From the Journals

PD-L1 correlates with worse sporadic, hereditary ccRCC outcomes



In patients with either sporadic or hereditary clear cell renal cell carcinoma, tumor expression of programmed death–ligand 1 (PD-L1) is associated with aggressive disease, investigators have found.

Analysis of tumor samples from patients with sporadic clear cell renal cell carcinoma (ccRCC) and others with Von Hippel-Lindau (VHL)–associated hereditary ccRCC showed that positive PD-L1 correlated with aggressive clinicopathologic features, reported Baoan Hong, MD, from Peking University First Hospital in Beijing, and colleagues.

“PD-L1 is a promising predictive biomarker for the utilization of PD-1/PD-L1 checkpoint inhibitors in ccRCC patients,” they wrote in Genitourinary Cancer.

The investigators conducted a retrospective analysis of PD-L1 expression and its potential correlation with disease features using samples from 129 patients with sporadic ccRCC and 26 patients with VHL disease who underwent partial or radical nephrectomy at their center from 2010 to 2017.

Sporadic ccRCC

The median age of patients with sporadic ccRCC was 61 years and the median tumor size was 4.3 cm. Of the 129 patients, 56 had pathological stage T1a at diagnosis, 44 had stage T1b, 8 had stage T2, and 21 had stage T3. In all, 25 patients had Fuhrman nuclear grade 3 tumors and 104 had grade 1 or 2 tumors. A total of 7 patients had metastases to lymph nodes, 41 had microvascular invasion, and 16 had tumor necrosis.

In all, 61 of these patients had PD-L1-positive tumors and 68 were PD-L1 negative. Positive PD-L1 was significantly associated with male gender (P = .025) and worse disease features, including higher T stage (P = .0011) and higher Fuhrman nuclear grade (P = .022).

After a median follow-up of 68 months, 9 patients in this group died and 17 others developed distant metastases or recurrent disease. Patients whose tumors were PD-L1 negative had significantly longer disease-free survival than patients with PD-L1-positive tumors, at a median 36 versus 28 months (P = .037).

VHL-associated ccRCC

Of the 26 patients with VHL-associated hereditary ccRCC (13 men and 13 women; median age, 42 years), 13 had pathological stage T1a disease, 7 had T1b, and 2 each has stage T2a, T3a, and T3b tumors. A total of 18 patients had Fuhrman nuclear grade 1 tumors and 8 had grade 2 tumors.

In this cohort, 17 patients had PD-L1-negative tumors, and 9 had PD-L1-positive tumors. PD-L1 expression was more common in patients with Fuhrman nuclear grade 2 tumors (six of eight cases). Patients with Fuhrman nuclear grade 1 tumors were more likely to be PD-L1 negative (15 of 18, P = .008). PD-L1 expression was not significantly correlated with either gender or tumor stage in this cohort.

There were no associations in this population between PD-L1 status and either age, tumor size, microvascular invasion, tumor necrosis, or lymph node metastases.

The investigators also compared the age of onset of all VHL-associated tumors in this cohort in PD-L1-positive versus PD-L1-negative patients, but found no statistically significant differences.

The authors acknowledged that the cohort sizes were small and that follow-up was relatively short, which could have a bearing on the analysis of associations between PD-L1 expression and disease features.

“Whether PD-L1 expression level in ccRCC is related to the effectiveness of PD-1/PD-L1 checkpoint inhibitor immunotherapy needs to be further investigated,” they wrote.

The study was supported by the National Natural Science Foundation of China and Special Health Development Research Project of Capital. The authors reported having no relevant disclosures.

SOURCE: Hong B et al. Clin Genitourin Cancer. 2018 Nov 13. doi: 10.1016/j.clgc.2018.11.001.

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