BERKELEY, CA (UroToday.com) - Renal tumor is the third urological neoplasm in frequency after prostate cancer and bladder cancer.
The most common histological type is clear cell renal cancer. Several factors, including the TNM stage, the form of presentation, the lymphatic invasion, grade of tumor necrosis, size, histological subtype, or nuclear grade have been proposed as prognostic factors.
The widespread use of Fuhrman classification is due to its proven relationship with other pathological variables (such as tumor stage) so it is included in the main prognostic models such as the UCLA Integrated Staging System or the Karakiewicz nomogram.(1)
However, this is a system with limitations. Thus, it is a subjective method, since it depends largely on the knowledge and skills of the pathologist. An inadequate sample or a defective system of conservation and fixing can alter the result. This classification is based mainly on nuclear characteristics - presence or not of nucleoli and their size. We must point out that sometimes this type of tumor can be quite heterogeneous, with areas of necrosis, areas of oncocytic differentiation, or sarcomatoid areas. In fact, up to a 3% of renal carcinomas may be framed within the group of “not classifiable.”
Thus, in the literature, we found papers in which the intra-variability and inter-observer is not inconsequential. Ficarra et al.(2) present a sample size similar to ours (388) and an interesting design, where a pathologist in a blind manner to a first classification, re-encoded 388 samples and evaluated the degree of concordance. The main conclusion revealed a degree of consistency in the classification of κ:0, 44 being the statistically significant difference. The work of Bektas et al.(3) compares the intra-variability and inter-observer nuclear Fuhrman grade with respect to systems of two and three degrees. 110 Patients with CRCC were included in this study and results were analyzed by five anatomopathologists. Better results were found in two degrees classification versus four degrees (index kappa for assessment intra/inter-observer of the classification in 4 degrees: 0,48/0,41 and for the classification in two degrees of 0,67/0,62).
So, there seems to be a need for revision of this classification to better fit the clinical practice. Our working hypothesis was to demonstrate that new classifications could retain the prognostic value. There are two important works, one American, one European, with a similar objective.
In 2007, Rioux-Leclercq et al.(4) validated the classifications, in two and three degrees, in a multicenter European study of 5453 patients. This work demonstrated that, classic Fuhrman grades or new classifications increased the ability to predict specific cancer mortality, metastasis, or recurrence in a 0.6% against models that did not include the Fuhrman classification or its variants. An important fact of this work is the selection of patients since it not only included patients with clear cell carcinoma but also those with papillary and chromophobe renal carcinoma. It has been demonstrated that the histological type can be a variable of confusion given the prognostic differences between the different histological subtypes.(5) With this premise, we have included only patients with CRCC - which is where it has been demonstrated that the GF is really useful.(6)
This is an important difference from the American study by Sun et al.,(7) which only included patients with CRCC. This study also concluded that the use of the classification into two or three groups maintained the prognostic value. However it pointed our attention in the heterogeneity of the evolution of patients with grade III and IV. Here, in our work, was where we observed a different risk on the probability of local recurrence, regional, metastasis, and cancer-specific survival between these two groups. Our results confirm the hypothesis that simplified Fuhrman grade classifications are as equally valid and accurate as the classic ones for the prognosis of CRCC. Dividing patients into low (I+II), intermediate (III), and high grade (IV) does not imply a loss of information with respect to the classical classification.
Our study has the obvious limitations of a retrospective work and a smaller sample size in comparison with other series, but the resulting conclusions are similar to those of other groups.
- Karakiewicz PI, Briganti A, Chun FK, et al. Multi-institutional validation of a new renal cancer-specific survival nomogram. J Clin Oncol 2007;25:1316–1322.
- Ficarra V, Martignoni G, Maffei N, et al. Original and reviewed nuclear grading according to the Fuhrman system. A multivariate analysis of 388 patients with conventional renal cell carcinoma.. Cancer 2005; 103:68–75.
- Bektas S., Bahadir B., Kandemir O., Barut F., Gul A., Ozdamar S. Intraobserver and interobserver variability of Fuhrman and modified Fuhrman Grading Systems for convencional renal cell carcinoma. Kaohsiung J Med Sci 2009;25:596–600
- Rioux-Leclercq N, Karakiewicz PI, Trinh QD, et al. Prognostic ability of simplified nuclear grading of renal cell carcinoma. Cancer 2007;109:868–874.
- Cheville JC, Lohse CM, Zincke H, et al. Comparison of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol. 2003;27:612–624.
- Medeiros LJ, Jones EC, Aizawa SA, et al. Grading of renal cell carcinoma: Workgroup No. 2. Cancer. 1997;80:990–991.
- Sun M, Lughezzani G, Jeldres C, Isbarn H, Shariat SF, Arjane P, A Proposal for Reclassification of the Fuhrman Grading System in Patients with Clear Cell Renal Cell Carcinoma. Eur Urol 2009;56:775 – 781
Eduardo Morán Pascual as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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