Editorial Comment to Localized non‐conventional renal cell carcinoma: Prediction of clinical outcome according to histology

Renal cell carcinoma (RCC) is not a single disease, but represents a heterogeneous disease each caused by a different gene. Recently, a significant alteration of the RCC classification has been shown, mainly as a result of the advances in our understanding of molecular pathology. VHL is the gene associated with clear cell RCC. In non-clear cell RCC, various genes have been identified from the investigation of hereditary forms.1 MET and fumarate hydratase are the genes associated with types 1 and 2 papillary RCC, respectively.1 BHD is the gene associated with chromophobe RCC.1 In addition, as the MiT family translocation RCC, Xp11 translocation RCC and t(6;11) RCC categories have been established.2 Thus, in recent years, progress has been made in discovering the genes responsible for non-clear RCC and in identifying the signals they mediate. In this issue of International Journal of Urology, Kim et al. reported the results of a single institutional retrospective study of East Asian patients with localized non-clear cell RCC that was designed to determine the outcomes of patients with this disease and the prognostic factors. The present study comprised patients with various subtypes of RCC, including 126 (33.7%) papillary cases; 164 (43.9%) chromophobe cases; eight (2.1%) collecting duct cases; 40 (10.7%) unclassified cases; and 16 (4.3%) Xp11.2 translocation cases.3 As expected from clinical practice and previous reports,4, 5 the chromophobe RCC showed the best prognosis, whereas the collecting duct of Bellini RCC showed the worst. Recently, a large multi-institutional international study of patients with metastatic RCC (n = 252) also reported that those with metastatic chromophobe RCC had the longest survival period among patients with non-clear cell RCC.5 Importantly, the study by Kim et al. also reported that these histological subtypes were removed as a prognostic factor from the multivariate model.3 As approximately 10% of patients with localized RCC showed recurrence of the disease, the overall survival period should depend more on the presence or absence of recurrence than on the length of the survival period between recurrence and death. The presence or absence of recurrence might depend on T stage, sarcomatoid differentiation and lymphovascular invasion rather than on the pathological subtype. This is similar to what was reported previously.4 Throughout the present study, I confirmed that it is possible to decide the clinical plan for patients with localized RCC regardless of the pathological subtypes. TNM stage and performance status can be used to determine whether or not the patient should undergo radical nephrectomy. However, as different subtypes might respond differently to different therapies, a treatment strategy that relies on histological subtypes should be considered once the patient develops metastatic disease. In order to improve the clinical outcome of “this rare entity”, the patients with non-clear cell RCC, further investigations should be designed to clarify the carcinogenic mechanism underlying this disease. None declared.