IJU this issue

Abstract

I would like to focus on two articles about renal cell carcinoma (RCC) that might interest experts. It has been believed that RCC in end-stage renal disease has a favorable prognosis in comparison with RCC in non-end-stage RCC. This might not be true, reflecting a lead-time bias because RCC arising in end-stage renal disease is likely to be found earlier as a result of periodic examinations. Song et al. (Seoul, Korea) described the clinical features of RCC arising in end-stage renal disease, and compared survival outcomes with a matched cohort in Korean patients. They collected data of 181 consecutive patients with end-stage renal disease RCC who had received surgical treatment between 1995 and 2011 at seven institutions in Korea. Data of 362 non-end-stage renal disease RCC patients, who received surgery at Asan Medical Center during the same period, were matched for clinicopathological parameters. They concluded that end-stage renal disease RCC seems to have comparable stage-specific recurrence-free, but poorer cancer-specific survival (CSS) and overall survival compared with non-end-stage renal disease RCC. Notably, the median tumor size was as low as 2.5 cm; however, CSS at 5 years was as low as 81.6%. This is unexpectedly poor survival. The percentage of clear cell RCC is only 63% in this cohort. It should be noted that the pathological features are not matched, because only end-stage-RCC has the two special pathological entities including clear cell papillary and acquired cystic disease-related. However, this study provides very important information that end-stage renal disease RCC has poorer CSS in contrast to the previous reports. It can be easily understood that overall survival in end-stage renal disease RCC patients in poorer because of the comorbidities. However, the poor CSS is not easily understood. Is the reason due to the host? The authors speculated that end-stage renal disease RCC patients might have suppressed immunological systems. A deteriorated immune system might be related to RCC recurrence. As an index of inflammation and host immunity, they used the neutrophil lymphocyte ratio. The neutrophil lymphocyte ratio had no impact on the survival outcomes. The next step is to clarify the molecular and biological features of end-stage renal disease RCC. Even if the subtype of RCC (clear cell, papillary or chromophore) is the same, the biological characteristics might be different. Therefore, deep sequences using next-generation sequencers might provide insight into this issue. Lynch syndrome is a multicancer syndrome, where colorectal cancer is most prevalent, characterized by the development of mismatch repair (MMR)-deficient tumors. In the urological field, Lynch syndrome is known for the involvement of upper urothelial cancer and prostate cancer. However, RCC has not been focused on. Therkildsen et al. (Copenhagen, Denmark) reported 13 RCC among 1445 mutation cancers in the Danish Cancer Registry. Interestingly, urothelial cancer have been linked to a mutation in MSH2, and RCC was associated with MLH1 in six cases, MSH2 in six cases and MSH6 in one case. In Lynch syndrome-associated tumors, marked infiltration of lymphocytes is observed. In accordance with this, Lynch syndrome has gained much attention for its optional treatment by immune checkpoint inhibitors. Colorectal tumors with a high Th1/cytotoxic T lymphocytes infiltrate had defects in MMR. Conceivably, increased mutational burden creates neoepitopes responsible for immune response. RCC is known for tumor-infiltrating lymphocytes. It is worth carrying out future studies to investigate the difference between lymphocytes in Lynch syndrome and conventional tumor-infiltrating lymphocytes. Furthermore, MMR-deficient tumors, either inherited or sporadic, might relate to the resistance of RCC to molecular targeted therapy. An optional approach to MMR gene testing needs to be introduced in specific clinicopathological situations including primary or secondary resistance by tyrosine kinase inhibitors. None declared.