4 in future TNM revisions.
There is little doubt that sinus invasion is the most common route of external extension and usually
involves sinus veins. The 2002 TNM pT3 revision to include sinus involvement should shift cases that
previously would have been categorized as pT1/pT2 to the pT3 category, thereby, improving the survival
curves for truly renal limited Stage 1 and 2 tumors, while worsening
survival curves for stage 3 disease (see Table 6).
Table 6: Preliminary data: Renal Limited Tumors vs Sinus Invasive Tumors
Patients with Metastases or Dead of Disease [Bonsib, S. unpublished data]
This will first require pathologists to incorporate a new strategy for specimen evaluation differing
from that learned during training or applied for years in practice. The protocol must emphasize
appropriately sampling of the tumor sinus interface. Secondly, academicians reporting outcome data
relative to tumor stage should consider the staging of archival material collected prior to 2002 as
suspect, and must consider only including cases accessioned after their laboratory implemented evaluation
protocols that satisfy the new staging definitions in future outcome analyses.
| ||< 6 months ||6-12 month ||1-3 years ||> 3 years ||Total|
|Sinus pos ||22/30 ||5/8 ||13/17 ||2/7 ||42/62 (68%)|
|Sinus neg ||1/17 ||1/11 ||1/21 ||0/10 ||3/60 (5%)|
|Total cases || || || || ||122 cases|
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- Han K-R, Bui MHT, Pantucl, AJ, et al. TNM T3a renal cell carcinoma: adrenal gland involvement is not the same as perinephric fat involvement. J Urol 169: 899-904, 2003.
- Thompson RH, Cheville, JC, Lohse CM, et al. Reclassification of patients with pT3 and pT4 renal cell carcinoma improves prognostic accuracy. Cancer 104:53-60, 2005.
- Frank I, Blute ML, Leibovich BC, et al. pT2 classification for renal cell carcinoma. Can its accuracy be improved?