Prognostic role of the immunohistochemical expression of proteins related to the renin-angiotensin system pathway in nonmetastatic clear cell renal cell carcinoma.

INTRODUCTION: Stage migration has been observed in renal cell carcinoma (RCC) in recent decades; however, mortality rates have continuously increased in some countries. Tumoral factors have been characterized as major predictors of RCC. Nonetheless, this concept can be improved by combining these tumoral factors with other variables, including biomolecular factors. PURPOSE: This study aimed to assess the immunohistochemical (IHC) expression and prognostic value of renin (REN), erythropoietin (EPO), and cathepsin D (CTSD), and to evaluate whether the concomitant expression of these markers can influence the prognostic outcomes in patients without metastasis. MATERIAL AND METHODS: In total, 729 patients with clear cell RCC (ccRCC) who underwent surgical treatment between 1985 and 2016 were evaluated. All the cases in the tumor bank were reviewed by dedicated uropathologists. The IHC expression patterns of the markers were assessed using a tissue microarray. REN and EPO were classified as "positive" or "negative" expression. CTSD was grouped into "absent or weak expression" or "strong expression." Associations between clinical and pathological variables and the studied markers, in addition to 10-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival rates, were described. RESULTS: REN and EPO expressions were positive in 70.6% and 86.6% of patients, respectively. Absent or weak and strong expressions of CTSD were observed in 58.2% and 41.3% of the patients, respectively. EPO expression had no impact on survival rates even when assessed concomitantly with REN. Negative REN expression was associated with advanced age, preoperative anemia, larger tumors, perirenal fat, hilum or renal sinus infiltration, microvascular invasion, necrosis, high nuclear grade, and clinical stages III to IV. In contrast, strong CTSD expression was associated with poor prognostic variables. The expression patterns of REN and CTSD were unfavorable predictors of the 10-year OS and CSS. In particular, the combination of negative REN and strong CTSD expression had a negative impact on these rates, including a higher risk of recurrence. CONCLUSION: Loss of REN expression and strong CTSD expression were independent prognostic factors in nonmetastatic ccRCC, particularly when the concomitant expression pattern of both markers was present. EPO expression did not influence survival rates in this study.

Advanced renal cell carcinoma (RCC) management: an expert panel recommendation from the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG).

PURPOSE: The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients. METHODS: Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session. RESULTS: The recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available. CONCLUSION: This manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations.

Prognostic value of PD-L1 expression for surgically treated localized renal cell carcinoma: implications for risk stratification and adjuvant therapies.

BACKGROUND: We aimed to evaluate the prognostic role of programmed-death receptor ligand (PD-L1) in a multinational cohort of patients with localized renal cell carcinoma (RCC). METHODS: Formalin-fixed paraffin-embedded blocks of 1017 patients from the Latin American Renal Cancer Group were analyzed. Tissue microarrays were immunostained for PD-L1 using a commercially available monoclonal antibody. Expression of PD-L1 in ⩾5% tumor cells was considered positive. PD-1 expression in immune cells was also assessed. All cases were reviewed twice based on antibody expression and compared with a positive control. Cox proportional hazard regression models were used to identify predictors of recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total of 738 cases with complete follow up met criteria. Median age was 57 [interquartile range (IQR): 49-64] years, and median follow up was 34 (IQR: 15-62.9) months. Median tumor size was 5 cm (IQR: 3.0-7.5 cm). Approximately 8.2% and 7.6% of tumors were PD-L1 and programmed cell-death 1 (PD-1) positive, respectively. PD-L1 and PD-1 positivity were significantly associated with higher tumor stage (both p < 0.001), and presence of tumor necrosis and lymphovascular multivariable analyses; PD-L1 positivity was found as a predictor of worse RFS [hazard ratio (HR) = 2.08, p = 0.05] and OS (HR = 2.61, p = 0.02). CONCLUSIONS: PD-L1 positivity was significantly associated with worse outcomes for patients with localized RCC at intermediate follow up. This marker may help stratify patients for stricter surveillance after surgical treatment and provide a basis for checkpoint-inhibitor therapy in the adjuvant setting.

Immunohistochemical expression of renin is a prognostic factor for recurrence in nonmetastatic renal cell carcinoma.

PURPOSE: To analyze the intratumoral immunohistochemical expression of renin and its value as a prognostic factor for recurrence in nonmetastatic clear cell renal cell carcinoma (ccRCC). METHODS: A total of 498 patients with nonmetastatic ccRCC from the Latin American Renal Cancer Group database who underwent partial or radical nephrectomy between 1990 and 2016 were selected. All cases were revised, and 2 distinct samples were obtained for tissue microarray construction. Ten years of follow-up was assessed, and disease-free survival rates (DFS) were analyzed. Renin expression was classified qualitatively as negative or positive. For the quantitative analysis, a cutoff was estimated using the maximum of the standardized log-rank statistic. RESULTS: Nuclear renin was qualitatively positive in 360 cases (72%) and negative in 138 (28%), whereas quantitatively, an equal number of cases had ≤35% or >35% renin-positive nuclei. The absence of renin expression was associated with high-grade tumors (by ISUP and Fuhrman classification, both P < 0.001), greater microscopic venous invasion (P = 0.046), and renal vein invasion (P = 0.026). In the multivariate analyses, qualitatively negative renin expression was an unfavorable prognostic factor for DFS (RR = 2.923, P < 0.001). With regard to quantitative renin expression, a cutoff of ≤35 was associated with worse DFS (RR = 4.085, P < 0.001). CONCLUSIONS: The intratumoral immunohistochemical expression of renin in patients with ccRCC provides valuable prognostic data regarding the likelihood of recurrence.

Renal cell cancer treatment: an expert panel recommendation from the Latin American cooperative group-genitourinary and the Latin American renal cancer group: focus on surgery.

BACKGROUND: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline. METHODS: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session. RESULTS: The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D. CONCLUSIONS: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.