Prognosis and Clinicopathological Characters of Adult TFEB-Altered Renal Cell Carcinoma: A Single Center Experience of 18 Cases.

INTRODUCTION: TFEB-altered renal cell carcinoma (RCC) is a rare entity characterized by the rearrangement of the TFEB gene or TFEB amplified. The therapeutic implications and long-term survival of TFEB-altered RCC remain unclear, especially for metastatic cases. MATERIALS AND METHODS: The current study initially enrolled 7604 consecutive RCC patients at our center and a total of 248 patients were selected for FISH and immunohistochemistry (IHC) analysis. Eventually, eighteen TFEB-altered RCC patients were identified. We then reported the clinical, morphological, IHC, and radiological features of these cases. RESULTS: The median age at initial diagnosis was 45 years, ranging from 18 years to 66 years. The majority of the TFEB-altered RCC patients were male (61.1%), with localized disease (T1-2N0M0, 77.8%). The median split TFEB fluorescent signal was 24%, ranging from 15%-80%. The morphological characteristics of TFEB-altered RCC were variable, with acinar, papillary, solid, or nest patterns. IHC and magnetic resonance imaging features of TFEB-altered RCC were nonspecific. Nine patients with localized disease received partial nephrectomy and five patients with localized disease received radical nephrectomy. During the median follow-up of 67 months, no signs of recurrence or metastasis were found in these patients. Two patients had distant metastasis and received axitinib plus PD-1 immunotherapy. One of them died at 40-month follow-up and another still alive at 88-month follow-up. CONCLUSION: TFEB-altered RCC is an extremely rare variant, exhibited mixed morphological characteristics. The radiological feature lack specificity, resembling clear cell RCC or papillary RCC. Genetic analyses including FISH analysis is crucial in the diagnosis of TFEB-altered RCC. For localized TFEB-altered RCC, both radical nephrectomy and partial nephrectomy conferred satisfactory prognosis. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy.

Dynamic alteration and prognostic significance of tumor-associated CD68+ and CD68+ PD-L1- macrophages in muscle-invasive bladder cancer treated with neoadjuvant chemotherapy.

BACKGROUND: The current study aimed to investigate the dynamic alteration and prognostic significance of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and PD-L1 status of immune cells in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC). METHODS: Multiplex immunofluorescence staining was performed to examine CD68+ TAM, CD4+ T cell, CD8+ T cell, FOXP3+ Treg cell, and PD-L1 expression in paired MIBC tissues (n = 54) before and after NAC. Patients were then divided into definite responders (DR), (≤pT1) and incomplete responders (IR). RESULTS: There was no significant difference between DR and IR cohorts for the immune cell infiltration levels at the baseline status. Tobacco history was identified to be associated with worse NAC efficacy. CD68+ (stroma area: p = 0.025; tumor area: p = 0.028; total area: p = 0.013) and CD68+ PD-L1- (stroma area: p = 0.035; tumor area: p = 0.013 total area: p = 0.014) TAMs infiltration levels decreased significantly after NAC, while there was no significant difference of CD68+ PD-L1+ and TILs. The infiltration of CD68+ (p = 0.033), CD68+ PD-L1- (p = 0.033), and CD68+ PD-L1+ (p < 0.001) TAMs in stroma area were significantly associated with poorer disease-free survival rate (DFS) of MIBC patients. CONCLUSION: CD68+ and CD68+ PD-L1- TAMs infiltration levels decreased significantly after NAC and pre-treatment TAM infiltration levels were independent prognostic factors for MIBC patients. While there was no sufficient evidence demonstrating that pre-treatment TILs or TAMs could predict response to NAC in MIBC patients.

Disease Management of Clinical Complete Responders to Neoadjuvant Chemotherapy of Muscle-Invasive Bladder Cancer: A Review of Literature.

Muscle-invasive bladder cancer (MIBC) is an aggressive disease requiring active management. Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is considered the standard treatment paradigm for MIBC patients, which could result in significant perioperative mortality and morbidity, as well as the significant alteration of the quality of life (QOL). Notably, multimodal bladder-preserving treatment strategies have been recommended for highly selected patients. Pathologic complete response (pCR) after NAC is a powerful prognostic indicator of survival for patients with MIBC. Clinical complete response (cCR) is then introduced as a complementary endpoint for pCR to assess disease status preoperatively. Bladder preservation strategy for patients who achieve cCR following NAC is emerging as a new treatment concept. However, the efficiency of the conservative strategy remains controversial. In this state-of-the-art review, we discuss the advantages and limitations of cCR and the feasibility and safety of bladder preservation strategy in highly selected MIBC patients who achieve cCR following NAC. We conclude that a conservative strategy can be considered a reasonable alternative to RC in carefully selected cCR MIBC patients, leading to acceptable oncological outcomes.