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

Abstract

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.

The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

“…If PD-L1 levels in tumor cells were linked to clinical and pathological features, the PD-L1 inhibitors would inhibit the tumor biology, such as invasion, recurrence, and metastasis, etc. In the study, PD-L1 was related to UTUC in T stage and tumor grade, and similar findings have been indicated in both UTUC and other types of tumors ( 23 , 24 , 32 , 33 ). Results indicated that PD-L1 could not promote the LVI of UTUC, while great heterogeneity existed in the five studies ( 13 , 15 – 17 , 24 ).…”

The prevalence and prognostic and clinicopathological value of PD-L1 and PD-L2 in renal cell carcinoma patients: a systematic review and meta-analysis involving 3,389 patients

“…Further well-designed, large cohort studies need to be conducted in order to confirm this trend. Additionally, as was revealed in a previous study (40), PD-L1 status was associated with the prognosis of kidney cancer patients which could help stratify patients for stricter surveillance.…”

“…In the remaining 94 records, 78 of records were excluded because they were study samples, not published in English, or did not have sufficient information for OS, PFS, DFS, or relapse-free survival (RFS) calculation. After screening for the form of data reporting, 16 retrospective cohort studies (3,389 patients) (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were pooled in the final meta-analysis (shown in Figure 1).…”

Epidemiology of Renal Cell Carcinoma

“…The IHC stain for the immunosuppressive marker programmed death ligand-1 (PDL1) has become especially predictive as PD-1 inhibitors like pembrolizumab and nivolumab have become the firstline standard of care in PDL1-positive metastatic disease [5]. PDL1-positive disease accounts for approximately 8.2% of cases and is associated with more advanced disease and lower survival [6]. Even PDL1-negative disease is highly resistant to chemotherapy and radiation therapy, other immunotherapies such as aldesleukin (IL-2) and targeted therapies (such as su-…”